Superior Cerebellum Research Articles

Extrastriatal degeneration correlates with deficits in the motor domain subscales of the UHDRS

IntroductionStriatal degeneration has significant behavioral effects in patients with Huntington's disease (HD). However, there is scant evidence of the possible contribution of extrastriatal regions to the motor alterations assessed within the different domains of the Unified Huntington's Disease Rating Scale (UHDRS). ObjectiveAnalyze if extrastriatal grey matter decrease in patients with HD correlates with motor performance assessed with the UHDRS and its different domains. MethodTwenty-two molecular diagnosed patients with incipient HD, and twenty-two control participants matched for sex and age participated in this study. Voxel-based morphometry (VBM) analyses were done to identify grey matter decrease in the HD patients, and its relationship with the motor deterioration measured with the UHDRS motor scale. To further explore this relationship, a principal component analysis (PCA) was done on the UHDRS domains scores. Then the average of each component was used as a covariate in a VBM analysis. Finally, individual sub-scores from each domain were also tested for correlations with the VBM results. ResultsIn addition to the striatal degeneration, the VBM analysis showed significant negative correlations between the global UHDRS scores and the cerebellum, insula and precuneus atrophy. The UHDRS PCA showed component-related negative correlations suggesting a specific impact of individual degnerations. Further analyses with the individual sub-scores showed more specific corelations, including: chorea, with right caudate and left posterior cingulate gyrus; ocular pursuit, with left precentral gyrus, left superior temporal gyrus, cerebellum culmen and right temporal lobe. Saccadic movements with left postcentral gyrus and left middle occipital gyrus. ConclusionIn the early stages of HD, it is possible to find correlations between behavioral alterations as measured with the UHDRS motor domains, and extrastriatal regions, including specific areas of the cerebellum, and insular, parietal and frontal cortices. These areas could contribute to the HD related impairments along with the classical deficits associated with the striatal degeneration.

Suprafloccular approach via the petrosal fissure and venous corridors for microvascular decompression of the trigeminal nerve: technique notes and clinical outcomes.

OBJECTIVE Surgical exposure and decompression of the entire trigeminal nerve in a conventional lateral supracerebellar approach can be challenging because of blockages from the superior petrosal vein complex, cerebellum, and vestibulocochlear nerve. The authors demonstrate a novel suprafloccular approach via the petrosal fissure and venous corridors that can be used as a substitute for the conventional route used to treat trigeminal neuralgia and present a consecutive series of patients and their clinical outcomes. METHODS Preoperative and postoperative clinical data from 420 patients who underwent this modified approach at Hangzhou First People's Hospital between March 2012 and May 2014 were reviewed. The technique expands the working space by opening the petrosal fissure and dissecting adhesions between the vein of the cerebellopontine fissure and the simple lobule as needed. Via 3 surgical corridors, the entire trigeminal nerve is exposed and decompressed thoroughly with minimal retraction of the surrounding vital structures. RESULTS The medial one-third of the trigeminal nerve accounted for the majority (275 [65.5%] cases) of neurovascular conflict sites. The lateral corridor was used in 219 (52.1%) cases, the medial corridor was used in 175 (41.7%) cases, and the intermediate corridor was used in 26 (6.2%) cases. The entire trigeminal nerve in each patient was accessed directly and decompressed properly. At the end of the 24-month follow-up period, the rate of excellent results (Kondo score of T0 or T1) was stable at approximately 90.5%. No complications were related directly to petrosal vein or vestibulocochlear nerve injury. CONCLUSIONS Based on data from the large patient series, the authors found this suprafloccular approach via the petrosal fissure and venous corridors provides full exposure and decompression of the entire trigeminal nerve, a high cure rate, and a low neurovascular morbidity rate.

Hemicerebellitis can drive handedness shift

BackgroundHemicerebellitisis a rare acquired condition, typical of the pediatric age. A residual switched handedness may develop after remission of acute cerebellar symptoms.Case presentationHerein we describe a motor functional MRI studyperformed in a 35-year old girl who had switched to left-handedness after acute right hemicerebellitis in childhood. During left hand tapping, we observed activation in the right primary sensori-motor cortex, right supplementary motor area and left superior cerebellum. During right hand tapping bilateral activations of primary sensori-motorcortex and superior cerebellum including the vermis and activation of the right supplementary motor area were observed. We speculate that during right hand tapping both the ipsilateral and contralateralpre-central gyri and the ipsilateral cerebellum would be engaged in order to recover the tapping internal model of action. From this perspective the ipsilateral pre-central gyrus might serve as are transmission station of information from the healthy cerebellum to the contralateral pre-central gyrus.ConclusionSelective damage of the right half of the cerebellum due to hemicerebellitis in childhood can drive shift of lateralized hand functions in the cerebrum.

Bimodal odor processing with a trigeminal component at sub- and suprathreshold levels

Odors are typically bimodal in nature, interacting with the olfactory and trigeminal systems. The trigeminal component may be noticed (e.g. menthol) or perceptually ignored, leading to different neural substrates being recruited during odor encoding. Therefore, the current study was designed to explore the perceptual and central-nervous activations in response to pleasant bimodal odors using functional magnetic resonance imaging (fMRI). In this study, healthy subjects were exposed to odorants alone (unimodal) or with a “cooling” trigeminal component (bimodal) at sub- and suprathreshold concentrations with a portable olfactometer in a 3T fMRI scanner. Within the scanner, subjects reported all odorants as pleasant and intensity increasing with trigeminal concentration. Many of the regions of interest [orbital frontal cortex (OFC), insula, thalamus, cerebellum, postcentral gyrus and cingulate cortex] were activated during bimodal odor conditions when contrasted with unimodal, and interestingly, most of these activations were seen prior to trigeminal perception (e.g. at a sub-threshold level). This includes large bilateral activations within the OFC, insula, cerebellum and parts of the cingulate cortex. Additionally, activation of the thalamus was seen early in the stages of bimodal odor encoding suggesting its role of mediating attention toward the presence of two stimuli. Lastly, intensity encoding during bimodal processing shows overlap of previously demonstrated simple trigeminal encoding areas (medial cingulate cortex) and the more complex olfactory encoding areas (bilateral insula, superior temporal gyrus, OFC, and cerebellum), but not the amygdala.

Altered gray matter volume and functional connectivity of the motor network inyoungdivers.

Motor learning and professional sports training can induce plastic changes in brain structures that are associated with distinct training demands. To testify the hypothesis of that regional gray matter structures in the motor-related cortex and its functional connectivity (FC) are altered in young divers. We undertook T1-voxel-based morphometry (VBM) structural and resting-state functional magnetic resonance imaging in groups of diving athletes (DAs) and demographically-matched healthy controls. Gray matter volume was lower in some regions in Das. By selecting the five most reduced regions, i.e. superior frontal gyrus, orbitofrontal cortex (OFC), insula, hippocampus, and cerebellum posterior lobe, as regions of interest (ROIs) for FC analysis, results showed that DAs had greater FC between the inferior temporal gyrus and superior frontal gyrus, OFC and cerebellum posterior lobe. Conversely, the divers had lesser FC between OFC and putamen, superior frontal gyrus and caudate. VBM differences suggest that diving training entails more effective synaptic and/or neuronal pruning processes in motor structures. Indeed, cortical volumetric decreases in the DAs group are associated with increased FC among certain motor-related regions. We conclude that motor learning in adolescence alters brain structure in association with changes in FC between the relevant cortical and subcortical regions.

18F]AV1451 POSITRON EMISSION TOMOGRAPHY IN SEMANTIC VARIANT PRIMARY PROGRESSIVE APHASIA

[18F]AV1451 is selective for Tau vs Beta-amyloid and vs alpha-synuclein. Binding in Alzheimer's disease shows strong correlations with phenotypic variants and severity. Studies in non-AD tauopathy are discordant, with significant binding in vivo contrasting with weak binding post mortem. Binding to TDP-43 pathology is poorly characterised. The semantic variant of primary progressive aphasia (svPPA) has a strong clinico-pathological correlation with TDP43 type C pathology at post mortem. We hypothesise that in cases clinically diagnosed with svPPA, [18F]AV1451 non-displaceable binding potential (BPND) is not increased compared with age-matched controls. 7 patients with svPPA and 12 controls underwent dynamic [18F]AV1451 PET. BPND was determined by kinetic modelling with a simplified reference tissue model (superior cerebellum). Partial volume corrected regional analysis of BPNDmaps was performed using PetSurfer following Freesurfer Desikan-Killiany cortical parcellation of 3T T1-MRI. We compared group BPND and tissue volume in each brain region using t-tests and quantifying effects with Cohen's d. We then assessed for distributional differences in BPND using hierarchical cluster analysis. Significant increases in [18F]AV1451 binding were seen in svPPA compared to controls. These were observed across left temporal lobe, in left fusiform gyrus, left insula and right amygdala (p<0.05 Bonferroni corrected). The effect size of the difference between svPPA and control binding was correlated with that of grey matter volume. Nonparametric hierarchical clustering classified svPPA with 86% sensitivity and 100% specificity. There is significantly increased [18F]AV1451 binding in regions where TDP43 pathology is known to be localised in svPPA and where atrophy was demonstrated in our cohort. Given the strong association between svPPA and TDP43 pathology it seems unlikely that all patients had undiagnosed Alzheimer's or Pick's pathology. The anatomical distribution is as expected for the clinical syndrome, undermining the previously proposed ‘off target’ binding sites, such as Iron, Calcium, Neuromelanin and Biondi ring tangles. Regardless of the molecular basis of [18F]AV1451 binding, the regionally selective binding we observe suggests a potential role as biomarker in longitudinal and therapeutic studies of svPPA. Post mortem validation will be useful in furthering our understanding of [18F]AV1451 binding in Frontotemporal lobar degeneration.

UNDERSTANDING THE MOLECULAR ETIOLOGY OF ALZHEIMER'S DISEASE ACROSS SEVEN DIFFERENT BRAIN REGIONS

Accumulating evidence shows certain brain regions are more susceptible to pathological and metabolic changes in Alzheimer's Disease (AD) comparing to others. However, lack of understanding of the association among affected brain regions and transcriptomic changes is impeding our understanding of AD etiology. To this end, using the recently released RNA-sequencing data from the 2114 samples of postmortem human brain tissues by the AMP-AD consortium, we identify mechanisms that are robustly conserved and that are different across multiple brain regions in AD. RNA samples were sequenced from 7 brain regions (dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG), superior temporal gyrus (STG), parahippocampal gyrus (PHG), frontal pole (FP), cerebellum (CBE) and temporal cortex (TCX)) collected across 4 different sources (the ROS and MAP (ROSMAP) cohort, the Mt. Sinai Brain Bank (MSBB) and the Mayo Brain Bank (MAYO)). Using both the clinical (i.e., CDR, cogdx) as well as neuropathological (i.e., braak, ceradsc) scores, a homogeneous subset of 411 control and 742 AD samples were selected. Adjusting for clinical and technical variations, gene-level differential expression was calculated separately within each study by mixed effect linear regression using CQN-VOOM normalization. Gene expression differences between AD versus control suggests DLPFC, PHG and TCX are affected in AD comparing to other brain regions. At an FDR of 5% and fold change of 1.2, 318 (DLPFC) genes in ROSMAP, 77 (FP), 22 (IFG), 322 (STG), and 1637 (PHG) genes in MSBB, 1835 (CER) and 4696 (TCX) genes in MAYO cohorts are differentially expressed. Meta-analysis across the three majorly affected regions shows 148 differentially expressed genes enriched for loss of synaptic transmission, inflammation response, and increased neurotransmitter transport. While all the 3 regions are enriched for astrocytes, only TCX region is enriched for AD GWAS loci. Our analysis identified a high-confidence set of genes that were differentially expressed in relation to AD in a consistent manner across 3 out of 7 brain regions. Future analytical efforts in the context of AMP-AD consortium are seeking to advance this understanding to identify robust disease mechanisms and to support target discovery through genomic analysis.

Anomalous prefrontal-limbic activation and connectivity in youth at high-risk for bipolar disorder

ObjectiveAbnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD. MethodsWe examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene. ResultsWhile viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortex ConclusionsSimilar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD.

Aberrant functional connectivity in patients with obstructive sleep apnea-hypopnea syndrome: a resting-state functional MRI study

The objective of this study was to investigate the change in the default mode network (DMN) in subjects with obstructive sleep apnea-hypopnea syndrome (OSAHS) using resting-state functional connectivity (rsFC). Functional magnetic resonance imaging (rs-fMRI) data were collected from twenty-nine subjects with OSAHS and twenty-six normal controls. The data were analyzed with the rsFC method and were compared between OSAHS subjects and controls. The Z-values of abnormal rsFC in different brain regions were correlated with clinical variables, including the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), Epworth sleepiness scale (ESS), Rey-osterrieth complex figure test (CFT-immediately), CFT-delay, Logical memory test-immediately (LMT-immediately), LMT-delay and Minimum mental state examination (MMSE). The rsFC showed significant increases in the left temporal cortex, right midfrontal cortex, and left precuneus cortex as well as decreases in the bilateral inferior parietal lobule (IPL), left medial prefrontal cortex (MPFC), left superior frontal cortex and right cerebellum in patients with OSAHS. The FC strength in the left precuneus showed a remarkable positive correlation with ODI(p = .032, r = .399)and CFT-delay scores (p = .043, r = .378). We found that the FC strength in the right cerebellum was positively correlated with the CFT-delay scores (p = .017, r = .441). FC strength in the right cerebellum and left IPL demonstrated a remarkable positive correlation with LMT-delay scores (p = .037,r = .389;p = .043 and r = .379, respectively). However, there was a strong negative correlation between the left MPFC region and ESS scores (p = .032, r = −.398). The abnormal rsFC in subjects with OSAHS indicated the compensatory change of brain function, which possibly provides an innovative approach and perspective on understanding the neural mechanism alteration of OSAHS-related cognition.

Brain Activity During Phonation in Women With Muscle Tension Dysphonia: An fMRI Study

The main objectives of this functional magnetic resonance imaging (fMRI) study are (1) to investigate brain activity during phonation in women with muscle tension dysphonia (MTD) in comparison with healthy controls; and (2) to explain the neurophysiological mechanism of laryngeal hyperfunction/tension during phonation in patients with MTD. Ten women with MTD and fifteen healthy women participated in this study. The fMRI experiment was carried out using a block design paradigm. Brain activation during phonation and exhalation was analyzed using BrainVoyager software. The statistical analysis of fMRI data has demonstrated that MTD patients control phonation by use of the auditory, motor, frontal, parietal, and subcortical areas similar to phonation control by healthy people. Comparison of phonation tasks in the two groups revealed higher brain activities in the precentral gyrus, inferior, middle and superior frontal gyrus, lingual gyrus, insula, cerebellum, midbrain, and brainstem as well as lower brain activities in the cingulate gyrus, superior and middle temporal gyrus, and inferior parietal lobe in the MTD group. No differences were found between the two groups regarding exhalation control. The findings in this study provide insight into phonation and exhalation control in patients with MTD. The imaging results demonstrated that in patients with MTD, altered (higher/lower) brain activities may result in laryngeal tension and vocal hyperfunction.

Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder

The objective of the present study was to research the patterns of Default Mode Network (DMN) deactivation in Obsessive Compulsive Disorder (OCD) in the transition between a resting and a non-rest emotional condition. Twenty-seven participants, 15 diagnosed with OCD and 12 healthy controls (HC), underwent a functional neuroimaging paradigm in which DMN brain activation in a resting condition was contrasted with activity during a non-rest condition consisting in the presentation of emotionally pleasant and unpleasant images. Results showed that HC, when compared with OCD, had a significant deactivation in two anterior nodes of the DMN (medial frontal and superior frontal) in the non-rest pleasant stimuli condition. Additional analysis for the whole brain, contrasting the resting condition with all the non-rest conditions grouped together, showed that, compared with OCD, HC had a significantly deactivation of a widespread brain network (superior frontal, insula, middle and superior temporal, putamen, lingual, cuneus, and cerebellum). Concluding, the present study found that OCD patients had difficulties with the deactivation of DMN even when the non-rest condition includes the presentation of emotional provoking stimuli, particularly evident for images with pleasant content.

Apathy is related to reduced activation in cognitive control regions during set-shifting.

Apathy is a prominent and influential symptom in several neurological and psychiatric disorders, but it also occurs in the healthy population. It has considerable impact on daily life functioning, in clinical as well as healthy samples. Even though cognitive control is thought to be disrupted in people with apathy, the exact neural underpinnings of apathy remain unclear. Because flexible shifting between behaviors (set-shifting) is crucial for goal-directed behavior, disruptions in set-shifting may underlie apathy. In this study, the neural correlates of apathy during set-shifting were studied in 34 healthy participants with varying levels of apathy, measured by the Apathy Evaluation Scale. During functional MRI scanning participants performed a set-shifting task, distinguishing between behavioral switches (a change in response to different stimuli), cognitive switches (a change in response rule), and salience decoupling (detecting a change in relevant stimuli). Regression analysis was used to assess the relationship between apathy and brain activation. Results showed that higher apathy scores were related to reduced activation in the medial superior frontal gyrus and cerebellum (Crus I/II) during cognitive set-shifting, but not behavioral shifting and salience decoupling. No relationship between apathy and accuracy or response time was found. These results support the idea that alterations in the neural basis of cognitive control, especially cognitive set-shifting, may contribute to apathy. Hum Brain Mapp 38:2722-2733, 2017. © 2017 Wiley Periodicals, Inc.

Brief Mental Training Reorganizes Large-Scale Brain Networks.

Emerging evidences have shown that one form of mental training—mindfulness meditation, can improve attention, emotion regulation and cognitive performance through changing brain activity and structural connectivity. However, whether and how the short-term mindfulness meditation alters large-scale brain networks are not well understood. Here, we applied a novel data-driven technique, the multivariate pattern analysis (MVPA) to resting-state fMRI (rsfMRI) data to identify changes in brain activity patterns and assess the neural mechanisms induced by a brief mindfulness training—integrative body–mind training (IBMT), which was previously reported in our series of randomized studies. Whole brain rsfMRI was performed on an undergraduate group who received 2 weeks of IBMT with 30 min per session (5 h training in total). Classifiers were trained on measures of functional connectivity in this fMRI data, and they were able to reliably differentiate (with 72% accuracy) patterns of connectivity from before vs. after the IBMT training. After training, an increase in positive functional connections (60 connections) were detected, primarily involving bilateral superior/middle occipital gyrus, bilateral frontale operculum, bilateral superior temporal gyrus, right superior temporal pole, bilateral insula, caudate and cerebellum. These results suggest that brief mental training alters the functional connectivity of large-scale brain networks at rest that may involve a portion of the neural circuitry supporting attention, cognitive and affective processing, awareness and sensory integration and reward processing.

Neuronal control of fixation and fixational eye movements.

Ocular fixation is a dynamic process that is actively controlled by many of the same brain structures involved in the control of eye movements, including the superior colliculus, cerebellum and reticular formation. In this article, we review several aspects of this active control. First, the decision to move the eyes not only depends on target-related signals from the peripheral visual field, but also on signals from the currently fixated target at the fovea, and involves mechanisms that are shared between saccades and smooth pursuit. Second, eye position during fixation is actively controlled and depends on bilateral activity in the superior colliculi and medio-posterior cerebellum; disruption of activity in these circuits causes systematic deviations in eye position during both fixation and smooth pursuit eye movements. Third, the eyes are not completely still during fixation but make continuous miniature movements, including ocular drift and microsaccades, which are controlled by the same neuronal mechanisms that generate larger saccades. Finally, fixational eye movements have large effects on visual perception. Ocular drift transforms the visual input in ways that increase spatial acuity; microsaccades not only improve vision by relocating the fovea but also cause momentary changes in vision analogous to those caused by larger saccades.This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.

Neural Networks for Time Perception and Working Memory.

Time is an important concept which determines most human behaviors, however questions remain about how time is perceived and which areas of the brain are responsible for time perception. The aim of this study was to evaluate the relationship between time perception and working memory in healthy adults. Functional magnetic resonance imaging (fMRI) was used during the application of a visual paradigm. In all of the conditions, the participants were presented with a moving black rectangle on a gray screen. The rectangle was obstructed by a black bar for a time period and then reappeared again. During different conditions, participants (n = 15, eight male) responded according to the instructions they were given, including details about time and the working memory or dual task requirements. The results showed activations in right dorsolateral prefrontal and right intraparietal cortical networks, together with the anterior cingulate cortex (ACC), anterior insula and basal ganglia (BG) during time perception. On the other hand, working memory engaged the left prefrontal cortex, ACC, left superior parietal cortex, BG and cerebellum activity. Both time perception and working memory were related to a strong peristriate cortical activity. On the other hand, the interaction of time and memory showed activity in the intraparietal sulcus (IPS) and posterior cingulate cortex (PCC). These results support a distributed neural network based model for time perception and that the intraparietal and posterior cingulate areas might play a role in the interface of memory and timing.

Speaking-related changes in cortical functional connectivity associated with assisted and spontaneous recovery from developmental stuttering

We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speaking-related functional connectivity between left hemispheric speech network nodes.We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control.Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network.These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12.

Coupling Realistic Computational Neural Model and Human Experimental Data: the Cerebellar Role in Eye Blink Conditioning and its Alteration due to Transcranial Magnetic Stimulation

Coupling Realistic Computational Neural Model and Human Experimental Data: the Cerebellar Role in Eye Blink Conditioning and its Alteration due to Transcranial Magnetic Stimulation

Child sexual abuse and the development of psychiatric disorders: a neurobiological trajectory of pathogenesis.

Child sexual abuse (CSA) is an important public health problem with long-standing neurobiological, developmental, and psychiatric abnormalities. The present review analyzes the long-term effects of CSA from a developmental, psychiatric morbidity, neurochemical and neurobiological perspective and then tries to posit a developmental neurobiological trajectory from CSA to the genesis of psychopathology in later life. The role of various neurotransmitters such as serotonin and dopamine affected by CSA are discussed. Serotonin abnormalities have been reported in various studies among participants exposed to CSA. Structures such as the prefrontal cortex, superior temporal gyrus, corpus callosum, parietal lobes, hippocampus, and cerebellum all demonstrate volumetric and structural changes in response to the trauma of CSA. Neurocognitive studies demonstrate memory and spatial awareness as well as decrements in general cognitive performance and memory when compared to normal individuals. The hypothalamic–pituitary–adrenal axis has also been implicated in CSA, and there is an alteration in corticotropin-releasing hormone response due to the continuous cumulative trauma of CSA. This paper also reviews a section on the role of genetic and epigenetic factors in the development of psychiatric disorders as a result of exposure to episodes of CSA where studies have demonstrated changes in DNA methylation in response to CSA. This review tries to hypothesize a developmental trajectory framework which is individual for every case where exposure to CSA may lead to psychopathology and psychiatric morbidity later in life. Rapid and emerging fields such as developmental traumatology in relation to CSA are also discussed.

The effects of olanzapine treatment on brain regional glucose metabolism in neuroleptic-naive first-episode schizophrenic patients.

The current study examined metabolic alterations associated with a positive response to olanzapine and identified brain regions associated with treatment-related improvement of symptoms in neuroleptic-naive first-episode schizophrenic patients using [18 F]fluoro-deoxy-glucose positron emission tomography analysis. Neuroleptic-naive first-episode schizophrenic patients who showed good or poor clinical responses to olanzapine were assessed using the Positive and Negative Syndrome Scale. Data were analyzed using statistical nonparametric mapping. Before treatment, responders showed significantly increased metabolism in the superior temporal gyrus and cerebellum compared with healthy controls. Glucose metabolism in responders was significantly increased after treatment in the left precentral gyrus, left postcentral gyrus, and left paracentral lobule, and significantly decreased in the left hypothalamus. An analysis of the Positive and Negative Syndrome Scale symptoms associated with olanzapine treatment revealed that "suspiciousness/persecution" scores were positively correlated with metabolic changes in the right superior frontal gyrus. These findings provide evidence of the neural mechanisms underlying the effects of olanzapine on metabolism in the early stages of schizophrenia.

Changing head model extent affects finite element predictions of transcranial direct current stimulation distributions

Objective. In this study, we determined efficient head model sizes relative to predicted current densities in transcranial direct current stimulation (tDCS). Approach. Efficiency measures were defined based on a finite element (FE) simulations performed using nine human head models derived from a single MRI data set, having extents varying from 60%–100% of the original axial range. Eleven tissue types, including anisotropic white matter, and three electrode montages (T7–T8, F3-right supraorbital, Cz–Oz) were used in the models. Main results. Reducing head volume extent from 100% to 60%, that is, varying the model’s axial range from between the apex and C3 vertebra to one encompassing only apex to the superior cerebellum, was found to decrease the total modeling time by up to half. Differences between current density predictions in each model were quantified by using a relative difference measure (RDM). Our simulation results showed that was the least affected (a maximum of 10% error) for head volumes modeled from the apex to the base of the skull (60%–75% volume). Significance. This finding suggested that the bone could act as a bioelectricity boundary and thus performing FE simulations of tDCS on the human head with models extending beyond the inferior skull may not be necessary in most cases to obtain reasonable precision in current density results.