Broadmann Area Research Articles

Examining the effects of prenatal alcohol exposure on performance of the sustained attention to response task in children with an FASD.

Prenatal alcohol exposure (PAE), the leading known cause of childhood developmental disability, has long-lasting effects extending throughout the lifespan. It is well documented that children prenatally exposed to alcohol have difficulties inhibiting behavior and sustaining attention. Thus, the Sustained Attention to Response Task (SART), a Go/No-go paradigm, is especially well suited to assess the behavioral and neural functioning characteristics of children with PAE. In this study, we utilized neuropsychological assessment, parent/guardian questionnaires, and magnetoencephalography during SART random and fixed orders to assess characteristics of children 8-12 years old prenatally exposed to alcohol compared to typically developing children. Compared to neurotypical control children, children with a Fetal Alcohol Spectrum Disorder (FASD) diagnosis had significantly decreased performance on neuropsychological measures, had deficiencies in task-based performance, were rated as having increased Attention-Deficit/Hyperactivity Disorder (ADHD) behaviors and as having lower cognitive functioning by their caretakers, and had decreased peak amplitudes in Broadmann's Area 44 (BA44) during SART. Further, MEG peak amplitude in BA44 was found to be significantly associated with neuropsychological test results, parent/guardian questionnaires, and task-based performance such that decreased amplitude was associated with poorer performance. In exploratory analyses, we also found significant correlations between total cortical volume and MEG peak amplitude indicating that the reduced amplitude is likely related in part to reduced overall brain volume often reported in children with PAE. These findings show that children 8-12 years old with an FASD diagnosis have decreased amplitudes in BA44 during SART random order, and that these deficits are associated with multiple behavioral measures.

Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential

Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measure genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compare them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identify 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions. Genes associated with the DMCs are linked to “Parkinson’s disease” and “metabolic pathway”, as well as the diseases of “severe intellectual disability” and “mood disorders”. Overall, our study highlights previously unreported DMCs offering insights into DLB pathogenesis with the possibility that some of these could be used as biomarkers of DLB in the future.

Proteomic profiling of postmortem prefrontal cortex tissue of suicide completers

Suicide is a leading cause of death worldwide, presenting a serious public health problem. We aimed to investigate the biological basis of suicide completion using proteomics on postmortem brain tissue. Thirty-six postmortem brain samples (23 suicide completers and 13 controls) were collected. We evaluated the proteomic profile in the prefrontal cortex (Broadmann area 9, 10) using tandem mass tag-based quantification with liquid chromatography–tandem mass spectrometry. Bioinformatics tools were used to elucidate the biological mechanisms related to suicide. Subgroup analysis was conducted to identify common differentially expressed proteins among clinically different groups. Of 9801 proteins identified, 295 were differentially expressed between groups. Suicide completion samples were mostly enriched in the endocannabinoid and apoptotic pathways (CAPNS1, CSNK2B, PTP4A2). Among the differentially expressed proteins, GSTT1 was identified as a potential biomarker among suicide completers with psychiatric disorders. Our findings suggest that the previously under-recognized endocannabinoid system and apoptotic processes are highly involved in suicide.

45698 Molecular Signatures of Cocaine Neurotoxicity in Human Brain Models

ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.

Proprioceptive Feedback from AMI Amputation Modulates Cortical and Subcortical Reorganization

Maladaptive cerebral neuroplasticity is a well-established consequence of limb amputation. However, little is known about the potentially causal role of neuromuscular feedback in preserving the cortical and subcortical structures essential for sensation and motor planning, or modulating phantom limb sensation and pain. In this investigation, we study the impact of the agonist-antagonist myoneural interface (AMI) amputation procedure, which preserves proprioceptive neuromuscular feedback, on subcortical and cortical reorganization. We perform neuroimaging on subjects with AMI amputation (AA, n = 10), traditional amputation (TA, n = 10) and no amputation (NA, controls, n = 10). While TAs demonstrate diminished subcortical gray matter volume in the pallidum, accumbens and thalamus (p < 0.05) as compared to NAs, AAs had no significant changes when compared to NAs (p < 0.05). Cortical thickness of Broadmann area 3a and 3b were also significantly increased in TAs, but remained unchanged in AAs, as compared to NAs (p < 0.05). Further, we find phantom limb sensation to be significantly correlated with the reorganization of the accumbens, thalamus, Broadmann area 3a and 3b, suggesting a potential mechanistic linkage to sensorimotor reorganization. The AMI amputation, by preserving afferent proprioceptive feedback, may minimize reorganization and promote conventional sensorimotor neurophysiological pathways.

Functional network analysis of the sub-regions of the primary motor cortex during rest.

The cytoarchitectonic properties of the primary motor cortex have shown two distinct sub-regions: Anterior Broadmann area 4 (BA4a) and Posterior Broadmann area 4 (BA4p). Some previous studies have suggested that these two sub-regions are functionally different and showed that in few fMRI experiments, these sub-regions may have different roles in brain functions. Resting-state fMRI (rsfMRI) is advanced technique that allows investigating in detail the functional connectivity and provides a greater understanding of the physiological behavior of different brain regions. In this study, 198 healthy subjects were examined using a region-based rsfMRI analysis to investigate whether BA4a and BA4p have similar or different connections to other brain networks. The finding shows that indeed these two sub-regions have distinct connectivity to different brain networks. BA4a has a greater connection to motor-related areas while BA4p has connections to nonmotor-related areas (such as sensory, attentional, and higher order regions), suggesting that these two sub-regions should be considered as two separate regions of interests.

4141 Molecular Signatures of Cocaine Toxicity in Postmortem Human Brain and Neurons

OBJECTIVES/GOALS: The goal of this project is to identify new therapeutic targets and biomarkers to treat or prevent cocaine toxicity by investigating proteomic, transcriptomic and epigenetic signatures of cocaine exposure in human subjects. METHODS/STUDY POPULATION: Cocaine is a highly addictive neurotoxic substance, and it is estimated that 1.9 million Americans are current users of cocaine. To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem dorsolateral prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine-exposed subjects and 17 controls. Future directions for this project include RNAseq and DNA methylation analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF IMPACT: Neuronal signatures found with this analysis can help us understand mechanisms of cognitive decline in long-term cocaine users as well as the acute effects on the brain of cocaine taken in overdose. With this work and future proposed studies, we can discover novel clinical biomarkers for cocaine neurotoxicity in patients with cocaine use disorder and determine readouts for future therapeutic development on cocaine addiction and overdose.

Mitochondrial DNA content and oxidation in bipolar disorder and its role across brain regions

The underlying pathology of bipolar disorder remains unknown, though evidence is accumulating to support a role of mitochondrial dysfunction. In this study, we aim to investigate electron transport chain complex I subunit NDUFS7 protein expression; mtDNA content; common deletion; and oxidation in the Broadmann area 24 (BA24), cerebellum, hippocampus, and prefrontal cortex from patients with bipolar disorder, schizophrenia, and non-psychiatric controls. Here, we demonstrate no changes in NDUFS7 in BA24, cerebellum or hippocampus, increases in mtDNA content in hippocampus of patients with bipolar disorder, and decreases in mtDNA oxidation in patients with bipolar disorder and schizophrenia, respectively. Paired analysis between BA24 and cerebellum reveal increases within NDUFS7 levels and mtDNA content in cerebellum of patients with bipolar disorder or schizophrenia. We found a positive correlation between NDUFS7 and mtDNA content (ND4 and ND5) when combining brain regions. Our study supports the involvement of mitochondrial dysfunction in bipolar disorder and schizophrenia.

Tracking the Effect of Cathodal Transcranial Direct Current Stimulation on Cortical Excitability and Connectivity by Means of TMS-EEG.

Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0–50, 50–100, and 100–150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffuse effect of anodal and no effect of cathodal tDCS over the parietal cortex. These results are consistent with the current literature: while anodal-excitatory and cathodal-inhibitory effects are well-established in the sensory and motor domains, both at physiological and behavioral levels, results for cathodal stimulation are more controversial for modulation of exitability of higher order areas.

Functional Magnetic Resonance Imaging Demonstrates That Hypnosis Is Conscious and Voluntary

Hypnosis is a condition of modified consciousness (monoideism) resulting from a mental representation able to produce psychological and physical effects. The general belief is that hypnosis is conscious and voluntary, but the practical demonstration of this hypothesis is far to be demonstrated. Twenty healthy highly hypnotizable volunteers were studied during through functional magnetic resonance imaging during a task. The task was necessary because functional magnetic resonance imaging gives no interesting results in neutral hypnosis. During the hypnotic task, the prefrontal dorso-lateral cortex, genual cortex, dorsal anterior cingulate cortex, and orbital portion of the inferior frontal convolution (i.e. the Broadmann areas 9, 25, 32 and 47) were activated. Such areas are associated to egoic consciousness and voluntary processes. The results show that the hypothesis that hypnosis is conscious and voluntary is correct.

A Neurolinguistic Investigation of Emotional Prosody and Verbal Components of Speech

Emotional prosody has a key role implication of timbre component, mood sense, and prosodic content. For this reason, it serves a highly important function for sense, the meaning to be reflected, and ability to provide effective communication. Due to its crucial role in verbal communication, it has a critical relationship within many disciplines such as linguistics, computer sciences, medicine, etc. Consequently, the knowledge of how the prosody sequence works in the brain will contribute to both language development and foreign language teaching as well as clinical evaluation of individuals with verbal communication difficulty. From this point of view, the current study takes an interdisciplinary perspective to address the investigation of brain localization of emotional prosody and verbal components of speech. In accordance with this purpose, the fNIRS technique was used. fNIRS has recently become popular as an emerging optical brain imaging technique for studying human brain. However, it is still not widespread compared to other neuroimaging techniques. This study was conducted on both 20 healthy native speakers of Turkish and English. Participants were recorded by using fNIRS while performing emotional prosody production and auditory stimulus tasks to measure the brain activation. Our results showed superior temporal gyrus, middle temporal gyrus, which includes primary and secondary auditory cortex, and superior temporal cortex, which comprises of temporal sulcus, were strongly activated by prosodies irrespective of emotional valence. Our findings also demonstrated left inferior frontal gyrus which comprises of pars triangularis; (Broadmann Area 45) and the frontal eye field (Broadmann Area 8) were significantly activated for happy, angry, and fearful prosodies.

Cerebral plasticity after contralateral cervical nerve transfer in human by longitudinal PET evaluation

ObjectThe treatment of brachial plexus avulsion injury remains a challenging problem. Admittedly, central nervous mechanisms play a significant role in the motor recovery of the paralyzed hand after peripheral nerve surgery. The present study aimed at investigating the relationship between cerebral reorganization and motor recovery after a unique peripheral crossing nerve transfer surgery in brachial plexus injury patients. MethodsIn the present study, two brachial plexus avulsion injury patients with were followed up for 4 years after contralateral C7 nerve transfer surgery. In the surgery, an intact nerve root from the intact limb was transferred to repair the injured nerves. One patient showed a good motor recovery in the paralyzed hand while the other showed relatively poor outcomes. In the longitudinal follow-up, 9 PET scans of the brain were conducted in both patients at regular intervals of every 6 months. A correlation analysis between cerebral glucose metabolism and flexion power of the paralyzed wrists and fingers was performed to investigate the involvement of brain reorganization during the process of motor recovery. ResultsThe cerebral glucose metabolism in the corpus callosum, premotor cortex (Broadmann Area 6) and the precuneus were found positively correlated with the motor recovery of the paralyzed hand in Patient A (P < .01). Positive correlation between the cerebral glucose metabolism and the motor recovery of the paralyze hand was only present in the corpus callosum in Patient B (P < .01). ConclusionCorpus callosum, premotor cortex and precuneus were related with motor recovery after contralateral cervical nerve transfer surgery. The accumulating activation of these cortical regions potentially represented the recovery of high-order motor networks and may have facilitated the motor recovery.

Can Functional Connectivity at Resting Brain in ADHD Indicate the Impairments in Sensory-Motor Functions and Face/Emotion Recognition?

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disease known to cause impairments in cognitive, sensory-motor functions and face/emotion recognition. This study aimed to examine the resting-state brain networks in children with ADHD using functional magnetic resonance imaging. We performed seed-to-voxel and region of interest (ROI) analyses including all Broadmann areas (BAs) comprehensively. Thirty right-handed children aged between 9 and 16 years (15 with ADHD and 15 typically developing control subjects closely matched for age and gender) were included. Ninety five brain regions including 84 BAs and 11 Default Mode network (DMN)-related regions (rsREL) were studied using seed-based and ROI-to-ROI analysis and connectivity measures were calculated (p < 0.001). Between-group differences were assessed by using t-statistics (p < 0.05). Seed-based analysis showed connectivity differences in the sensory-motor and face/emotion recognition regions in both groups. The between-group whole-brain comparison showed greater magnitude of activation in children with ADHD than in control subjects in brain regions that included the face/emotion recognition system and prefrontal cortex based on ROI-to-ROI analysis. This work revealed that the sensory-motor regions and regions related to face/emotion recognition showed atypical functional connectivities in ADHD patients compared to the controls. Observation of the differences in these regions supports previous findings in the literature based on task-based functional magnetic resonance imaging (fMRI) studies. Our study exhibited that these atypical differences can also occur in the resting brain. These results suggest that further investigations of regions related to motor-sensory and face/emotion recognition are required to better understand ADHD.

EP 23. Bilateral epidural prefrontal cortical stimulation (EpCS) over fronto-polar and mid-frontal gyrus accesses mood regulation networks: Evidence from diffusion tensor imaging

Introduction The functional neuroanatomy of depression involves the prefrontal, cingulate and insular cortices, the amygdala, the nucleus accumbens and the hippocampus. The anterior and lateral prefrontal cortices are different in their cognitive and emotional integration roles and their modulation of sub-cortical regions. Both offer a distinct opportunity for targeted antidepressant treatments. Epidural prefrontal cortical stimulation (EpCS) is a unique therapeutic approach. It is more direct than transcranial magnetic stimulation (TMS) or vagus nerve stimulation (VNS), safer than deep brain stimulation (DBS) and, when applied chronically can reduce negative emotional arousal, increases stress tolerance and possibly lead to fewer relapses than observed with antidepressant pharmacotherapy Question Document the direct anatomical connections accessed with bilateral EpCS over fronto-polar and mid-frontal gyrus using diffusion tensor imaging (DTI). Methods Five patients treatment-resistant depression were implanted with bilateral EpCS leads over fronto-polar and mid-frontal gyrus. Patients underwent structural imaging (high resolution T1-weighted (T1w) MRI image and a DTI with 32 gradient directions) before surgery and a CT scan post-implantation. Image analysis was performed using the FMRIB Software Library. BA25, BA10 and BA46 areas, and Amygdala were extracted from the Broadmann area template to serve as guides for tractography. Similarly, individual EpCS paddles identified on CT scan were also transformed. First, an affine (12 parameter model) registration was applied to register Broadmann template onto T1w images and then T1w onto DTI data. Transformations were then applied to the guides. Second, a binary mask of the brain was extracted and applied to all images after correction for eddy currents. BedpostX was then run on the preprocessed data to generate the basis for probabilistic tractography using ProbtrackX. Estimation of tracts was done probabilistically, using a dual-fiber model with 5000 tract-following samples at each voxel. All tractography was done in each subject’s native space. Eight tractography combinations (left & right) were performed: BA10/BA46 as seeds for tractography and Amygdala/BA25 as waypoints masks. Similar approached was applied with EpCS actual lead masks. The resulting fibers were then thresholded at 0.01 (99% likelihood of connectivity) and then binarized, and transferred into MNI152 standard space for cross-subject analysis using a non-linear registration. To generate population-based probability fibers, all subjects’ individual fibers were added up and used as a basis for calculation of a mean image. Finally, the resulting mean fiber was thresholded to show voxels common to 80% or more of the subjects. Results All patients showed robust connections of different pathways in both left and right hemispheres. The resulting pathways connected to each seed combination are shown in Fig. 1 . Electrodes implanted over both BA10 and BA46 areas resulted in direct activation of axons that primarily project from BA10 or BA46 to BA25 and Amygdala, and extend to the cingulum bundle and to the middle occipital gyrus. Conclusion This is the first demonstration of EpCS direct anatomical access to the medial and lateral mood regulation networks. Encouraging clinical data have been reported elsewhere with 3 patients out of 5 showing remission at 7 months (Nahas et al., 2010) and at 5 years (Williams et al., under review). Bilateral anterior and lateral EpCS promises to be an innovative new treatment for a highly morbid disease through adaptive cortical governance of limbic structures but larger studies are needed.

Inter- and Intradigit Somatotopic Map of High-Frequency Vibration Stimulations in Human Primary Somatosensory Cortex.

Although more about the somatotopic mapping of fingers continues to be uncovered, there is lack of mapping attempts regarding the integration of within-finger and across-finger somatotopic coordinates in Broadmann area (BA) 3. This study aimed to address the issue by finding an inter-/intradigit somatotopic map with high-frequency (250 Hz) vibrotactile stimulation. Functional magnetic resonance imaging (fMRI) data were acquired while stimulation was applied to 3 phalanxes (distal [p1], intermediate [p2], and proximal [p3] phalanx) of 4 fingers (index, middle, ring, and little finger) for a total of 12 finger–phalanx combinations for a human. Inter-, intra-, and inter-/intradigit distances were calculated from peak activation coordinates in BA 3 for each combination. With regard to interdigit dimensions, the somatotopic coordinates proceeded in the lateral-to-medial direction for the index, middle, ring, and little fingers consecutively. This trend is comparable to that generated from low-frequency stimulation modalities (flutter stimulation). The somatotopic distances between fingers were greatest when p1 was compared across fingers. From an intradigit perspective, stimulation on p1, p2, and p3 yielded BA 3 peak coordinates aligned along the anterior-to-posterior and inferior-to-superior directions for all fingers. An inter-/intradigit map exhibited a radially propagating trend of distances calculated with respect to index p1 as a reference point; this provided an integrated view of inter- and intradigit somatotopies, which are traditionally discussed separately. We expect such an inter-/intradigit somatotopic map approach to contribute in generating a comprehensive somatotopic model of fingers.

FMRI Adaptation between Action Observation and Action Execution Reveals Cortical Areas with Mirror Neuron Properties in Human BA 44/45.

Mirror neurons (MNs) are considered to be the supporting neural mechanism for action understanding. MNs have been identified in monkey’s area F5. The identification of MNs in the human homolog of monkeys’ area F5 Broadmann Area 44/45 (BA 44/45) has been proven methodologically difficult. Cross-modal functional MRI (fMRI) adaptation studies supporting the existence of MNs restricted their analysis to a priori candidate regions, whereas studies that failed to find evidence used non-object-directed (NDA) actions. We tackled these limitations by using object-directed actions (ODAs) differing only in terms of their object directedness in combination with a cross-modal adaptation paradigm and a whole-brain analysis. Additionally, we tested voxels’ blood oxygenation level-dependent (BOLD) response patterns for several properties previously reported as typical MN response properties. Our results revealed 52 voxels in left inferior frontal gyrus (IFG; particularly BA 44/45), which respond to both motor and visual stimulation and exhibit cross-modal adaptation between the execution and observation of the same action. These results demonstrate that part of human IFG, specifically BA 44/45, has BOLD response characteristics very similar to monkey’s area F5.

A possible relationship between disturbed interhemispheric asymmetry and a decrease in perineuronal oligodendrocytes in schizophrenia

To specify a possible role of oligodendrocyte deficit in the development of interhemispheric asymmetry. Perineuronal oligodendrocytes were counted in layer III, Broadmann area 39, in Nissl-stained sections in both hemispheres of post-mortem brain samples of patients with schizophrenia and controls (healthy people). The left-hemispheric asymmetry of perineuronal oligodendrocytes was found in the control group. A decrease of this parameter by 22% and the absence of the interhemispheric asymmetry were noted in patients with schizophrenia. It has been concluded that perineuronal oligodendrocyte deficit in the inferior parietal cortex in schizophrenia can contribute significantly to disturbed interhemispheric asymmetry of this brain structure.

Attenuation of dendritic spine density in the perirhinal cortex following 17β-Estradiol replacement in the rat.

Intraperirhinal cortex infusion of 17-β estradiol (E2) impairs object-recognition memory. However, it is not currently known whether this hormone modulates synaptic plasticity in this structure. Most excitatory synapses in the central nervous system are located on dendritic spines, and elevated E2 levels influence the density of these spines in several brain areas. The goal of the present study was to determine whether differences in dendritic spine density in the perirhinal cortex are observed following high E2 replacement in ovariectomized rats. The density of total spines, and mushroom-shaped (i.e. mature) spines were compared between a high E2 replacement (10 µg/kg/day, s.c.) and a no replacement condition. The perirhinal cortex is subdivided into Broadmann's area 35 and 36 and so group comparisons were made within each sub-region separately. High E2 replacement resulted in lower density of mushroom-shaped spines in area 35 relative to no replacement. There was no effect of high E2 replacement on dendritic spine density in area 36. These findings are consistent with the idea that higher E2 levels reduce dendritic spine density in area 35, which may result from spine shrinkage, or reduced synapse formation. This study provides preliminary evidence for a mechanism through which E2 may impair object-recognition memory.

Immediate cerebral metabolic changes induced by discontinuation of deep brain stimulation of subcallosal cingulate gyrus in treatment-resistant depression

BackgroundPositron emission tomography (PET) studies have shown that the antidepressant effect of chronic deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) may be consequence of modifications of brain metabolism at key structures involved in depression. Like clinical benefits, these metabolic changes may reverse when the stimulation is discontinued, even preceding clinical worsening. However no data on immediate effects of DBS discontinuation are available. The aim of this study was to determine immediate cerebral metabolism changes during a short switch-off of electrical stimulation in implanted patients with treatment-resistant depression (TRD) who had achieved clinical improvement after a period of chronic DBS. MethodsSeven patients with TRD who had been previously implanted for DBS in SCG were included. After a period of clinical stabilization two consecutive FDG-PET were acquired, the first with active stimulation and the second after 48h of inactive stimulation. A HAMD-17 to assess depressive symptoms was performed before both scans. Analyses were performed with SnPM8. ResultsInactive stimulation was characterized by metabolism decreases in dorsal anterior cingulate (Broadmann Area, BA24), premotor region (BA6) and putamen with respect to active stimulation. No clinical changes according to HAMD-17 were detected. LimitationsThe main limitation of this study is the small sample size. ConclusionOur results point to immediate effects of DBS discontinuation on metabolism of brain depressive network which precede clinical changes, helping to disentangle the rationale behind DBS efficacy in TRD.

Self-reported functional impairment in individuals at clinical high-risk for psychosis

us to examine developmental trajectories that may be associated with psychopathology in these children at risk. The current study will investigate cortical abnormalities by measuring gray matter volume in children and adolescences at lowand high-risk of developing bipolar disorder. Methods: To date, nineteen partially-affected high-risk (HR) offspring (average age = 13.73 (2.81) years, 8 females), and 11 ageand sex-matched healthy controls (HC) (average age = 13.18 (2.74) years, 4 females) have been recruited for this study. Offspring were not excluded if they were diagnosed with depression, attention, behavioural or anxiety-related disorders. Highresolution magnetic resonance structural brain images were taken using a General Electric 3 Tesla scanner. Structural brain scans were analyzed using the CIVET pipeline in CBRAIN to extract measures of cortical thickness. Results: Preliminary whole-brain vertex-wise analyses suggest a significant difference in cortical thickness between HR and HC offspring. HR children had significantly thinner gray matter volumes in the left middle temporal gyrus, Broadmann area 21 (t = 3.98 and t = 3.92), the left superior frontal gyrus, Broadmann area 6 (t = 3.72) and the left parahippocampal gyrus, Broadmann area 27 (t = 3.57) compared to HC offspring. Conclusions: Our results suggest that cortical differences exist between HC children and symptomatic HR bipolar offspring. Specifically, we detected decreased cortical thickness in frontal and temporal areas of children at high risk of developing bipolar disorder.