Abstract: Sustained volitional attention and working memory capacity was examined for the first time in people with Friedreich ataxia (FRDA). We administered subtests of the Test of Everyday Attention to 16 individuals with molecularly confirmed FRDA and gender-, age-, and IQ-matched controls. Clinically significant impairment in working memory and sustained volitional attention was evident. Working memory deficits correlated significantly with GAA repeat number on the shorter allele of the FXN gene, and separately, with disease severity, as measured by the Friedreich Ataxia Rating Scale score. Sustained volitional attention was not correlated with disease parameters, suggesting that this impairment may not be related to the disease process in a simple way. The deficits observed may be the result of disruption to corticocerebellar pathways, or directly related to the cortical and/or cerebellar pathology evident in people with FRDA. (JINS, 2011, 17, 196-200)
Notes: Klopper, Felicity Delatycki, Martin B. Corben, Louise A. Bradshaw, John L. Rance, Gary Georgiou-Karistianis, Nellie
Abstract: Friedreich's ataxia (FRDA) is the most common early onset inherited ataxia with clinical manifestations, including gradual progression of unremitting cerebellar-sensory ataxia, peripheral sensory loss, loss of lower limb tendon reflexes and hypertrophic cardiomyopathy. Although atrophy of the superior cerebellar peduncle (SCP) has been reported in several magnetic resonance imaging (MRI) studies of FRDA, the relationship of SCP changes to genetic and clinical features of FRDA has not been investigated. We acquired T1-weighted MRI scans in 12 right-handed individuals with FRDA, homozygous for a GAA expansion in intron 1 of FXN, as well as 13 healthy age-matched controls. The corrected cross-sectional areas of the right (left) SCP in the individuals with FRDA (R, 20 +/- 7.9 mm(2); L, 25 +/- 5.6 mm(2)) were significantly smaller than for controls (R, 68 +/- 16 mm(2); L, 78 +/- 17 mm(2)) (p < 0.001). The SCP volumes of individuals with FRDA were negatively correlated with Friedreich's ataxia rating scale score (r = -0.553) and disease duration (r = -0.541), and positively correlated with the age of onset (r = 0.548) (p < 0.05). These findings suggest that structural MR imaging of the SCP can provide a surrogate marker of disease severity in FRDA and support the potential role of structural MRI as a biomarker in the evaluation of neurodegenerative diseases and therapies.
Notes: Akhlaghi, Hamed Corben, Louise Georgiou-Karistianis, Nellie Bradshaw, John Storey, Elsdon Delatycki, Martin B. Egan, Gary F.
Abstract: The bodily boundaries in amputees may seem to be more malleable than in non-amputees, given the propensity for a phantom limb to embody a mirror-reflected hand. However, in the present investigation, in which phantom-limb illusions within body space are induced and manipulated, we found that perceiving phantom sensations and illusory embodiment does not require amputation. Surprisingly, in the present modified rubber-hand illusion, We found that simultaneous stroking or stimulation of the participant's target hand was not necessary to induce illusions of embodiment and corresponding perceptual illusions. We tested this upper-limb paradigm in fourteen upper-limb amputees and twenty-six controls (including fourteen lower-limb amputees). We propose a model for embodiment of a rubber or real hand passively observed in a mirror. In this model, passive observation of the hand in the mirror triggers body representations (body image and body schema), most likely through activation of the posterior parietal cortex and temporo-parietal junction. Activity in these regions heightens awareness of peripersonal space and increases tactile sensitivity, and may subsequently enhance perception of illusory touch and embodiment. Furthermore, sense of embodiment may be more apparent to the participant when the hand is threatened; however, embodiment may even be strengthened when the motor system is engaged, evoking motor schemata to support the more easily induced perceptual embodiment via body image.
Notes: Giummarra, Melita J. Georgiou-Karistianis, Nellie Nicholls, Mike E. R. Gibson, Stephen J. Bradshaw, John L.
Abstract: Pain synaesthetes experience pain in a presensitised region when observing or imagining another person in pain. We conducted an upper-limb embodiment study using a modified rubber-hand illusion in which lower-limb amputees originally participated as control subjects for the upper-limb amputees. While we found all subjects experienced topographic illusory sensations, we also serendipitously found that lower-limb amputee pain synaesthetes experienced pain or a motor response in their phantom leg when the embodied hand was threatened (eg with a retractable knife, mousetrap, or syringe) or submitted to high-frequency stimulation (eg vibration). Embodiment illusions were brought about by touching, manipulating, or threatening a rubber or real hand which was observed through a mirror so that it was superimposed upon the target hand (phantom hand for upper-limb amputees, or real hand in others). Participants included eight pain synaesthetes (six lower-limb amputees, one upper-limb amputee, and one nonamputee), and thirty-one controls (eight lower-limb amputees, twelve upper-limb amputees, and eleven nonamputees). We documented participant's subjective reports, together with quantitative measures including the Questionnaire Measure of Emotional Empathy. We found no association between pain synaesthesia and empathy scores. On the basis of related literature we suggest that pain synaesthetes likely experienced phantom-leg pain because (a) the motor system was already engaged during visual capture; (b) threatening stimuli, to which they are hyper-vigilant, triggered avoidance or 'escape' motor schemata; and (c) there could be no feedback confirming that initiated motor schemata for the phantom limb were successfully performed. Ultimately, we have further defined this new condition, synaesthesia for pain, as not only having a sensory pain component, but also a key motor component, manifesting itself in avoidance, contraction, and withdrawal 'actions'.
Notes: Giummarra, Melita J. Fitzgibbon, Bernadette M. Georgiou-Karistianis, Nellie Nicholls, Michael E. R. Gibson, Stephen J. Bradshaw, John L.
Abstract: Phantom limb perception almost invariably follows limb amputation, and can be characterized by various corporeal and proprioceptive qualities. We report a study of 283 amputees, which administered a structured questionnaire to systematically determine the relative frequency and nature of various bodily aspects of phantom limb perception. These include the size, shape, posture, and telescoping of the phantom; exteroceptive sensations of itch, touch, pressure, vibration, temperature, and 'electric' sensations; and prosthesis embodiment. Phantom limbs were generally found to be characterized by properties that parallel those of the intact body, although with anatomically impossible configurations sometimes being perceived. We suggest that both the internal limb image and limb schemata play a significant role in the continued perception of phantom limbs.
Notes: Giummarra, Melita J. Georgiou-Karistianis, Nellie Nicholls, Michael E. R. Gibson, Stephen J. Chou, Michael Bradshaw, John L. xD;Part 4
Abstract: Motor overflow refers to involuntary movement or muscle activity coinciding with voluntary movement. We examined whether 16 young adults (18-30 years) and 16 older adults (50-80 years) could voluntarily inhibit overflow. Participants performed a finger pressing task, exerting 50% of their maximal force. Overflow was concurrently recorded in the non-task hand. In the first condition, participants were not made aware of their motor overflow. Then participants, though informed of it, were asked to ignore their overflow. Finally, participants were requested to inhibit overflow with, and then without visual feedback, or vice versa. Overflow was exacerbated when older adults were unaware of it, and was reduced once they were informed. For young adults there was no significant difference between these conditions. Both Age Groups could significantly reduce overflow when so requested, independent of visual feedback. Thus motor overflow can be modulated by higher order cognitive control with directed attention. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.
Notes: Addamo, Patricia K. Farrow, Maree Bradshaw, John L. Moss, Simon Georgiou-Karistianis, Nellie
Abstract: Objective The striatum and its projections are thought to be the earliest sites of Huntington's disease (HD) pathology. This study aimed to investigate progression of striatal pathology in symptomatic HD using diffusion tensor imaging. Method Diffusion weighted images were acquired in 18 HD patients and in 17 healthy controls twice, 1 year apart. Mean diffusivity ( MD) was calculated in the caudate, putamen, thalamus and corpus callosum, and compared between groups. In addition, caudate width was measured using T1 high resolution images and correlated with caudate MD. Correlation analyses were also performed in HD between caudate/putamen MD and clinical measures. Results MD was significantly higher in the caudate and putamen bilaterally for patients compared with controls at both time points although there were no significant MD differences in the thalamus or corpus callosum. For both groups, MD did not change significantly in any region from baseline to year 1. There was a significant negative correlation between caudate width and MD in patients at baseline but no correlation between these parameters in controls. There was also a significant negative correlation between Mini-Mental State Examination scores and caudate MD and putamen MD at both time points in HD. Conclusions It appears that microstructural changes influence cognitive status in HD. Although MD was significantly higher in HD compared with controls at both time points, there were no longitudinal changes in either group. This finding does not rule out the possibility that MD could be a sensitive biomarker for detecting early change in preclinical HD.
Notes: Sritharan, Anusha Egan, Gary F. Johnston, Leigh Horne, Malcolm Bradshaw, John L. Bohanna, India Asadi, Hamed Cunnington, Ross Churchyard, Andrew J. Chua, Phyllis Farrow, Maree Georgiou-Karistianis, Nellie
Abstract: This paper reviews the current literature on "empathy for pain", the ability to understand pain observed in another person, in the context of a newly documented form of pain empathy "synaesthesia for pain". In synaesthesia for pain a person not only empathises with another's pain but experiences the observed or imagined pain as if it was their own. Neural mechanisms potentially involved in synaesthesia for pain include "mirror systems": neural systems active both when observing an action, or experiencing an emotion or sensation and when executing the same action, or personally experiencing the same emotion or sensation. For example, we may know that someone is in pain in part because observation activates similar neural networks as if we were experiencing that pain ourselves. We propose that synaesthesia for pain may be the result of painful and/or traumatic experiences causing disinhibition in the mirror system underlying empathy for pain. We will discuss this theory in the context of a documented group of amputees who experience synaesthesia for pain in phantom limbs. (C) 2009 Elsevier Ltd. All rights reserved.
Notes: Fitzgibbon, Bernadette M. Giummarra, Melita J. Georgiou-Karistianis, Nellie Enticott, Peter G. Bradshaw, John L.
Abstract: Neuroimaging is fundamental to identifying quantifiable and objective biomarkers in symptomatic and pre-diagnostic Huntington's disease (HD). However, the challenge remains to find reliable biomarkers with high sensitivity and specificity that can be used to track the functional decline over time and test efficacy of therapeutic intervention. While many recent studies have focused on neuroimaging techniques based on brain hemodynamic activity, comparatively fewer have utilized electroencephalography (EEG) and event-related potentials (ERPs). This review aims to summarise and integrate key electroencephalographical findings from the last two decades in symptomatic and pre-diagnostic HD, in context with recent neuroimaging data, and to use this information to identify promising candidate markers for future research and clinical consideration. (C) 2010 Elsevier B.V. All rights reserved.
Notes: Nguyen, Lan Bradshaw, John L. Stout, Julie C. Croft, Rodney J. Georgiou-Karistianis, Nellie
Abstract: Synaesthesia for pain is a phenomenon where a person experiences pain when observing or imagining another in pain Anecdotal reports of this type of experience have most commonly occurred in individuals who have lost a limb Distinct from phantom pain synaesthesia for pain is triggered specifically in response to pain in another Here we provide the first preliminary investigation into synaesthesia for pain in amputees to determine the incidence and characteristics of this intriguing phenomenon Self-referring amputees (n=74) answered questions on synaesthesia for pain within a broader survey of phantom pain Of the participants 162% reported that observing or imagining pain in another person triggers their phantom pain Further understanding of synaesthesia for pain may provide a greater insight to abnormal empathic function in clinical populations as well as therapeutic intervention for at risk groups (C) 2010 Elsevier Ltd All rights reserved
Notes: Fitzgibbon, Bernadette M. Enticott, Peter G. Rich, Anina N. Giummarra, Melita J. Georgiou-Karistianis, Nellie Tsao, Jack W. Weeks, Sharon R. Bradshaw, John L.
Abstract: The cerebellar and spinocerebellar dysfunction seen in Friedreich ataxia (FRDA) has known effects on motor function. Recently, it was suggested that people with FRDA may also have impairment in motor planning, either because of cortical pathology or because of cerebello-cortical projections. Fifteen adults with FRDA and 15 matched controls completed a task requiring reciprocating movements between two buttons on a tapping board. Occasionally there was one of three "oddball" stimuli requiring reprogramming of movement. These were change in (1) direction, (2) extent or (3) direction and extent. We hypothesized that people with FRDA would have prolonged movement times due to their movement disorder, and that changes in preparation time would be affected in a way similar to controls, unless there was impairment in motor planning in FRDA. Movement execution and, to a lesser degree, movement preparation were impaired in individuals with FRDA. We argue this points to disturbed cortical function. There was a significant negative correlation between age of onset and all three reprogramming conditions, suggesting an impact of FRDA on developing motor planning. Future studies will be required to establish whether this dysfunction is due to cerebellar impairment interrupting cerebro-ponto-cerebello-thalamo-cerebral loops, primary cortical pathology or a combination of the two.
Notes: Corben, Louise A. Delatycki, Martin B. Bradshaw, John L. Horne, Malcolm K. Fahey, Michael C. Churchyard, Andrew J. Georgiou-Karistianis, Nellie
Abstract: Motor overflow refers to involuntary movement or muscle activity that may coincide with voluntary movement. This study examined factors influencing motor overflow in 17 children (8-11 years), and 17 adults (18-35 years). Participants performed a finger pressing task by exerting either 33% or 66% of their maximal force output using their dominant or non-dominant hand. Attention was manipulated by tactile stimulation to one or both hands. Overflow relative to the target force was greater in children compared to adults, and at the lower target force for both groups, but was not influenced by attentional stimulation. Childhood overflow was greater when the left-hand performed the task. Although an immature motor system may underlie an inability to suppress involuntary movement, childhood overflow may provide motor stabilization. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.
Notes: Addamo, Patricia K. Farrow, Maree Hoy, Kate E. Bradshaw, John L. Georgiou-Karistianis, Nellie
Abstract: Freezing of gait (FOG) has been identified as one of the main contributors to gait disturbances in Parkinsons disease. While the pathophysiology remains enigmatic, several factors such as step length and the sequence effect (step to step reduction in amplitude) may lead to the occurrence of FOG. It was hypothesized that by reducing step length, FOG episodes would present more frequently if a significant sequence effect (measured as a regression slope) was co-existent in the subject. Twenty-six participants with Parkinsons disease were separated clinically into a freezing (PD FOG, n 16) and non-freezing (PD FOG, n 10) group, with 10 age-matched control participants. Testing involved walking trials where preferred step length was set at 100, 75, 50 and 25 of normalized step length. The number of FOG episodes increased in the 50 condition and further increased in the 25 condition compared to other conditions. The participants with FOG also demonstrated a larger average regression slope, with significant differences in the 75, 50 and 25 conditions when compared to the PD FOG and control groups. There were no significant differences when comparing the slope of the PD FOG and control group, indicating the reduced step length and the sequence effect may have led to the occurrence of FOG. These findings support the possible dual requirement of a reduced step length and a successive step to step amplitude reduction to lead to FOG.
Notes: Chee, Rachel Murphy, Anna Danoudis, Mary Georgiou-Karistianis, Nellie Iansek, Robert xD;Part 8
Abstract: Guidelines for assessing fitness to drive in individuals with neurodegenerative disorders, such as Parkinson's disease (PD), are subjective. It is therefore timely to review the current status of the literature not only for health professionals who are required to assess fitness to drive, but also for the development of future research directions. This review, in the context of PD, outlines the complex changes in driving behaviours, motor vehicle crash rates, driving simulator and on-road driving ability assessments, the relationship between disease severity, duration, medication dose and driving performance, the relationship between driving and neuropsychological test performance, and the effect of dopaminergic medications on driving. While it provides a current overview of the ongoing research, more comprehensive research is required for the full and proper development of policies and guidelines for assessing fitness to drive in PD. Crown Copyright (c) 2008 Published by Elsevier Ltd. All rights reserved.
Notes: Klimkeit, Ester I. Bradshaw, John L. Charlton, Judith Stolwyk, Rene Georgiou-Karistianis, Nellie
Abstract: This study investigated the influence of attentional and motor demands on motor overflow in 17 healthy young (18-35 years) and 17 older adults (60-80 years). Participants performed a finger pressing task by exerting either 33% or 66% of their maximal force output using their dominant or nondominant hand. Overflow was concurrently recorded in the passive hand. Attention was manipulated via a tactile stimulus presented to one or both hands for certain trials. Results showed that older adults exhibited greater overflow than young adults and that the effect of target force was exacerbated in older adults. Further, only older adult overflow was increased when tactile stimulation was directed to one or both hands. Increased overflow in older adults may result from bilateral cortical activation that is influenced by increased task demands. To perforin comparatively to younger adults, older adults may compensate for age-related brain changes by recruiting increased cortical network.
Notes: Addamo, Patricia K. Farrow, Maree Hoy, Kate E. Bradshaw, John L. Georgiou-Karistianis, Nellie
Abstract: The negative symtptoms of schizophrenia are perhaps the Most unremitting and burdensome features of the disorder. Negative symptoms have been associated with distinct motor, cognitive and neuropathological impairments, possibly stemming from prefrontal dysfunction. Eye movement paradigms can be used to investigate basic sensorimotor functions, as well as higher order cognitive aspects of motor control such as inhibition and spatial working memory - functions subserved by the prefrontal cortex. This study investigated inhibitory control and spatial working memory in the saccadic system of 21 patients with schizophrenia (10 with high negative symptoms scores and I I with low negative symptom scores) and 14 healthy controls. Tasks explored suppression of reflexive saccades during qualitatively different tasks, the generation of express and anticipatory saccades, and the ability to respond to occasional, unpredictable ("oddball") targets that occurred during a sequence of well-learned, reciprocating saccades between horizontal targets. Spatial working memory was assessed using a single and a two-step memory-guided task (involving a visually-guided saccade during the delay period). Results indicated significant increases in response suppression errors, as well as increased response selection impairments, during the oddball task, in schizophrenia patients with prominent negative symptoms. The variability of memory-guided saccade accuracy was also increased in patients with prominent negative symptom scores. Collectively, these findings provide further support for the proposed association between prefrontal dysfunction and negative symptoms. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
Notes: Winograd-Gurvich, Caroline Fitzgerald, Paul B. Georgiou-Karistianis, Nellie Millist, Lyn White, Owen
Abstract: Deficits in cortical inhibition (CI) have been implicated in the pathophysiology of schizophrenia, including decreased transcallosal inhibition (TCI). A closely related phenomenon, which has not yet been studied in schizophrenia, is transcallosal facilitation (TCF). TO and TCF are thought to maintain a complimentary existence, allowing for the performance of tasks such as unilateral voluntary movement. Therefore, deficient TCI may lead to abnormal expression of TCF. This study aims to confirm the presence of TCI deficits in schizophrenia, and to examine TCF. Thirty consenting participants took part in the study (15 with schizophrenia and 15 healthy controls), although not all were able to complete all aspects of the study. TO and TCF were measured using dual-pulse transcranial magnetic stimulation methodologies. Patients with schizophrenia exhibited significantly less TO than controls; there was no difference in TCF, however. The lack of significant TCF findings is discussed in light of the methodological limitations, while the theoretical significance of deficient TO to the pathophysiology of schizophrenia is considered. (c) 2007 Elsevier Ltd. All rights reserved.
Notes: Hoy, Kate E. Georgiou-Karistianis, Nellie Layeock, Robin Fitzgerald, Paul B.
Abstract: Motor disturbances are frequently reported in schizophrenia, particularly in association with negative symptoms, and may reflect frontostriatal dysfunction. This study investigated the timing of self-paced and reprogrammed saccades in 21 patients with schizophrenia, 11 with and 10 without prominent negative symptoms, as compared with 14 healthy controls. Results indicated that schizophrenia patients with increased negative symptoms scores had increased intraindividual variability in their timing of self-paced and reprogrammed saccades and performed saccades with increased peak velocities. It is possible that increased variability may reflect frontostriatal impairments and increased peak velocity may reflect serotonin changes or prefrontal cortex dysfunction. NeuroReport 19:1435-1439 (C) 2008 Wolters Kluwer Health \ Lippincott Williams & Wilkins.
Notes: Gurvich, Caroline T. Fitzgerald, Paul B. Georgiou-Karistianis, Nellie White, Owen B.
Abstract: Bodily experience is a complex, mostly unconscious, process that requires the integration of multiple sensory inputs. This paper reviews the sensory systems involved in internal representations of the body-primarily the proprioceptive, motor, vestibular, and visual systems. Various neurological disorders are defined by aberrations in bodily experience-including the perceptual ablation or disembodiment of body parts, "filling in" of amputated body parts, or reduplication of body parts. These perceptual aberrations are discussed and their implications for the central and peripheral systems involved in updating and retrieving internal representations of the body are highlighted. Bodily perception and egocentric frames of reference can be experimentally manipulated through visual capture (e.g., using rubber limbs), functional adaptation and embodiment of tools and prostheses, and changes in afferent sensory feedback (e.g., through stimulation of muscle spindles). These perceptual illusions are described, and discussed for their implications for the mechanisms underlying bodily perception. (c) 2007 Elsevier Ltd. All rights reserved.
Notes: Giummarra, Melita J. Gibson, Stephen J. Georgiou-Karistianis, Nellie Bradshaw, John L.
Abstract: Magnetic Resonance Imaging (MRI), functional MRI (fMRI) and Diffusion Tensor Imaging (DTI) have been central to characterisation of abnormalities in brain structure and function in both clinical and preclinical Huntington's disease (HD). One current challenge in clinical HD research is the identification of sensitive and reliable biomarkers to detect progressive neurodegeneration and neural dysfunction, which could be used to assess the effect of therapeutic intervention on brain structure and function in a HD clinical trial. To this end, both established and novel neuroimaging approaches could potentially provide sensitive, reliable and non-invasive tools to assess long-term and dynamic effects of treatment on specific brain regions, including their microstructure and connectivity. This review examines contributions from structural MRI, fMRI and DTI studies to our current understanding of preclinical and clinical HD, and critically appraises MRI methods potentially suitable for both scientific characterisation and for use as biomarkers in HD clinical trials. A combined neuroimaging approach incorporating structural MRI, fMRI and DTI is yet to be realised in HD clinical trials, however if proven to be sensitive and reliable, these methods could potentially serve as biomarkers for use in future clinical drug trials in HD. (C) 2008 Elsevier B.V. All rights reserved.
Notes: Bohanna, India Georgiou-Karistianis, Nellie Hannan, Anthony J. Egan, Gary F.
Abstract: Research in preclinical mutation carriers for Huntington's disease (HD) aims to find measures sensitive to preclinical decline. This study investigated attentional abilities in mutation carriers and noncarriers. Mutation carriers demonstrated a normal "attentional blink" during rapid serial visual presentation, normal covert visual orienting, and normal directing of attention to tactile stimuli. However, they were more likely than noncarriers to make anticipatory responses before target presentation. Additionally, those closer to estimated onset of HD demonstrated larger "inhibition of return" effects. The findings suggest potential changes in cognitive inhibition of unwanted responses, and in automatic inhibition of visual orienting, in preclinical HD.
Notes: Farrow, Maree Churchyard, Andrew Chua, Phyllis Bradshaw, John L. Chiu, Edmond Georgiou-Karistianis, Nellie
Abstract: Previous studies on aging and attention typically examine group differences between younger and older adults, rather than seeing aging as a continuous process. Using correlational analyses, this study examined progressive changes in the magnitude of the attentional blink (AB) associated with aging. Increased age was found to be significantly associated with the ability to detect the second target (T2), whereby older age was correlated with the production of a longer and more pronounced AB; this supports the proposition that aging is associated with reduced inhibitory processes and selective attention. It was also found that AB performance somewhat improves between ages 18-39 years, but tends to decline from 40 years of age onward, providing an interesting and novel finding that AB effects may become more sensitive at this point in time. The AB task may prove useful in the assessment of selective attention in normal healthy adults, as well as changes associated with pathological aging.
Abstract: Background. Previous research has confirmed the presence of increased motor overflow in schizophrenia. There are essentially two theories regarding the cortical origins of overflow. Recent research suggests that both may be correct, and that the cortical origin of overflow is highly dependent upon the population in which it presents. Motor overflow, due to an abnormally active ipsilateral corticospinal tract, may indicate a potentially severe brain abnormality arising in early development. In contrast, bilaterally active corticospinal tracts accounting for overflow probably represent a naturally occurring response during fatiguing contractions. Method. The cortical origins of motor overflow in 20 participants with schizophrenia and 20 normal controls were investigated through the use of a number of transcranial magnetic stimulation (TMS) protocols. Results. Each of the experimental protocols employed independently supported the contention that overflow was originating in the hemisphere contralateral to the involuntary movement. Conclusions. Results indicated that the origins of overflow in schizophrenia are the same as those seen in the normal control group, i.e. motor overflow seems to be due to the presence of bilaterally active corticospinal tracts. Potential explanations for greater motor overflow seen in schizophrenia are discussed.
Notes: Hoy, Kate E. Georgiou-Karistianis, Nellie Laycock, Robin Fitzgerald, Paul B.
Abstract: Motor overflow refers to overt involuntary movement, or covert muscle activity, that sometimes co-occurs with voluntary movement. Various clinical populations exhibit overflow. Motor overflow is also present in healthy children and the elderly, although in young adults, overt overflow is considered abnormal unless elicited under conditions of extreme force or muscle fatigue. Current theories of overflow imply that the corpus callosum may mediate production of this phenomenon. However, given that the corpus callosum is a conduit enabling the transfer of cortical information, surprisingly few studies have considered the cortical or subcortical structures underlying overflow. This review considers the developmental trend of motor overflow production, specifically in the upper-limbs, and the mechanisms thought to underlie this age-related phenomenon. Potential neurological correlates of motor overflow will be discussed in conjunction with higher order attentional processes which also regulate motor overflow production. Future research investigating the impact of attentional processes on overflow production may be particularly valuable for designing rehabilitation strategies for patients experiencing induced pathological overflow or conversely, to develop techniques to encourage the recovery of movement function in individuals with paretic limbs. Crown Copyright(C)C 2007 Published by Elsevier B.V. All rights reserved.
Notes: Addamo, Patricia K. Farrow, Maree Hoy, Kate E. Bradshaw, John L. Georgiou-Karistianis, Nellie
Abstract: Background: Huntington's disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. Aim: To assess the functional connectivity between prefrontal brain regions in patients with Huntington's disease, compared with normal controls, using functional magnetic resonance imaging. Patients and methods: 20 patients with Huntington's disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington's disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex. Results: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington's disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington's disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington's disease between the left anterior cingulate and prefrontal regions. Conclusions: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington's disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington's disease. It is speculated whether significantly greater levels of activation in patients with Huntington's disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.
Notes: Thiruvady, D. R. Georgiou-Karistianis, N. Egan, G. F. Ray, S. Sritharan, A. Farrow, M. Churchyard, A. Chua, P. Bradshaw, J. L. Brawn, T-L Cunnington, R.
Abstract: Patients with Parkinson's disease (PD) have difficulty performing tasks relying on inhibitory control and working memory, functions of the prefrontal cortex. Eye movement paradigms can be used to investigate basic sensorimotor functions and higher order cognitive aspects of motor control. This study investigated inhibitory control and spatial working memory in the saccadic system of 13 individuals with mild-moderate PD and 13 age-matched controls. Tasks explored suppression of reflexive saccades during qualitatively different tasks, generation of express and anticipatory saccades, and the ability to respond to occasional, unpredictable ("oddball") targets that occurred during a sequence of well-learned, reciprocating saccades between horizontal targets. Spatial working memory was assessed using single and two-step (involving a visually guided saccade during the delay period) memory-guided tasks. Results for the PD group indicated an increased percentage of response selection errors during an oddball task, reduced suppression of inappropriate reflexive saccades during memory-guided tasks (but not during fixation or saccade-engagement tasks), and an increased percentage of express and anticipatory saccades. Spatial working memory was preserved in the PD group during single and two-step memory-guided tasks. These findings are consistent with dysfunction within fronto-striatal and prefrontal-collicular pathways influencing suppression and selection of eye movements. (c) 2007 Movement Disorder Society.
Notes: Gurvich, Caroline Georgiou-Karistianis, Nellie Fitzgerald, Paul B. Millist, Lyn White, Owen B.
Abstract: Phantom limbs provide valuable insight into the mechanisms underlying bodily awareness and ownership. This paper reviews the complexity of phantom limb phenomena (proprioception, form, position, posture and telescoping), and the various contributions of internal constructs of the body, or body schema, and neuromatrix theory in explaining these phenomena. Specific systems and processes that have received little attention in phantom limb research are also reviewed and highlighted as important future directions. These include prosthesis embodiment and extended physiological proprioception (i.e., the extension of the body's "area of influence" that thereby extends one's innate sense of proprioception), mirror neurons and cross-referencing of the phantom limb with the intact limb (and the related phenomena of perceiving referred sensations and mirrored movements in the phantom from the intact limb). The likely involvements of the body schema and the body-self neuromatrix, mirror neurons, and cross-callosal and ipsilateral mechanisms in phantom limb phenomena all suggest that the perception of a "normal" phantom limb (that is, a non-painful phantom that has the sensory qualities of an intact limb) is more than likely an epiphenomenon of normal functioning, action understanding and empathy, and potentially may even be evolutionarily adaptive and perhaps necessary. Phantom pain, however, maybe a maladaptive failure of the neuromatrix to maintain global bodily constructs. (C) 2007 Elsevier B.V. All rights reserved.
Notes: Giummarra, Melita J. Gibson, Stephen J. Georgiou-Karistianis, Nellie Bradshaw, John L.
Notes: Cited By (since 1996): 17 xD;Export Date: 2 December 2010 xD;Source: Scopus xD;CODEN: NUPSA xD;PubMed ID: 17321554 xD;Language of Original Document: English xD;Correspondence Address: Georgiou-Karistianis, N.; School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Vic. 3800, Australia; email: nellie.georgiou-karistianis@med.monash.edu.au xD;Tradenames: Signa, General Electric; SPM2, Wellcome Department of Imaging Neuroscience, United Kingdom xD;Manufacturers: Wellcome Department of Imaging Neuroscience, United Kingdom; General Electric xD;References: Antonini, A., Leenders, K.L., Eidelberg, D., [11C]raclopride-PET studies of the Huntington's disease rate of progression: Relevance of the trinucleotide repeat length (1998) Annals of Neurology, 43, pp. 253-255; Aron, A.R., Watkins, L., Sahakian, B.J., Task-set switching deficits in early-stage Huntington's disease: Implications for basal ganglia function (2003) Journal of Cognitive Neuroscience, 15, pp. 629-642; Aylward, E.H., Anderson, N.B., Bylsma, F.W., Frontal lobe volume in patients with Huntington's disease (1998) Neurology, 50, pp. 252-258; Aylward, E.H., Rosenblatt, A., Field, K., Caudate volume as an outcome measure in clinical trials for Huntington's disease: A pilot study (2003) Brain Research Bulletin, 62, pp. 137-141; Aylward, E.H., Sparks, B.F., Field, K.F., Onset and rate of striatal atrophy in preclinical Huntington's disease (2004) Neurology, 63, pp. 66-72; Bartenstein, P., Weindl, A., Spiegel, S., Central motor processing in Huntington's disease. 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Abstract: Negative symptoms generally refer to a reduction in normal functioning. In schizophrenia they encompass apathy, anhedonia, flat affect, avolition, social withdrawal and, on some accounts, psychomotor retardation. Negative symptoms have been identified in other psychiatric disorders, including melancholic depression, and also in neurological disorders, such Parkinson's disease. Achieving a better understanding of negative symptoms constitutes a priority in mental health. Primarily, negative symptoms represent an unrelenting, intractable and disabling feature for patients, often amounting to a severe burden on families, carers and the patients themselves. Identifying and understanding subgroups within disorders may also contribute to the clinical care and scientific understanding of the pathophysiology of these disorders. The purpose of this paper is to review the current literature on negative symptoms in schizophrenia and explore the idea that negative symptoms may play an important role not only in other psychiatric disorders such as melancholic depression, but also in neurological disorders, such as Parkinson's disease. In each disorder negative symptoms manifest with similar motor and cognitive impairments and are associated with comparable neuropathological and biochemical findings, possibly reflecting analogous impairments in the functioning of frontostriatal-limbic circuits. (c) 2006 Elsevier Inc. All rights reserved.
Notes: Winograd-Gurvich, C. Fitzgerald, P. B. Georgiou-Karistianis, N. Bradshaw, J. L. White, O. B.
Abstract: Patients with Parkinson's disease (PD) manifest difficulty in initiation and execution of movements, particularly when movements are sequential, simultaneous or repetitive. Eye movements are particularly effective in evaluating motor impairments. We utilized a series of saccadic eye movement paradigms to explore the ability of 13 patients with mild-moderate PD and 13 age-matched healthy controls to self-pace saccades between two continuously illuminated targets, before and after an externally cued tracking period, and respond to unexpected changes in task demand. The latter was explored by measuring saccadic responses to unexpected "oddball" targets that appeared during a well-learned reciprocating sequence of saccades, in either the opposite direction to that expected or at twice the anticipated extent. Results indicated that all participants demonstrated a marked increase in saccade amplitudes from the externally cued saccade tracking to the self-paced saccades. Unexpectedly, this difference was magnified in PD patients. Self-paced saccades before externally cueing were also more frequent than requested in the PD group, but timing improved following external cueing. The second key finding was that while patients were able to respond to unexpected changes in target amplitude, performance was more variable (in terms of latency and accuracy) when responding to unexpected changes in target direction. Hence, beneficial effects of external cueing on the timing of self-paced saccades may be mediated through cortical regions, placing less emphasis on striatal regions known to be compromised in PD. Additionally, responding to changes in saccade direction (but not amplitude) may rely on basal ganglia circuitry. (c) 2006 Elsevier B.V. All rights reserved.
Notes: Winograd-Gurvich, C. Georgiou-Karistianis, N. Fitzgerald, P. B. Millist, L. White, O. B.
Abstract: There is limited documentation regarding cognitive function in individuals with Friedreich ataxia (FRDA), possibly because FRDA is widely held to predominantly affect the spinal cord, peripheral sensory nerves and cerebellum and not to affect cognition. Traditionally, the cerebellum has been thought to coordinate voluntary movement and motor tone, posture and gait. However, recent studies have implicated the cerebellum in a range of cognitive functions including executive function, visuospatial organisation and memory. We review the available data on cognitive function and neuroimaging in FRDA and the role of the cerebellum in cognitive function. We conclude with recommendations for future research including correlating cognitive function in individuals with FRDA with possible determinants of disease severity, such as age of onset and the causative genetic mutation. [References: 57]
Notes: Brain Research Bulletin. 70(3):197-202, 2006 Jul 31. xD;Review
Abstract: Background: Neuroimaging studies of Huntington disease (HD) gene carriers have shown that characteristic striatal atrophy begins long before symptom onset, but findings regarding the presence of preclinical functional deficits are inconsistent. Objective: To further investigate potential motor and cognitive deficits in presymptomatic gene carriers (PSGCs), and relationships between performance and estimated proximity to HD symptom onset. Method: PSGCs and age-matched controls performed motor tasks involving cued sequential button presses, and cognitive tasks involving simple and complex choice responses to visuospatial stimuli. Results: PSGCs demonstrated similar motor performance speed, and nonsignificantly slower cognitive reaction times, to controls. PSGCs made more errors than controls to stimuli requiring a spatially incongruent response, possibly suggesting some difficulty in inhibiting automatic responses. Movement times for motor conditions where little advance information was provided, and reaction times for low demand cognitive tasks, were positively correlated with PSGCs' estimated probability of symptom onset within 5 years. Conclusions: Response speed was slower for those PSGCs estimated to have higher probabilities of close onset. These findings suggest that to provide improved knowledge of how HD begins, knowledge that may be used in clinical trials, future research should further explore relationships between function and proximity to onset.
Notes: Farrow, Maree Chua, Phyllis Churchyard, Andrew Bradshaw, John L. Chiu, Edmond Georgiou-Karistianis, Nellie
Abstract: Motor disturbances in major depressive disorder (MDD) are increasingly recognized and may differentiate melancholic, from non-melancholic depression. Motor impairments in melancholic depression have been likened to Parkinson's disease and proposed to have a frontostriatal basis. This study investigated self-pacing and reprogramming skills, thought to rely on frontostriatal functioning, in groups of healthy individuals (n = 15), non-melancholic depression patients (n = 10) and melancholic depression patients (n = 9) using ocular motor tasks. Self-paced saccades were requested to be performed at a rhythm of I Hz between two continuously illuminated targets, before and after external cueing. Saccade reprogramming, for direction and amplitude, was explored using a saccadic "oddball" task. Results indicated no group differences for accuracy, intersaccadic intervals (during the self-paced task), latency or peak velocity. However, the melancholic group showed greater intrasubject variability of latencies than the control group, lower peak saccade velocities compared to the non-melancholic group, and reduced accuracy of the primary saccade when compared to the control and the non-melancholic groups. These findings provide further support for distinct motor impairments associated with melancholia that may reflect frontostriatal abnormalities. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
Notes: Winograd-Gurvich, Caroline Georgiou-Karistianis, Nellie Fitzgerald, Paul B. Millist, Lyn White, Owen B.
Abstract: Background: Major depressive disorder may be a heterogeneous disorder, yet melancholic depression is the most consistently described subtype, regarded as qualitatively different to non-melancholic depression in terns of cognitive and motor impairments. Eye movement studies in depression are infrequent and findings are inconclusive. Methods: This study employed a battery of saccadic eye movement tasks to explore reflexive saccades, as well as higher order cognitive aspects of saccades including inhibitory control and spatial working memory. Nineteen patients with major depressive disorder (9 melancholic; 10 non-melancholic) and 15 healthy controls participated. Results: Differences were revealed between melancholic and non-melancholic patients. Melancholia was associated with longer latencies, difficulty increasing peak velocities as target amplitudes increased, and hypometric primary saccades during the predictable protocol. In contrast, the non-melancholic depression group performed similarly to controls on most tasks, but saccadic peak velocity was increased for reflexive saccades at larger amplitudes. Limitations: Most patients were taking antidepressant medication. Conclusions: The latency increases, reduced peak velocity and primary saccade hypometria with more severe melancholia may be explained by functional changes in the fronto-striatal-collicular networks, related to dopamine dysfunction. In contrast, the serotonergic system plays a greater role in non-melancholic symptoms and this may underpin the observed increases in saccadic peak velocity. These findings provide neurophysiological support for functional differences between depression subgroups that are consistent with previous motor and cognitive findings. (c) 2006 Elsevier B.V All rights reserved.
Abstract: A predictive central-cueing paradigm was used to compare visuospatial deficits in patients with Parkinson's (PD) and Huntington's diseases (HD), employing directionally valid and invalid visual cues over a range of stimulus onset asynchronies (SOA) to elicit a saccadic response. Compared to age-matched control groups, both PD and HD patients responded erroneously to cue stimuli more frequently, increasing significantly over longer SOAs. Both valid and invalid cues resulted in elevated latencies compared to un-cued visually guided saccades, the associated 'cost' of invalid cueing significantly greater than that for valid cueing, over all SOAs. Unlike control subjects, PD and HD patients demonstrated temporal variation with cue presentation. For PD patients, latencies following directionally invalid cues were significantly longer for intermediate SOAs, suggesting difficulty overcoming a build-up of inhibitory activity over time. No validity effect was found at 1000 ms. For HD patients, latencies for validly cued saccades with 150 ms SOAs were shorter than latencies for no-cue trials, representing a 'benefit' of valid cueing. For 500 ms SOAs latencies were comparably elevated following directionally valid and invalid cues, and for 1000 ms SOAs neither cue condition resulted in increased latencies. These findings reflect the consequence of disruption to the balance of activity over the basal ganglia facilitatory and inhibitory pathways. Imbalance in PD resulted in difficulty sustaining goal-directed behaviour, and in HD, difficulty gating inappropriate behaviour. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
Abstract: An attentional blink (AB) paradigm was used to assess the ability of Tourette syndrome (TS) participants to detect and correctly identify two red target letters (T1 and T2) in a rapid serial visual presentation (RSVP) task. An AB was demonstrated for both patients and controls; identification of the second target (T2) was impaired when it appeared within 200 - 500 ms of the first (T 1). Interestingly, there was no difference between the groups in AB duration or magnitude. While there was a trend for reduced T2 identification in the TS group, this was not significant. Analysis of pre-target and post-target intrusion errors for T2 identification (as a function of T1-T2 interval) was conducted and, once again, no significant group differences were demonstrated. These results are indicative of a relative preservation of selective attention in TS.
Notes: Georgiou-Karistianis, Nellie Gardner, Betina Vardy, Yvette Evans, Natalie Bradshaw, John L. Shapir, Icmron Sheppard, Dianne
Abstract: While research suggests that normal ageing is associated with compromised divided attentional processing abilities, such studies are comparatively few in comparison to other areas of attention (e.g. selective attention). The current study sought to examine age-related effects in divided attention using a global/local paradigm in three normal healthy age groups: younger adults (20-40 years), middle-aged (40-60 years), and older adults (61-80 years). In three experiments we sought to examine the ability to process local/global stimuli, ability to divide and switch attention, as well as the influence of a cue on target performance. Experiment 1 revealed global precedence and interference for all age groups; older adults were overall significantly slower in their response times. Experiments 2 and 3 suggest an age-related impairment in dividing and switching attention, which may begin as early as middle age. The findings are considered to reflect reduced inhibitory mechanisms, as well as possible neurobiological changes in the normal ageing process. (c) 2006 Elsevier B.V. All rights reserved.
Abstract: Core symptoms of Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD) may be attributed to an impairment in inhibitory control. Neuropsychological studies have addressed inhibition in both disorders, but findings have been inconsistent. The aim of this study was to examine cognitive inhibition, using a semantic Simon effect paradigm, in patients with TS and OCD. Furthermore, to address comorbidity a group of TS + OCD patients was also examined. Results indicated that patients with TS and OCD were affected by the inhibitory components of the task. TS groups performed similarly to controls on simple and choice RT tasks, but were particularly compromised as increasingly complex inhibitory demands were imposed. OCD patients were slower and committed more errors than controls, especially in the more cognitively demanding conditions, and were particularly disadvantaged by incongruent stimulus-response compatibilities. Findings implicate possible fronto-striatal dysfunction, are consistent with previously reported inhibitory deficits in TS and OCD, and support the theory that comorbid TS + OCD is more closely linked to pure TS than OCD. (c) 2006 Elsevier Inc. All rights reserved.
Notes: Rankins, D. Bradshaw, J. L. Georgiou-Karistianis, N.
Abstract: Trajectories of saccadic eye movements can be modulated by the presence of a competing visual distractor. It is proposed that the superior colliculus (SC) controls the initial deviation through competitive lateral interactions. Given the ramifications of connections between basal ganglia (BG) thalamo-cortical circuitry and the SC, it was anticipated that this modulation would be differentially effected in those with Huntington's disease, which in its early stages is primarily a disorder of the BG. Horizontal deviation was determined for exogenously driven and endogenously driven vertical saccades in the presence of peripheral distractors. For neurologically healthy participants, the initial trajectories of both saccade types curved away from distractor locations, as predicted. However, for HD participants exogenous saccades consistently deviated leftwards, irrespective of distractor location. Endogenous saccades also revealed anomalous horizontal deviation, with significant leftward deviation evident for saccades directed upward and significant rightward deviation for saccades directed downward. Further, both groups generated a comparable proportion of erroneous responses to distractor stimuli, but only neurologically healthy participants demonstrated a response time advantage for compatible target/distractor presentation. These results suggest anomalous regulation of distractor-related activity in HD.
Abstract: Cognitive impairments in patients with basal ganglia dysfunction are primarily revealed where performance relies on internal, voluntary control processes. Evidence suggests that this also extends to impaired control of more automatic processes, including visuospatial attention. The present study used a non-predictive peripheral cueing paradigm to compare and contrast visuospatial deficits in patients with Parkinson's disease (PD) with those previously revealed in patients with Huntington's disease (HD) (Fielding et al., 2006a). Compared to age-matched controls, both PD and HD patients exhibited increased distractibility or poor fixation, however only PD patients responded erroneously to cue stimuli more frequently than control subjects. All subjects demonstrated initial facilitation for valid versus invalid cues following the shorter stimulus-onset asynchronies (SOAs) and a performance decrement at the longer SOAs (inhibition of return), although there was a clear differentiation between these groups for immediate SOAs. Unlike both control and PD subjects, where IOR manifested between 350 and 1000 msec, IOR was evident as early as 150 msec for HD patients. Further, for PD patients, spatially valid cues resulted in hyper-reflexivity following 150 msec SOAs, with saccadic latencies shorter than those generated in response to un-cued targets. Thus contrasting deficits were revealed in PD and HD, emphasizing the important contribution of the basal ganglia in the control of more automatic behaviors.
Abstract: A non-predictive peripheral cueing paradigm was used to evaluate visuospatial attentional deficits in symptomatic HD patients, employing spatially valid and invalid visual cues over a range of stimulus onset asynchronies (SOA) to elicit a saccadic response. Although both patients and controls demonstrated initial facilitation for valid versus invalid cues following the shortest SOA, and a performance decrement (inhibition of return), at the longest SOA, a clear differentiation between these groups was found for the intermediate SOAs. Unlike controls, where IOR manifested between 350 and 1000 ms, IOR was evident as early as 150 ms for HD patients. Further, the benefit of valid cueing correlated significantly with the level of impairment. Although patients exhibited poor fixation, principally attributable to saccadic intrusions, they were capable of appropriately suppressing a purely stimulus-driven response to the cue. A similar proportion of erroneous saccades to the cue were generated by both groups prior to stimulus onset. also correlating significantly with level of impairment. These results are discussed with respect to neural processes implicated in spatial cueing and within the context of reduced inhibitory activity of the BG in HD. 2005 Elsevier B.V. All rights reserved.
Abstract: This study utilised a finger force task to investigate the influence of attention and age on the occurrence of motor overflow in the form of mirror movements in neurologically intact adults. Forty right-handed participants were recruited from three age groups: 20-30 years, 40-50 years, and 60-70 years. Participants were required to maintain a target force using both their index and middle fingers, representing 50% of their maximum strength capacity for that hand. Attention was directed to a hand by activating a bone conduction vibrator attached to the small finger of that hand. Based on Cabeza's (2002) model of hemispheric asymmetry reduction ill older adults, it was hypothesised that mirror movements would increase with age. Furthermore, it was expected that when the attentional demands of the task were increased, motor overflow occurrence would be exacerbated for the older adult group. The results obtained provide support for the model, and qualified support for the hypothesis that increasing the attentional demands of a task results in greater motor overflow. It is proposed that the association between mirror movements and age observed in this study may result from an age-related increase in bihemispheric activation that occurs in older adults, who, unlike younger adults, benefit from bihemispheric processing for task performance.
Abstract: Neuropsychological and neuromiaging studies implicate attentional difficulties in obsessive-compulsive disorder (OCD), but results are inconsistent due possibly to sample heterogeneity and lack of control of comorbid disorders, such as Tourette's syndrome (TS). Nevertheless, it has been suggested that OCD symptomatology may be a result of overfocused attention at a local level. Therefore, this study aimed to examine the ability of OCD patients (pure and comorbid OCD + TS) to process local and global stimuli. Using a local-global paradigm, participants were required to respond to the directed level (local or global) of various stimuli. Results indicate that pure OCD participants were impaired on the global task, whereas comorbid OCD + TS participants had difficulty processing local information. Results are consistent with previously reported lateralisation anomalies and suggest that OCD negatively affects the ability to process hierarchically presented stimuli. (c) 2005 Elsevier Inc. All rights reserved.
Abstract: Background: This study investigated the nature and functioning of the visual-spatial inhibition of return (IOR) phenomenon in children with "pure" Tourette's syndrome (TS), and those with comorbid forms of TS. Method: Children with TS-only and "TS + comorbid" (TS + ADHD +/- OCD) and matched controls performed the inhibition of return (IOR) task, which involved responding to left and right visual targets appearing on a computer screen that were preceded by congruent or incongruent exogenous visual cues. Results: The TS-only group performed similarly on the IOR task to the controls. When the TS-only group was subdivided into children with mild and severe TS symptoms, a post hoc comparison between the controls and severe TS symptom children revealed that these TS children had a reduced magnitude of IOR for targets appearing in the right visual field. The comparison between the TS + comorbid and controls revealed an atypical IOR pattern for the TS + comorbid group. They displayed a loss of normal facilitatory and inhibitory effects for right visual field targets. Conclusions: The findings suggest abnormalities in attentional "disengage" and "move" mechanisms in TS when directing attention to the right visual field, which may reflect left posterior parietal, superior colliculus, and midbrain pathology.
Abstract: Disturbances of walking have been described in people with Huntington's disease (HD), although the nature of the deficits have not yet been well defined. The purpose of this investigation was to determine whether people with HD have a deficit in the regulation of footstep timing during walking. The footstep patterns of 30 people with HD and 30 matched comparisons were measured at self-selected slow, preferred, and fast speeds. Subjects were also instructed to match their footsteps to auditory metronome cues set at 80 and 120 beats per minute. Gait speed, cadence, stride length, and double limb support as a percentage of the gait cycle were measured using a computerized foot-switch system. People with HD demonstrated a disorder in their ability to regulate cadence, manifest as a reduced step frequency when walking at preferred speed and when required to increase their speed. For all walking conditions, people with HD had increased variability of footstep cadence. They also had difficulty synchronizing their footstep timing to an auditory cue. For all walking conditions, people with HD had reduced stride length. Thus, in HD, there is a disorder in the regulation of footstep timing, with increased variability, a restricted cadence range, difficulty synchronizing footsteps to an auditory cue and reduced stride length. The exact neural correlates of this timing disorder are yet to be determined. (C) 2004 Movement Disorder Society.
Abstract: This study sought to evaluate impaired response tendencies and modulation of automatic processes in Parkinson's disease (PD), utilising a saccadic Simon task with stimulus-response (S-R) compatibility determined on the basis of cue shape. The appearance of either a circle or a square in one of two boxes presented peripherally required the generation of a leftward or rightward horizontal saccade, respectively. These goal-directed responses were considered behaviourally relevant to an examination of visuospatial performance. Although response times are typically faster when stimulus and response are spatially compatible than when they are not, sequence-dependent modulation of this effect results in large differences between S-R compatible and S-R incompatible trials when stimulus and response are spatially compatible in the preceding trial, and reduced or absent differences when stimulus and response are spatially incompatible in the preceding trial. Unlike control subjects, PD patients demonstrated significantly shorter saccadic latencies overall, compared to a baseline condition involving endogenously-driven saccades. Patients also responded erroneously to cue stimuli with greater frequency. Analyses of both saccadic latency and errors to cue demonstrated a Simon effect (relatively faster response for S-R compatible trials), irrespective of the preceding trial. This suggests impaired modulation of the Simon effect in PD, consistent with predictions of inhibitory dysfunction, or impaired episodic memory. These results demonstrate the pivotal role of the basal ganglia in the regulation of context-dependent neural activity. (c) 2005 Elsevier B.V All rights reserved.
Abstract: We investigated both motor overflow and ability to control voluntary movement in patients with Huntington's disease (HD). We hypothesised that, compared with controls, overflow would be significantly greater in HD participants and that they would exhibit poorer control of voluntary movement. In a finger flexion task, participants had to maintain target forces representing 25, 50, or 75% of the maximum strength capacity for whichever finger was performing the task; overflow was measured in the corresponding finger of the non-responding hand. HD participants exhibited significantly greater motor overflow than controls, and more difficulty controlling the target force with the active hand. In addition, the degree of overflow in HD participants positively correlated with overall UHDRS motor symptom severity. The presence of exacerbated motor overflow in HD, and its correlation with symptom severity, is an important finding worthy of further investigation.
Abstract: Motor overflow refers to the involuntary movements which may accompany the production of voluntary movements. While overflow is not usually seen in the normal population, it does present in children and the elderly, as well as those suffering certain neurological dysfunctions. Advancements in methodology over the last decade have allowed for more convincing conclusions regarding the cortical origins of motor overflow. However, despite significant research, the exact mechanism underlying the production of motor overflow is still unclear. This review presents a more comprehensive conceptualization of the theories of motor overflow, which have often been only vaguely defined. Further, the major findings are explored in an attempt to differentiate the competing theories of motor overflow production. This exploration is done in the context of a range of neurological and psychiatric disorders, in order to elucidate the possible underlying mechanisms of overflow. (C) 2004 Elsevier B.V. All rights reserved.
Abstract: Obsessive-compulsive disorder (OCD) is characterized by repetitive obsessions and/or compulsions that interfere with daily functioning. Neuropsychological studies have suggested that such perseverative behaviors may be due to underlying attentional deficits. Inhibition of return (IOR) is an adaptive mechanism that is thought to assist visual search by biasing attention after a critical, short interval to novel, previously unattended areas. Therefore, this study aimed to examine Whether deficient IOR mechanisms could underlie some of the attentional, and perhaps, behavioral, problems, reported in OCD patients. Using a computerized TOR paradigm, participants were required to respond to a target that appeared at either the same or different location to a precue that was presented either 100 ms or 700 ms earlier. Results indicate that patients had a reduced TOR for targets presented in the left visual field, suggesting lateralized anomalies in shifting attention. Results are consistent with lateralization anomalies previously reported in OCD.
Abstract: The occurrence of motor dysfunction as a sign of schizophrenia, in addition to being a side effect of medication, has received considerable support in recent years. The current study aimed to systematically investigate both the presence and pattern of one such motor dysfunction, motor overflow. It was hypothesised that patients with schizophrenia would show significantly greater motor overflow than controls, and that the pattern of motor overflow occurrence would also vary significantly between the groups. A finger flexion task was used to examine the presence and pattern of motor overflow. Subjects were asked to maintain target forces, using either their index or small finger, representing 25, 50 or 75% of the maximum strength capacity for whichever finger was performing the task. Patients were found to exhibit significantly greater motor overflow than controls. There were also significant findings with respect to the patterns of motor overflow produced, specifically in regards to fine motor control and performance variability. In summary, patients differed significantly from controls in both the degree and pattern of overflow exhibited. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
Abstract: Presymptomatic individuals carrying the gene for Huntington's disease (HD) provide researchers with a unique opportunity of learning more about the neuropathophysiology, symptom onset, behavioural functioning, and mediating factors of this fatal disease. In this review, we attempt to demonstrate that research over the last 8 years, since the isolation of the gene, has remained at large controversial. Although we are aware of some of the factors that can influence age at onset and disease progression, we are still unable to determine exactly when an individual will develop HD symptoms, and how fast these symptoms will progress. In an era rapidly advancing with respect to therapeutic intervention that could forestall the onset and progression of HD, systematic research with improved inclusion criteria is paramount. A greater understanding of the time course of the disease would be beneficial not only in monitoring the effectiveness of future treatments, but also in determining the most appropriate time to administer them. Finally, we present various ethical considerations, as well as put forward various recommendations that could assist in better diagnosing preclinical deficits in presymptomatic individuals. (C) 2002 Elsevier Science Inc. All rights reserved.
Abstract: Eye movement abnormalities can be distinctive and suggestive of a specific pathophysiology. To further investigate the deficits in the control of saccades in patients with Huntington's disease (HD), we investigated the ability of I I HD patients and I I matched controls to perform visually-guided saccades. We adopted reflexive saccade tasks involving predictable and unpredictable sequences, at different amplitudes of target step (10degrees, 20degrees, 30degrees, 40degrees), as well as voluntary self-paced saccades. Prolongation of initiation was observed in the HD group as the target amplitude of predictable saccades increased. During the self-paced saccade task, the HD patients had increased intersaccadic intervals, performed fewer saccades in the allocated time and displayed an increased temporal variability in comparison to the controls. Furthermore, hypometric primary saccades, and an increased number of corrective saccades, were observed during both reflexive and voluntary saccades in the HD group. The delayed initiation of large saccades, deficits in voluntary, self-paced saccades, impaired saccadic accuracy and increased corrective saccades in HD, were interpreted in light of other ocular motor and limb studies, and appear to be due to damage to the fronto-striatal loop, including the supplementary eye fields, as well as possible brainstem and cerebellar involvement. (C) 2003 Elsevier Ltd. All rights reserved.
Abstract: Tourette's Syndrome (TS) is a basal ganglia (BG) disorder characterized by involuntary motor and vocal tics, impairment of voluntary motor function. and attentional dysfunctions. This experiment aimed to investigate motor reprograrnming and inhibitory control in adult TS patients. Ten TS patients and 10 age- and sex-matched controls performed sequences of movements in response to the illumination of LED lights, and were required to interrupt a predictable. reciprocating sequence of leftward and rightward movements in order to move to an unpredictable target that occurred either in the direction opposite to that expected. or in the opposite direction and at twice the expected distance. Results showed that TS patients were no slower than controls in reprogramming the direction and distance of movements, thus showing no overall deficits in inhibitory control. Of interest, however. was a directional asymmetry (right bias) in movement preparation time in TS patients. Patients with TS may have a superiority in allocating attentional resources toward the right side. contralateral to the implicated reduced BG volume in this disorder. These findings extend earlier work reporting anomalous BG lateralization in TS.
Abstract: Movement-related potentials (MRPs) reflect increasing cortical activity related to the preparation and execution of voluntary movement. Execution and preparatory components may be separated by comparing MRPs recorded from actual and imagined movement. Imagined movement initiates preparatory processes, but not motor execution activity. MRPs are maximal over the supplementary motor area (SMA), an area of the cortex involved in the planning and preparation of movement. The SMA receives input from the basal ganglia, which are affected in Huntington's disease (HD), a hyperkinetic movement disorder. In order to further elucidate the effects of the disorder upon the cortical activity relating to movement, MRPs were recorded from ten HD patients, and ten age-matched controls, whilst they performed and imagined performing a sequential button-pressing task. HD patients produced MRPs of significantly reduced size both for performed and imagined movement. The component relating to movement execution was obtained by subtracting the MRP for imagined movement from the MRP for performed movement, and was found to be normal in HD. The movement preparation component was found by subtracting the MRP found for a control condition of watching the visual cues from the MRP for imagined movement. This preparation component in HD was reduced in early slope, peak amplitude, and post-peak slope. This study therefore reported abnormal MRPs in HD. particularly in terms of the components relating to movement preparation, and this finding may further explain the movement deficits reported in the disease.
Abstract: The ability of Huntington's disease patients to co-ordinate their two hands with and without external cueing was investigated. Twelve Huntington's disease patients and sex- and age-matched controls performed a bimanual cranking task at two speeds (0.5 Hz, 1.5 Hz) and phase relationships (in-phase, anti-phase), with and without an external metronome cue. Data were sampled at 200 Hz, and raw displacement data for each hand, mean and standard deviation measures of the relative positions of the two hands and their velocities were then calculated. All participants could perform the in-phase movement, at both speeds; however, the Huntington's disease patients were more variable and less accurate than the control participants, particularly at the fast speed. While controls could perform the anti-phase movement, in which rotation of the cranks differed by 180 degrees at both speeds, Huntington's disease patients were unable to do so at either speed, reverting to the in-phase movement at the slow speed. An external metronome cue did not improve the performance of the Huntington's disease patients, which differentiated this group from patients suffering from Parkinson's disease. The Huntington's disease patients' inability to perform the anti-phase movement may be due to damage to the basal ganglia and its output regions.
Abstract: Little research has been conducted to examine sequential motor functioning of children with Tourette's syndrome (TS) and attention deficit hyperactivity disorder (ADHD). Movement sequencing performance for a group of 12 children with TS and 24 children with ADHD children (12 taking and 12 not taking stimulant medication) and matched control subjects was examined using a serial choice reaction time button-pressing procedure. Aspects of movement preparation and execution were measured for 10 sequential two-way choice points along a response board that extinguished the illuminated target buttons at certain specific times contingent on the previous button press or release. The level of advance information was systematically reduced to provide three levels of reduction of advance information. including no reduction, moderate reduction, and high reduction. Children with TS and ADHD (unmedicated) showed larger increases in down time, reflecting aspects of movement preparation, for the highest level of reduction of advance information than did their respective control groups. These deficits are suggestive of underlying frontostriatal dysfunction. Furthermore, the normalization of performance for children with ADHD taking stimulant medication assists in the confirmation of the validity of such a clinical diagnosis and seems to add to the clinical efficacy of this form of treatment, which has previously been associated with improvements for predominantly attentional and inhibitory symptoms of ADHD.
Abstract: Gilles de la Tourette syndrome is characterised by ties, although patients also commonly present with attentional problems. This experiment aimed to ascertain whether TS patients have problems in orienting attention, via the use of a vibrotactile choice reaction time task. Participants were required to push a button in response to a faint vibration delivered to the index finger. Prior to each stimulus vibration, a pre-cue (valid, neutral or invalid) was administered to the finger. The performance benefits and costs participants gained from valid and invalid precues were calculated. Contrary to our prediction TS patients did not show significantly different costs or benefits. Furthermore, both patients and controls showed an equal and increased benefit in the crossed arm posture, compared to the uncrossed. These results suggest TS patients do not generally have problems in orienting attention. In addition, in the tactile modality, both patients and controls may benefit from directed attention when difficulty levels are maximal.
Abstract: We investigated the role of the basal ganglia (BG) in motor imagery in patients with Huntington's disease (HD). A visually guided pointing task assessed whether patients could predict actual movement time (MT) through motor imagery. Executed and imagined movements were performed when vision was constrained centrally, or was free to move. Participants completed a series of imagined and actual movements, with and without central fixation, between two target circles. Patients with HD and controls' imagined MTs were significantly faster than their executed MTs. In compliance with Fitt's law, both actual and imagined MTs increased as a function of increasing task difficulty. We conclude that motor imagery is relatively preserved in HD.
Abstract: We report a pair of monozygotic Huntington's disease (HD) twins who, although sharing identical CAG repeat lengths, not only present with marked differences in clinical symptoms but also behavioral abilities as measured by our experimental procedures. Both HD twins and two healthy control subjects were tested twice over 2 years. Patient A was generally more impaired at a motor level, whereas Patient B showed greater attentional impairment; Patient B, however, showed more progressive deterioration. The control subjects' performance remained consistent over the 2-year interval. Patient A clinically had the more hyperkinetic hypotonic variant of the disease, whereas Patient B, who was the more impaired, presented with a more hypokinetic hypertonic (rigid) variant. The influences of epigenetic pre- and postnatal environmental factors should not be ignored.
Abstract: Gilles de la Tourette syndrome (TS) is a basal ganglia (BG) disorder, associated not only with hyperkinetic movements but also with attentional impairments. This experiment sought to ascertain whether overt direct visual attention would influence tactile attentional performance in TS, via the use of a vibrotactile choice reaction time procedure involving biased probabilities of event occurrence. Participants were required to look (i.e., direct gaze) either at the hand receiving the most (expected) vibrations, or the hand less often stimulated (the unexpected), for both crossed and uncrossed arm postures. Contrary to our predictions, gaze did not influence attentional performance in TS patients. Furthermore, patients were found not to be sensitive to distributions of event probability; that is, they did not demonstrate normal expectancy effects like controls. Attentional deficits in TS (as in Parkinson's disease, another BG disorder) may pertain more to difficulties in holding rather than in shifting the focus of attention. Moreover, directing attention towards the unexpected locus in the crossed arm posture improved overall performance in both patients and controls, suggesting that increased task demands (e.g., crossed arm posture), and/or unexpected stimulus location, may be alleviated by directed attention. These impairments may stem from dysfunction in the circuits linking the frontal lobes with the BG.
Abstract: This experiment sought to ascertain whether overt gaze (i.e., directed attention) would influence attentional performance in Huntington's disease (HD), via the use of a vibrotactile choice reaction time procedure involving biased probabilities of event occurrence. Subjects looked (i.e., direct gaze) either at the hand receiving the most (expected) vibrations, or the hand less often stimulated (the unexpected), for both crossed and uncrossed arm postures. Patients with HD showed performance advantages when directing attention (i.e., gaze) at the responding hand, especially for expected events. Patients with HD, however, were not sensitive to distributions of event probability in the uncrossed arm posture, nor when looking away from the responding hand. With the crossed arm posture, and when directing attention at the expected side, patients with HD became more sensitive to distributions of event probability. In HD, there may be a disruption of fronto-striatal circuitry on both cortical and subcortical levels which may account for impairments both in holding and shifting attention.
Abstract: Objectives-This study adopted a concurrent task design and aimed to quantify the efficiency and smoothness of voluntary movement in Tourette's syndrome via the use of a graphics tablet which permits analysis of movement profiles. In particular, the aim was to ascertain whether a concurrent task (digit span) would affect the kinematics of goal directed movements, and whether patients with Tourette's syndrome would exhibit abnormal functional asymmetries compared with their matched controls. Methods-Twelve patients with Tourette's syndrome and their matched controls performed 12 vertical zig zag movements, with both left and right hands (with and without the concurrent task), to large or small targets over long or short extents. Results-With short strokes, controls showed the predicted right hand superiority in movement time more strongly than patients with Tourette's syndrome, who instead showed greater hand symmetry with short strokes. The right hand of controls was less force efficient with long strokes and more force efficient with short strokes, whereas either hand of patients with Tourette's syndrome was equally force efficient, irrespective of stroke length, with an overall performance profile similar to but better than that of the controls' left hand. The concurrent task, however, increased the force efficiency of the right hand in patients with Tourette's syndrome and the left hand in controls. Conclusions-Patients with Tourette's syndrome, compared with controls, were not impaired in the performance of fast, goal directed movements such as aiming at targets; they performed in certain respects better than controls. The findings clearly add to the growing literature on anomalous lateralisation in Tourette's syndrome, which may be explained by the recently reported loss of normal basal ganglia asymmetries in that disorder.
Abstract: This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movement profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand in its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its. effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.
Abstract: Patients with hyperkinetic basal-ganglia disorders (Huntington's disease, HD; and Tourette's syndrome, TS) have difficulty with spatially incongruent stimulus-response configurations, the Simon effect, and with inhibiting inappropriate responses in a conditionality paradigm. However Parkinson's disease (PD) patients with hypokinetic basal-ganglia disorder show normal (for their age) conditionality and congruency effects, probably because the task is extremely sensitive to aging and PD patients are typically older than HD and TS individuals. Overall, HD patients were by far the most affected, reflecting the likely greater involvement of the caudate (with its predominantly cognitive role) than the putamen; the latter structure, with a predominantly motor involvement, is the more affected in PD.
Abstract: The extent to which individual discrete movements of Parkinson's disease (PD) patients could be facilitated by external cues was addressed in a simple sequential button-pressing task. A total of 16 PD patients and their individually age- and sex-matched controls participated. By systematically varying the placement of an auditory cue in each discrete movement of the sequence, the locus that best facilitated each person's performance could be determined. When the placement of the cue was individually tailored for each individual in the movement cycle, and a selected subset of such movements were individually cued, it was found to significantly facilitate sequential movement only for the PD patients and not the controls. However, the benefit accruing to PD patients from such selective cuing was far less than when all such movements in a sequence receive cuing, indicating the probable role of response set in Parkinsonian facilitation. A second experiment, this time involving 12 PD patients and their matched controls, examined the extent of dependence of PD patients' performance on external information. Although Parkinsonian performance was improved by the presence of advance visual information, as predicted, nevertheless the provision of irrelevant delayed cues failed to disrupt performance. Although PD patients did not therefore appear stimulus bound, they may nevertheless depend extensively on external stimuli in performing sequential movements. It was concluded that problems in the smooth sequencing of movements is a major aspect of the movement deficit in PD, which could perhaps be attributed to loss of automatic internal cuing mechanisms from the dysfunctional basal ganglia.
Abstract: Huntington's disease (HD) and Tourette's syndrome (TS) are two basal ganglia (BG) disorders, associated not simply with hyperkinetic movements but also with attentional impairments. The purpose of this experiment was to evaluate the attention deficits reported in HD and TS via the use of a vibrotactile choice reaction time (CRT) procedure involving biased probabilities of event occurrence. We attempted to ascertain whether HD and TS patients are impaired in their ability to shift their attention to an unexpected location, or when they have to hold attention to an expected location. The results demonstrate that HD patients, as compared to controls, experience difficulties in shifting their attention from expected to unexpected spatial locations; this effect was exacerbated with the adoption of a crossed arm configuration. On the other hand, TS patients' performance, although slower overall, was not qualitatively greatly different from that of the controls. We had previously found, with a similar paradigm, that Parkinson's disease patients instead manifest problems in holding or maintaining attention to an expected locus. We conclude that HD patients experience considerable difficulties in allocating attentional resources between expected and unexpected event occurrences, perhaps due to pervasive subcortical damage and dysfunction in the circuits linking the frontal lobes with the BG. In TS, a similar if milder functional rather than structural deficit may be reflected in a pattern of responses which resembles a weaker version of the HD response pattern. Copyright (C) 1996 Elsevier Science Ltd.
Abstract: To identify the focus of impairment in the performance of sequential movements in Huntington's disease (HD) patients, the extent of their reliance on external advance information was examined. Twelve patients with HD and their age-matched controls performed a series of button-presses at sequential choice points along a response board. A sequential pathway was designated, and with each successive button press, advance visual information was systematically reduced to various extents in advance of each move. HD patients, like previously studied parkinsonian patients, were particularly disadvantaged with high levels of reduction in advance information, and as a consequence, both their initiation and execution of movements progressively slowed with each successive element in the response sequence. The pattern of results was not affected whether or not patients were taking neuroleptic medication, nor did performance on a variety of cognitive measures correlate with motor performance. Control subjects' performance, on the other hand, remained constant in terms of both initiation and execution with each of the three levels of reduction in advance information. We conclude that HD patients, like parkinsonian patients, who also suffer from a basal ganglia (BG) disorder, require external visual cues to sequence motor programs effectively. Our findings suggest that with HD there may be abnormalities in a central mechanism that controls switching between movement segments within an overall motor plan. The BG, which provide internal cues necessary for component sequencing, may be disrupted, thereby impairing the ability to use such internally generated cues to guide movement.
Abstract: Tourette's syndrome and Huntington's disease have long been clinically associated with attentional deficits. In this study, we aimed to determine the nature and quantify the extent of such deficits. A technique was devised to ascertain the efficiency with which Tourette's syndrome and Huntington's disease patients could shift and direct attention away from naturally expected stimulus-response (S-R) linkages. This was done by varying the relationships formed between stimulus and response location. Attentional efficiency was indicated by relative speed of responding to relevant (congruent) and irrelevant (incongruent) stimuli, in a paradigm developed from the Simon effect. There were five conditions progressively increasing in complexity. The stimuli consisted of left and right pointing arrows and, in some cases, various conditionality manipulations were also employed, such that in the presence of a certain symbol (i.e. 'x') the nature of the response had to be reversed, whereas in the presence of an alternative symbol (i.e. '='), the response was compatible with the direction of the arrow. As predicted, Tourette's syndrome and Huntington's disease patients, regardless of medication or depression status and unlike controls, were particularly disadvantaged in responding to various conflicting S-R configurations. Tourette's syndrome and Huntington's disease patients may experience difficulties in making attentional shifts, or in inhibiting inappropriate responses; they may also be more susceptible (than controls) to the conflict that can arise when the spatial code formed for the stimulus is irrelevant for selecting the appropriate response. We conclude that our findings support the notion that cognitive deficits in Tourette's syndrome and Huntington's disease may stem from abnormalities of the major pathways interconnecting the basal ganglia and the frontal lobes.
Abstract: Tourette's syndrome is a chronic neurological disorder manifested by involuntary motor ties and vocalisations. Because the basal ganglia have been implicated in the pathology underlying Tourette's syndrome, the present two procedures, both involving sequential movements, sought to determine the extent to which patients with Tourette's syndrome were reliant on, and could utilise different levels of advance information. Patients with Tourette's syndrome were found to be more reliant than controls on external visual cues to execute rather than to initiate a motor programme. When there was a high level of reduction in advance information - that is, a visual pathway to be followed was extinguished well in advance of each successive movement - executions progressively slowed as the sequence was traversed. Similarly, if no advance information was provided before each move, movement execution was slower than that of controls. The movement initiation times of patients with Tourette's syndrome were, however, similar to those of controls, as were their movement execution times when advance visual information was available. It seems that patients with Tourette's syndrome, like parkinsonian patients who are known to have a basal ganglia disorder, require external sensory cues to sequence a motor programme effectively. The present study found evidence consistent with the hypothesis that patients with Tourette's syndrome, like patients with Parkinson's disease, may be dysfunctional in internal switching mechanisms. Alternatively, with limited visual guidance, patients with Tourette's syndrome, regardless of medication or depression state, may require more time to plan and programme each next submovement, and under such conditions may require external visual cues to direct attention effectively to given targets. Although the underlying pathogenesis is still speculative, it is concluded that there is much to support the notion that Tourette's syndrome may stem from abnormalities of the major pathways between the basal ganglia and the frontal lobes.
Abstract: To identify the focus of impairment in the performance of sequential movements of patients with Parkinson's disease, the extent of their reliance on external cues was examined. Eighteen patients with idiopathic Parkinson's disease and their matched controls performed a series of button presses at sequential choice points along a response board. The illuminated pathway to be followed successively extinguished ahead of each move according to three levels of reduction of external cues. Patients with Parkinson's disease were particularly disadvantaged with high levels of reduction of external cueing in terms both of movement preparation time (button down time) and movement execution time (movement time between buttons). Moreover, with high levels of reduction of external cueing, patients with Parkinson's disease were particularly subject to progressive slowing (movement time, not down time) further down the sequence. The basal ganglia may help Method generate internal cues for releasing successive stages of a predefined movement sequence.
Abstract: Our animal studies suggest that the basal ganglia provide an internal non-specific cue to trigger movement and imply that Parkinson's disease involves a deficiency in this cueing mechanism. Indeed parkinsonian patients typically rely upon external visual cues. To assess the effects of such non-specific cueing mechanisms on movement, we examined patients' utilization of a variety of auditory cues. Ten patients suffering from Parkinson's disease, and their matched controls, pressed buttons at a series of two-way choice points sequentially down a pathway, both when the latter remained illuminated throughout its length, and when it had to be followed from memory alone. In other experimental conditions, auditory cues were also provided, either contingent upon the previous response, at its initiation (a medium level of advance information) or at its completion (a low level of advance information), or as a series of regularly paced (non-contingent) auditory cues (from a metronome). In addition to error data, we recorded down time (DT, time to initiate each next response) and movement time (MT), time to execute each next response). However, both DT and MT measurements showed that parkinsonian patients were enormously disadvantaged by the absence of external cues. While contingent auditory cues were of some help, the performance of patients with Parkinson's disease was dramatically improved by the provision of non-contingent auditory information. Moreover, parkinsonian patients, unlike controls, were greatly affected by the length of individual sub-movements, especially in the absence of external cues. When the pathway to be followed remained illuminated, sub-movement length had little effect. We conclude that for well-learnt, predictable sequences the basal ganglia provide a non-specific internal cue that is necessary for switching between one movement and the next in a movement sequence, and also for development of preparatory activity for each sub-movement in the sequence.
Notes: Corben, L. A. Akhalghi, H. Georgiou-Karistianis, N. Bradshaw, J. L. B. Egan, G. F. Storey, E. Churchyard, A. J. Delatycki, M. B. xD;20th Meeting of the European-Neurological-Society xD;Jun 19-23, 2010 xD;Berlin, GERMANY xD;Suppl. 1
Notes: Gurvich, C. Fitzgerald, P. Georgiou-Karistianis, N. Millist, L. White, O. xD;10th International Congress on Schizophrenia Research xD;Apr 02-06, 2005 xD;Savannah, GA
