Abstract: Elevated blood levels of S100B in neuropsychiatric disorders have so far been mainly attributed to glial pathologies. However, increases or dysfunction of adipose tissue may be alternatively responsible. Our study assessed S100B serum levels in 60 adult subjects without a prior history of neuropsychiatric disorders. S100B concentrations were closely correlated with the body mass index (BMI, range 18-45kg/m(2)) as well as levels of leptin and adipocyte-type fatty acid-binding protein (A-FABP/FABP4) that are well-known adipose-related factors. Effect sizes as measured by Cohen's d indicated medium (0.8>d>0.5) to strong effects (d>0.9) of BMI on S100B blood levels. In conclusion, physiological S100B levels in humans appear to closely reflect adipose tissue mass, which should therefore be considered as an important confounding factor in clinical studies examining the role of S100B.
Abstract: Animal studies suggest that dopaminergic neuromodulation is critical for hippocampal memory formation. Compatible with this notion, recent functional imaging evidence in humans showed that reward modulates the hippocampus-dependent formation of episodic memories through activation of areas belonging to the mesolimbic dopaminergic system, including the ventral striatum and substantia nigra/ventral tegmental area (SN/VTA). However, the amygdala is also closely embedded within this mesolimbic circuitry with reciprocal connections to the SN/VTA, raising the possibility that emotionally valenced stimuli might also interact with hippocampal encoding through dopaminergic neuromodulation. By the same token, emotional processing in the amygdala might be affected by reward-related processing in the mesolimbic system. In an event-related functional magnetic resonance imaging study, reward-related activity in the ventral striatum was enhanced by the concurrent presentation of emotionally positive but not emotionally negative stimuli. Emotional processing in the amygdala, on the other hand, was not affected by reward. One day after study, recollection of the positive stimuli was better when they were associated with reward at encoding as compared with unrewarded positive stimuli. The findings are compatible with the notion that the output of the reward system and memory formation in the hippocampus is influenced by positive emotional valence and suggest that the ventral striatum is a key structure for this modulation.
Abstract: Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the dorsomedial prefrontal cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.
Abstract: Criminal responsibility requires that the offender has acted on the base of his own free will. Recently, the existence of such a "free will" has been questioned in the light of new neuroscientific findings which show that an astonishingly large part of a decision appears to be determined by neuronal structures and imprintings. Especially pathologic forms of aggression are closely linked to neurobiological factors. In the USA the prevalence of neuropsychiatric diseases in prisoners has been shown to be markedly above population average. Prevalence in german prisoners, on the contrary, has not yet been carefully examined. Here, we present two cases of violent offenders detained in prison in whom years after their conviction structural brain pathology was discovered that had most probably interfered with their "free will". On the background of these cases it appears evident that it is necessary to assess the prevalence of neuropsychiatric disorders in violent offenders in german prisons as well as to regularly examine in the course of their trial whether violent offenders suffer from such disorders. Furthermore, it appears appropriate to generally shift the focus of social handling of violent offenders from a punishment- and expiation-centered to a treatment-, monitoring- and integration-based approach.
Abstract: CONTEXT: Pedophilic crime causes considerable public concern, but no causative factor of pedophilia has yet been pinpointed. In the past, etiological theories postulated a major impact of the environment, but recent studies increasingly emphasize the role of neurobiological factors, as well. However, the role of alterations in brain structures that are crucial in the development of sexual behavior has not yet been systematically studied in pedophilic subjects. OBJECTIVE: To examine whether pedophilic perpetrators show structural neuronal deficits in brain regions that are critical for sexual behavior and how these deficits relate to criminological characteristics. DESIGN: Amygdalar volume and gray matter of related structures that are critical for sexual development were compared in 15 nonviolent male pedophilic perpetrators (forensic inpatients) and 15 controls using complementary morphometric analyses (voxel-based morphometry and volumetry). Psychosocial adjustment and sexual offenses were also assessed. RESULTS: Pedophilic perpetrators showed a significant decrease of right amygdalar volume, compared with healthy controls (P = .001). We observed reduced gray matter in the right amygdala, hypothalamus (bilaterally), septal regions, substantia innominata, and bed nucleus of the striae terminalis. In 8 of the 15 perpetrators, enlargement of the anterior temporal horn of the right lateral ventricle that adjoins the amygdala could be recognized by routine qualitative clinical assessment. Smaller right amygdalar volumes were correlated with the propensity to commit uniform pedophilic sexual offenses exclusively (P = .006) but not with age (P = .89). CONCLUSIONS: Pedophilic perpetrators show structural impairments of brain regions critical for sexual development. These impairments are not related to age, and their extent predicts how focused the scope of sexual offenses is on uniform pedophilic activity. Subtle defects of the right amygdala and closely related structures might be implicated in the pathogenesis of pedophilia and might possibly reflect developmental disturbances or environmental insults at critical periods.
Abstract: BACKGROUND: Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. METHODS: Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. RESULTS: Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. CONCLUSIONS: Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.
Abstract: With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection.
Abstract: Hippocampal sclerosis in temporal lobe epilepsy (TLE) is often associated with hippocampal atrophy. This study assessed whether such atrophy is correlated with loss of gray matter volume in other brain regions. In 16 patients with TLE and clear magnetic resonance imaging-based evidence of hippocampal sclerosis, hippocampal volumes were determined manually and the local gray matter (LGM) amount was estimated throughout the entire brain using voxel-based morphometry. Voxelwise correlations between the volume of the sclerotic hippocampus and LGM were computed. The pattern of voxels whose LGM correlated with hippocampal volume outlined remarkably well the anatomy of the extended limbic system and included the parahippocampal region, cingulate gyrus throughout its extent, basal forebrain, thalamic nuclei, medial orbitofrontal areas and the insula. These correlations emerged mainly on the side ipsilateral to the affected hippocampus but were also found contralaterally. No such correlations were found in a group of 16 healthy controls. The present data show that hippocampal volume loss in TLE is associated with a widespread limbic systems atrophy. These findings are helpful to better understand the functional deficit and reorganization often found in temporal lobe epilepsy and will also provide a basis to assess neural plasticity in the limbic system for those patients who will undergo curative temporal lobe surgery.
Abstract: Pedophilic crimes reliably elicit considerable public interest. The number of pedophilic offenses is not negligible and therefore pedophilic sexual orientation as a fundament of these crimes is an major public health issue. Its importance notwithstanding, no consistent pathogenetic concept of pedophilic orientation has been developped yet. Specifically the pathogenetic role of neurobiological factors such as disturbances of neuronal development and structural alterations of frontotemporal brain areas that have been described in pedophilia before has not yet been determined. On the basis of recent advances in the understanding of neurobiological underpinnings of the development and regulation of sexual behavior we propose a neurobiological model accounting for the development of a pedophilic sexual orientation. According to this model damage to structures constituting the âextended amygdalaâ impairs the assignment of sexual appetence to pheromonal and other sensory cues, normally occurring in the course of puberty. Consequently an infantile sexual orientation with a disturbed binding behavior develops in conjunction with an normal adult sexual drive. The assumption of such a neurobiological basis of pedophilic sexual orientation is an etiopathogenetic model that integrates personality traits previously described in pedophilic patients as well as pathologic alterations of brain structure.
Abstract: Semantic relatedness among items is a powerful means by which interference effects can be evoked. Control of semantic interference involves executive processes such as monitoring and mobilization of processing resources engaged in episodic memory retrieval (retrieval effort). A median split was used to distinguish subjects with high and low retrieval effort in a task requiring control of semantic interference. Only subjects with large differences in reaction time for the interference condition compared to a control condition showed frontal event-related brain potentials (ERP) that were more positive-going for the interference condition compared to the non-interference condition. These differences were interpreted as reflecting processes associated with retrieval effort.
Abstract: The age-related structural changes of the human hippocampus are not entirely understood. The goal of the present investigation was to understand better the nature of age-related hippocampal changes by a comparative MR-analysis of four complementary aspects of hippocampal integrity: total volume, metabolite concentration, neuron to glial cell ratio and amount of extracellular diffusion space for water. To that end, we applied MR-based methods of manual and computerized (voxel-based morphometry) volumetry, diffusion-weighted imaging and 1H MR spectroscopy to characterize specific age-related hippocampal effects in a group of 22 healthy old adults in comparison with a group of 13 healthy younger adults. Age-related reductions of the hippocampal N-acetyl aspartate to creatine/choline ratio together with only marginal age-related reductions in hippocampal volumes and increases in diffusion parameters suggest that the process of aging affects mainly the metabolic status of the hippocampus with little equivalent age-related changes in hippocampal cell density. The metabolic changes are unspecific as they are not restricted to the hippocampus but equally occur in measures obtained from extrahippocampal temporal lobe regions.
Abstract: Dercum's disease (lipomatosis dolorosa) is a relatively unknown illness. The disorder usually affects middle-aged females. Subcutaneous fatty tissue deposits may occur in many parts of the body. The upper arms, elbows, stomach wall, buttocks, thighs, or knees are most commonly affected. Severe hyperalgesia is found on light pressure and touch. Analgesics or pain-modulating drugs usually have little or no effect. The following case report demonstrates successful symptomatic treatment of the otherwise nearly unbearable complaints: intravenous infusions of 5 mg/kg body weight of lidocaine over 30-90 min may give pain relief lasting several weeks or even months. Alternatively, patients are treated with 150-750 mg orally administered mexiletine daily. Surgical excision or liposuction of these fatty tissue deposits have shown significant reduction of pain. However, this effect reduces over time and recurrences often develop.
Abstract: A central question in psycholinguistic research is when various types of information involved in speaking (conceptual/semantic, syntactic, and phonological information) become available during the speech planning process. Competing theories attempt to distinguish between parallel and serial models. Here, we investigated the relative time courses of conceptual and syntactic encoding in a tacit picture-naming task via event-related brain potential (ERP) recordings. Participants viewed pictures and made dual-choice go/no-go decisions based on conceptual features (whether the depicted item was heavier or lighter than 500 g) and syntactic features (whether the picture's German name had feminine or masculine syntactic gender). In support of serial models of speech production, both the lateralized readiness potential, or LRP (related to response preparation), and the N200 (related to response inhibition) measures indicated that conceptual processing began approximately 80 msec earlier than syntactic processing.
Abstract: Prefrontal activation is a consistent finding in functional neuroimaging studies of episodic memory retrieval. In the present study we aimed at a further analysis of prefrontal neural systems involved in the executive control of context-specific properties in episodic memory retrieval using an event-related fMRI design. Nine subjects were asked to learn two 20-item word lists that consisted of concrete nouns assigned to four semantic categories. Ten items of both word lists referred to the same semantic category. Subjects were instructed to determine whether nouns displayed in random order corresponded to the first 20-item target list. The interference evoked by the retrieval of semantically related items of the second list resulted in significantly longer reaction times compared to the noninterference condition. Contrasting the interference against the noninterference retrieval condition demonstrated an activation pattern that comprised a right anterior cingulate and frontal opercular area and a left-lateralized dorsolateral prefrontal region. Trial averaged time series revealed that the PFC areas were selectively activated at the interference condition and did not respond to the familiarity of learned words. These findings suggest a functionally separable role of prefrontal cortical areas mediating processes associated with the executive control of interfering context information in episodic memory retrieval.
Abstract: Synesthesia is a perceptual condition in which stimulation in one sensory modality elicits a concurrent sensation in another. The authors studied possible electrophysiological correlates of synesthetic experience in 17 subjects claiming to continuously experience chromatic-graphemical synesthesia and a matched control group. Subjects had to respond to one of four numbers and one of six letters by pressing a button. Even-related potentials (ERPs) were recorded from multiple scalp sites. Most synesthetic subjects reported strong synesthetic perceptions during the experiment. The ERPs of both groups showed a distinct P300 component when subjects encountered the assigned target number or letter. Synesthetic subjects had significantly and clearly more positive waveform over frontal and prefrontal scalp regions than control subjects for target and nontarget stimuli. This electrophysiological marker is discussed in terms of cortical inhibition in synesthetic subjects and the role of prefrontal regions in multisensory integration.
Abstract: To explain processing differences between regular (e.g., start/started) and irregular (e.g., think/thought) word formation linguistic models posit either a single mechanism handling both morphological clusters or separate mechanisms for regular and irregular words. The purpose of the present study is to investigate how these processing differences map onto brain processes by assessing electrophysiological effects of English past tense forms, using the repetition priming paradigm. Event-related brain potentials (ERPs) were recorded from 59 scalp sites as 19 subjects read stem forms of regular and irregular verbs from a list of 1152 words; the stem forms were either preceded (5-9 intervening items) by their past tense forms (=primed condition) or by past tense forms of unrelated verbs (=unprimed condition). The difference between the ERPs to the primed and unprimed stems was taken as a measure of morphological priming. We found that the ERPs to regular verbs were clearly different from those to irregular verbs: the former were associated with an N400 reduction in the primed condition; primed irregular verb stems, however, showed no such effect. Control conditions demonstrated that the N400 modulation for regular verbs cannot be attributed to formal (i.e., phonological or orthographical) priming. These ERP effects indicate that regular verbs serve as more powerful primes for their corresponding stem forms than irregular past tense forms, suggesting that regular (but not irregular) past tense forms may be decomposed into stem plus affix.
Abstract: We conceive of time as a sequential order of real-world events, one event following another from past to present to future. This conception colours the way we speak of time ("we look forward to the time") and, as we show here, the way we process written statements referring to the temporal order of events, in real time. Terms such as 'before' and 'after' give us the linguistic freedom to express a series of events (real or imaginary) in any order. However, sentences that present events out of chronological order require additional discourse-level computation. Here we examine how and when these computations are carried out by contrasting brain potentials across two sentence types that differ only in their initial word ('After' X, Y versus 'Before' X, Y). At sites on the left frontal scalp, the responses to 'before' and 'after' sentences diverge within 300 ms; the size of this difference increases over the course of the sentences and is correlated with individual working-memory spans. Thus, we show that there are immediate and lasting consequences for neural processing of the discourse implications of a single word on sentence comprehension.
