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Objective The classical homunculus of the human primary somatosensory cortex (S1) established by Penfield has mainly portrayed the functional organization of convexial cortex, namely Brodmann area (BA) 1. However, little is known about the functions in fissural cortex including BA2 and BA3. We aim at drawing a refined and detailed somatosensory homunculus of the entire S1. Methods We recruited 20 patients with drug-resistant focal epilepsy who underwent stereo-electroencephalography for preoperative assessments. Direct electrical stimulation was performed for functional mapping. Montreal Neurological Institute coordinates of the stimulation sites lying in S1 were acquired. Results Stimulation of 177 sites in S1 yielded 149 positive sites (84%), most of which were located in the sulcal cortex. The spatial distribution of different body-part representations across the S1 surface revealed that the gross medial-to-lateral sequence of body representations within the entire S1 was consistent with the classical “homunculus”. And we identified several unreported body-part representations from the sulcal cortex, such as forehead, deep elbow and wrist joints, and some dorsal body regions. Conclusions Our results reveal general somatotopical characteristics of the entire S1 cortex and differences with the previous works of Penfield. Significance The classical S1 homunculus was extended by providing further refinement and additional detail.

BACKGROUND AND PURPOSE: Idiopathic sudden sensorineural hearing loss is an acute unexplained onset of hearing loss. We examined the central auditory pathway abnormalities in patients with unilateral idiopathic sudden sensorineural hearing loss using diffusion spectrum imaging and the relationships between hearing recovery and diffusion spectrum imaging parameters. MATERIALS AND METHODS: Forty-eight patients with unilateral idiopathic sudden sensorineural hearing loss with a duration of ≤2 weeks (range, 8.9 ± 4.3 days) and 20 healthy subjects underwent diffusion spectrum imaging tractography. Hearing levels were evaluated using a pure-tone average at initial presentation and 3-month follow-up. Clinical characteristics and MR imaging findings were assessed. RESULTS: Compared with healthy control subjects, the generalized fractional anisotropy values of patients decreased significantly in the bilateral posterior limbs of the internal capsule, with no differences between the ipsilateral and contralateral sides. The quantitative anisotropy values decreased in the Brodmann area 41, contralateral medial geniculate body, bilateral lateral lemniscus, anterior limb of internal capsule, middle temporal gyrus, and anterior corona radiata. Furthermore, at 3-month follow-up, 14 patients had

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01225-3.

Migraine seriously affects the physical and mental health of patients because of its recurrence and the hypersensitivity to the environment that it causes. However, the pathogenesis and pathophysiology of migraine are not fully understood. We addressed this issue in the present study using an autodynamic functional connectome model (A-DFCM) with twice-clustering to compare dynamic functional connectome patterns (DFCPs) from resting-state functional magnetic resonance imaging data from migraine patients and normal control subjects. We used automatic localization of segment points to improve the efficiency of the model, and intergroup differences and network metrics were analyzed to identify the neural mechanisms of migraine. Using the A-DFCM model, we identified 17 DFCPs—including 1 that was specific and 16 that were general—based on intergroup differences. The specific DFCP was closely associated with neuronal dysfunction in migraine, whereas the general DFCPs showed that the 2 groups had similar functional topology as well as differences in the brain resting state. An analysis of network metrics revealed the critical brain regions in the specific DFCP; these were not only distributed in brain areas related to pain such as Brodmann area 1/2/3, basal ganglia, and thalamus but also located in regions that have been implicated in migraine symptoms such as the occipital lobe. An analysis of the dissimilarities in general DFCPs between the 2 groups identified 6 brain areas belonging to the so-called pain matrix. Our findings provide insight into the neural mechanisms of migraine while also identifying neuroimaging biomarkers that can aid in the diagnosis or monitoring of migraine patients.

AIM The aim of this study was to evaluate brain glucose metabolism by means of [18F]-fluoro-deoxygluycose (F-FDG) PET in a group of patients presenting dysautonomic syndrome after human papilloma virus (HPV) immunization. METHODS Medical records of patients, referred to the 'Second Opinion Medical Consulting Network' Medical Centre (Modena, Italy) diagnosed with dysautonomic syndrome were searched. Inclusion criteria were presence in the medical history of adverse drug reactions following HPV vaccine; a Montreal Cognitive Assessment score

Background: The combination of structural and functional analyses is a biologically valid approach that offers methodological advantages in autism spectrum disorder (ASD) neuroimaging science. The paucity of studies combining these methods constitutes an important knowledge gap. In this study, we investigate structural abnormalities and their associated functional differences in a developmentally homogeneous ASD cohort. Methods: Whole-brain voxel-based morphometry (VBM) analyses were performed on 28 ASD participants and 38 age-matched typically developing healthy controls (HC) to derive gray matter (GM) volume differences. The anatomically relevant clusters identified by VBM served as seed regions of interest (ROI) for resting-state functional-connectivity (RsFc) analysis. Results: Whole-brain VBM analyses revealed significant right lateralized GM volume abnormality in the ASD group, with lower GM volumes in cerebellar lobules VIIb/VIIIa (cluster 1) and significantly higher GM volumes in posterior middle/superior temporal gyri (Brodmann area [BA] 21/22, cluster 2) compared with HC. Whole-brain RsFc analysis in high-functioning ASD (HF-ASD) revealed significant hypoconnectivity of the cerebellar VBM cluster with the right cerebral cortical regions of superior parietal lobule (BA 7) and occipital pole (BA 19) (overlapping with dorsal attention and visual networks, respectively). Cerebral cortical VBM cluster (cluster 2) revealed significant hypoconnectivity in HF-ASD with other task-positive cerebral cortical including the left lateral prefrontal cortex (frontoparietal network) and some aspects of the insula (ventral attention network) and ectopic positive connectivity (lack of anticorrelations) with posterior cingulate cortex and medial prefrontal cortex (default mode network). Conclusions: The cerebro-cerebellar intrinsic functional dysconnectivity based on the whole-brain VBM-derived ROIs may advance our understanding of the compensatory mechanisms associated with ASD and offer cerebellum as a potential target for diagnostic, predictive, prognostic, and therapeutic interventions in ASD. Our findings also provide additional support indicating that functional abnormalities as indexed by RsFc exist in ASD, and highlight that there is likely a relationship between structural and functional abnormalities in this disorder. Impact statement Our findings indicate that functional differences as indexed by resting-state functional connectivity exist in autism spectrum disorder (ASD), and highlight that there is likely a relationship between structural and functional abnormalities in this disorder. Future developments in neuroimaging research should continue investigating structural and associated functional differences in ASD, and in this way complement the behavioral characterization of this disorder, potentially improving diagnosis, prognosis, and prediction.

Objective To identify the spectrotemporal changes and sources in patients that could “turn on” tinnitus with multichannel electroencephalography (EEG) system. Methods Multichannel EEG was recorded from six patients during the Tinnitus-On and Tinnitus-Off states. The EEG power spectrum and eLORETA-based sources were measured. Results There was a global increase in delta and theta during Tinnitus-On plus large changes in alpha 1 and alpha 2. During the Tinnitus-On state, many new sources in delta, theta, alpha 1 and gamma bands emerged in the opposite hemisphere in the inferior temporal gyrus (Brodmann area, BA 20), middle temporal gyrus (BA 21), lateral perirhinal cortex (BA 36), ventral entorhinal cortex (BA 28) and anterior pole of the temporal gyrus (BA 38). Conclusions The emergence of new delta, theta and gamma band sources in the inferior temporal gyrus (BA 20), middle temporal gyrus (BA 21) and lateral perirhinal cortex (BA 36) plus the appearance of new delta and theta sources in the ventral entorhinal cortex (BA28) and anterior pole of the temporal lobe (BA 38) may comprise a network capable of evoking the phantom sound of tinnitus by simultaneously engaging brain regions involved in memory, sound recognition, and distress which together contribute to tinnitus severity. Significance The sudden appearance of new sources of activity in the opposite hemisphere within the inferior temporal gyrus, middle temporal gyrus and perirhinal cortex may initiate the perception of tinnitus perception.

In this study, we aimed to compare the oscillatory dynamics accompanying self-referential and non-self-referential stimulus-independent thoughts. Electroencephalograms were recorded in 30 healthy participants who were asked to press buttons classifying their spontaneous thoughts as self-referential or non-self-referential. EEG data were analyzed using independent component analysis in conjunction with dipole localization. Self-referential thoughts, as compared to non-self-referential thoughts, were accompanied by more pronounced decreases of theta, alpha, and beta spectral power in the anterior hub of the default-mode network, in the left lateral prefrontal, motor/somatosensory, and temporal cortices. These oscillatory dynamics are interpreted as a reflection of autobiographical memory retrieval intrinsic to self-referential thoughts. Abbreviations: BA: Brodmann area; BOLD: blood oxygenation level-dependent; DMN: default mode network; EEG: electroencephalogram; ERSP: event-related spectral perturbations; fMRI: functional magnetic resonance imaging; PCC: posterior cingulate cortex; PET: positron emission tomography; PFC: prefrontal cortex; SIT: stimulus-independent thought; WM: working memory.

The study aimed to determine alterations in intrinsic brain activity in retinitis pigmentosa (RP) individuals using the amplitude of low-frequency fluctuation (ALFF)/fractional amplitude of low-frequency fluctuation (fALFF) method. Sixteen RP individuals (10 men and six women) and 14 healthy controls (HCs) (six men and eight women) closely matched in age, sex, and education were enrolled in the study. The ALFF/fALFF method was applied to compare different intrinsic brain activities between the RP group and the HC group. The relationship between the mean ALFF/fALFF signal values of different brain regions and the visual measurements in RP group was analyzed by Pearson correlation. Compared with HCs, RP individuals had significantly lower ALFF values in the bilateral lingual gyrus (LIGG)/cerebellum posterior lobe [Brodmann area (BA) 17,18], but lower fALFF values in the bilateral LIGG/cerebellum anterior lobe (BA 17,18). Meanwhile, RP individuals had significantly higher ALFF in the bilateral precuneus cortex/middle cingulate cortex (BA 7,31), as well as higher fALFF values in the left superior/middle frontal gyrus (BA 9,10) and bilateral supplementary motor area (BA 6,8) (voxel-level P

Cognitive reappraisal plays an important role in individuals' mental health and adaptation and depends on individual differences in emotion differentiation. However, it is unclear how individual differences in emotion differentiation modulate the electrocortical dynamics of cognitive reappraisal. To this end, we employed event-related potentials (ERPs) and source analysis to characterize temporal dynamics and cortical functions of cognitive reappraisal related with positive emotion differentiation. The electroencephalogram (EEG) data from 36 participants (aged 18-25 years) were recorded when they were required to view neutral, pleasant emotional stimuli, or positively reappraise neutral emotional stimuli. Results showed that, compared with the individuals with low positive emotion differentiation, the individuals with high positive emotion differentiation presented larger late positive potential (LPP) amplitude enhancement during positive reappraisal. Source analysis further found that individuals with high positive emotion differentiation exhibited more activations in the middle frontal gyrus (Brodmann area [BA] 11), superior temporal gyrus (BA 38), and inferior frontal gurus (BA 47) when they implemented cognitive reappraisal as compared with their counterparts. Our findings deepen our understanding of the dynamic cortical organization of how positive emotion differentiation impacts cognitive reappraisal and informs cognitive reappraisal interventions for individuals with low emotion differentiation.

Objective To investigate altered prefrontal white matter integrity in complex regional pain syndrome (CRPS) and its relation with the degree of pain catastrophizing. Design Cross-sectional study. Setting University hospital. Participants Twenty-one CRPS patients and 49 patients without CRPS (N=70). Interventions Not applicable. Main Outcome Measures The fractional anisotropy values within the prefrontal regions reflecting the structural integrity of white matter were measured in CRPS patients and patients without CRPS using diffusion tensor imaging. The degree of pain catastrophizing was also evaluated in CRPS patients. Results The structural integrity of the prefrontal white matter was lower in CRPS patients than in patients without CRPS (P=.03). In addition, lower structural integrity in the prefrontal cortex was correlated with a higher degree of pain catastrophizing among CRPS patients (r= −0.54, P=.01). Conclusions Our findings suggest that pain catastrophizing, which is frequently reported in patients with CRPS, may be associated with the dysfunction of the prefrontal white matter.

Retrosplenial cortex (RSC) plays a key role in various cognitive functions. The fiber connectivity of RSC had been reported in rodent and primate studies by tracer injection methods To explore structural and functional connectivity of two sub-regions of RSC, Brodmann area (BA)29 and BA30, we constructed fiber connectivity networks of two sub-regions by diffusion tensor imaging (DTI) tractography based on diffusion magnetic resonance imaging (MRI) and functional connectivity networks by resting-state functional MRI. The BA29 network showed fiber connections with auditory cortex and functional connections with BA21. Both fiber and functional connections show that BA30 network includes visual cortex. Furthermore, BA30 had fiber connections with hippocampus, thalamus, and prefrontal cortex. We suggest that (1) structural connectivity reflects functional connectivity in some degree. (2) BA29 mainly received and processed sound information from auditory cortex, while BA30 mainly received and processed scene information from visual cortex.

Rationale, aims, and objectives Paced Auditory Serial Addition Test (PASAT) is used for assessment of information processing speed, attention, and working memory, which are the most frequently affected cognitive domains in multiple sclerosis (MS) patients, and may be significantly affected by fatigue. However, the effect of fatigue and mood on the PASAT performance in MS patients translationally validated by fMRI has not been studied yet. The aim of this study is to investigate the translational validity of the PASAT, using fMRI during a paced visual serial addition test (PVSAT) paradigm in patients with relapsing remitting MS (RRMS) and to assess the impact of fatigue and mood on test performance. Methods Fourteen patients with RRMS in remission and 14 healthy controls, matched by sex, age, and educational status, were enrolled in the study. The subjects underwent a standard neurological examination, neuropsychological evaluation with the PASAT 3', fMRI scanning with a PVSAT paradigm, and Beck Depression Inventory. All patients were assessed by the Modified Fatigue Impact Scale. Results Paced Auditory Serial Addition Test score was lower in patients (41.4 ± 15.5 vs 51.6 ± 7.5, P = .035). A moderate negative correlation (P = -0.563, P = 0.036) was found between PASAT and MIFS scores. The fMRI scanning showed significant activations in several clusters that differed between patients and controls. The patient group presented wider cluster activation; Brodmann area (BA) 6-bilaterally; left BA7, 8, and 9; and right BA40, while controls presented with activations in left BA6 and BA44. Significant negative correlations between PASAT score and cortical activations in left BA23, right BA32, and left BA7 were observed in patients only. Conclusion Our results show that poorer performance on the PASAT is associated with higher activation in areas connected with working memory, attention, and emotional processes during the fMRI assessment with PVSAT paradigm, which provides evidence for the translational validity of the PASAT in patients with RRMS.

The importance of insula in speech control is acknowledged but poorly understood, partly due to a variety of clinical symptoms resulting from insults to this structure. To clarify its structural organization within the speech network in healthy subjects, we used probabilistic diffusion tractography to examine insular connectivity with three cortical regions responsible for sound processing (Brodmann area (BA) 22), motor preparation (BA 44) and motor execution (laryngeal/orofacial primary motor cortex, BA 4). To assess insular reorganization in a speech disorder, we examined its structural connectivity in patients with spasmodic dysphonia (SD), a neurological condition that selectively affects speech production. We demonstrated structural segregation of insula into three non-overlapping regions, which receive distinct connections from BA 44 (anterior insula), BA 4 (mid-insula) and BA 22 (dorsal and posterior insula). There were no significant differences either in the number of streamlines connecting each insular subdivision to the cortical target or hemispheric lateralization of insular clusters and their projections between healthy subjects and SD patients. However, spatial distribution of the insular subdivisions connected to BA 4 and BA 44 was distinctly organized in healthy controls and SD patients, extending ventro-posteriorly in the former group and anterio-dorsally in the latter group. Our findings point to a structural segregation of the insular sub-regions, which may be associated with the different aspects of sensorimotor and cognitive control of speech production. We suggest that distinct insular involvement may lead to different clinical manifestations when one or the other insular region and/or its connections undergo spatial reorganization.

While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation. During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cerebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), putamen and ipsilesional OP1 predicted motor outcome measured 6 months later (adjusted-R2 = 0.85; bootstrap p, Highlights • Motor recovery after stroke can be robustly predicted using a passive task fMRI paradigm. • Sensorimotor network activity is decreased in moderate to severe stroke patients relative to healthy controls • Compensatory mechanisms in severe stroke involve both the dorsal (MI BA4a), and the ventral (OP1 and OP4) sensorimotor stream

Background: Pessimistic thinking about the future is one of the cardinal symptoms of major depressive disorder (MDD) and is an important domain of cognitive functioning associated with hopelessness. Neuroimaging studies have shown that the frontopolar cortex (Brodmann area [BA] 10) is involved in thinking about the future and demonstrated that patients with MDD have dysfunctions in BA10. However, the relationship between pessimistic thinking about the future and brain activity is unclear. Hence, we aimed to compare brain activity during future-thinking between patients with MDD and healthy individuals. Methods: We assessed 23 patients with current MDD and 23 healthy individuals. Participants were instructed to imagine the future or to recall the past using the future-thinking paradigm with four distinct temporal conditions (distant future, near future, distant past, and near past) during functional MRI. Resting-state functional MRI was also performed to explore the functional connectivity of BA10. Results: Compared with healthy individuals, patients with MDD had greater negative thinking about the distant future and exhibited increased activation in the medial BA10 when imagining the distant future, following small-volume correction focusing on the frontopolar a priori region of interest (family-wise error correction p

Dorsolateral prefrontal cortex (DLPFC) and temporal pole (TP) are brain regions that display abnormalities in bipolar disorder (BD) patients. DNA methylation — an epigenetic mechanism both heritable and sensitive to the environment — may be involved in the pathophysiology of BD. To study BD-associated DNA methylomic differences in these brain regions, we extracted genomic DNA from the postmortem tissues of Brodmann Area (BA) 9 (DLPFC) and BA38 (TP) gray matter from 20 BD, ten major depression (MDD), and ten control age-and-sex-matched subjects. Genome-wide methylation levels were measured using the 850 K Illumina MethylationEPIC BeadChip. We detected striking differences between cortical regions, with greater numbers of between-brain-region differentially methylated positions (DMPs; i.e., CpG sites) in all groups, most pronounced in the BD group, and with substantial overlap across groups. The genes of DMPs common to both BD and MDD (hypothetically associated with their common features such as depression) and those distinct to BD (hypothetically associated with BD-specific features such as mania) were enriched in pathways involved in neurodevelopment including axon guidance. Pathways enriched only in the BD-MDD shared list pointed to GABAergic dysregulation, while those enriched in the BD-only list suggested glutamatergic dysregulation and greater impact on synaptogenesis and synaptic plasticity. We further detected group-specific between-brain-region gene expression differences in ODC1, CALY, GALNT2, and GABRD, which contained significant between-brain-region DMPs. In each brain region, no significant DMPs or differentially methylated regions (DMRs) were found between diagnostic groups. In summary, the methylation differences between DLPFC and TP may provide molecular targets for further investigations of genetic and environmental vulnerabilities associated with both unique and common features of various mood disorders and suggest directions of future development of individualized treatment strategies.

Background and purpose: The aim of the study was to evaluate the metabolic correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of e2 as a risk factor for cognitive impairment. Methods: A total of 159 ALS cases underwent APOE and ALS-related genes analysis, neuropsychological assessment and cerebral 18F-2-fluoro-2-deoxy-Dglucose positron emission tomography. The APOE genotype was regressed against whole brain metabolism as assessed by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with age, sex, education, type of onset and C9orf72 status as covariates. Results: Brain metabolism was significantly positively correlated with APOE genotype from e2/e2 to e3/e4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the e2/e2 extreme. Conclusions: We found a highly significant, relatively lower metabolism in association with the e2 allele in extra-motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of e2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.

Although structural and functional neuroimaging techniques have recently been used to investigate the mechanisms of sexual attraction to children, a hallmark of pedophilic disorder, the differences in the processing of child sexual stimuli between men attracted to children and those attracted to adults remain unclear. Here, our purpose was to identify through positron emission tomography the brain responses of 15 male outpatients with pedophilic disorder to validated visual sexual stimuli depicting children (VSSc) and to compare them with 15 male healthy controls matched for sexual orientation (to female or male adults), age, and handedness. The patients' sample comprised both offenders and non-offenders. In response to VSSc, the between-groups analysis showed that activation in the right inferior temporal cortex [Brodmann area (BA) 20] was lower in patients than in controls. Moreover, in patients but not in controls, the presentation of VSSc induced an activation in a more caudal region of the right inferior temporal gyrus (BA 37) and in the left middle occipital gyrus (BA 19). In addition, in patients the level of activation in the caudal right inferior temporal gyrus was positively correlated with ratings of sexual arousal elicited by VSSc, whereas this correlation was negative in BA 20. These results implicate the right inferior temporal gyrus as a possible candidate area mediating sexual arousal in patients with pedophilic disorder and suggest that two of its areas play opposite, i.e., activating and inhibitory, roles., Highlights • Images of children activate the pedophilic patients' right Brodmann area (BA) 37. • Images of children (IC) activate the pedophilic patients' left BA 19. • Right BA37 activation correlates with pedophilic patients' rating of sexual arousal. • IC induce lower right BA 20 activation in pedophilic patients than in controls.

Previous data suggest that the right temporo-parietal junction (rTPJ) may have a specific role in abnormal body perception (ABP), including out-of-body experience. We tested this hypothesis with inhibitory (1 Hz) and excitatory (15 Hz) repetitive transcranial magnetic stimulation (rTMS) of the rTPJ and a control site (CS, 5 cm posterior to the rTPJ along the lateral sulcus direction in Brodmann area 19R) in 35 healthy adults. ABP frequency was higher with 1 Hz than with 15 Hz rTMS but unaffected by the rTMS site (rTPJ/CS). Response to an own-body transformation task were delayed with 1 Hz compared to 15 Hz rTMS but also unaffected by rTMS site. ABP from rTMS at both sites induced electroencephalographic power decrease in all frequencies at left anterior and central cortical sites. Our data suggest that inhibitory rTMS can lead to ABP. However, the rTPJ may not play a specific role in this process.

Background/objectives Over the last ten years, an increasing number of authors have used the theta burst stimulation (TBS) protocol to investigate long-term potentiation (LTP) and long-term depression (LTD)-like plasticity non-invasively in the primary motor cortex (M1) in healthy humans and in patients with various types of movement disorders. We here provide a comprehensive review of the LTP/LTD-like plasticity induced by TBS in the human M1. Methods A workgroup of researchers expert in this research field review and discuss critically ten years of experimental evidence from TBS studies in humans and in animal models. The review also includes the discussion of studies assessing responses to TBS in patients with movement disorders. Main findings/discussion We discuss experimental studies applying TBS over the M1 or in other cortical regions functionally connected to M1 in healthy subjects and in patients with various types of movement disorders. We also review experimental evidence coming from TBS studies in animals. Finally, we clarify the status of TBS as a possible new non-invasive therapy aimed at improving symptoms in various neurological disorders.

Creativity plays an important role in numerical problem solving. Although the neural underpinnings of creativity have been studied over decades, very little is known about neural mechanisms of the creative process that relates to numerical problem solving. In the present study, we employed a numerical analogical reasoning task with functional Magnetic Resonance Imaging (fMRI) to investigate the neural correlates of divergent production of rules in numerical analogical reasoning. Participants performed two tasks: a multiple solution analogical reasoning task and a single solution analogical reasoning task. Results revealed that divergent production of rules involves significant activations at Brodmann area (BA) 10 in the right middle frontal cortex, BA 40 in the left inferior parietal lobule, and BA 8 in the superior frontal cortex. The results suggest that right BA 10 and left BA 40 are involved in the generation of novel rules, and BA 8 is associated with the inhibition of initial rules in numerical analogical reasoning. The findings shed light on the neural mechanisms of creativity in numerical processing.

Reductions in gray matter volume of the medial prefrontal cortex (mPFC), especially the rostral and subgenual anterior cingulate cortex (rACC, sgACC) are a widely reported finding in major depressive disorder (MDD). Inflammatory mediators, which are elevated in a subgroup of patients with MDD, activate the kynurenine metabolic pathway and increase production of neuroactive metabolites such as kynurenic acid (KynA), 3-hydroxykynurenine (3HK) and quinolinic acid (QA) which influence neuroplasticity. It is not known whether the alterations in brain structure and function observed in major depressive disorders are due to the direct effect of inflammatory mediators or the effects of neurotoxic kynurenine metabolites. Here, using partial posterior predictive distribution mediation analysis, we tested whether the serum concentrations of kynurenine pathway metabolites mediated reductions in cortical thickness in mPFC regions in MDD. Further, we tested whether any association between C-reactive protein (CRP) and cortical thickness would be mediated by kynurenine pathway metabolites. Seventy-three unmedicated subjects who met DSM-IV-TR criteria for MDD and 91 healthy controls (HC) completed MRI scanning using a pulse sequence optimized for tissue contrast resolution. Automated cortical parcellation was performed using the PALS-B12 Brodmann area atlas as implemented in FreeSurfer in order to compare the cortical thickness and cortical area of six PFC regions: Brodmann areas (BA) 9, 10, 11, 24, 25, and 32. Serum concentrations of kynurenine pathway metabolites were determined by high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) detection, while high-sensitivity CRP concentration was measured immunoturbidimetrically. Compared with HCs, the MDD group showed a reduction in cortical thickness of the right BA24 (p

Neuroticism, a core personality trait characterized by a tendency towards experiencing negative affect, has been reported to be higher in people with temporal lobe epilepsy (TLE) compared with healthy individuals. Neuroticism is a known predictor of depression and anxiety, which also occur more frequently in people with TLE. The purpose of this study was to identify abnormalities in whole-brain resting-state functional connectivity in relation to neuroticism in people with TLE and to determine the degree of unique versus shared patterns of abnormal connectivity in relation to elevated symptoms of depression and anxiety. Ninety-three individuals with TLE (55 females) and 40 healthy controls (18 females) from the Epilepsy Connectome Project (ECP) completed measures of neuroticism, depression, and anxiety, which were all significantly higher in people with TLE compared with controls. Resting-state functional connectivity was compared between controls and groups with TLE with high and low neuroticism using analysis of variance (ANOVA) and t-test. In secondary analyses, the same analytics were performed using measures of depression and anxiety and the unique variance in resting-state connectivity associated with neuroticism independent of symptoms of depression and anxiety identified. Increased neuroticism was significantly associated with hyposynchrony between the right hippocampus and Brodmann area (BA) 9 (region of prefrontal cortex (PFC)) (p 0.005), representing a unique relationship independent of symptoms of depression and anxiety. Hyposynchrony of connection between the right hippocampus and BA47 (anterior frontal operculum) was associated with high neuroticism and with higher depression and anxiety scores (p 0.05), making it a shared abnormal connection for the three measures. In conclusion, increased neuroticism exhibits both unique and shared patterns of abnormal functional connectivity with depression and anxiety symptoms between regions of the mesial temporal and frontal lobe.

Treatment-resistant depression (TRD) occurs in many patients and causes high morbidity and mortality. Because TRD subjects are particularly difficult to study especially longitudinally, biological data remain very limited. In a preliminary study to judge feasibility and power, 25 TRD patients were referred from specialty psychiatric practices. All were severely and chronically depressed and mostly had comorbid psychiatric disorders as is typical in TRD. Nine patients were able to complete all required components of the protocol that included diagnostic interview; rating scales; clinical magnetic resonance imaging; medication washout; treatment with maximally tolerated olanzapine-fluoxetine combination for 8 weeks; and pre- and post-treatment fluorodeoxyglucose positron emission tomography. This drug combination is an accepted standard of treatment for TRD. Dropouts arose from worsening depression, insomnia, and anxiety. One patient remitted; three responded. A priori regions of interest included the amygdala and subgenual cingulate cortex (sgACC; BA25). Responders showed decreased metabolism with treatment in the right amygdala that correlated with clinical response; no significant changes in BA25; better response to treatment the higher the baseline BA25 metabolism; and decreased right ventromedial prefrontal metabolism (VMPFC; broader than BA25) with treatment which did not correlate with depression scores. The baseline metabolism of all individuals showed heterogeneous patterns when compared to a normative metabolic database. Although preliminary given the sample size, this study highlights several issues important for future work: marked dropout rate in this study design; need for large sample size for adequate power; baseline metabolic heterogeneity of TRD requiring careful subject characterization for future studies of interventions; relationship of amygdala activity decreases with response; and the relationship between baseline sgACC and VMPFC activity with response. Successful treatment of TRD with olanzapine-fluoxetine combination shows changes in cerebral metabolism similar to those seen in treatment-responsive major depression.

Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway that is essential to maintaining cellular redox balance. G6PD is especially plentiful in brain, and its deficiency has been linked to mood and psychotic disorders. We measured G6PD activity spectrophotometrically in four groups of 15 parietal somatosensory association cortex [Brodmann area (BA) 7] tissue samples (N = 60) from individuals with bipolar disorder (BPD); nonpsychotic unipolar major depression (UPD); schizophrenia (SCZ), and controls without psychiatric illness (CON). We report for the first time brain G6PD activity levels in these disorders. G6PD activity did not differ by brain group. In BPD and SCZ brains, however, it correlated significantly and inversely with percent of hexokinase 1 (HK1) in the tissue homogenate mitochondrial fraction as determined previously in another set of tissue samples obtained from the same brains and brain region. The correlation in SCZ brains lost statistical significance after controlling for brain pH. This finding indicates a positive relationship in BPD brains between G6PD activity and HK1 mitochondrial detachment, an indicator of mitochondrial impairment associated with increased mitochondrial generation of reactive oxygen species. We speculate that this relationship could be evidence that G6PD activity is proportionate to and may be a compensatory response to oxidative stress in the BA7 region of BPD brains. Future research should focus on clarifying the relationships among G6PD activity, markers of oxidative stress, brain pH, and evidence of mitochondrial impairment, particularly HK1 mitochondrial detachment, in brains of individuals with G6PD deficiency, BPD and SCZ.

When axonal fibres approach or leave the cortex, their trajectories tend to closely follow the cortical convolutions. To quantify this tendency, we propose a three-dimensional coordinate system based on the gyral geometry. For every voxel in the brain, we define a “radial” axis orthogonal to nearby surfaces, a “sulcal” axis along the sulcal depth gradient that preferentially points from deep white matter to the gyral crown, and a “gyral” axis aligned with the long axis of the gyrus.\ud \ud When compared with high-resolution, in-vivo diffusion MRI data from the Human Connectome Project, we find that in superficial white matter the apparent diffusion coefficient (at b = 1000) along the sulcal axis is on average 16% larger than along the gyral axis and twice as large as along the radial axis. This is reflected in the vast majority of observed fibre orientations lying close to the tangential plane (median angular offset

The FMR1 premutation is an expansion of the CGG repeat island in the FMR1 gene to between 55 and 200 repeats. Evidence suggests that as well as conferring risk for neurodegeneration, the premutation is also associated with increased risk for autistic traits and psychiatric symptoms. An emotional processing fMRI task was used to examine the response to a change in emotional arousal in 17 male carriers and 17 matched controls. A psychiatric symptom checklist (SCL-90-R), autism spectrum and empathy quotients (AQ and EQ), and the Ekman Faces Test were used to investigate clinical symptoms and emotional processing. Carriers exhibited significantly lower activation compared to controls at the bilateral superior parietal lobe, bilateral Brodmann Area (BA) 17 (V1), right intraparietal area and right BA18 (V2) when comparing high and low arousal conditions. Group by age analyses were not significant. Assessments revealed that carriers displayed significantly worse symptoms of psychiatric symptoms and higher levels of autistic traits, as well as impaired facial emotion recognition. No measurements revealed an association with age. Here, we show significantly altered emotional processing in carriers which display stability over age, suggesting that, unlike degenerative aspects, emotional symptoms may be consistent over the lifespan in carriers.

The basic steps in building up language involve binding words of different categories into a hierarchical structure. To what extent these steps are universal or differ across languages is an open issue. Here we examine the neural dynamics of phrase structure building in Chinese—a language that in contrast to other languages heavily depends on contextual semantic information. We used functional magnetic resonance imaging and dynamic causal modeling to identify the relevant brain regions and their dynamic relations. Language stimuli consisted of syntax‐driving determiners, semantics‐embedded classifiers, and nonverbal symbols making up for two‐component sequences manipulated by the factors structure (phrase/list) and number of words (2‐word/1‐word). Processing phrases compared with word lists elicited greater activation in the anterior part of Broca's area, Brodmann area (BA) 45, and the left posterior superior/middle temporal gyri (pSTG/pMTG), while processing two words against one word led to stronger involvement of the left BA 45, BA 44, and insula. Differential network modulations emerging from subparts of Broca's area revealed that phrasal construction in particular highly modulated the direct connection from BA 44 to left pMTG, suggesting BA 44’s primary role in phrase structure building. Conversely, the involvement of BA 45 rather appears sensitive to the reliance on lexico‐semantic information in Chinese. Against the background of previous findings from other languages, the present results indicate that phrase structure building has a universal neural basis within the left fronto‐temporal network. Most importantly, they provide the first evidence demonstrating that the structure‐building network may be modulated by language‐specific characteristics.

Purpose To investigate if abnormal interhemispheric homotopic functional connectivity were accompanied by corresponding anatomic connectivity changes in primary open-angle glaucoma (POAG) patients, and to relate connectivity changes with retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were performed in 16 POAG patients and 19 healthy controls. Indices of interhemispheric homotopic functional connectivity and the underlying anatomic connectivity changes were derived with voxel-base whole-brain voxel-mirrored homotopic connectivity (VMHC) analyses and VMHC-guided probabilistic tractography. Pearson correlation analyses were used to explore the correlations between interhemispheric homotopic functional connectivity changes and anatomic connectivity alterations, and RNFL and GCC thickness. Results Reduced VMHC values between bilateral homotopic cortical areas located in Brodmann area (BA)17, BA18, and BA19. Decreased anatomic connectivity connecting bilateral visual cortical areas inside BA17 and BA18 were observed in POAG patients. Furthermore, positive correlations between average RNFL thickness and reduced VMHC values of BA17 (r = 0.572, P = 0.021)/BA18 (r = 0.600, P = 0.014)/BA19 (r = 0.550, P = 0.027) are found using Pearson correlation analyses. Conclusions Combinations of interhemispheric homotopic functional connectivity and anatomic connectivity changes may help to elucidate the mechanism of interhemispheric synchronization injury in POAG patients. Reduced VMHC values positively correlate with glaucomatous changes of RNFL thickness, which strengthens the hypothesis that POAG affects the visual cortex using a novel functional MRI characteristic.

For human olfactory functional MRI studies, the primary olfactory cortex (POC) suffers severe magnetic susceptibility artifacts, which adversely influences the detectability and reproducibility of the olfactory fMRI data and its clinical applications. The goal of this work is to assess the impacts of the image artifacts on the detectability and reproducibility of the olfactory activation in the POC. The severity of artifacts in the POC were classified into three levels using a Subjective Artifact score (SA_score). The mean temporal signal-to-noise ratio (tSNR) of the fMRI data acquired by a given MRI sequence and olfactory activation (β value) in POC were evaluated and compared to the concurrent activations in the primary visual cortex (Brodmann area 17, BA17) by an odor-visual association paradigm using ninety-nine normal human subjects. Our study revealed that the mean tSNR in POC was above the threshold for reliable detection of the functional activation signal, and, consequently, the mean olfactory activations in the POC were not significantly different from those in BA17. The reproducibility of the activation in the POC was assessed by a random half-split stimulation of a test-retest experiment. The overlap of the activation maps for all the trials (n = 1000) in the POC were not statistically different from that observed in BA17. These results show that the detectability and reproducibility of olfactory activation in the presence of susceptibility artifacts in the POC was at similar level of that in the visual cortex.

Background Hoarding disorder (HD) is a disease concept newly presented in DSM-5. As far as we know, no studies have examined the structural changes relevant to hoarding by applying the diagnostic criteria of HD in DSM-5. In the present study, we aimed to find abnormalities in gray matter (GM) structures of patients with HD. Methods Seventeen patients who met the DSM-5 criteria for HD, 17 obsessive-compulsive disorder (OCD) patients, and 17 healthy controls (HCs) participated in this study. All participants underwent MRI scanning of the brain by a 3.0-Tesla MRI scanner. In a voxel-based morphometric procedure, preprocessed GM structural images were used to compare the three groups. Thereafter we investigated the correlation between the clinical data (age of onset, symptomatic severity) and GM volume. Results The HD group showed a significantly increased GM volume compared to the OCD and healthy control groups (p

Self-disorder is a hallmark characteristic of schizophrenia. This deficit may stem from an inability to efficiently integrate multisensory bodily signals. Twenty-nine schizophrenia patients and thirty-one healthy controls underwent resting-state fMRI in this study. A data-driven method, functional connectivity density mapping (FCD), was used to investigate cortical functional connectivity changes in the patients. Areas with significantly different FCD were chosen to calculate functional connectivity maps. The schizophrenia patients exhibited increased local FCD in frontal areas while demonstrating decreased local FCD in the primary sensorimotor area and in the occipital lobe. The functional connectivity analysis illustrated decreased functional connectivity between visual areas and the primary sensorimotor area. These findings suggest disturbed integration in perception–motor processing, which may contribute to mapping the neural physiopathology associated with self-disorder in schizophrenia patients. Clinical Trial Registration Chinese Clinical Trial Registry. Registration number. ChiCTR-RCS-14004878.

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism.

Trichotillomania is characterized by repetitive pulling out of one's own hair. Impaired response inhibition has been identified in patients with trichotillomania, along with gray matter density changes in distributed neural regions including frontal cortex. The objective of this study was to evaluate impaired response inhibition and abnormal cortical morphology as candidate endophenotypes for the disorder. Subjects with trichotillomania (N = 12), unaffected first-degree relatives of these patients (N = 10), and healthy controls (N = 14), completed the Stop Signal Task (SST), a measure of response inhibition, and structural magnetic resonance imaging scans. Group differences in SST performance and cortical thickness were explored using permutation testing. Groups differed significantly in response inhibition, with patients demonstrating impaired performance versus controls, and relatives occupying an intermediate position. Permutation cluster analysis revealed significant excesses of cortical thickness in patients and their relatives compared to controls, in right inferior/middle frontal gyri (Brodmann Area, BA 47 & 11), right lingual gyrus (BA 18), left superior temporal cortex (BA 21), and left precuneus (BA 7). No significant differences emerged between groups for striatum or cerebellar volumes. Impaired response inhibition and an excess of cortical thickness in neural regions germane to inhibitory control, and action monitoring, represent vulnerability markers for trichotillomania. Future work should explore genetic and environmental associations with these biological markers.

Optical coherence tomography (OCT) is an optical technique that uses backscattered light to highlight intrinsic structure, and when applied to brain tissue, it can resolve cortical layers and fiber bundles. Optical coherence microscopy (OCM) is higher resolution (i.e., 1.25 μm) and is capable of detecting neurons. In a previous report, we compared the correspondence of OCM acquired imaging of neurons with traditional Nissl stained histology in entorhinal cortex layer II. In the current method-oriented study, we aimed to determine the colocalization success rate between OCM and Nissl in other brain cortical areas with different laminar arrangements and cell packing density. We focused on two additional cortical areas: medial prefrontal, pre-genual Brodmann area (BA) 32 and lateral temporal BA 21. We present the data as colocalization matrices and as quantitative percentages. The overall average colocalization in OCM compared to Nissl was 67% for BA 32 (47% for Nissl colocalization) and 60% for BA 21 (52% for Nissl colocalization), but with a large variability across cases and layers. One source of variability and confounds could be ascribed to an obscuring effect from large and dense intracortical fiber bundles. Other technical challenges, including obstacles inherent to human brain tissue, are discussed. Despite limitations, OCM is a promising semi-high throughput tool for demonstrating detail at the neuronal level, and, with further development, has distinct potential for the automatic acquisition of large databases as are required for the human brain.

Neuroimaging and post-mortem studies have implicated altered myelin integrity and oligodendrocyte abnormalities in the dysfunction of neuronal network in schizophrenia, including the prefrontal cortex, Brodmann area (BA) 10. Pyramidal neurons in layer 5 of BA10 are the important link of reciprocal frontal cortical-basal ganglia-thalamic circuits altered in schizophrenia. Previously, we found ultrastructural dystrophic and degenerative alterations of oligodendrocytes in layer 5 of BA10 in schizophrenia. The aim of the study was to estimate the numerical density (Nv) of oligodendrocytes in layer 5 of BA10 in schizophrenia as compared to normal controls. 17 chronic schizophrenia subjects and 22 healthy matched controls were studied in Nissl-stained sections using optical disector method. Group differences were analyzed using ANCOVA followed by post hoc Duncan's test. The Nv of oligodendrocytes was significantly lower (- 32%, p 0.001) in the schizophrenia group as compared to the control group. Young controls (age 50 years old) showed significantly higher Nv of oligodendrocytes as compared to elderly controls (age 50 years old). Young and elderly schizophrenia subgroups did not differ significantly. Both control subgroups have significantly higher Nv of oligodendrocytes as compared to the schizophrenia subgroups. Decreased Nv of oligodendrocytes found in layer 5 of BA10 may be the result of dystrophic and destructive alterations and/or disrupted development of oligodendrocytes in schizophrenia.

In this study, functional near-infrared spectroscopy (fNIRS) was used to examine the brain activation and connectivity in occipitotemporal cortex during Chinese character recognition (CCR). Eighteen healthy participants were recruited to perform a well-designed task with three categories of stimuli (real characters, pseudo characters, and checkerboards). By inspecting the brain activation difference and its relationship with behavioral data, the left laterality during CCR was clearly identified in the Brodmann area (BA) 18 and 19. In addition, our novel findings also demonstrated that the bilateral superior temporal gyrus (STG), bilateral BA 19, and left fusiform gyrus were also involved in high-level lexical information processing such as semantic and phonological ones. Meanwhile, by examining functional brain networks, we discovered that the right BA 19 exhibited enhanced brain connectivity. In particular, the connectivity in the right fusiform gyrus, right BA 19, and left STG showed significant correlation with the performance of CCR. Consequently, the combination of fNIRS technique with functional network analysis paves a new avenue for improved understanding of the cognitive mechanism underlying CCR.

Neurons in the somatosensory cortex are exquisitely sensitive to mechanical stimulation of the skin surface. The location, velocity, direction, and adaptation of tactile stimuli on the skin's surface are discriminable features of somatosensory processing, however the representation and processing of dynamic tactile arrays in the human somatosensory cortex are poorly understood. The principal aim of this study was to map the relation between dynamic saltatory pneumatic stimuli at discrete traverse velocities on the glabrous hand and the resultant pattern of evoked BOLD response in the human brain. Moreover, we hypothesized that the hand representation in contralateral Brodmann Area (BA) 3b would show a significant dependence on stimulus velocity. Saltatory pneumatic pulses (60 ms duration, 9.5 ms rise/fall) were repetitively sequenced through a 7-channel TAC-Cell array at traverse velocities of 5, 25, and 65 cm/s on the glabrous hand initiated at the tips of D2 (index finger) and D3 (middle finger) and sequenced towards the D1 (thumb). The resulting hemodynamic response was sampled during 3 functional MRI scans (BOLD) in 20 neurotypical right-handed adults at 3T. Results from each subject were inserted to the one-way ANOVA within-subjects and one sample t-test to evaluate the group main effect of all three velocities stimuli and each of three different velocities, respectively. The stimulus evoked BOLD response revealed a dynamic representation of saltatory pneumotactile stimulus velocity in a network consisting of the contralateral primary hand somatosensory cortex (BA3b), associated primary motor cortex (BA4), posterior insula, and ipsilateral deep cerebellum. The spatial extent of this network was greatest at the 5 and 25 cm/s pneumotactile stimulus velocities.

It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca's region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24% (n = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare (n = 2, 4%). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.

The aim of the present study was to explore the modifications of EEG power spectra and EEG connectivity of resting state (RS) condition in patients with post-traumatic stress disorder (PTSD). Seventeen patients and seventeen healthy subjects matched for age and gender were enrolled. EEG was recorded during 5 min of RS. EEG analysis was conducted by means of the standardized Low Resolution Electric Tomography software (sLORETA). In power spectra analysis PTSD patients showed a widespread increase of theta activity (4.5–7.5 Hz) in parietal lobes (Brodmann Area, BA 7, 4, 5, 40) and in frontal lobes (BA 6). In the connectivity analysis PTSD patients also showed increase of alpha connectivity (8–12.5 Hz) between the cortical areas explored by Pz-P4 electrode. Our results could reflect the alteration of memory systems and emotional processing consistently altered in PTSD patients.

The N2 subcomponents of event-related potentials are known to reflect early attentional processes. The anterior N2 may reflect conflict monitoring, whereas the posterior N2 may be involved in target detection. The aim of this study was to identify the brain areas involved in the generation of the N2 subcomponents, in order to define the spatiotemporal dynamics of these attentional processes. We recorded 128-channel electroencephalograms in 15 healthy controls performing a three-stimulus visual oddball task and identified standard-, distracter- and target-elicited N2 components. Individual N2 sources were localized using standardized-weighted-low-resolution-electromagnetic-tomography (swLORETA). Comparative analyses were performed with a non-parametric permutation technique. Common N2 generators were observed in the Brodmann area (BA) 24 of the anterior cingulate cortex (ACC). The posterior cingulate cortex and the central precuneus were more involved in distracter processing, whereas the anterior precuneus and BA 32 of the ACC were target-specific. In accordance with previous demonstration of the frontoparietal cortex's critical role in attentional processes, these new data shed light on the ACC's role in conflict monitoring and its interaction with other median and frontoparietal structures in early attentional processes.

Embodied cognition offers an approach to word meaning firmly grounded in action and perception. A strong prediction of embodied cognition is that sensorimotor simulation is a necessary component of lexical-semantic representation. One semantic distinction where motor imagery is likely to play a key role involves the representation of manufactured artefacts. Many questions remain with respect to the scope of embodied cognition. One dominant unresolved issue is the extent to which motor enactment is necessary for representing and generating words with high motor salience. We investigated lesion correlates of manipulable relative to nonmanipulable name generation (e.g., name a school supply; name a mountain range) in patients with nonfluent aphasia (N = 14). Lesion volumes within motor (BA4, where BA = Brodmann area) and premotor (BA6) cortices were not predictive of category discrepancies. Lesion symptom mapping linked impairment for manipulable objects to polymodal convergence zones and to projections of the left, primary visual cortex specialized for motion perception (MT/V5+). Lesions to motor and premotor cortex were not predictive of manipulability impairment. This lesion correlation is incompatible with an embodied perspective premised on necessity of motor cortex for the enactment and subsequent production of motor-related words. These findings instead support a graded or "soft" approach to embodied cognition premised on an ancillary role of modality-specific cortical regions in enriching modality-neutral representations. We discuss a dynamic, hybrid approach to the neurobiology of semantic memory integrating both embodied and disembodied components.

Despite the significance of human touch, brain responses to interpersonal manual touch have been rarely investigated. We used functional magnetic resonance imaging to study brain activity in eight healthy adults whose left hand was touched by two individuals, in separate runs and in 20-s blocks, either by holding, smoothing, or poking. Acceleration was measured from both the subject's and the touching person's hands for postimaging control of the stimuli. Independent component analysis of the functional magnetic resonance imaging data unraveled three functional networks involving the primary somatosensory cortex (SI). One network comprised the contralateral and another the ipsilateral Brodmann area 3. The third network included area 2 bilaterally, left-hemisphere middle temporal gyrus and dorsolateral prefrontal regions, ventral prefrontal cortices bilaterally, and middle cingulate cortex. The response shapes and polarities varied between the three networks. The contralateral area 3 differentiated the responses between the three types of touch stimuli, and the response magnitudes depended on the variability of the touch within each block. However, the responses of the other two networks were strikingly similar to all stimuli. The subjects' reports on the pleasantness of the touch did not correlate with the characteristics of the SI responses. These findings imply area-specific processing of the natural human touch in three networks including the SI cortex, with only area 2 connected to a functional network of brain areas that may support social interaction.

Introduction Inferring connectivity between brain regions has been raising a lot of attention in recent decades. Copula directional dependence (CDD) is a statistical measure of directed connectivity, which does not require strict assumptions on probability distributions and linearity. Methods In this work, CDDs between pairs of local brain areas were estimated based on the fMRI responses of human participants watching a Pixar animation movie. A directed connectivity map of fourteen predefined local areas was obtained for each participant, where the network structure was determined by the strengths of the CDDs. A resampling technique was further applied to determine the statistical significance of the connectivity directions in the networks. In order to demonstrate the effectiveness of the suggested method using CDDs, statistical group analysis was conducted based on graph theoretic measures of the inferred directed networks and CDD intensities. When the 129 fMRI participants were grouped by their age (3–5 year‐old, 7–12 year‐old, adult) and gender (F, M), nonparametric two‐way analysis of variance (ANOVA) results could identify which cortical regions and connectivity structures correlated with the two physiological factors. Results Especially, we could identify that (a) graph centrality measures of the frontal eye fields (FEF), the inferior temporal gyrus (ITG), and the temporopolar area (TP) were significantly affected by aging, (b) CDD intensities between FEF and the primary motor cortex (M1) and between ITG and TP were highly significantly affected by aging, and (c) CDDs between M1 and the anterior prefrontal cortex (aPFC) were highly significantly affected by gender. Software The R source code for fMRI data preprocessing, estimation of directional dependences, network visualization, and statistical analyses are available at https://github.com/namgillee/ CDDforFMRI.

BACKGROUND: : Multiple subpial transection (MST) is a potential surgical treatment for patients with epileptogenic foci located in cortical areas with higher functions. As neurosurgical teams have become more experienced with MST, the original technique has adapted. OBJECTIVE: : To report our 6-year experience with a modified MST technique. METHODS: : The population included 62 consecutive patients with medically refractory epilepsy treated by MST, with a follow-up period ranging from 2 to 9 years. MST was performed on gyri under neuronavigation and guided by intraoperative electrocorticography. We performed radiating MST from a single cortical entry point. The MST technique was described according to the number of transections performed and the Brodmann areas (BAs) involved. Any MST-related complications were registered and followed up. Clinical outcome was described in terms of seizure suppression or reduction according to the Engel modified classification. RESULTS: : Twelve patients underwent MST alone (MSTa), and 50 had MST with another procedure. The main MST sites were BA 4 (61%) and 3, 1, 2 (58%); in 22% of cases, MST was performed in BA 44, 22, 39, and 40. Permanent neurological deficits were observed in 4 (6.4%) patients; 2 minor deficits were MST related (3.2%). A reduction in the seizure rate of at least 50% was seen in 79% of patients (MSTa group, 75%), and 42% became seizure free (MSTa group, 33%). CONCLUSION: : This study demonstrates the efficacy and low morbidity of radiating MST performed under neuronavigation and intraoperative electrocorticography. ABBREVIATIONS: : BA, Brodmann areaEEG, electroencephalogramFDG, 18-fluorodeoxyglucoseioECoG, intraoperative electrocorticographyMRE, medically refractory epilepsyMST, multiple subpial transectionMSTa, multiple subpial transection aloneMST+, multiple subpial transection with other procedures.

It is well-known that physical exercise can affect cognition and the frontal lobe is an important structure involved in motor function and cognition. Furthermore, many functional neuroimaging studies have demonstrated that cortical activation patterns of hand and leg movements differ. However, no study has been undertaken to identify differences between the frontal activation patterns generated by hand and leg movements. In the present study, the frontal activation patterns associated with finger and toe movements, as visualized by functional MRI, were investigated and compared. Twelve healthy volunteers were recruited. Functional MRI was performed using a 1.5 T Philips Gyroscan Intera. Flexion-extension movements of fingers or toes were performed in one extremity. Regions of interest (ROIs) were set at the primary sensory-motor cortex (SM1: Brodmann area [BA] 1, 2, 3, 4), the premotor area (PMA: BA 6), and the prefrontal cortex (PFC: BA 8, 9, 10, 11, 46). In SM1, finger movements (10,809) induced more activation than toe movements (5349). On the other hand, in the PMA and PFC, toe movements (PMA: 4201, PFC: 921) induced more activation than finger movements (PMA: 2887, PFC: 912) respectively. In the analysis of relative voxel counts in the PMA and PFC versus the SM1, toe movements generated more activation in the PMA and PFC than finger movements. The PMA and PFC were more activated by toe than finger movements, although the SM1 was more activated by finger movements.

Despite a large body of research, extant findings on the functional role of left inferior frontal gyrus (LIFG) in phonological and semantic fluency are still controversial. Based on cross-study comparisons, a recent meta-analysis of neuroimaging results suggests that posterior-dorsal (Brodmann area, BA, 44) and anterior-ventral parts (BA 45) of LIFG contribute differentially to processes of phonologically and semantically cued word retrieval, respectively. In contrast, a subsequent functional magnetic resonance imaging experiment failed to validate the proposed dissociation using a within-subjects design. In particular, no evidence for a specific role of BA 45 in semantic fluency was found. Here, we resolve this apparent controversy by showing that the conflicting findings can be accounted for when considering the influence of task demands and individual ability on resulting functional magnetic resonance imaging activation patterns. By comparing phonological versus semantic fluency, higher activation was robustly observed in BA 44. For the opposite comparison, higher activation was found in dorsal BA 45; however, this was more pronounced in posterior-dorsal parts of BA 45 for low-performing subjects and was only apparent in anterior-dorsal parts of BA 45 under high demands on controlled semantic retrieval. Our results thus disclose important determinants for detecting a functional segregation of LIFG in verbal fluency that also have implications for the controversial findings in previous lesion studies. Moreover, the present parcellation of dorsal BA 45 corresponds well with anatomical evidence suggesting a subdivision into an anterior (45A) and posterior part (45B) and may therefore represent evidence for its functional significance in humans.

The organization of the language network undergoes continuous changes during development as children learn to understand sentences. In the present study, functional magnetic resonance imaging and behavioral measures were utilized to investigate functional activation and functional connectivity (FC) in three-year-old (3yo) and six-year-old (6yo) children during sentence comprehension. Transitive German sentences varying the word order (subject-initial and object-initial) with case marking were presented auditorily. We selected children who were capable of processing the subject-initial sentences above chance level accuracy from each age group to ensure that we were tapping real comprehension. Both age groups showed a main effect of word order in the left posterior superior temporal gyrus (pSTG), with greater activation for object-initial compared to subject-initial sentences. However, age differences were observed in the FC between left pSTG and the left inferior frontal gyrus (IFG). The 6yo group showed stronger FC between the left pSTG and Brodmann area (BA) 44 of the left IFG compared to the 3yo group. For the 3yo group, in turn, the FC between left pSTG and left BA 45 was stronger than with left BA 44. Our study demonstrates that while task-related activation was comparable, the small behavioral differences between age groups were reflected in the underlying functional organization revealing the ongoing development of the neural language network., Highlights • We examined functional connectivity of sentence processing in 3- and 6-year-olds. • Performance-matched age groups activated left pSTG for processing complex syntax. • 6-year-olds had stronger connectivity between left BA44 and pSTG than 3-year-olds. • 3-year-olds had greater connectivity between left BA45 and pSTG than BA44 and pSTG. • Functional connectivity results could be related to behavioral performance.

The somatotopic representation of the tactile stimulation on the finger in the brain is an essential part of understanding the human somatosensory system as well as rehabilitation and other clinical therapies. Many studies have used vibrotactile stimulations and reported finger somatotopic representations in the Brodmann area 3 (BA 3). On the contrary, few studies investigated finger somatotopic representation using pressure stimulations. Therefore, the present study aimed to find a comprehensive somatotopic representation (somatotopic map and inter- and intra-digit distance) within BA 2 of humans that could describe tactile stimulations on different joints across the fingers by applying pressure stimulation to three joints-the first (p1), second (p2), and third (p3) joints-of four fingers (index, middle, ring, and little finger). Significant differences were observed in the inter-digit distance between the first joints (p1) of the index and little fingers, and between the third joints (p3) of the index and little fingers. In addition, a significant difference was observed in the intra-digit distance between p1 and p3 of the little finger. This study suggests that a somatotopic map and inter- and intra-digit distance could be found in BA 2 in response to pressure stimulation on finger joints.