Abstract: BACKGROUND: Hippocampal atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippocampal size can help differentiate the two disorders. METHODS: We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippocampus and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. RESULTS: Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippocampus size and gray and white matter volumes were not different. WMHs and amygdala but not hippocampal volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippocampus volume significantly correlated with new visual learning. CONCLUSIONS: Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippocampal atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippocampus volume relates to episodic memory, especially right hippocampus and new visual learning. A longitudinal study of these subjects will determine whether hippocampal atrophy is a late development in VaD.

Abstract: The study examined sex-related differences in regional gray matter (GM) in 44-48 year old healthy individuals. T1-weighted MRI scans were acquired in 411 subjects aged 44-48 from a random community sample and optimized voxel-based morphometry was applied to detect regional GM difference between men and women, correcting for effects of age, years of education, handedness, and total intracranial volume (TIV). Men had larger brain volumes and higher white matter (WM) to TIV ratios compared with women. Women had higher GM to TIV ratios than men. After controlling for age, years of education, handedness, and TIV, there were no significant differences between men and women in the total GM volumes. Regional sex dimorphism was present, with men having more GM volume in midbrain, left inferior temporal gyrus, right occipital lingual gyrus, right middle temporal gyrus, and both cerebellar hemispheres. Women showed more GM in dorsal anterior, posterior and ventral cingulate cortices, and right inferior parietal lobule. Our results suggest sex dimorphism in GM in middle aged healthy individuals, which is not likely to be explained by brain pathology. These differences may provide the structural brain basis for sex differences in certain cognitive functions.

Abstract: OBJECTIVE: To investigate structural abnormalities in bipolar disorder (BD) using optimized voxel-based morphometry (VBM) in closely matched patients and controls, and to examine the relationship of clinical features with regional gray matter (GM) volumes. METHODS: Twenty-four patients (six male) aged 19-59 years (mean=38.21 years, SD=11.04 years) with DSM-IV bipolar I disorder were compared with 25 control subjects, matched on age, sex, and years of education. VBM analyses were conducted on high-resolution T1-weighted brain magnetic resonance imaging to detect regional GM volume differences between groups, ensuring statistical correlation for age, sex and total intracranial volumes. Within the patient groups, regional GM changes were also investigated. RESULTS: Compared to controls, BD patients had increased GM volume in left parahippocampal gyrus and decreased GM volume in left middle temporal gyrus. Family history, psychotic symptoms and lithium status were associated with regional GM abnormalities in BD patients. CONCLUSIONS: This study presents evidence of gray matter volume abnormalities in adults with bipolar I disorder. Regional variation in relation to clinical factors suggests a neurobiological basis for clinical heterogeneity and posits the possibility of trait deficits.

Abstract: A comparison of the clinical and pathophysiological features of postictal psychosis and brief interictal or alternating psychosis was undertaken to examine if the underlying mechanisms are distinct in these 2 conditions. A selective review of the published literature in English on epilepsy and brief psychosis was carried out. The literature indicates that even though brief postictal and alternating psychoses are considered to be separate syndromes, they have a number of similarities. It can be argued that the underlying pathomechanisms are common, with the brain's inhibitory processes in response to seizures playing a key role in the development of the psychosis. These homeostatic mechanisms manifest as electrophysiological, cerebral blood flow, and neurotransmitter and receptor changes. Both syndromes are likely to be associated with prolonged inhibition in limbic circuits, with further seizures modifying the psychosis depending upon whether it is associated with disinhibition or hypersynchrony involving enhanced inhibition. The neurotransmitter with a key role is GABA, although ionic currents, catecholamines, opiates, adenosine, glutamate, and nitric oxide play a role. Brief postictal and alternating psychoses provide an opportunity to understand the complex relationships between epilepsy and schizophrenia-like brief psychotic episodes, and this understanding can assist in their management.

Abstract: OBJECTIVE: To examine sex differences in white matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI), reported to be more severe in older women. METHODS: A random community sample of 228 men and 204 women, aged 60-64, underwent brain MRI scans. WMHs on T2-weighted FLAIR MRI scans were measured using an automated procedure. Subjects were assessed for physical health, cognitive function, vascular risk factors and Apolipoprotein E (APOE) genotyping. RESULTS: Women had more WMHs in both deep and periventricular regions. Hypertension, heart disease and high homocysteine were significant determinants in men and current smoking in women. Hormone replacement therapy and APOE*E4 allele did not have an association with WMHs. WMHs were related to reduced processing speed in men, and had an association with poor physical health and lowered grip strength in both sexes. CONCLUSION: WMHs are more common in women, with somewhat different putative causes and consequences than men, but >80% of the variance in their causation remains unexplained. The focus in the investigation of WMHs should move beyond the examination for cerebrovascular disease.

Abstract: BACKGROUND: Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have mostly involved once-daily treatment, with positive but modest clinical results. This study tested the efficacy and safety of twice-daily rTMS over 2 weeks. METHOD: Thirty-eight depressed subjects enrolled in a double-blind, sham-controlled trial of twice-daily rTMS (left prefrontal cortex, 10 Hz, 110% intensity, 1500 stimuli per session) over 2 weeks. Mood and neuropsychological functioning were assessed weekly by blind raters, using the Montgomery-Asberg Depression Rating Scale (MADRS) as the primary outcome measure, plus the Hamilton Rating Scale for Depression (HRSD) and self-report measures. After the blind period, 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS. RESULTS: Subjects were moderately treatment resistant. Active treatment resulted in significantly greater improvement than sham over the 2-week blind period on one outcome measure only (MADRS p<0.05). Subjects showed further improvement over the 6 weeks of active rTMS. Neuropsychological test scores did not change significantly. CONCLUSIONS: rTMS given twice daily was effective and safe, with no adverse neuropsychological effects.

Abstract: OBJECTIVE: To describe the 1- and 12-month prevalence of mental disorders, their demographic correlates, and their impact on service utilization and disability in individuals 65 years of age and over in a comprehensive epidemiological survey of mental health in Australia. METHODS: A noninstitutionalized national probability sample of elderly Australian residents was interviewed as part of the Australian National Mental Health and Well-being Survey (NMHWS). The prevalence of International Classification of Diseases, Tenth Revision and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition mental disorders was estimated from the Composite International Diagnostic Interview and other screening instruments. RESULTS: Of 1,792 elderly NMHWS respondents, 13% reported symptoms consistent with a mental disorder in the past 1 month, and 16% reported symptoms consistent with a mental disorder in the past 12 months. Women experienced higher rates of affective disorders and generalized anxiety disorder and had lower rates of substance abuse compared with men. After excluding cognitive disorder, increasing age was associated with less likelihood of having symptoms of any mental disorder. Older age and never having been married were associated with less likelihood of having symptoms of an affective disorder. Those with cognitive impairment were more likely to have had symptoms consistent with an affective disorder. Comorbidity was predictive of increasing disability on the 12-item Short Form but rates of mental health consultation were low, even for those with multiple disorders. CONCLUSION: Community-dwelling elderly Australians experience substantial rates of mental disorders. Demographic correlates of mental disorder in this elderly population appear to differ from those established in younger populations. Mental disorder in elderly Australians is associated with significant disability, but rates of specialist mental health consultation is low, even for those with multiple comorbidities. The reasons for this must be examined.

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Abstract: OBJECTIVE: This article examines the influence of sociodemographic, biological, and health variables on Mini-Mental State Exam (MMSE) performance, and assesses how the diversity of the population should be reflected in the MMSE cutoff scores used for screening. METHODS: The sociodemographic profiles and MMSE scores of adults aged 65-years and over who participated in the Australian National Mental Health and Well-being Survey were assessed (N = 1,792). RESULTS: The regression models showed that older age, education levels, language spoken at home and in country of birth, socioeconomic status (SES), occupation, sex, and presence of a mood disorder made significant and unique contributions to performance on the MMSE. The individual (univariate) influence of each factor ranged from -2.61 to 0.09 points, with non-English speaking background (NESB) making the biggest impact. Based on a MMSE score of < or =23 points, 7.7% of the Australian elderly population screened positive for cognitive impairment that may be indicative of dementia. In those scoring < or =23 points, the multivariate model accounted for 24.61% of the variance. CONCLUSION: Many sociodemographic variables and the presence of a mood disorder influence MMSE performance. Using conventional cutoff scores for screening will lead to a high rate of false positives in older adults (75+ years), those with NESB, and those with low SES, and is insensitive for those with high education. The authors suggest simple rules for the correction of the impact of these variables.

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Abstract: ABSTRACT BACKGROUND: To determine the efficacy and tolerability of repetitive transcranial magnetic stimulation (rTMS) as a treatment for obsessive compulsive disorder (OCD) in a double-blind placebo-controlled study.MethodSubjects with treatment-resistant OCD were randomized to rTMS (n=10) or sham rTMS (n=8) for 10 sessions of daily stimulation over the left dorsolateral prefrontal cortex (DLPFC), with subjects and raters being blind to the treatment. Subjects were offered an open extension of up to 20 sessions of rTMS. RESULTS: The two groups did not differ on change in Yale-Brown Obsessive Compulsive Scale (YBOCS) or Maudsley Obsessive-Compulsive Inventory scores over 10 sessions, with or without correction for depression ratings. Over 20 sessions, there was a significant reduction in total YBOCS scores, but not after controlling for depression. rTMS over 20 sessions was well tolerated.ConclusionTwo weeks of rTMS over the left DLPFC is ineffective for treatment-resistant OCD.

Abstract: OBJECTIVES: To determine the neural responses invoked in the recognition of facial fear and disgust in euthymic bipolar patients as compared with healthy subjects. METHODS: This study examined 10 female euthymic bipolar patients, and 10 suitably matched healthy subjects using functional magnetic resonance imaging (fMRI) while subjects were engaged in an explicit facial emotion recognition task involving fear, disgust and neutral expressions. The activation paradigm involved nominating the facial expression using specified response keys. Behavioural data were collected and analysed and both within-group (Fear versus Neutral; Disgust versus Neutral) and random-effects between-group analyses were performed on fMRI data using BrainVoyager (Brain Innovations, Maastricht, the Netherlands). RESULTS: Patients were equally accurate in identifying facial expressions as healthy subjects but were slower to respond, especially with respect to fear and disgust. Responses to fear and disgust (within-group analyses) resulted in activation of anticipated brain regions such as amygdala and insula, respectively. However, between-group random effects analysis revealed differential responses to both disgust and fear in both healthy subjects and euthymic bipolar patients such that euthymic bipolar patients responded largely to fear and healthy subjects responded more so to disgust. This partitioning of responsiveness was reflected by differential activation involving the hippocampus and amygdala. CONCLUSIONS: Greater responsiveness to fear with hippocampal activation in patients perhaps reflects recollection of traumatic events associated with past experiences of illness or simply the use of a more mnemonic (hippocampal) as opposed to affective (amygdala) approach when performing the task. It is possible that in bipolar disorder, prefrontal-subcortical network dysfunction that relegates neural processing to limbic regions is impaired and that clinically euthymic bipolar patients, although able to accurately and effectively identify emotions such as fear and disgust, are limited in their ability to interpret their salience. The implications of these findings are discussed.

Abstract: OBJECTIVE: The prevalence of mental disorders in the elderly is disputed. The debate in this area can be informed by data from large population surveys that contain sufficient elderly participants. The aim of the present paper was to provide the first direct comparison of the prevalence and demographic correlates of ICD-10 anxiety and affective disorders in the middle-aged and the elderly. METHOD: The 12 month prevalence and demographic correlates of affective and anxiety disorders were compared in a community sample of middle-aged and elderly Australian residents who took part in the Australian National Mental Health and Well-being Survey (NMHWS). RESULTS: One in seven middle-aged participants and one in 16 elderly participants experienced symptoms consistent with any anxiety or affective disorder in the preceding 12 months. Compared to the middle-aged participants, the elderly had lower rates for most affective and anxiety disorders, and for the combined presence of any disorder. Demographic correlates of mental disorder, especially marital status, were different for the two groups. CONCLUSIONS: Community-dwelling elderly in Australia have lower rates of mental disorder compared to the middle-aged. Differences in demographic correlates between groups support the notion that the determinants of mental disorder in the elderly differ substantially from those in middle age.

Abstract: OBJECTIVE: To examine the structural abnormalities in the amygdala in stroke patients and see what contribution the amygdala may make to psychopathology and cognitive dysfunction related to stroke, because the amygdala has important roles in the processing of emotions, cognitive function, and psychiatric disorders. METHODS: The authors assessed 47 stroke/transient ischemic attack (TIA) patients 3-6 months after the event and 54 comparison healthy subjects, using neuropsychological tests, medical and psychiatric examination and magnetic resonance imaging (MRI) brain scans. Volumetric T1-weighted MRI was used to obtain amygdala volumes by manual tracing. RESULTS: Stroke/TIA patients had smaller right amygdalar volume, more white matter hyperintensities (WMHs), and larger lateral ventricles. The amygdala was smaller in stroke/TIA patients with cognitive impairment compared to those without impairment. The right amygdala volume was negatively correlated with visual new learning and not related to depression, anxiety, irritability, agitation or apathy at baseline or 12-month follow-up. However, baseline amygdala volume was negatively correlated with Hamilton depression scores at 12 months in healthy comparison subjects. Hypertension and atrial fibrillation, and to a lesser extent WMHs, were predictors of amygdala volume. CONCLUSION: The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment. This may partly be accounted for by hypertension, white matter lesions, and atrial fibrillation. It is not related to psychopathology except that small amygdalae may increase vulnerability to depression.

Abstract: OBJECTIVE: To investigate the frequency and correlates of depression at 3 and 15 months after stroke. METHODS: A total of 164 consecutive eligible stroke patients and 100 comparison subjects received extensive medical, psychiatric, and neuropsychological assessments; a subset also received magnetic resonance imaging scans. Comprehensive assessments included ratings for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major or minor depression at 3-6 months (index assessment) and 15 months (follow-up assessment) after stroke. The comparison subjects, who were similar in age and sex, were similarly assessed twice, 12 months apart. RESULTS: Major or minor depression was present in 12.0% of stroke patients at index assessment and in 20.7% at follow-up which included 18 new cases (13.4%). By follow-up, stroke patients with depression had significantly greater impairment of functional ability and global cognition than nondepressed stroke patients or comparison subjects. Depression was not associated with age, intellectual decline prior to stroke or side or severity of stroke. Patients who experienced a TIA or stroke during the follow-up, who had developed dementia by three months or who were not living with a relative or partner were more likely to be depressed at follow-up. Dementia at 3 months predicted depression, but the reverse did not hold. CONCLUSION: Depression may be less frequent after stroke than previously reported and is related to cumulative vascular brain pathology rather than side and severity of single strokes. Clinicians should strive to slow the progression of cerebrovascular disease and encourage greater social support.

Abstract: OBJECTIVE: This cross-sectional study examined the prevalence and characteristics of depression in subjects with mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health Through Life 60+ (PATH 60+) Project. METHOD: A total of 2551 community-dwelling individuals in the age range 60-64 years were recruited randomly through the electoral roll. They were screened using a short cognitive battery and those who screened positive underwent detailed medical and neuropsychological assessments. There were 29 subjects who fulfilled the Mayo Clinic criteria for MCI and these were compared to 520 controls. Subjects were evaluated for depression symptoms and DSM-IV major and minor depression syndromes. RESULTS: Subjects with MCI had more minor depression and higher scores on a symptom scale. However, a multivariate examination of specific symptoms showed that the differences were confined to only two motivation-related symptoms ("felt slowed up" and "little interest or pleasure"). CONCLUSION: Motivation-related depressive symptoms are more relevant in subjects with MCI than mood-related symptoms.

Abstract: BACKGROUND: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer's disease (AD) subjects on a verbal recognition memory task. METHODS: Eighteen early AD and 10 matched healthy control subjects underwent split-dose (99m)Tc-HMPAO (Ceretec) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. RESULTS: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. CONCLUSIONS: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.

Abstract: This cross-sectional study aimed at determining the clinical and structural brain magnetic resonance imaging correlates of mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health through Life 60+ project. 2,551 community-dwelling individuals in the age range of 60-64 years were recruited randomly through the electoral roll. They were screened using Mini-Mental State Examination and a short cognitive battery. Those who screened positive underwent detailed medical and neuropsychological assessments. Of the 224 subjects who screened positive, 117 underwent a detailed assessment. Twenty-nine subjects fulfilled the Mayo Clinic criteria for MCI. Magnetic resonance imaging scans were analyzed for 26 subjects with MCI as well as normal controls. Subjects were clinically evaluated for depressive symptoms and major and minor depression syndromes. Logistic regression analysis was performed predicting MCI from anterior and mid-ventricular brain ratios, cortical atrophy measures, hippocampal volumes, volumes of amygdala and white matter hyperintensities after adjusting for age, gender, years of education, depression and physical disability. None of the neuroanatomical substrates appeared as predictors of MCI. The only predictors were higher depression scores and fewer years of education. Structural neuroimaging may not have an added advantage in the detection of MCI in middle-aged community-dwelling subjects. It may be that this age group is too young for such brain changes to be identified.

Abstract: Both brain atrophy and T2-weighted white matter hyperintensities (WMH) are common findings in the brains of asymptomatic elderly individuals as well as in disease-specific brains. The study of the relationship between these two salient features is therefore important. To investigate such a relationship, we performed a brain magnetic resonance imaging (MRI) study on 397 asymptomatic individuals aged between 60 and 64 years, who were recruited randomly from a large community sample. WMH were delineated on T2-weighted fluid attenuation inversion recovery (FLAIR) whole brain scans using an automated procedure. The results showed that gray matter reduction, subarachnoid CSF (SA-CSF) increase and lateral ventricular dilation were significantly correlated with WMH load. Deep white matter hyperintensity (DWMH) had significant correlation with all three global atrophy indices, but periventricular white matter hyperintensity (PVWMH) was correlated only with gray matter volume. Voxel-based morphometric (VBM) analysis showed that regional gray matter reduction correlated more closely with WMH load of the proximate region than with WMH elsewhere. The results suggest that WMH have a relationship with brain atrophy in middle age, although the study cannot determine which process, i.e. the development of WMH or atrophy, is primary. The study also demonstrates that DWMH has a more significant relationship with structural brain changes, and may therefore be more functionally relevant than PVWMH. Further delineation of this relationship needs a longitudinal study of the changes in both WMH and indices of brain atrophy.

Abstract: BACKGROUND: Dementia following stroke is common but its determinants are still incompletely understood. METHODS: In the Sydney Stroke Study, we performed detailed neuropsychological and medical-psychiatric assessments on 169 patients aged 50-85 years, 3-6 months after a stroke, and 103 controls with a majority of both groups undergoing MRI brain scans. Stroke subjects were diagnosed as having vascular mild cognitive impairment (VaMCI) or vascular dementia (VaD) or no cognitive impairment by consensus. Demographic, functional, cerebrovascular risk factors and neuroimaging parameters were examined as determinants of dementia using planned logistic regression. RESULTS: 21.3% of subjects were diagnosed with VaD, with one case in those aged 50-59 years, 24% in those aged 60-69 years and 23% in those 70-79 years. There was no difference by sex. The prevalence of VaMCI was 36.7%. VaD subjects had lower premorbid intellectual functioning and had 0.9 years less education than controls. The VaD and VaMCI groups did not differ from the no cognitive impairment group on any specific cerebrovascular risk factor, however overall those with impairment had a greater number of risk factors. They did not differ consistently on depression severity, homocysteine levels and neuroimaging parameters (atrophy, infarct volume and number of infarcts) except for an excess of white matter lesions on MRI and greater number of infarcts in the VaD and VaMCI groups. On a series of logistic regression analyses, stroke volume and premorbid function were significant determinants of cognitive impairment in stroke patients. CONCLUSION: Post-stroke dementia and MCI are common, especially in older individuals. Cerebrovascular risk factors are not independent risk factors for VaD, but stroke volume is a significant determinant of dementia. Premorbid functioning is a determinant of post- stroke impairment.

Abstract: The effect of putative cerebrovascular risk factors on gray matter volume in a community-dwelling, non-demented 60- to 64-year-old cohort was investigated. Cranial T1-weighted MRI scans were obtained in 337 adults and voxel-based morphometric analyses were applied to detect regional gray matter volume differences related to hypertension, diabetes, smoking, and hyperlipidemia in men and women, respectively. Hypertension-related gray matter volume reduction was found in right superior, bilateral medial frontal, left superior temporal and left precentral gyri in men. No regional differences in gray matter related to hypertension were seen in women. Conversely, female but not male smokers had more gray matter volume in right fusiform gyrus and right temporal subgyral gray matter. No differences were observed in gray matter volume in association with diabetes or hyperlipidemia for men or women. Our results suggest that there are different patterns of regional effects in gray matter volume in relation to different cerebrovascular risk factors, and sex differences for the same risk factors.

Abstract: OBJECTIVE: To determine the relationship of lung function to brain anatomical parameters and cognitive function and to examine the mediating factors for any relationships. METHODS: A random sub-sample of 469 persons (men = 252) aged 60-64 years from a larger community sample underwent brain magnetic resonance imaging scans and pulmonary function tests (forced vital capacity, FVC, forced expiratory volume in the first second, FEV(1)). Subjects were assessed for global cognitive function, episodic memory, working memory, information processing speed, fine motor dexterity and grip strength. The magnetic resonance imaging scans were analysed for overall brain atrophy, subcortical atrophy (ventricle-to-brain ratio, VBR), hippocampal volume, and white matter hyperintensity (WMH) volume. RESULTS: FEV(1) had a significant negative correlation with overall brain atrophy and VBR in men. The FEV(1)/FVC ratio had a significant correlation with WMHs in both men and women. In regression models that controlled for sex, age, height, level of activity, smoking, chronic respiratory disease and education, FEV(1) and FVC were significant predictors of VBR but no other structural brain measure. Pulmonary function was also significantly related to information processing speed and fine motor dexterity. Male subjects with chronic respiratory disease had more deep WMHs. Path analyses to examine if structural measures mediated between lung function and cognition, and whether markers of inflammation and oxidative stress or cortisol mediated between lung function and brain measures were negative. CONCLUSIONS: Decreased lung function is related to poorer cognitive function and increased subcortical atrophy in mid-adult life. Presence of chronic respiratory disease may be related to deep WMHs in men.

Abstract: Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.

Abstract: RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic effects in animal models. Preliminary animal studies suggest that this agent has the capacity to reverse cholinergic dysfunction and that it may impact on regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer's disease (AD) of mild severity underwent high resolution split-dose single photon emission computed tomography (SPECT) during performance of a verbal recognition and control task, both before and after 18 weeks treatment with melameline or placebo. SPECT images were coregistered with individual's magnetic resonance imaging scans allowing extraction of rCBF values from multiple anatomical regions of interest (ROI). The effect of milameline was examined in eight individuals who were found after unblinding to be taking active drug. Effects of milameline were most apparent in the frontal regions, basal ganglia and thalamus. In the group as a whole, the greatest increase in rCBF due to milameline treatment was observed in the left globus pallidus. Response to milameline treatment was associated with increases in rCBF in the cingulate gyrus bilaterally, and less so for the left thalamus. Milameline-related increases in rCBF values were exaggerated by the verbal recognition task. Milameline has a demonstrable effect on cerebral blood flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear most prominent in frontal and subcortical regions in AD subjects. The effects on rCBF appear to be augmented by the performance of a cognitively demanding task, raising the possibility that such tasks could assist in building an awareness of the functional neuropsychopharmacology of drugs designed for cognitive enhancement.

Abstract: OBJECTIVE: We aimed to examine the longitudinal change in proton magnetic resonance spectroscopy ((1)H-MRS) visible metabolites (N-acetyl aspartate [NAA], creatine [Cr], choline [Cho], and myo-Inositol [mI]) in brains of elderly individuals over 3 years and relate them to cognitive function. METHODS: Neurologically and psychiatrically normal volunteers (n = 40) were examined at baseline and 3 years later with (1)H-MRS in two voxels (frontal white matter n = 29, and occipitoparietal gray matter n = 36) and with detailed neuropsychological assessments. Longitudinal analyses were performed with age, educational level, sex, and white matter hyperintensities (WMH) in voxels as covariates. RESULTS: Frontal mI was significantly increased over time in male participants, but all other metabolites were stable over time. Neuropsychological performance was not significantly changed over 3 years, and there was no relationship between change in metabolite levels and change in neuropsychological function. CONCLUSIONS: MRS-visible metabolites are stable in elderly persons over 3 years, with the exception of mI which shows an increase. Increasing mI may be a marker of aging or a preclinical neurodegenerative process. MRS changes do not correlate with change in neurocognitive function during aging.

Abstract: A recently published study used the interference strategy of transcranial magnetic stimulation (TMS) to demonstrate the role of the right posterior parietal cortex (PPC) in the mental rotation of alphanumeric stimuli. We used similar stimulation parameters over the same left and right PPC regions, and examined the ability to rotate more complex 3D Shepard and Metzler (1971) images. There was reduced accuracy of performance with both right and left PPC stimulation for different angles of rotation of the visual stimuli. Right PPC stimulation led to reduced accuracy to rotate stimuli by 1200, whereas left PPC stimulation affected 180 degrees C rotation. We hypothesise that the two hemispheres make different contributions to the processing underlying visuospatial mental imagery: the right PPC is important for spatial rotations through smaller angles; the left hemisphere has a unique role when the stimuli to be compared are rotated through 180 degrees C, a task that engages verbal strategies due to the well-documented special nature of enantiomorphs.

Abstract: BACKGROUND: Case control studies have supported a relationship between low folic acid and vitamin B112 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. METHOD: A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. RESULTS: Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. CONCLUSIONS: Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.

Abstract: In spite of its wide availability, single photon emission computerized tomography (SPECT) scanning is uncommonly used in the assessment of Alzheimer's disease (AD) and related dementias. In light of recent advances in scanning protocols and image analysis, SPECT needs to be re-examined as a tool in the diagnosis of dementia. A total of 18 subjects with early AD and 10 healthy elderly control subjects were examined with high resolution SPECT during the performance of a simple word discrimination task. SPECT images were coregistered with individual magnetic resonance imaging scans, allowing delineation of predetermined neuroanatomical Regions of Interest (ROI). There was a gradation of regional cerebral blood flow (rCBF) values in both groups, with the lowest values being in the hippocampus and the highest in the striatum, thalamus and cerebellum. Compared to healthy controls, AD subjects demonstrated lower relative rCBF in parietal and prefrontal cortices. Analysis of individual ROI demonstrated bilateral reduction of rCBF in prefrontal poles, posterior temporal and anterior parietal cortex, and unilateral reduction of rCBF in left dorsolateral prefrontal cortex, right posterior parietal cortex and the left cingulate body. There were no significant differences for hippocampal, occipital or basal ganglia rCBF. Discriminant function analysis indicated that rCBF in the prefrontal polar regions achieved the best classification of cases. SPECT has utility in the diagnostic assessment of AD if standardized and semiquantitative techniques are used.

Abstract: Ageing is associated with cognitive decline, with some studies indicating that this decline can be mostly accounted for by slowing of information processing speed. Whilst it is likely that this is associated with age-related changes in fronto-subcortical neuronal circuits, such changes are not visible on routine neuroimaging. We examined the integrity of this brain region using proton magnetic resonance spectroscopy (1H MRS) and hypothesised that functional changes measured by 1H MRS would be associated with cognitive performance. Fifty-nine healthy elderly subjects (age 58-85 years) underwent single-voxel 1H MRS in frontal white matter and occipito-parietal gray matter, and a comprehensive neuropsychological battery. The results showed a significant correlation between frontal white matter NAA/H2O and a composite measure of neuropsychological performance representing speed of information processing, attentional function and visual memory, controlling for age and sex. This research highlights the importance of the relationship between regional brain changes and cognitive function in the ageing brain, and suggests that MRS may be a sensitive marker of subclinical change in cognition.

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Abstract: This epidemiological study aimed at determining the prevalence of mild cognitive impairment (MCI) in 60- to 64-year-old individuals using different diagnostic criteria. Community dwelling individuals (n = 2,551) in the age range of 60-64 years were recruited randomly through the electoral roll. They were screened using the MMSE and a short cognitive battery, and those who screened positive underwent detailed medical and cognitive assessments. Extant MCI-related diagnoses were established by consensus. Predictive regression models on the sub-sample were used to determine population prevalence for the diagnoses. Of the 224 subjects who screened positive for MCI, 112 underwent a detailed assessment and 74% met the criteria for at least one recognised diagnosis of mild cognitive deficit (MCI and related diagnoses). By predictive regression modelling, the prevalence of any MCI diagnosis was 13.7% (95% CI 9.1-30.2) in the population of 60- to 64-year-olds. The estimated prevalence rates for specific diagnoses were: MCI 3.7%, ageing-associated cognitive decline 3.1%, Clinical Dementia Rating score (0.5) 2.8%, age-associated memory impairment 1%, other cognitive disorders 0.9%, and mild neurocognitive disorder 0.6%. Agreement on 'caseness' between various proposed diagnoses was at best fair and generally poor. Memory and other cognitive problems not meeting the threshold for dementia are relatively common in 60- to 64-year-old individuals living in the community. The prevalence rate varies up to six-fold according to the diagnostic criteria applied, with limited overlap between diagnoses. There is an urgent need for standardization of the criteria.

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Abstract: OBJECTIVE: To determine the impact of white matter hyperintensities (WMHs) on physical health and cognitive function in 60-64 year old individuals residing in the community. METHODS: A subsample of 478 persons aged 60-64 from a larger community sample underwent brain magnetic resonance imaging (MRI) scans. WMHs on T2 weighted FLAIR (fluid attenuated inversion recovery) MRI scans were assessed using an automated procedure. Subjects were assessed for global cognitive function, episodic memory, working memory (digit span), information processing speed (Symbol Digit Modalities Test; SDMT), fine motor dexterity (Purdue Pegboard), and grip strength, and completed the Physical Component Summary of the Short Form Health Survey (SF-12). Regression analyses were used to examine the effect of WMHs on physical and cognitive function. RESULTS: Deep and periventricular WMHs were present in all subjects, with women having slightly more lesions than men. WMHs were significantly associated with poorer reported physical health on the SF-12 scale, after adjusting for depression, cognitive function, and brain atrophy. WMHs were also related to lower scores on the Purdue Pegboard test, grip strength, choice reaction time, and SDMT, but not on tests of episodic memory, working memory, general intellectual function, and global cognitive function. On regression analyses, the Purdue Pegboard test and grip strength were related to physical disability. CONCLUSION: WMHs are common, albeit mild, in middle adult life. They are associated with physical disability, possibly through reduced speed, fine motor coordination, and muscular strength. They are also related to slowed information processing speed but not other cognitive functions.

Abstract: The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.

Abstract: Between 1973 and 1995, a total of 76 patients were treated with bilateral stereotactic, orbitomedial lesions for resistant severe depression at the Neuropsychiatric Institute, Sydney, Australia. On follow up after a mean 14.4 years, 24 (31.6%) subjects were confirmed dead, with six having committed suicide. Of the 52 patients still alive (mean age 62.9 years), 23 were interviewed in detail, and lesions verified in 18 with magnetic resonance imaging (MRI). On a 6-point global outcome rating scale, rated by consensus between two independent psychiatrists, five (22.7%) were judged to be completely recovered and another 11 (50%) showed significant improvement. The improvement was noted within days or weeks of the surgery. Adverse effects were epilepsy (2 subjects), marked personality change (1), weight gain (2), and mild personality change (5). Any reported cognitive impairment was mild. No definite predictors of improvement were identified.

Abstract: BACKGROUND: The frequency and clinical, neuropsychological and neuroimaging correlates of apathy in patients who have had a stroke are inadequately defined.METHOD: A total of 167 consecutive patients admitted to the stroke units of two university hospitals after an ischaemic stroke and 109 controls received extensive medical, psychiatric and neuropsychological assessments; a subset received a magnetic resonance imaging (MRI) scan. The groups were matched for sex and age. Patients were assessed 3-6 months after their stroke. The sample for this study comprised 135 patients and 92 controls who completed the Apathy Evaluation Scale (AES).RESULTS: Apathy was present in 26.7% of stroke patients compared to 5.4% of controls. Apathetic stroke patients were older, more functionally dependent and had lower Mini-Mental State Examination (MMSE) scores than those without apathy. Apathy was not associated with risk factors for cerebrovascular disease or stroke severity. There was a weak but significant correlation between apathy and self-reported depression but not with clinician-rated depression. Neuropsychologically, after correction for age, premorbid intelligence (IQ) and depression, apathy was associated with reduced attention and speed of information processing. On neuroimaging there were trends for associations of apathy with the extent of hyperintensities in the right hemisphere and right fronto-subcortical circuit, but not with total stroke volume or number of strokes.CONCLUSIONS: Apathy is common following a cerebrovascular event. Presence of apathy may be related to older age and right fronto-subcortical pathway pathology, rather than stroke severity. It is associated with functional impairment and cognitive deficits.

Abstract: Transcranial magnetic stimulation (TMS) has been proposed as a treatment for depression and anxiety disorders. While the antidepressant effect has been modelled in animals, there have been few attempts to examine a possible anxiolytic effect of repetitive TMS (rTMS) in animal models. We administered 18 days of rTMS to male Sprague-Dawley rats. On days 10 through 18, rats were tested in several anxiety models (social interaction, emergence, elevated plus-maze, and predator odor avoidance) and in the forced swim test. No group differences were apparent on any of the anxiety models, while TMS produced an antidepressant effect in the forced swim test. Interestingly, on day 1 of the forced swim test, the home cage control group displayed increased swimming behaviour compared with sham-treated animals, suggesting an observable level of stress may have accompanied sham treatment. The results from the forced swim test suggested that TMS had modest antidepressant properties, but it did not show anxiolytic properties in the models examined. The study also suggested that stress associated with handling should be taken into account in the interpretation of TMS studies in animals.

Abstract: BACKGROUND: Frontotemporal dementia (FTD) is difficult to diagnose in the early stages and may be misdiagnosed as Alzheimer's disease (AD) or as a psychiatric disorder. This study aimed to investigate neuropsychological function in FTD of mild severity and compare it to that of mild AD and healthy control participants. METHODS: The study comprised 11 individuals with FTD, 29 with AD and 27 healthy controls. Participants completed a comprehensive neuropsychological assessment in which each area of cognitive function was examined with several widely used clinical tests. Test scores were converted to age-corrected scaled scores and combined to form indices for six areas of cognitive function. These indices were attention, psychomotor speed, memory acquisition, memory recall, executive function and constructional ability. RESULTS: The FTD group performed below the level of the controls in all areas except constructional ability. FTD and AD groups showed distinct patterns of neuropsychological performance. The FTD group showed predominantly executive dysfunction with less impaired memory function, while the AD group showed the opposite pattern. The capacity of the tests to discriminate between groups was good overall, with 90% of the total sample correctly classified. Predictive success for the FTD group was 64%, given a base rate of 16%. CONCLUSION: Administration of a comprehensive neuropsychological protocol including several tests of executive function allows increased certainty about accurate clinical diagnosis of mild FTD.

Abstract: Movement disorders such as Parkinson's disease and Tourette's syndrome, primarily manifest during wakefulness, intrude into sleep. There are some disorders, however, such as periodic limb movements in sleep, restless legs syndrome, paroxysmal nocturnal dystonia, bruxism, and somnambulism, which occur primarily during sleep. The diagnosis and management of these disorders pose a challenge to neuropsychiatric practice, not only because they may be difficult to distinguish from other neuropsychiatric disorders, but also because psychiatric disorders are often co-morbid with them. Study of these disorders is necessary for an understanding of the interaction of sleep and movement, and how disturbance in one may affect the other.

Abstract: OBJECTIVE: To identify the brain regions associated with emotional processing in euthymic bipolar patients. METHODS: The study examined 12 euthymic bipolar patients using functional magnetic resonance imaging (fMRI) while performing an emotional Stroop (eStroop) task. The task comprised emotionally valent and neutral words presented in alternating blocks that was designed to implicitly induce affect. In conjunction with fMRI, galvanic skin responses (GSR) were measured to monitor arousal. RESULTS: Euthymic bipolar patients had diminished activation in response to the affective stimuli in both cortical and subcortical brain regions when compared with healthy subjects. In particular, patients had less activation in the left ventral prefrontal cortex suggesting a potential trait deficit. Patients were slower to react than healthy controls, but did not differ with respect to accuracy. CONCLUSIONS: Euthymic bipolar patients are perhaps constrained in their ability to engage affective processing. Diminished ventral prefrontal cortex activation corroborates previous reports of a potential trait deficit, suggesting that 'all is not well in euthymia', although the effects of medication cannot be overlooked.

Abstract: OBJECTIVE: Compulsive individuals are habitually indecisive, and indecision reaches its pathological apex in obsessive-compulsive disorder (OCD). With the increasing interest in the neurobiology of decision-making, it may be useful to conceptualize OCD as a disorder of decision-making. METHOD: A selective review of the neurobiological studies of the decision-making process was performed, and the convergence with the understanding of the neurobiology of OCD examined. RESULTS: The dorsolateral, orbitofrontal and anterior cingulate cortices are engaged in multiregion neural subsystems that interact with each other to retain information online, manipulate options, make choices and maintain goals. These interact with the limbic regions, especially the amygdala, in relation to history of reward and emotional valence relating to a choice, and the basal ganglia for behavioural execution. Abnormalities in these regions also characterize OCD and related disorders, therefore leading to problems in making some decisions that are affect-laden by nature or association. CONCLUSION: Conceptualizing OCD as a disorder of decision-making leads to new approaches for its investigation, and novel strategies for both physical and behavioural-cognitive treatments.

Abstract: The development of a rating scale for neuroleptic malignant syndrome (NMS) is described. The clinical and laboratory features of NMS were categorised into six domains after a thorough literature review and examination of patients. The reliability of this scale was established on 25 NMS patients and 50 control subjects based on chart reviews. A factor analysis supported a six-factor solution. The validity of the scale was indicated by the relationship of the severity rating to duration of illness and outcome. The inter-rater reliability of the scale was established prospectively in 10 subjects. The scale offers a measure of severity of NMS in the clinical setting so as to support the clinical diagnosis, monitor patients and determine their progress. The scale may be applicable not only to NMS or suspected NMS but also to NMS-like syndromes such as lethal catatonia.

Abstract: Homocysteine (Hcy) has been implicated as a risk factor for vascular disease as well as brain atrophy. There is evidence to implicate Hcy in increased oxidative stress, DNA damage, the triggering of apoptosis and excitotoxicity, all important mechanisms in neurodegeneration. Hcy is also prothrombotic and proatherogenic, and causes damage to the vessel wall. It is related to brain atrophy in older individuals, and possibly to white matter hyperintensities (WMH) in the brain. Epidemiological evidence and longitudinal data support Hcy as a risk factor for cognitive impairment and Alzheimer's Disease (AD). This may be due to cerebrovascular as well as direct neurotoxic mechanisms. Its role in Parkinson Disease (PD) is less well supported. High Hcy has been suggested as a mediating factor in alcohol-related brain atrophy. The high prevalence of hyperhomocysteinemia in the population and its easy treatability make Hcy an interesting amino acid for future intervention studies in the prevention of degenerative brain disorders. Intervention studies are necessary to confirm its aetiological role.

Abstract: The neurophysiological basis of cognition is relatively unexplained, with most studies reporting weak relationships between cognition and measures of brain function, such as event-related potentials, brain size and cerebral blood flow. Magnetic resonance spectroscopy (MRS) is an in vivo method used to detect neurochemicals within the brain that are relevant to certain brain processes. The most widely used methods are 1H-MRS and 31P-MRS, which detect compounds that contain hydrogen and phosphorus, respectively. Recent studies have shown that the absolute concentrations or ratios of these neurochemicals, in particular N-acetyl aspartate (NAA), which is associated with neuronal viability, correlate with performance on neuropsychological tests or other measures of cognitive function in normal subjects. Many studies in adults and children have shown a relationship between neurometabolite values and cognitive status or extent of cognitive dysfunction in various neurological and neuropsychiatric disorders. We review these studies and conclude that MRS has potential applications for the study of cognitive processes in health and disease and may be used clinically for differential diagnosis, the early detection of pathology and the examination of longitudinal change.

Abstract: OBJECTIVE: To characterize the neuropsychological profile of vascular cognitive impairment (VCI) and vascular dementia (VaD). METHODS: The authors examined 170 patients with stroke or TIA at 3 to 6 months after the vascular event, and 96 age-matched healthy controls, with detailed neuropsychological and medical-psychiatric assessments, with a majority (66.7%) undergoing MRI brain scans. The subjects were diagnosed as having VaD, VCI, or no cognitive impairment by consensus. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. RESULTS: VaD subjects had disturbance in all cognitive domains, with verbal memory, especially retention, being less affected. VCI subjects had similar but less severe disturbance. The domains that best discriminated cognitively impaired from unimpaired patients were abstraction, mental flexibility, information processing speed, and working memory. Cognitive impairment had a significant correlation with deep white matter hyperintensities, but not with volume and number of infarctions, even though the VaD subjects had larger infarct volumes than VCI subjects. The MRI variables did not provide additional discrimination between subgroups. CONCLUSIONS: The cognitive deficits in VaD and VCI are characterized by disturbance of frontal functions, with less verbal memory impairment. VaD and VCI differ in severity but not pattern of disturbance. The brain lesions that best account for these deficits are noninfarct subcortical white matter and gray matter changes due to ischemia. The picture of VaD/VCI presented shows subcortical deficits embellished by cognitive deficits from cortical infarctions.

Abstract: BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) on T2-weighted MRI are common in stroke patients and healthy elderly individuals. The detailed anatomical distribution of these lesions in stroke patients has not been examined. METHODS: A total of 112 stroke or transient ischemic attack patients and 87 matched control subjects from the Sydney Stroke Study underwent MRI scans that included a T2-weighted fluid-attenuated inversion recovery (FLAIR) sequence. WMHs were delineated from each FLAIR MRI by an automated method. Region of interest and voxel-wise statistical parametric mapping approaches were applied to examine the volume, distribution, and severity of WMHs of the patient and control groups, and subgroups with large or lacunar infarcts. RESULTS: Stroke subjects had significantly more WMHs than controls in all brain regions except the occipital lobe and in all arterial territories except the anterior callosal and anterior medial lenticulostriate. In the frontotemporal regions, average WMH volumes in patients were >3.5x those in controls. The total number of discrete WMHs was not different in the 2 groups, but stroke patients had more large (>20 mm) and high-intensity lesions. Subjects with lacunar infarcts had more WMHs than those with large infarcts, who, in turn, had more WMHs than control subjects. Lacunar infarction subjects had more WMHs than subjects with large thromboembolic or cardioembolic strokes. Those with anterior arterial territory infarction had more WMHs in the frontal regions. Subjects with single or multiple lacunes did not differ in volumes of WMHs. CONCLUSIONS: Stroke patients have significantly more WMHs in nearly every brain region than healthy controls. Those with lacunar infarcts are particularly affected. WMHs represent a significant proportion of the ischemic lesion burden in stroke and transient ischemic attack patients.

Abstract: OBJECTIVE: To examine the progression of neuropsychological deficits in stroke patients with and without cognitive impairment. METHODS: The authors assessed the Sydney Stroke Study cohort 1 year after index assessment with detailed neuropsychological and medical-psychiatric assessments. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. Changes in cognitive test scores were compared between groups and predictors of cognitive change examined. RESULTS: Patients (n = 128) had a mean decline of 0.83 (SD 2.2) points on the Mini-Mental State Examination (MMSE) compared to an increase of 0.76 (1.3) in controls (n = 78) (p < 0.0001), and a small but significant decline in informant ratings of function and cognition. The decline on a composite index of cognitive function was not significantly different in the groups after correction for age, education, and index assessment cognitive function. Stroke/transient ischemic attack patients, however, had greater decline in verbal memory and visuoconstructive function. The occurrence of an interval stroke (n = 14) significantly increased the cognitive decline to a mean 2.0 points on the MMSE. The rate of change had a significant correlation (r = 0.24) with white matter hyperintensity volume at index assessment. On regression analysis the only predictor of cognitive change was years of education, which had a protective function. CONCLUSIONS: Subjects with cerebrovascular disease have a slow decline in cognitive functioning in the absence of further cerebrovascular events, although the occurrence of such an event accentuates the dysfunction. Education plays a protective role.

Abstract: A case of ectopic ovarian pregnancy is presented occurring in a 24 years old woman after natural conception. The clinical diagnosis was ruptured tubal pregnancy. Gross findings were suggestive of ruptured corpus luteum cyst on exploration. The histopathological examination of specimen brought forward the diagnosis of ovarian pregnancy.

Abstract: BACKGROUND: The efficacy and safety of bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, placebo-controlled study. METHOD: Nineteen medication-resistant depressed subjects were randomly assigned to 3 weeks of active or sham rTMS. Effects on mood and neuropsychological function were assessed. RESULTS: Both groups improved significantly in mood over the 3 weeks, but there was no significant difference between active and sham treatments. There were no significant neuropsychological effects. CONCLUSIONS: Bilateral rTMS was not superior to sham in treating resistant depression in this pilot study, but caused no neuropsychological impairment.

Abstract: BACKGROUND: Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk factor for cognitive impairment. METHODS: We examined 95 stroke subjects 3 months after their strokes, and 55 healthy comparison subjects, with a detailed neuropsychological assessment, and MRI brain scans in a proportion (n = 97). Baseline measurements of tHcy, serum folate and B(12), creatinine and plasma fibrinogen levels were obtained. RESULTS: tHcy levels were higher in the stroke subjects by a mean 34%. These levels were significantly correlated with the first factor of a principal component analysis of the neuropsychological data, after controlling for age, folate, B(12) and creatinine levels. The correlation of Hcy levels was particularly significant with frontal-executive functioning and attention. tHcy levels were significantly correlated with number of infarcts and total stroke volume in the stroke group, but not with T(2)-weighted deep white matter hyperintensity scores, after correction for age. In the control group, tHcy levels were significantly correlated with ventricle-to-brain ratios as measures of brain atrophy. CONCLUSION: This study provides evidence that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function. The major component of this association is accounted for by small and large strokes, but non-vascular neurotoxic effects of tHcy also appear to play a role. tHcy must receive greater attention as a risk factor for cognitive impairment.

Abstract: Traumatic brain injury (TBI) can result in serious and disabling neuropsychiatric disorders, such as cognitive deficits and personality change, as well as severe and chronic psychosis. This review focuses on the relationship between TBI and schizophrenia-like psychosis (SLP) including its epidemiology, diagnostic criteria, clinical presentation, psychopathology, risk factors, and pathophysiology. The relationships between post-traumatic epilepsy and SLP, and brain trauma and schizophrenia, are also discussed. The risk of SLP does increase after TBI. The clinical presentation has considerable overlap with primary schizophrenic disorder, with a prominence of persecutory and other delusions and auditory hallucinations, as well as a lack of negative symptoms. The onset is often gradual, with a subacute or chronic course. More severe and diffuse brain injury, especially of the temporal and frontal lobes, is the most prominent risk factor. Genetic load may also play a role, but presence of epilepsy could be a protective factor. Further large and systematic longitudinal studies are needed.

Abstract: BACKGROUND: High and low frequency repetititve transcranial magnetic stimulation (rTMS) are both effective in treating depression but have contrary effects on motor cortical activity. This study aimed to understand further the mechanisms of action of high and low frequency rTMS by examining their acute effects on regional cerebral blood flow (rCBF) in depressed patients. METHOD: Eighteen depressed subjects underwent brain single photon emission computerized tomography (SPECT) scanning using split-dose 99mTc-HMPAO, and were examined during sham and active rTMS to the left prefrontal cortex, at 15 Hz or 1 Hz (N=9 each). Relative rCBF changes were examined by statistical parametric mapping and by regions of interest analysis. RESULTS: High (15 Hz) frequency rTMS resulted in relative rCBF increases in the inferior frontal cortices, right dorsomedial frontal cortex, posterior cingulate and parahippocampus. Decreases occurred in the right orbital cortex and subcallosal gyrus, and left uncus. Low (1 Hz) frequency rTMS led to increased relative rCBF in the right anterior cingulate, bilateral parietal cortices and insula and left cerebellum. High frequency rTMS led to an overall increase, whereas low frequency rTMS produced a slight decrease, in the mean relative rCBF in the left dorsolateral prefrontal cortex. CONCLUSIONS: High (15 Hz) and low (1 Hz) frequency rTMS led to different frontal and remote relative rCBF changes, which suggests different neurophysiological and possibly neuropsychiatric consequences of a change in frequency of rTMS.

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Abstract: BACKGROUND: Repetitive transcranial magnetic stimulation has been demonstrated in humans as well as in animal models to have an antidepressant effect, but the optimal frequency of stimulation is not known. We examined this question in a rat model of depression. METHODS: Young male Sprague-Dawley rats were allocated to two placebo (restraint and sham transcranial magnetic stimulation), one active control (imipramine), and four transcranial magnetic stimulation groups at 1, 5, 15 and 25 Hz and 1000 stimuli each. The Porsolt Swim Test was performed on day 1 (experiment 1). In an extension (experiment 2), the treatments were repeated on days 2 through 5, and the Swim Test repeated on days 3, 5, and 7. RESULTS: After one treatment session, all transcranial magnetic stimulation groups had significantly reduced immobility times compared with sham stimulation (p =.000), but the higher frequencies (15 and 25 Hz) did not differ significantly from lower (1 and 5 Hz) frequencies. After three sessions, all transcranial magnetic stimulation groups were different from placebo, and the rapid transcranial magnetic stimulation groups had lower immobility times than the slow transcranial magnetic stimulation groups (p =.035). After five sessions, only 15- and 25-Hz groups were different from control, and on day 7, only the 25-Hz group had reduced immobility. There was an overall difference between fast and slow transcranial magnetic stimulation (p =.010), and 1 Hz was different from the other three transcranial magnetic stimulation conditions (p =.016). CONCLUSIONS: Repetitive transcranial magnetic stimulation reduces immobility time in the Forced Swim Test model of depression, suggesting an antidepressant effect, which is evident at a range (1-25 Hz) of frequencies. With repeated administration, the findings suggest that the antidepressant effect of the higher frequencies, as for imipramine, is likely to be sustained, although the model used for this (i.e., repeating the Swim Test) requires further validation.

Abstract: The authors examined the association of total plasma homocysteine (Hcy) levels with measures of atrophy and white matter disease on MRI scans in 36 healthy elderly individuals. Hcy had a significant positive relationship with lateral ventricle-brain ratios in the anterior (r = 0.49) and middle (r = 0.43) ventricular regions as measures of central atrophy, but not with cortical atrophy or white matter hyperintensities. In a logistic regression analysis, elevated Hcy was a significant determinant of increased anterior ventricle-brain ratio (> or =0.34) after controlling for age, folate, B12, creatinine, and white matter disease (OR = 2.3; CI, 1.03-5.09).

Abstract: BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain. METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later. RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject. CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.

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Abstract: Akathisia is a complex neurobehavioural side effect of neuroleptics and some other drugs which is characterised by subjective report and objective manifestations of restlessness. Its pathophysiology is poorly understood and there are many limitations to its investigation in humans. This paper reviews the various attempts that have been made in modelling acute akathisia in animals. Homologous as well as isomorphic models have been attempted, but most models are partial as they reproduce either the subjective or the objective features of the syndrome. None of the available models has been fully validated. Neuroleptic-induced defecation in the rat, even though constrained by a lack of symptom similarity and thereby face validity, has been most studied as a model of subjective akathisia. Rat models of restlessness, in particular those involving the use of serotonergic drugs or lesions of the ventral tegmentum or medial prefrontal cortex, are interesting partial models that should be further investigated. Neuroleptic-induced akathisia is observed in primates and has been modelled in dogs, and these should be studied further for their validation. It is also necessary to consider the subtypes of akathisia in the attempts to develop these models.

Abstract: BACKGROUND: Carefully designed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation (TMS) in psychiatric disorders. A major methodological concern is the design of the "sham" control for TMS. An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment. Strategies employed so far include alterations in the position of the stimulating coil, but there has been little systematic study of their validity. In this study, we investigated the effects of different coil positions on cortical activation and scalp sensation. METHODS: In nine normal subjects, single TMS pulses were administered at a range of intensities with a "figure eight" coil held in various positions over the left primary motor cortex. Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle. Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed. RESULTS: None of the coil positions studied met the criteria for an ideal sham. Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex. CONCLUSIONS: The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive "stimulation." Further research is needed to develop the best sham condition for a range of applications.

Abstract: The neuropsychological functioning of adults with Attention Deficit Hyperactivity Disorder (ADHD) was compared to that of healthy controls and individuals with mild psychiatric disorders including attentional complaints. Thirty adults in each group were examined on the Conners' Continuous Performance Test (CPT) and measures of attention, executive function, psychomotor speed, and arithmetic skills. The ADHD group performed lower than healthy controls on most measures. However when compared to the psychiatric group, the performances of the ADHD group were not significantly lower on any of the measures. The predictive power of the tests was poor in discriminating ADHD from psychiatric disorder. Implications for the clinical diagnosis of ADHD are discussed.

Abstract: OBJECTIVE: This paper aims to provide an overview of the current knowledge on neuroleptic-induced tardive dyskinesia (TD) in relation to its clinical features, risk factors, pathophysiology and management. METHOD: The published literature was selectively reviewed and assessed. RESULTS: Tardive diskinesia is a common neurological side-effect of neuroleptic medication, the cumulative incidence of which increases with increasing duration of treatment. Its clinical manifestations are diverse and subsyndromes have been described. Many risk factors for TD are now recognised, but increasing age remains pre-eminent as a risk factor. The pathophysiology of TD is not completely understood. Of the neurotransmitter hypotheses, the dopamine receptor supersensitivity hypothesis and the gamma-aminobutyric acid insufficiency hypothesis are the main contenders. There is increasing recognition that TD may in fact be caused by neuroleptic-induced neuronal toxicity through free radical and excitotoxic mechanisms. The occurrence of spontaneous dyskinesias in schizophrenic patients and even healthy subjects suggests that neuroleptics act on a substratum of vulnerability to dyskinesia. As no effective treatment for TD is available, the primary emphasis is on prevention. Many drugs can be tried to reduce symptoms in established cases. The increasing use of atypical neuroleptics has raised the possibility of a lower incidence of TD in the future. CONCLUSIONS: After four decades of clinical recognition, the pathophysiology of TD is still not understood and no effective treatment is available. Its prevention with the optimal usage of currently available drugs and regular monitoring of patients on long-term neuroleptic treatment remain the best strategies to reduce its impact.

Abstract: OBJECTIVE: This paper examines clinical and neuroscientific evidence to address the question whether high doses of stimulant drugs offer additional advantages in the treatment of adult attention deficit hyperactivity disorder (ADHD) and at what cost. It attempts to arrive at a reasonable upper limit of dosage for clinical purposes. METHOD: The study involves a selective review of the treatment studies of ADHD in children and adults and an examination of the pharmacokinetic and pharmacodynamic data on psychostimulants in humans and animals. RESULTS AND CONCLUSIONS: The clinical and experimental data justify the use of chronic low-dose stimulant treatment of ADHD in adults, with the recommended upper limit of dose being 1 mg/kg for methylphenidate and 0.5 mg/kg for dexamphetamine. There is no empirical evidence of greater improvement with higher doses and any beneficial effect is likely to be compromised by the adverse effects, some of which can be very serious. The recommended doses should be exceeded only after careful consideration and objective documentation of beneficial and adverse consequences. Monitoring of drug levels in blood may be of some value for compliance or pharmacokinetic considerations, as there is a direct relationship between blood and brain levels as well as dopamine transporter occupancy. These recommendations are tentative and further clinical research is warranted.

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Abstract: The published literature suggests that degeneration of the subcorticofrontal networks may underlie cognitive ageing, but appropriate methods to examine this in vivo have been lacking. Proton Magnetic Resonance Spectroscopy ((1)H-MRS) has now been used in a number of clinical studies to assess cerebral pathophysicochemistry and recently has been utilized to examine the relationship between neurochemical markers and cognitive functioning in normal individuals. Results have been somewhat conflicting and difficult to interpret. To further clarify the role of the cognitive spectroscopy technique, we measured N-acetylaspartate (NAA) levels in the frontal subcortical white matter and the occipitoparietal grey matter and correlated them with performance in different cognitive domains in a group of twenty healthy elderly individuals. Subjects underwent whole brain T(1)- and T(2)-weighted magnetic resonance imaging (MRI), dual voxel short echo-time (1)H-MRS, and a comprehensive neuropsychological assessment. Individual tests of executive and attentional abilities, and a principal components composite score reflecting these skills, but not measures of memory or verbal abilities, were correlated with NAA concentration in the frontal white matter only. These relationships were independent of other neurocognitive predictors of executive impairment such as age, midventricular dilation, frontal white matter disease, and presenescent verbal proficiency. This study suggests the ability of (1)H-MRS to differentiate anatomically distinct neurochemical markers related to specific cognitive abilities. In particular, neurometabolic fitness of the frontal subcortical-cortical axonal fibers may be important in mediating fluid intellectual processing. Longitudinal MRS studies are required to determine if the present results reflect different rates of neurocellular degeneration or preexisting individual differences in neuronal density.

Abstract: BACKGROUND: Of the midline brain structures, abnormalities have been demonstrated in the corpus callosum and cerebellum in young schizophrenic patients. Whether similar abnormalities are also present in late-onset schizophrenia (LOS) is not known. METHODS: The mid-sagittal cross-sectional areas of brain regions, in particular the corpus callosum and cerebellum, on magnetic resonance imaging were examined in a group of patients with late-onset schizophrenia (N = 25) and contrasted with two comparison groups - early-onset schizophrenia (EOS) (N = 24) and healthy volunteers (NC) (N = 30) matched for age and gender. RESULTS: While the mean corpus callosum area in the LOS group was smaller than in the EOS (by 10.2%) and NC (by 6.2%) groups, the three groups did not differ statistically in the corpus callosum area or the corpus callosum to cerebrum ratios. The cross-sectional cerebellar areas or the cerebellum: cerebrum ratios also did not differ across the groups. The brainstem was smaller in the schizophrenic groups because of smaller cross-sectional areas of the pons, a statistically significant difference which could not be accounted for by any gross lesions on visual inspection. CONCLUSION: We found no abnormality in the mid-sagittal area of the corpus callosum and cerebellum in our early- or late-onset schizophrenia subjects. The significance of the finding of a smaller pontine cross-sectional area is unclear and speculation on it awaits independent replication using a volumetric measure.

Abstract: There has been a recent upsurge of interest in the clinical features of and risk factors for vascular dementia, and consensus is emerging on its diagnostic characteristics. We discuss these features and risk factors and the main intervention strategies, both for treatment and prevention.

Abstract: BACKGROUND: The concept of vascular dementia (VaD) is currently in a state of evolution. Memory impairment is emphasized as a primary criterion, reflecting the influence of AD on the concept of dementia. We have systematically reviewed whether the nature of neuropsychological dysfunction is distinct in AD and VaD, and whether similar defining criteria for the concept of dementia in both disorders can be supported. METHODS: We searched five bibliographic databases (Medline, Biological Abstracts, EMBASE, PsychINFO, PsychLIT) for research articles in which VaD and AD had been compared using neuropsychological tests and that met criteria for scientific merit. RESULTS: Of the 45 studies, 18 were excluded because of inadequacies, and the remaining 27 were analyzed. There were a number of similarities of dysfunction between VaD and AD. However, when matched for age, education, and severity of dementia, VaD patients had relatively superior function in verbal long-term memory and more impairment in frontal executive functioning compared with AD patients. Interpretation of the results is limited by uncertainty in diagnostic criteria for VaD, possible inclusion bias due to use of clinical diagnosis alone, possible overlap of AD and VaD, and the methodologic shortcomings of some studies. CONCLUSIONS: The neuropsychological differentiation of VaD from AD was consistent with the different neuroimaging findings in the two disorders, and argues for differential criteria for the definition of the syndromes. The simple application of Alzheimer's dementia criteria to VaD, with the inclusion of cerebrovascular disease etiology, may not be sufficient to capture the uniqueness of VaD.

Abstract: OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse effect of neuroleptic medication, with no satisfactory treatment currently available. Electroconvulsive therapy (ECT) has been anecdotally reported to be effective in its treatment. We review 45 published case reports of ECT for NMS and describe nine new cases, to examine its effectiveness, the likelihood of adverse reactions, and the theoretical implications of such treatment. METHOD: The authors used Medline to identify reports in the English literature where ECT was used in cases of suspected NMS. In addition, the charts of patients referred to the second author for treatment of NMS were reviewed and cases in which ECT used were identified. RESULTS: The case reports suggest that ECT is effective in many individuals with NMS, even when drug therapy has failed. The response is usually apparent after a few treatments, generally up to six. The response is not predictable on the basis of age, gender, psychiatric diagnosis or any particular feature of NMS including catatonia. Electroconvulsive therapy is a relatively safe treatment in NMS, although the risk of cardiovascular complications should be considered. Malignant hyperthermia due to the anaesthesia associated with ECT has not been reported in patients with NMS, and succinylcholine has been used safely with the exception of one report of fever and raised creatine kinase levels and another report of hyperkalemia. CONCLUSIONS: Electroconvulsive therapy is the preferred treatment in severe NMS, cases where the underlying psychiatric diagnosis is psychotic depression or catatonia, and in cases where lethal catatonia cannot be ruled out. The effectiveness of ECT for the treatment of NMS has theoretical implications for the relationship between NMS and catatonia, and the possible pathophysiological mechanisms that underlie these disorders.

Abstract: Dementia is common among patients with cerebrovascular disease, particularly in a setting of one or more clinically evident strokes. Prior cohort and case studies have suggested that the cognitive syndrome of vascular dementia is characterized by predominant executive dysfunction, in contrast to the deficits in memory and language function that are typical of patients with Alzheimer disease. The course of cognitive decline may also differ between those dementia subtypes, with many, but not all, patients with vascular dementia exhibiting a stepwise course of decline caused by recurrent stroke and most patients with Alzheimer disease exhibiting a gradually progressive course of decline. The findings of prior studies of the cognitive syndrome of vascular dementia must be interpreted with caution, however, because of (1) possible inaccuracies in the determination of the dementia subtype and the loss of precision that might result from pooling heterogeneous subgroups of patients with vascular dementia, (2) difficulties inherent in identifying a pattern of strengths and weaknesses in patients who are required to have memory impairment and other deficits to meet operationalized criteria for dementia, and (3) the use of limited test batteries whose psychometric properties are incompletely understood. Specific questions that should be addressed by future studies are discussed.

Abstract: Startle reflex responses were studied in 15 normal human subjects using weak (88 dB) and strong (114 dB) auditory stimuli in the orbicularis oculi, masseter, sternocleidomastoid, trapezius, deltoid, biceps, forearm flexors and quadriceps muscles. With the subjects in the relaxed state, no consistent responses were seen with the weak stimuli, and with the strong stimuli responses were only present in orbicularis oculi muscles. When the above muscles were in a state of voluntary contraction, the strong stimuli produced complex responses which were not always excitatory in nature, with muscle relaxation being noted in a number of stimulation sequences. Repetitive weak and strong stimuli were used to study habituation effects in the orbicularis oculi muscles. The repetitive strong stimuli produced a wide range of response patterns, indicating a high inter-individual variability in habituation. In two subjects, no habituation effects were present. Our study supports the high intra-individual variability of the startle response, and suggests that this response is affected by the state of muscle contraction at the time of stimulation. Startle response is more easily elicited in a state of muscular contraction. Future studies of startle reflex should take this into consideration.

Abstract: An increase in emotional defecation in rats in a well-habituated environment induced by neuroleptic drugs (NDef) has been proposed as a model for neuroleptic-induced akathisia. We examined the effects of dopamine receptor antagonists and agonists on this model. A selective dopamine D1 antagonist (SCH 23390) and a selective D2 antagonist (raclopride) induced increased defecation at higher doses, and demonstrated a synergistic effect at lower doses. Selective D1 (SKF 82958) and D2 (quinpirole) agonists did not have a significant effect on defecation, nor did they reverse the effect of haloperidol. In a further pilot study, we explored the effects of typical and atypical neuroleptics on this model. The haloperidol and risperidone treated rats produced more faecal boli than those treated with clozapine, thioridazine and chlorpromazine, with the former being non-significantly greater than the vehicle-treated group. The results of our studies suggest that NDef is most probably an effect of central dopamine antagonism that is not specific to D1 or D2 receptors, but that the two receptor subtypes have a synergistic effect. It is unlikely to be due to actions of neuroleptics on 5HT2 or alpha1 receptors as has sometimes been suggested. The results have implications for our understanding of the pathogenesis of akathisia.

Abstract: BACKGROUND: A 1991 survey showed high levels of drug resistance among tuberculosis patients in New York, NY. As a result, the tuberculosis control program was strengthened, including expanded use of directly observed therapy and improved infection control. METHODS: We collected isolates from every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1994; results were compared with those in the April 1991 survey. RESULTS: From 1991 to 1994, the number of patients decreased from 466 to 332 patients. The percentage with isolates resistant to 1 or more antituberculosis drugs decreased from 33% to 24% (P < .01); with isolates resistant to at least isoniazid decreased from 26% to 18% (P < .05); and with isolates resistant to both isoniazid and rifampin decreased from 19% to 13% (P < .05). The number of patients with isolates resistant to both isoniazid and rifampin decreased by more than 50%. Among never previously treated patients, the percentage with resistance to 1 or more drugs decreased from 22% in 1991 to 13% in 1994 (P < .05). The number of patients with consistently positive culture results for more than 4 months decreased from 130 to 44. A history of antituberculosis treatment was the strongest predictor of drug resistance (odds ratio = 3.1; P < .001). Human immunodeficiency virus infection was associated with drug resistance among patients who never had been treated for tuberculosis. CONCLUSIONS: Drug-resistant tuberculosis declined significantly in New York City from 1991 to 1994. Measures to control and prevent tuberculosis were associated with a 29% decrease in the proportion of drug resistance and a 52% decrease in the number of patients with multidrug-resistant tuberculosis.

Abstract: The motor response pattern of the audiogenic startle reflex was studied in 15 Tourette's syndrome (TS) patients and 15 normal, age-matched control subjects, using auditory stimuli at 88 and 114 dB. The louder stimuli readily elicited responses in the orbicularis oculi (in all subjects), masseter, sternomastoid, trapezius, deltoid, and biceps (in most subjects) muscles, with a few subjects having responses in the forearm flexors and quadriceps. The TS subjects did not differ from controls in the onset latency, amplitude, and first peak latency of the reflex response in any of the muscles. Rates of habituation in the orbicularis oculi muscle were widely variable across the subjects, and the two groups did not differ overall in the habituation rates. Our study does not support the reports of an abnormal audiogenic startle reflex in TS.

Abstract: Neuroleptic-induced defecation in rats in a well-habituated environment has been proposed as a model of the subjective component of akathisia. In this study, we examined the effects of two lipophilic beta-adrenoceptor antagonists - the non-selective drug propranolol and the relatively beta1-selective metoprolol - and one non-selective hydrophilic drug nadolol in this model. Young male Wistar rats were randomly assigned to one of eight groups (n = 12 in each group) and treated with haloperidol or vehicle, with or without one of the beta-antagonists. Haloperidol-treated rats had higher bolus counts than vehicle-treated rats, and this increase was significantly reversed by the lipophilic but not the hydrophilic beta-antagonists. This finding is consistent with the reported anti-akathisia effects of these drugs in humans, suggesting that this effect is central in origin and achievable with relatively selective beta1-antagonism. The B-antagonist drugs significantly reduced the cataleptic effect of haloperidol and this effect warrants further examination.

Abstract: Alzheimer's disease affects up to 100,000 people in Australia, but pharmacological treatment has only been available in recent years. Currently available drugs provide modest relief of symptoms for varying periods of time but have no proven preventive action against the disease.

Abstract: Needle and surface EMG recordings were made from the left corrugator supercilii and zygomaticus major muscles, and the skin overlying them, in 12 right-handed normal subjects during imagined and posed sad, happy and angry states. The surface and needle EMG recordings showed good correspondence for the corrugator and zygomaticus major muscles within each individual subject. Considerable inter-subject and inter-emotion variability was, however, observed. The surface to needle concordance was poor when the EMG activity itself was low. While this study does not suggest that specific surface EMG recordings from the face are inappropriate, it provides a note of caution when the activity is low.

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Abstract: OBJECTIVES: To assess the extent and nature of psychosurgery currently being performed in Australia and New Zealand, and the present status of legislation regulating its practice. METHODS: Details of current legislation were obtained through inspection of statutes and direct communication with Departments of Health. All full and associate members of the Neurosurgical Society of Australasia were surveyed by postal questionnaire. Ninety-eight neurosurgeons were surveyed, of whom 72 (73%) replied. RESULTS: In the 1980s a mean of nine (SD, 5.9) operations were performed per year; about two were performed per year in the late 1980s. Ninety per cent of these operations were performed at one centre in Sydney. The most common indications were severe and medically intractable depression and obsessive-compulsive disorder. Surgery is now exclusively stereotactic and involves the creation of lesions in the orbitomedial frontal or cingulate tracts or a combination of the two. The nature and type of surgery are comparable to those in other centres in the Western world. Regulatory legislation is in place in most, but not all, States in Australia and in New Zealand. CONCLUSIONS: Further developments of other forms of psychiatric treatments may make psychosurgery, in its present form and at its present level of validation, redundant. If it is to have a resurgence, it would have to be based on a much sounder theoretical premise, and a stronger demonstration of efficacy and predictability of effect.

Abstract: OBJECTIVE: To study the use of psychoactive drugs for the treatment of long-stay developmentally disabled individuals in an institution in New South Wales. SETTING: Three wards dedicated to the long-term care of developmentally disabled individuals situated on the premises of a large psychiatric hospital. SUBJECTS: All residents (n = 53) of these wards in August 1989. METHOD: All subjects were examined by the author. Charts and medication records were extensively reviewed. Mental retardation was classified by DSM-III-R criteria. Categorisation of problem behaviour was done with the assistance of nurses, who also supplied information on behavioural problems and functional level and completed checklists of self-injurious and stereotypic behaviour. A standardised neurological examination was performed and scales for abnormal involuntary movements completed. RESULTS: The most commonly used drugs were the neuroleptics, with 60.4% of subjects currently receiving one or more neuroleptic drug at relatively large doses. The use of these drugs was not associated with current or past psychiatric illness, but was more closely related with the severity of problem behaviour. Thirty-four per cent of the subjects receiving neuroleptics had dyskinetic movements suggestive of tardive dyskinesia, and 30% had mild tremor. Antidepressant, anxiolytic and sedative drugs were used less commonly. The management of epilepsy was considered to be suboptimal. CONCLUSION: Even though studies over the last two decades have consistently highlighted the problem of overmedication of intellectually handicapped individuals in institutions, the problem does not seem to have been redressed in at least some institutions.

Abstract: A major factor in the aetiology of illness is the behaviour of individuals with regard to certain risks and hazards of the environment. The Maori of New Zealand have been shown to be at greater risk of illness and death than their non-Maori counterparts. It is estimated that a significant proportion of this excess morbidity and mortality can be attributed to at least four behavioural factors: smoking, obesity, alcohol use and accidents. This paper examines the inter-cultural differences in these factors, both from a contemporary and an historical perspective. Some of the reasons for the continuation of these adverse patterns of behaviour are explored, in particular the role of psycho-cultural stress. Some possible mechanisms of effecting behavioural change in modern Maori society are discussed.

Abstract: This paper reports a longitudinal study of 19 patients diagnosed as having pseudodementia more than a decade earlier. In only one patient was the earlier diagnosis changed to definite dementia and, in this patient, there were strong indicators that such a diagnosis should have been made initially. In a second patient, dementia could not be excluded. The remaining patients did not show evidence of a dementing illness and the courses of the illnesses resembled the primary psychiatric disorders responsible for the pseudodementia. The results validate the clinical utility of the term "pseudodementia".

Abstract: This paper is an attempt to integrate the available research, clinical data and literary information concerning the developmental experiences of the New Zealand Maori. The Maori developmental pattern in the traditional society is compared with that of the Caucasian, mostly Anglo-Saxon, New Zealander (Pakeha), highlighting the contrasting elements while at the same time accommodating considerable overlap between the two postulated developmental patterns. The Maori personality development is seen as being characterized by an indulgent and permissive infancy, a withdrawal of this succorance during childhood, which is characterized by prominent peer-orientation, and a reintegration into adult society during adolescence with gradual maturation of social roles subsequently. The disruption of this pattern as a result of urbanization and Westernization is discussed, along with its adverse consequences. The recent initiatives by the Maori community to preserve the old traditions take the developmental issues into consideration, and although it is too early to judge their success or otherwise, they look quite promising.

Abstract: Whakama is a psychosocial and behavioural construct in the New Zealand Maori which does not have any exact equivalent in Western societies although shame, self-abasement, feeling inferior, inadequate and with self-doubt, shyness, excessive modesty and withdrawal describe some aspects of the concept. It is an important construct in order to understand the interaction of the Maori with each other and with the Caucasian New Zealander, the behaviour of the Maori in cross-cultural settings, and the clinical presentations of some Maori patients. This paper examines some of the meanings of whakama, its various behavioural manifestations and its possible causes. The clinical relevance to psychiatry is emphasized.

Abstract: A series of technological advances have made it possible to closely monitor electrophysiological and behavioural manifestations of episodic clinical events over prolonged periods of time, with the ability to review the records at leisure or to submit them to computer analysis. The more promising techniques are time-locked video/EEG monitoring, cable telemetry, radiotelemetry, ambulatory cassette recording, intensive plasma anti-epileptic drug monitoring and continuous neuropsychological monitoring. The greatest promise of these techniques is for the diagnosis, research and management of epilepsy. For psychiatry, they offer additional help in the differential diagnosis of non-epileptic events from epilepsy, the most important of which are psychogenic seizures and episodes of aggression. This paper discusses the potential role of these techniques in the assessment of non-epileptic events and transient cognitive impairment in clinical psychiatry.

Abstract: A patient is described who developed frequent blinking and blepharospasm after long-term treatment with trifluoperazine, whose condition improved dramatically after the cessation of the drug. The implications of this for our understanding of the manifestations and natural course of the late-onset side-effects of neuroleptic drugs are discussed. This case further supports the role of dopaminergic mechanisms in the aetiology of Meige's syndrome, which has blepharospasm and oromandibular dystonia as its main manifestations.

Abstract: Two patients with the acquired immunodeficiency syndrome (AIDS), who had no past psychiatric history, developed a mania-like illness soon after commencing treatment with zidovudine. The neurotoxic effects of zidovudine have been described previously, but to our knowledge no reports of a psychiatric disorder that is related to the drug have appeared. Our report emphasizes the need to monitor patients with AIDS for neuropsychiatric problems.

Abstract: A middle-aged woman with a recurrent depressive illness showed worsening of her tardive dyskinesia during the depressive phases, with improvement on remission.

Abstract: This paper discusses three concepts, mana, tapu and noa, that lie at the heart of Maori culture. These concepts are inter-related and concern power and influence, with political (or secular) authority implicit in mana and ritual (or religious) authority determined by tapu and noa. The paper explores their importance for the understanding of the ethnic views on aetiology and management of illness, the mechanisms of social organization and control, and the behaviour of individuals. Although the belief in these concepts exists in only an attenuated form in modern Maori society, their importance becomes obvious to any psychiatrist or physician working with Maori patients.

Abstract: This paper compares psychiatric illness in the contemporary Maori with that in the non-Maori New Zealander. The ethnic data available are all from secondary sources. The limitations of this and the problems of achieving a satisfactory definition of "a Maori" are discussed. The data suggest that the Maori have a slightly greater risk of psychiatric hospitalization than the non-Maori. First admission rates for schizophrenia are higher for the Maori, as are the readmission rates. First admission rates for major affective illness are roughly comparable in the two groups, and those for neuroses and neurotic depression are lower in the Maori. Rates of admission for alcohol abuse, alcohol dependence and personality disorders are much higher for the Maori male aged 20-40 years and this group is at greatest risk of psychiatric hospitalization. A larger proportion of Maori are admitted involuntarily, especially under the Criminal Justice Act. The median stay in hospital is not longer for the Maori but their re-admissions are more frequent. The Maori have shown an increase in first psychiatric admission rates since the 1950s, with rapid increases in the early 60s and the 80s. The rates for psychotic disorders have been relatively constant and the most significant changes have been for alcohol abuse, alcohol dependence and personality disorders. The author relates this historical change to socioeconomic and politico-cultural factors, particularly the stress of rapid urbanization.

Abstract: This paper examines the dynamics of teh psychotherapeutic relationship between a Maori Elder and Maori psychiatric patients. The functioning of an Elder was examined over a period of 9 months in a psychiatric unit. A content analysis was performed on audiovisual records of 10 interviews conducted by the Elder on five psychiatric patients. The results of this analysis were used to construct a theoretical paradigm of the Elder-Patient Transaction and to contrast it with psychodynamic psychotherapy and pastoral counseling. Distinctive features of relationship, content of the sessions and the issues of dominance and dependence are discussed, and possible mechanisms of change are mentioned.

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Abstract: Koro is an unusual psychogenic syndrome reported, until recently, predominantly in men of the Chinese race who live in southern China and south-east Asia. Issues concerning its phenomenology, diagnosis and nosology are still controversial. This paper describes an epidemic of koro in north-east India. A psychiatric analysis of thirty-one cases is presented. Probable reasons for the rapid spread of the illness are discussed. The majority of the individuals affected were from the lower socio-economic strata, were poorly educated and in the age group of 20-40 years. Many women were affected. There was no evidence of significant premorbid or sexual psychopathology in most cases. Some patients had a number of episodes but with only minor residual symptoms. The author compares these findings with earlier reports and discusses the implications for its nosology and psychodynamics.

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