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The temporal pole (TP) is an associative cortical region required for complex cognitive functions such as social and emotional cognition. However, mapping the TP with functional magnetic resonance imaging is technically challenging and thus understanding its interaction with other key emotional circuitry, such as the amygdala, remains elusive. We exploited the unique advantages of stereo-electroencephalography (sEEG) to assess the responses of the TP and the amygdala during the perception of emotionally salient stimuli of pictures, music and movies. These stimuli consistently elicited high gamma responses (70–140 Hz) in both the TP and the amygdala, accompanied by functional connectivity in the low frequency range (2–12 Hz). Computational analyses suggested that the TP drove this effect in the theta frequency range, modulated by the emotional valence of the stimuli. Notably, cross-frequency analysis indicated the phase of theta oscillations in the TP modulated the amplitude of high gamma activity in the amygdala. These results were reproducible across three types of sensory inputs including naturalistic stimuli. Our results suggest that multimodal emotional stimuli induce a hierarchical influence of the TP over the amygdala.

Adaptive brain function requires that sensory impressions of the social and natural milieu are dynamically incorporated into intrinsic brain activity. While dynamic switches between brain states have been well characterised in resting state acquisitions, the remodelling of these state transitions by engagement in naturalistic stimuli remains poorly understood. Here, we show that the temporal dynamics of brain states, as measured in fMRI, are reshaped from predominantly bistable transitions between two relatively indistinct states at rest, toward a sequence of well-defined functional states during movie viewing whose transitions are temporally aligned to specific features of the movie. The expression of these brain states covaries with different physiological states and reflects subjectively rated engagement in the movie. In sum, a data-driven decoding of brain states reveals the distinct reshaping of functional network expression and reliable state transitions that accompany the switch from resting state to perceptual immersion in an ecologically valid sensory experience., The transition from resting to perceiving one’s milieu requires a fundamental reorganization of brain activity. Here, the authors show how a fundamental reshaping of brain state dynamics supports perceptual engagement in naturalistic stimuli.

The temporal pole (TP) is an associative cortical region required for complex cognitive functions such as social and emotional cognition. However, functional mapping of the TP with functional magnetic resonance imaging is technically challenging and thus understanding of its interaction with other key emotional circuitry, such as the amygdala, remain elusive. We exploited the unique advantages of stereo-electroencephalography (SEEG) to assess the responses of the TP and the amygdala during the perception of emotionally salient stimuli of pictures, music and movies. These stimuli consistently elicited high gamma responses (70-140 Hz) in both the TP and the amygdala, accompanied by functional connectivity in the low frequency range (2-12 Hz). Computational analyses suggested the TP driving this effect in the theta-alpha frequency range and which was modulated by the emotional salience of the stimuli. Of note, cross-frequency analysis indicated the phase of theta-alpha oscillations in the TP modulated the amplitude of high gamma activity in the amygdala. These results were reproducible with three types of stimuli including naturalistic stimuli suggesting a hierarchical influence of the TP over the amygdala in non-threatening stimuli.

The momentary global functional state of the brain is reflected in its electric field configuration and cluster analytical approaches have consistently shown four configurations, referred to as EEG microstate classes A to D. Changes in microstate parameters are associated with a number of neuropsychiatric disorders, task performance, and mental state establishing their relevance for cognition. However, the common practice to use eye-closed resting state data to assess the temporal dynamics of microstate parameters might induce systematic confounds related to vigilance levels. Here, we studied the dynamics of microstate parameters in two independent data sets and showed that the parameters of microstates are strongly associated with vigilance level assessed both by EEG power analysis and fMRI global signal. We found that the duration and contribution of microstate class C, as well as transition probabilities towards microstate class C were positively associated with vigilance, whereas the sign was reversed for microstate classes A and B. Furthermore, in looking for the origins of the correspondence between microstates and vigilance level, we found Granger-causal effects of vigilance levels on microstate sequence parameters. Collectively, our findings suggest that duration and occurrence of microstates have a different origin and possibly reflect different physiological processes. Finally, our findings indicate the need for taking vigilance levels into consideration in resting-sate EEG investigations.

Electroencephalogram (EEG) microstates that represent quasi‐stable, global neuronal activity are considered as the building blocks of brain dynamics. Therefore, the analysis of microstate sequences is a promising approach to understand fast brain dynamics that underlie various mental processes. Recent studies suggest that EEG microstate sequences are non‐Markovian and nonstationary, highlighting the importance of the sequential flow of information between different brain states. These findings inspired us to model these sequences using Recurrent Neural Networks (RNNs) consisting of long‐short‐term‐memory (LSTM) units to capture the complex temporal dependencies. Using an LSTM‐based auto encoder framework and different encoding schemes, we modeled the microstate sequences at multiple time scales (200–2,000 ms) aiming to capture stably recurring microstate patterns within and across subjects. We show that RNNs can learn underlying microstate patterns with high accuracy and that the microstate trajectories are subject invariant at shorter time scales (≤400 ms) and reproducible across sessions. Significant drop in the reconstruction accuracy was observed for longer sequence lengths of 2,000 ms. These findings indirectly corroborate earlier studies which indicated that EEG microstate sequences exhibit long‐range dependencies with finite memory content. Furthermore, we find that the latent representations learned by the RNNs are sensitive to external stimulation such as stress while the conventional univariate microstate measures (e.g., occurrence, mean duration, etc.) fail to capture such changes in brain dynamics. While RNNs cannot be configured to identify the specific discriminating patterns, they have the potential for learning the underlying temporal dynamics and are sensitive to sequence aberrations characterized by changes in metal processes. Empowered with the macroscopic understanding of the temporal dynamics that extends beyond short‐term interactions, RNNs offer a reliable alternative for exploring system level brain dynamics using EEG microstate sequences.

A receptor map of serotonin distribution is integrated into a model of the dynamic activity of the brain under the effects of LSD. The approach opens new avenues to understand experimental manipulations of healthy brain activity and offers a novel drug-discovery platform.

Resting-state fMRI studies have gained widespread use in exploratory studies of neuropsychiatric disorders. Graph metrics derived from whole brain functional connectivity studies have been used to reveal disease-related variations in many neuropsychiatric disorders including major depression (MDD). These techniques show promise in developing diagnostics for these often difficult to identify disorders. However, the analysis of resting-state datasets is increasingly beset by a myriad of approaches and methods, each with underlying assumptions. Choosing the most appropriate preprocessing parameters a priori is difficult. Nevertheless, the specific methodological choice influences graph-theoretical network topologies as well as regional metrics. The aim of this study was to systematically compare different preprocessing strategies by evaluating their influence on group differences between healthy participants (HC) and depressive patients. We thus investigated the effects of common preprocessing variants, including global mean-signal regression (GMR), temporal filtering, detrending, and network sparsity on group differences between brain networks of HC and MDD patients measured by global and nodal graph theoretical metrics. Occurrence of group differences in global metrics was absent in the majority of tested preprocessing variants, but in local graph metrics it is sparse, variable, and highly dependent on the combination of preprocessing variant and sparsity threshold. Sparsity thresholds between 16 and 22% were shown to have the greatest potential to reveal differences between HC and MDD patients in global and local network metrics. Our study offers an overview of consequences of methodological decisions and which neurobiological characteristics of MDD they implicate, adding further caution to this rapidly growing field.

Myoclonus-dystonia is an autosomal dominantly inherited movement disorder clinically characterized by myoclonic jerks and dystonic movements of the upper body. Functional imaging and structural gray matter imaging studies in M-D suggest defective sensorimotor integration and an association between putaminal volume and severity of dystonia, possibly because of neuronal plasticity. As we expect changes in the connections between the cortical and subcortical regions, we performed a combination of white matter voxel-based morphometry (wVBM) and diffusion tensor imaging (DTI) to detect macro- and microstructural white matter changes, respectively, in DYT-11 mutations carriers (M-D). Sixteen clinically affected DYT-11 mutation carriers and 18 control subjects were scanned with 3-Tesla MRI to compare white matter volume, fractional anisotropy, and mean diffusivity between groups. In DYT11 mutation carriers, increased white matter volume and FA and decreased mean diffusivity werefound in the subthalamic area of the brain stem, including the red nucleus. Furthermore, decreased mean diffusivity was found in the subgyral cortical sensorimotor areas. The white matter changes found in the subthalamic area of the brain stem, connecting the cerebellum with the thalamus, are compatible with the hypothesis that abnormal function in M-D involves a network that includes the cerebellum, brain stem, and basal ganglia. Whether these changes are causative or an effect of M-D requires further study. (C) 2012 Movement Disorder Society

Objectives. To explore sensory gating deficits in subjects at Ultra High Risk (UHR) for psychosis before and after transition to a first psychotic episode. Methods. Sensory gating was assessed with the paired click paradigm in 61 UHR subjects, of whom 18 (30%) made a transition to psychosis (UHR + T) over a 3-year follow-up period and 28 matched healthy controls. Subjects were assessed at inclusion and again after approximately 18 months. P50, N100 (N1) and P200 (P2) sensory gating was established using the amplitude on the first (S1) and second (S2) click, the ratio-(S2/S1) and the difference score (S1-S2). Psychopathology was also assessed. Results. At baseline, UHR + T subjects presented smaller N1 difference scores compared to UHR + NT subjects and controls. The N1 difference score contributed modestly to the prediction of a first psychotic episode. Repeated measure analyses revealed smaller N1 and P2 S1 amplitudes, smaller P2 difference scores and larger P2 ratio's at follow-up compared to baseline in UHR + T subjects. Conclusion. The N1 difference score may be helpful in predicting a first psychosis. N1 and P2 sensory gating measures also showed alterations between the prodromal phase and the first psychosis, suggesting that these changes may relate to the onset of a frank psychotic episode.

Background: Myoclonus-dystonia is an autosomal dominantly inherited movement disorder clinically characterized by myoclonic jerks and dystonic postures or movements of the upper body. Functional imaging studies in other, mainly heterogeneous groups of dystonia do agree on dysfunction of the striato-pallido-thalamo-cortical circuit.Objective: To study cerebral activation patterns with functional magnetic resonance imaging in a genetically defined homogeneous group of patients with dystonia.Design, Setting, and Patients: Thirteen clinically affected SGCE mutation carriers and 11 control subjects were studied in a case-control study.Intervention: A finger-tapping motor task was performed in a block design using 3.0-T magnetic resonance imaging.Main Outcome Measures: Blood oxygenation level-dependent signals were compared between groups.Results: In SGCE mutation carriers, we observed significant hyperresponsiveness in contralateral inferior parietal cortical areas, ipsilateral premotor and primary somatosensory cortex, and ipsilateral cerebellum during the motor task compared with healthy control subjects.Conclusions: The cortical activation patterns in SGCE mutation carriers during this motor task point to a disorganized sensorimotor integration in this uniform group of patients with dystonia and are consistent with functional neuroimaging studies in other types of (hereditary) dystonia.

Background P300 abnormalities indicate changes in information processing and are one of the most reliable biological markers of schizophrenia. We sought to investigate whether abnormalities in P300 (P3) or other event-related potentials are also present in subjects at ultra high risk (UHR) for developing psychosis and whether they are helpful in predicting transition to psychosis. Methods The N1, N2, N2b, P2, and P3 amplitudes were assessed in 61 UHR subjects, of whom 18 subjects (30%) made a transition to psychosis over a 3-year follow-up period (UHR + T: age 20.4 years) and 43 (70%) did not (UHR + NT: age 19.3 years), and 28 age- and intelligence-matched healthy control subjects (age 20.0 years). Psychopathology was also assessed. Results The UHR + T subjects showed smaller parietal P3 amplitudes, compared with control subjects and UHR + NT subjects. Moreover, the N2b was higher in control subjects compared with both UHR groups. We found no differences in N1 or P2 components between the groups, and our UHR subjects did not exhibit bilateral P3 asymmetry. Reduced P3 amplitudes were the best predictor for subsequent psychosis in the UHR group. The P3 reduction was related to increased social anhedonia and withdrawal and a lower global assessment of social functioning and social personal adjustment. Conclusions The UHR + T subjects showed reduced parietal P3 amplitudes. In addition, a reduced P3 amplitude was the best predictor for subsequent psychosis. If replicated, these findings might contribute to a more accurate prediction of a first psychotic episode. Furthermore, reduced social functioning might be related to information processing deficits in UHR subjects.

Objective: To find an adequate tool to assess the auditory startle reflex (ASR) in children.Methods: We investigated the effect of stimulus repetition, gender and age on several quantifications of the ASR. ASR's were elicited by eight consecutive auditory stimuli in 27 healthy children. Electromyographic activity of orbicularis oculi, masseter, sternocleidomastoid, deltoid, abductor pollicis brevis, quadriceps muscles and the sympathetic skin response were recorded. ASR parameters (response probability in % and magnitude in area-under-the-curve) were: (1) combined response of all six muscles (2) blink response.Results: Response probabilities were 78% in orbicularis oculi (median latency 41 ms), 17% in sternocleidomastoid (median latency 66 ms), 10% in masseter (median latency 66 ms) and lower in other muscles. The ASR combined response probability and the sympathetic skin response significantly decreased with the repetitive stimuli, but the blink response probability did not. The magnitude (area-under-the-curve) of both the blink response and the combined response did not decrease with the repetitive stimuli. There were no gender or age effects.Conclusion: As in adults, the blink response and the combined response of multiple muscles show different habituation patterns in children.Significance: Investigation of multiple muscles seems appropriate to quantify the ASR in children. (C) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The origin Of myoclonus ill patients with complex regional pain syndrome (CRPS) is unknown. Eight patients with CRPS related myoclonus were clinically evaluated and Studied with intermuscular and corticomuscular coherence analysis. Jerks were present at test, aggravated during action and were frequently associated with tremulousness or dystonia. Electromyography demonstrated a burst duration ranging from 25 to 240 ins with burst frequencies varying from

Object: While pseudo-continuous arterial spin labeling (pCASL) is a promising imaging technique to visualize cerebral blood flow, it is also (acoustically) very loud during labeling. In this paper, we reduced the labeling loudness on our scanner by increasing the interval between the RF pulses from the literature standard of 1.0 ms. We also propose recommendations to reduce the loudness on scanners of the same type at other sites. Materials and methods: First, the sound pressure level (SPL) was both simulated and measured as a function of the labeling interval (1.0-1.8 ms) and longitudinal position in the scanner (-10 to +10 cm, relative to isocenter). Subsequently, we selected the labeling interval with the lowest overall SPL for the SPL-optimized pCASL sequence. Nine volunteers were scanned to compare raw signal intensity, temporal signal-to-noise ratio (tSNR) and labeling efficiency between the SPL-optimized and the standard PCASL sequence. Results: Sound pressure level measurements on our scanner showed that loudness was reduced by 6.5 dB at the approximate location of the ear by adjusting the labeling interval to 1.4 ms. Furthermore, image quality was not affected, since no significant differences in signal intensity, tSNR and labeling efficiency were observed. Conclusion: By increasing the pCASL labeling interval, acoustic noise in the pCASL sequence was reduced with 6.5 dB, while image quality was preserved. © 2013 ESMRMB.

Background: Myoclonus-dystonia (MD) is a movement disorder characterized by myoclonic jerks, dystonic postures and psychiatric co-morbidity. A mutation in the DYT11 gene underlies half of MD cases. We hypothesize that MD results from a dysfunctional basal ganglia network causing insufficient inhibitory motor control. To test this hypothesis functional MRI (fMRI) was performed using a validated "Go/No go" task, in order to localize blood-oxygen-level dependence (BOLD) effects corresponding to Response Inhibition (RI).Methods: Twenty-four MD patients (fifteen DYT11 positive) and 24 matched controls responded with a button press to Go (Go-Response) or No go (referred to as 'Stop') cues, resulting in analyses of accurate response suppression to Stop cues (Stop-Inhibit), and incorrect responses to Go cues (Go-Inhibit), or to Stop cues (Stop-Response).Results: Response accuracy in patients was impaired due to frequent Go-Inhibit errors. Image analysis of the Stop-Inhibit contrast demonstrated frontal, caudate and cingular activity in both groups. Compared to controls, MD patients showed increased primary motor cortex and insular activation. During Go-Inhibit trials, patients revealed increased activity in the contralateral thalamus (ventral lateral nucleus) and dorso-lateral-prefrontal cortex. In a post-hoc analysis comparing MD patients, DYT11 positive patients demonstrated anterior cerebellum hyperactivation on all contrasts and increased putaminal activation in the Stop-Response contrast.Conclusions: This study demonstrates a distinct association of motor symptoms in MD with the ventral lateral nucleus of the thalamus. Cerebellar dysfunction distinguishes DYT11 positive from negative patients. We suggest that MD might be best considered as a disorder of the cortico-ponto-cerebello-thalamo-cortical system. (C) 2013 Elsevier Inc. All rights reserved.

Myoclonus-dystonia is an autosomal dominantly inherited movement disorder clinically characterized by myoclonic jerks and dystonic movements of the upper body. Functional imaging and structural gray matter imaging studies in M-D suggest defective sensorimotor integration and an association between putaminal volume and severity of dystonia, possibly because of neuronal plasticity. As we expect changes in the connections between the cortical and subcortical regions, we performed a combination of white matter voxel-based morphometry (wVBM) and diffusion tensor imaging (DTI) to detect macro- and microstructural white matter changes, respectively, in DYT-11 mutations carriers (M-D). Sixteen clinically affected DYT-11 mutation carriers and 18 control subjects were scanned with 3-Tesla MRI to compare white matter volume, fractional anisotropy, and mean diffusivity between groups. In DYT11 mutation carriers, increased white matter volume and FA and decreased mean diffusivity were found in the subthalamic area of the brain stem, including the red nucleus. Furthermore, decreased mean diffusivity was found in the subgyral cortical sensorimotor areas. The white matter changes found in the subthalamic area of the brain stem, connecting the cerebellum with the thalamus, are compatible with the hypothesis that abnormal function in M-D involves a network that includes the cerebellum, brain stem, and basal ganglia. Whether these changes are causative or an effect of M-D requires further study.

Humans vary in their ability to delay gratification and impulsive decision making is a common feature in various psychiatric disorders. The level of delay discounting is a relatively stable psychological trait, and therefore neural processes implicated in delay discounting are likely to be based on the overall functional organization of the brain (under task-free conditions) in which state-dependent shifts from baseline levels occur. The current study investigated whether delay discounting can be predicted by intrinsic properties of brain functioning. Fourteen healthy male subjects performed a delay discounting task. In addition, resting state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (¹H MRS) were used to investigate the relationship between individual differences in delay discounting and molecular and regional measures of resting state (baseline) activity of dorsal anterior cingulate cortex (dACC). Results showed that delay discounting was associated with both dACC glutamate concentrations and resting state functional connectivity of the dACC with a midbrain region including ventral tegmental area and substantia nigra. In addition, a neural pathway was established, showing that the effect of glutamate concentrations in the dACC on delay discounting is mediated by functional connectivity of the dACC with the midbrain. The current findings are important to acknowledge because spontaneous intrinsic brain processes have been proposed to be a potential promising biomarker of disease and impulsive decision making is associated with several psychiatric disorders.

Background: Functional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.Objective: Aim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.Methods: Simultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.Results: Analysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.Conclusion: EMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.

Background: Motivational and cognitive abnormalities are frequently reported in pathological gambling. However, studies simultaneously investigating motivational and cognitive processing in problematic gamblers are lacking, limiting our understanding of the interplay between these systems in problematic gambling. Studies in non-clinical samples indicate that interactions between dorsal "executive" and ventral "affective" processing systems are necessary for adequate responses in various emotive situations. Methods: We conducted a generalized Psycho-Physiological Interaction (gPPI) analysis to assess the influence of affective stimuli on changes in functional connectivity associated with response inhibition in 16 treatment seeking problematic gamblers (PRGs) and 15 healthy controls (HCs) using an affective Go-NoGo fMRI paradigm including neutral, gambling-related, positive and negative pictures as neutral and affective conditions. Results: Across groups, task performance accuracy during neutral inhibition trials was positively correlated with functional connectivity between the left caudate and the right middle frontal cortex. During inhibition in the gambling condition, only in PRGs accuracy of task performance was positively correlated with functional connectivity within sub-regions of the dorsal executive system. Group interactions showed that during neutral inhibition, HCs exhibited greater functional connectivity between the left caudate and occipital cortex than PRGs. In contrast, during inhibition in the positive condition, PRGs compared to HCs showed greater functional connectivity between the left caudate and occipital cortex. During inhibition trials in the negative condition, a stronger functional connectivity between the left caudate and the right anterior cingulate cortex in PRGs compared to HCs was present. There were no group interactions during inhibition in the gambling condition. Conclusions: During gamble inhibition PRGs seem to benefit more from functional connectivity within the dorsal executive system than HCs, because task accuracy in this condition in PRGs is positively correlated with functional connectivity, although the groups show similar connectivity patterns during gamble inhibition. Greater functional connectivity between the ventral affective system and the dorsal executive system in PRGs in the affective conditions compared to HCs, suggests facilitation of the dorsal executive system when affective stimuli are present specifically in PRGs. © 2012 van Holst et al.

Background: Myoclonus-dystonia is an autosomal dominantly inherited movement disorder, clinically characterized by myoclonic jerks and dystonic postures or movements. A previous functional magnetic resonance imaging study showed altered cortical activation patterns in clinically affected SGCE mutation carriers when compared with controls consistent with defective sensorimotor integration. Genetically, the disorder is characterized by the maternal imprinting mechanism; ie, patients who inherit the mutation from their fathers will develop symptoms. However, several clinically manifest patients with myoclonus-dystonia who inherited the mutation from their mother have been described.Objective: To compare cerebral activation patterns of paternally inherited SGCE mutation carriers are with maternally inherited mutation carriers and a control group.Design: Case-control study using functional magnetic resonance imaging.Participants: Eight paternally inherited SGCE mutation carriers, 8 asymptomatic or slightly affected (4 of 8) symptomatic maternally inherited mutation carriers, and 11 control subjects.Interventions: Participants were studied using a 3-T functional magnetic resonance imaging scanner with a finger tapping task.Results: When paternal and maternal gene mutation carriers were compared, hyperresponsiveness was seen in the contralateral secondary somatosensory cortex. When maternal mutation carriers and control subjects were compared, hyperresponsiveness of the ipsilateral cerebellum and supplementary motor area were found. Using a nonparametric analysis to study only the 4 clinically asymptomatic patients, no significant differences were found between groups. Contrast estimates were plotted for the known affected sensorimotor brain areas, showing intermediate activation in maternally inherited mutation carriers, even when this was performed for only the 4 clinically unaffected mutation carriers.Conclusions: The results suggest biased gene expression based on parent of origin rather than a strictly dichotomous maternal imprinting mechanism, consistent with clinical observations.

Dysfunction of cerebral white matter (WM) is a potential factor underlying the neurobiology of schizophrenia. People with 22q11 deletion syndrome have altered brain morphology and increased risk for schizophrenia, therefore decreased WM integrity may be related to schizophrenia in 22q11DS. We measured fractional anisotropy (FA) and WM volume in 27 adults with 22q11DS with schizophrenia (n = 12, 22q11DS SCZ+) and without schizophrenia (n = 15, 22q11DS SCZ−), 12 individuals with idiopathic schizophrenia and 31 age-matched healthy controls. We found widespread decreased WM volume in posterior and temporal brain areas and decreased FA in areas of the frontal cortex in the whole 22q11DS group compared to healthy controls. In 22q11DS SCZ+ compromised WM integrity included inferior frontal areas of parietal and occipital lobe. Idiopathic schizophrenia patients showed decreased FA in inferior frontal and insular regions compared to healthy controls. We found no WM alterations in 22q11DS SCZ+ vs. 22q11DS SCZ−. However, there was a negative correlation between FA and PANSS scores (Positive and Negative Symptom Scale) in the whole 22q11DS group in the inferior frontal, cingulate, insular and temporal areas. This is the first study to investigate WM integrity in adults with 22q11DS. Our results suggest that pervasive WM dysfunction is intrinsic to 22q11DS and that psychotic development in adults with 22q11DS involves similar brain areas as seen in schizophrenia in the general population.

We investigated the course of Event Related Potentials (ERP) from prior to until shortly after a first psychotic episode in subjects at Ultra High Risk (UHR) for psychosis. N1, N2, N2b, P2 and P3 amplitudes were assessed using an auditory active oddball paradigm in 15 UHR subjects who made a transition to psychosis (UHR+T) at follow up, 23 subjects without a transition (UHR+NT) and 17 matched healthy controls at inclusion and again after approximately 18 months. Repeated-measures analyses revealed no significant time effects for any of the ERP components. However, an interaction effect was found for N1 amplitudes. Post-hoc analyses showed that N1 amplitudes were smaller at follow up compared to baseline only in UHR+T subjects. P3 amplitudes showed no further reduction after psychotic onset. These findings suggest that discernable ERP components behave differently during progression from the prodromal phase to the first psychotic episode. These findings may give insight in pathophysiological mechanisms underlying the genesis of psychosis.

Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity in 10 healthy volunteers. In addition to blood-oxygen-level-dependent (BOLD) contrast we assessed the effect of dopaminergic depletion on prolactin response, peripheral markers for dopamine and norepinephrine. In the placebo condition we found increased activation in the left caudate and left cingulate gyrus during anticipation of reward. In the α-methylparatyrosine condition there was no significant brain activation during anticipation of reward or loss. In α-methylparatyrosine, anticipation of reward vs. loss increased activation in the right insula, left frontal, right parietal cortices and right cingulate gyrus. Comparing placebo versus α-methylparatyrosine showed increased activation in the left cingulate gyrus during anticipation of reward and the left medial frontal gyrus during anticipation of loss. α-methylparatyrosine reduced levels of dopamine in urine and homovanillic acid in plasma and increased prolactin. No significant effect of α-methylparatyrosine was found on norepinephrine markers. Our findings implicate distinct patterns of BOLD underlying reward processing following dopamine depletion, suggesting a role of dopaminergic neurotransmission for anticipation of monetary reward.

The pathophysiology of Myoclonus-Dystonia (MD), an autosomal dominantly inherited movement disorder is largely unknown. In different forms of dystonia abnormal intermuscular coherence is present. The objective of this study was to investigate whether the myoclonic and dystonic features are the result of an abnormal common drive to the muscles in M-D. Coherence analysis was performed in 20 DYT11 mutation carriers (MC) and 13 healthy controls during resting condition and during weak isometric contraction of the arm and neck. The EMG-EMG coherence analysis showed significantly increased intermuscular 3 to 10 Hz coherence in 4 DYT11 MC with clinical pronounced (mobile and static) dystonia. This coherence was not present in DYT11 MC with mild (static) dystonia and/or predominating myoclonus. The EEG-EMG analysis showed significant 15 to 30 Hz coherence during weak isometric contraction of the arm in five healthy controls, but in none of the DYT11 MC. The intermuscular coherence in the low frequency band in DYT11 MC with predominant dystonia is concordant with the previously described coherence in dystonia and suggests that the pathophysiology of M-D shares common pathophysiological features with dystonia. The absence of 15 to 30 Hz EEG-EMG coherence in DYT11 MC may reflect abnormal motor activation caused by an altered cortical drive because of the basal ganglia dysfunction. (c) 2007 Movement Disorder Society

Publisher Summary Listing's law can be achieved in two ways. First, neural activation of extraocular muscles could be encoded by the central nervous system. However, this requires complex calculations of the central nervous system. Secondly, it could be implemented by the anatomical structure of the ocular motor plant and then neural commands have to be encoded only in two dimensions. Simulations with a dynamical model show that commutative eye movements can be generated solely by the anatomical structure of the eye globe. A necessary condition then is that during eye rotations to a specific location the extraocular muscles are kept in the same plane. In patients with congenital nystagmus (CN), rotations of the eye do not obey Listing's law. Simulations with the dynamical model demonstrate that this could be explained an aberrant anatomical structure, resulting in cross-talk between the horizontal, vertical, and torsional planes.

Background The brain reward circuitry innervated by dopamine is critically disturbed in schizophrenia. This study aims to investigate the role of dopamine-related brain activity during prediction of monetary reward and loss in first episode schizophrenia patients. Methods We measured blood–oxygen-level dependent (BOLD) activity in 10 patients with schizophrenia (SCH) and 12 healthy controls during dopamine depletion with α-methylparatyrosine (AMPT) and during a placebo condition (PLA). Results AMPT reduced the activation of striatal and cortical brain regions in SCH. In SCH vs. controls reduced activation was found in the AMPT condition in several regions during anticipation of reward and loss, including areas of the striatum and frontal cortex. In SCH vs. controls reduced activation of the superior temporal gyrus and posterior cingulate was observed in PLA during anticipation of rewarding stimuli. PLA patients had reduced activation in the ventral striatum, frontal and cingulate cortex in anticipation of loss. The findings of reduced dopamine-related brain activity during AMPT were verified by reduced levels of dopamine in urine, homovanillic-acid in plasma and increased prolactin levels. Conclusions Our results indicate that dopamine depletion affects functioning of the cortico-striatal reward circuitry in SCH. The findings also suggest that neuronal functions associated with dopamine neurotransmission and attribution of salience to reward predicting stimuli are altered in schizophrenia.