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Background It is difficult to distinguish bipolar disorder (BD) from major depressive disorder (MDD), especially with the initial depressive episode. In this study, we compared neural activities of BD and MDD patients during the first-episode (FE) to investigate common and distinct neural activities and further explore predictive indicators in the two diseases. Methods FE-MDD patients were performed resting state functional magnetic resonance imaging and followed up after scanning. After follow-up, FE-MDD patients were regrouped into FE-BD and FE-MDD patients. The study included 24 FE-BD patients, 28 FE-MDD patients, and 30 age- and sex-matched healthy controls (HC) to investigate neural activities with regional homogeneity (ReHo) analysis among the 3 groups. Results Compared to HC, FE-BD patients displayed significantly higher ReHo values in the superior frontal gyrus, the medial superior frontal gyrus within right-side cerebral hemisphere than FE-MDD patients and HC. Compared to HC, FE-BD and FE-MDD patients displayed significant decreased ReHo values in the paracentral lobule, the precuneus and the median cingulate and paracingulate gyrus within bilateral cerebral hemisphere, and the postcentral gyrus and the precentral gyrus within the right-side. FE-BD displayed significant lower ReHo values than FE-MDD patients in these regions. Limitations The potential effects of medicine, age, course of disease and handedness on results could not be ignored. Conclusions Abnormal neural activities of frontoparietal network may provide common and distinct markers to affective disorders and scientific basis for further prediction researches of affective disorders.

Background Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes. Methods We compared ALFF differences by MRI between cLBP subjects (90) and HCs (74), conducted a discriminative analysis to validate the results, and explored structural changes in key brain regions of cLBP. We also compared ALFF changes in cLBP patients after pain-exacerbating manoeuvres. Results ALFF was increased in the post-/precentral gyrus (PoG/PrG), paracentral lobule (PCL)/supplementary motor area (SMA), and anterior cingulate cortex (ACC), and grey matter volume was increased in the left ACC in cLBP patients. PCL/SMA ALFF reliably discriminated cLBP patients from HCs in an independent cohort. cLBP patients showed increased ALFF in the insula, amygdala, hippocampal/parahippocampal gyrus, and thalamus and decreased ALFF in the default mode network (DMN) when their spontaneous low back pain intensity increased after the pain-exacerbating manoeuvre. Conclusions Brain low-frequency oscillations in the PCL, SMA, PoG, PrG, and ACC may be associated with the neuropathology of cLBP. Low-frequency oscillations in the insula, amygdala, hippocampal/parahippocampal gyrus, thalamus, and DMN are sensitive to manoeuvre-induced spontaneous back pain intensity changes.

Background REM sleep behaviour disorder (RBD) occurs frequently in patients with synucleinopathies such as Parkinson's disease, dementia with Lewy body, or multiple system atrophy, but may also occur as a prodromal stage of those diseases; and is termed idiopathic RBD (iRBD) when not accompanied by other symptoms. Cholinergic degeneration of the mesopontine nuclei have been described in synucleinopathies with or without RBD, but this has not yet been explored in iRBD. We sought to assess cholinergic neuronal integrity in iRBD using PET neuroimaging with the 18F-fluoroethoxybenzovesamicol (FEOBV). Methods The sample included 10 participants evenly divided between healthy subjects and patients with iRBD. Polysomnography and PET imaging with FEOBV were performed in all participants. Standardized uptake value ratios (SUVRs) were compared between the two groups using voxel wise t-tests. Non-parametric correlations were also computed in patients with iRBD between FEOBV uptake and muscle tonic and phasic activity during REM sleep. Results Compared with healthy participants, significantly higher FEOBV uptakes were observed in patients with iRBD. The largest differences were observed in specific brainstem areas corresponding to the bulbar reticular formation, pontine coeruleus/subcoeruleus complex, tegmental periacqueductal grey, and mesopontine cholinergic nuclei. FEOBV uptake in iRBD was also higher than in controls in the ventromedial area of the thalamus, deep cerebellar nuclei, and some cortical territories (including the paracentral lobule, anterior cingulate, and orbitofrontal cortex). Significant correlation was found between muscle activity during REM sleep, and SUVR increases in both the mesopontine area and paracentral cortex. Conclusion We showed here for the first time the brain cholinergic alterations in patients with iRBD. As opposed to the cholinergic depletion described previously in RBD associated with clinical Parkinson's disease, increased cholinergic innervation was found in multiple areas in iRBD. The most significant changes were observed in brainstem areas containing structures involved in the promotion of REM sleep and muscle atonia. This suggests that iRBD might be a clinical condition in which compensatory cholinergic upregulation in those areas occurs in association with the initial phases of a neurodegenerative process leading to a clinically observable synucleinopathy.

International audience; The supplementary motor area (SMA) has been shown to be involved in interval timing but its precise role remains a matter of debate. The present study was aimed at examining, by means of intracerebral EEG recordings, the time course of the activity in this structure, as well as in other functionally connected cortical (frontal, cingulate, insular and temporal) areas, during a visual time reproduction task. Four patients undergoing stereo-electroencephalography (SEEG) for presurgical investigation of refractory focal epilepsy were enrolled. They were selected on the presence of depth electrodes implanted within the SMA. They were instructed to encode, keep in memory and then reproduce the duration (3, 5 and 7 s) of emotionally-neutral or negative pictures. Emotional stimuli were used with the aim of examining neural correlates of temporal distortions induced by emotion. Event-related potentials (ERPs) were analyzed during three periods: During and at the extinction of the target interval (TI) and at the beginning of the reproduction interval (RI). Electrophysiological data revealed an ERP time-locked to TI-offset whose amplitude varied monotonically with TI-duration. This effect was observed in three out of the four patients, especially within the SMA and the insula. It also involved the middle and anterior cingulate cortex, the superior, middle and inferior frontal gyri and the paracentral lobule. These effects were modulated by the prior TI-duration and predicted variations in temporal reproduction accuracy. In contrast, modulations of ERPs with TI-duration, emotion or temporal performance during the target or the reproduction interval were modest and less consistent across patients. These results demonstrate that, during reproduction of supra-second time intervals, the SMA, in concert with a fronto-insular network, is involved at the end of the target interval, and suggest a role in the duration categorization and decision making operations or alternatively in the preparedness of the timing of the future movement that will be executed during the reproduction phase.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with social communication deficits and restricted/repetitive behaviors and is characterized by large-scale atypical subcortical-cortical connectivity, including impaired resting-state functional connectivity between thalamic and sensory regions. Previous studies have typically focused on the abnormal static connectivity in ASD and overlooked potential valuable dynamic patterns in brain connectivity. However, resting-state brain connectivity is indeed highly dynamic, and abnormalities in dynamic brain connectivity have been widely identified in psychiatric disorders. In this study, we investigated the dynamic functional network connectivity (dFNC) between 51 intrinsic connectivity networks in 170 individuals with ASD and 195 age-matched typically developing (TD) controls using independent component analysis and a sliding window approach. A hard clustering state analysis and a fuzzy meta-state analysis were conducted respectively, for the exploration of local and global aberrant dynamic connectivity patterns in ASD. We examined the group difference in dFNC between thalamic and sensory networks in each functional state and group differences in four high-dimensional dynamic measures. The results showed that compared with TD controls, individuals with ASD show an increase in transient connectivity between hypothalamus/subthalamus and some sensory networks (right postcentral gyrus, bi paracentral lobule, and lingual gyrus) in certain functional states, and diminished global meta-state dynamics of the whole-brain functional network. In addition, these atypical dynamic patterns are significantly associated with autistic symptoms indexed by the Autism Diagnostic Observation Schedule. These converging results support and extend previous observations regarding hyperconnectivity between thalamic and sensory regions and stable whole-brain functional configuration in ASD. Dynamic brain connectivity may serve as a potential biomarker of ASD and further investigation of these dynamic patterns might help to advance our understanding of behavioral differences in this complex neurodevelopmental disorder.

There is growing interest in dynamic approaches to functional brain connectivity (FC), and their potential applications in understanding atypical brain function. In this study, we assess the relative sensitivity of cross recurrence quantification analysis CRQA) to identify aberrant FC in patients with neuropsychiatric systemic lupus erythematosus (NPSLE) in comparison with conventional static and dynamic bivariate FC measures, as well as univariate (nodal) RQA. This technique was applied to resting-state fMRI data obtained from 45 NPSLE patients and 35 healthy volunteers (HC). Cross recurrence plots were computed for all pairs of 16 frontoparietal brain regions known to be critically involved in visuomotor control and suspected to show hemodynamic disturbance in NPSLE. Multivariate group comparisons revealed that the combination of six CRQA measures differentiated the two groups with large effect sizes ( . 214 > η 2 > . 061 ) in 40 out of the 120 region pairs. The majority of brain regions forming these pairs also showed group differences on nodal RQA indices ( . 146 > η 2 > . 09 ) Overall, larger values were found in NPSLE patients vs. HC with the exception of FC formed by the paracentral lobule. Determinism within five pairs of right-hemisphere sensorimotor regions (paracentral lobule, primary somatosensory, primary motor, and supplementary motor areas), correlated positively with visuomotor performance among NPSLE patients ( p . 001 ). By comparison, group differences on static FC displayed large effect sizes in only 4 of the 120 region pairs ( . 126 > η 2 > . 061 ), none of which correlated significantly with visuomotor performance. Indices derived from dynamic, temporal-based FC analyses displayed large effect sizes in 11 / 120 region pairs ( . 11 > η 2 > . 063 ). These findings further support the importance of feature-based dFC in advancing current knowledge on correlates of cognitive dysfunction in a clinically challenging disorder, such as NPSLE.

Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners (N=22), we investigated the effect of levodopa (L-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in L-dopa-induced behavioral benefits. Relative to placebo, L-dopa increased BOLD signal variability in task-relevant temporal, inferior frontal, parietal and cingulate regions. On the connectome level, however, L-dopa diminished functional integration across temporal and cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity in more than two thirds of the participants and to different degrees. Hypo-integration co-occurred with relative hyper-connectivity in paracentral lobule and precuneus, as well as posterior putamen. Both, L-dopa-induced BOLD signal variability modulation and functional connectome modulations proved predictive of an individual’s L-dopa-induced gain in behavioral performance, namely response speed and perceptual sensitivity. Lastly, L-dopa-induced modulations of BOLD signal variability were correlated with L-dopa-induced modulation of nodal connectivity and network efficiency. Our findings underline the role of dopamine in maintaining the dynamic range of, and communication between, cortical systems, and their explanatory power for inter-individual differences in benefits from dopamine during cognitive performance.

The performance of the human brain depends on how effectively its distinct regions communicate, especially the regions which are more strongly connected to each other than to other regions, or so called “rich-clubs”. The aim of the current work is to find a connectivity pattern between the three brain rich-club regions without any a priori assumptions on the underlying network architecture. Rich-clubs for the analysis were previously identified with structural MRI. Functional magnetic resonance imaging (fMRI) data from 25 healthy subjects (1000 time points from each one) was acquired and Transfer Entropy (TE) between fMRI time-series from rich-clubs was calculated. The significant results at the group level were obtained by testing against the surrogate data generated on a novel approach. We found stable causal interactions between rostral Anterior Cingulate Cortex L and Dorsal Anterior Cingulate Cortex L, dorsal Anterior Cingulate Cortex L and Paracentral Lobule R but not vice versa. Our work provides an approach to causal analysis of experimental data and demonstrates the applicability to real fMRI study.

Functional neuroimaging studies have reported alterations in cortical activity indicating glaucoma as a progressive neurodegenerative disease. Hence the current study aimed to assess the cortical activity using high-density EEG in patients with mild glaucoma during resting state. Treatment-naive 37 patients with primary open angle glaucoma (POAG), 34 patients with primary angle closure glaucoma (PACG), and 32 healthy controls were included in the study. Resting state EEG i.e., eyes closed (EC) and eyes open conditions (EO) were acquired using 128-channel for 3 min. After preprocessing, the current density of 6239 voxels of the data was estimated using sLORETA. In comparison to healthy controls, PACG had higher activity at cingulate gyri, medial and superior frontal gyri during EO only. POAG had significantly higher activity at precentral gyrus and middle frontal gyrus during EC, whereas at cingulate gyri, frontal gyri, precentral gyri, paracentral lobule, sub-gyral region, postcentral gyrus, and precuneus during EO. POAG had significantly higher activity at precuneus and cuneus compared to PACG during EO. Intraocular pressure and mean-deviation of visual fields had a positive correlation with cortical activity. Results of the study indicate physiological alterations not only at the level of retina but also at brain even in the early stages of the disease. These alterations in the cortical activity were more in POAG than PACG. Controlling the IOP alone might be insufficient in glaucoma because of widespread alterations in cortical activity. These findings might enhance the current understanding of cortical involvement in glaucoma.

Previous studies using resting-state functional magnetic resonance imaging (fMRI) have found abnormal functional connectivity in patients with major depressive disorder (MDD). Yet, effect of distance thresholds on local functional connectivity changes in MDD is largely unknown. Here, we used resting-state fMRI data and functional connectivity strength (FCS) method to test local functional connectivity differences at different distance thresholds between 47 drug-naive patients with MDD and 47 healthy controls. For the distribution of functional brain hubs with high local FCS, the overall changing trend from distance thresholds of 10mm to 100mm was from lateral to medial. Compared to controls, MDD patients exhibited decreased local FCS independent of distance threshold in the sensorimotor system (postcentral gyrus, paracentral lobule, and supplementary motor area). MDD Patients exhibited increased local FCS in the inferior temporal gyrus at two lower distance thresholds (20mm and 30mm) and a higher distance threshold (100mm). In addition, MDD patients showed increased local FCS in the putamen at higher distance thresholds (80-100mm). These findings suggest that local functional connectivity abnormalities in MDD are dependent on distance thresholds and that future studies should take the distance thresholds into account when measuring local functional connectivity in MDD.

Theta burst stimulation (TBS) has emerged as a promising tool for the treatment of swallowing disorders; however, the short-term after-effects of brain activation induced by TBS remain unknown. Here, we measured the changes in spontaneous brain activation using the amplitude of low-frequency fluctuation (ALFF) approach in subjects who underwent different TBS protocols. Sixty right-handed healthy participants (male, n=30; female, n=30; mean age=23.5y) were recruited in this study and randomly assigned to three groups that underwent three different TBS protocols. In group 1, continuous TBS (cTBS) was positioned on the left hemisphere of the suprahyoid muscle cortex. For group 2, intermittent TBS (iTBS) was placed on the left hemisphere of the suprahyoid muscle cortex. Group 3 underwent combined cTBS/iTBS protocols in which iTBS on the right hemisphere was performed immediately after completing cTBS on the left suprahyoid muscle cortex. Compared to pre-TBS, post-cTBS showed decreased ALFF in the anterior cingulate gyrus (BA 32); post-iTBS induced an increase in ALFF in the bilateral precuneus (BA 7); and post-cTBS/iTBS induced a decrease in ALFF in the brainstem, and resulted in increased ALFF in the middle cingulate gyrus (BA 24) as well as the left precentral gyrus (BA 6). Compared the effect of post-TBS protocols, increased ALFF was found in left posterior cerebellum lobe and left inferior parietal lobule (BA 40) (post-cTBS vs post-iTBS), and decreased ALFF exhibited in paracentral lobule (BA 4) (post-iTBS vs post-cTBS/iTBS). These findings indicate that multiple brain areas involved in swallowing regulation after stimulation of TBS over the suprahyoid muscles. cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation. Moreover, iTBS can eliminate the after-effects of cTBS applied on the contralateral swallowing cortex and alter the activity of contralateral motor cortex and brainstem. Our findings provide a novel evidence for the short-term effect of TBS on spontaneous brain activation.

Individuals differ systematically in their vulnerability to injustice. Previous studies have developed the efficient measurement of justice sensitivity from four perspectives (victim, observer, beneficiary, and perpetrator), and examined its effect on interpersonal interactions, but little is known about the neural correlates of justice sensitivity. The present study used regional homogeneity (ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions correlated with individual differences in justice sensitivity. Results showed that victim sensitivity was positively associated with ReHo of the paracentral lobule; observer sensitivity was positively associated with the temporal pole; beneficiary sensitivity was positively associated with bilateral dorsolateral prefrontal cortex (DLPFC) and negatively correlated with the amygdala; and perpetrator sensitivity was negatively associated with bilateral orbital frontal cortex (OFC), and positively correlated with the dorsal striatum. Our results revealed the associations between individual differences in justice sensitivity and intrinsic brain activity, and implicated the underlying differences among the four perspectives.

Objective Here we investigate the process of neurodegeneration in amyotrophic lateral sclerosis (ALS). The relationship between the cortical field spreading of glucose metabolic decreases in the primary motor cortex (PMC) and the progression of corresponding extremity dysfunction was evaluated using [ 18 F] fluoro-deoxyglucose (FDG)-positron emission tomography (PET). Methods Patients with ALS underwent [ 18 F] FDG-PET and the resulting datasets were individually contrasted against healthy controls using the NEUROSTAT software. The extent ratio was defined as the proportion of pixels with a significant Z-score decrease within regions of the primary motor cortex (precentral gyrus or paracentral lobule) opposite to the impaired upper extremities (UEs) or lower extremities (LEs), respectively. Clinical symptoms in all extremities were assessed using an upper motor neuron (UMN) score and the MRC (Medical Research Council) sum score upon physical examination. Cross-sectional correlations were analysed between clinical symptoms, the duration of these symptoms, and the extent ratio. Results Nineteen regions of the primary motor cortex corresponding to symptomatic limb in 10 participants were evaluated. In the corresponding region of the primary motor cortex, the extent ratio increased (same meaning as hypometabolic area spread) in association with symptom duration (r s =0.5, p =0.03). Neither UMN nor lower motor neuron (LMN) scores were correlated with symptom duration. Three out of 19 impaired regions did not show upper motor neuron (UMN) signs upon physical examination. The extent ratio and UMN score-controlled symptom duration were partially correlated (r s =0.5, p =0.05). Conclusions In patients with ALS, glucose metabolism decreased in the impaired side of the primary motor cortex depending on the clinical symptom progression in the corresponding extremities, regardless of the presence of clinical UMN signs. A decrement in glucose metabolism on FDG-PET corresponding to symptoms in the primary motor cortex might be an indicator of the time-dependent course of ALS neurodegeneration.

Objectives In brain 18 F-FDG PET data intensity normalization is usually applied to control for unwanted factors confounding brain metabolism. However, it can be difficult to determine a proper intensity normalization region as a reference for the identification of abnormal metabolism in diseased brains. In neurodegenerative disorders, differentiating disease-related changes in brain metabolism from age-associated natural changes remains challenging. This study proposes a new data-driven method to identify proper intensity normalization regions in order to improve separation of age-associated natural changes from disease related changes in brain metabolism. Methods 127 female and 128 male healthy subjects (age: 20 to 79) with brain 18 F-FDG PET/CT in the course of a whole body cancer screening were included. Brain PET images were processed using SPM8 and were parcellated into 116 anatomical regions according to the AAL template. It is assumed that normal brain 18 F-FDG metabolism has longitudinal coherency and this coherency leads to better model fitting. The coefficient of determination R 2 was proposed as the coherence coefficient, and the total coherence coefficient (overall fitting quality) was employed as an index to assess proper intensity normalization strategies on single subjects and age-cohort averaged data. Age-associated longitudinal changes of normal subjects were derived using the identified intensity normalization method correspondingly. In addition, 15 subjects with clinically diagnosed Parkinson's disease were assessed to evaluate the clinical potential of the proposed new method. Results Intensity normalizations by paracentral lobule and cerebellar tonsil, both regions derived from the new data-driven coherency method, showed significantly better coherence coefficients than other intensity normalization regions, and especially better than the most widely used global mean normalization. Intensity normalization by paracentral lobule was the most consistent method within both analysis strategies (subject-based and age-cohort averaging). In addition, the proposed new intensity normalization method using the paracentral lobule generates significantly higher differentiation from the age-associated changes than other intensity normalization methods. Conclusion Proper intensity normalization can enhance the longitudinal coherency of normal brain glucose metabolism. The paracentral lobule followed by the cerebellar tonsil are shown to be the two most stable intensity normalization regions concerning age-dependent brain metabolism. This may provide the potential to better differentiate disease-related changes from age-related changes in brain metabolism, which is of relevance in the diagnosis of neurodegenerative disorders.

The overestimation of the relationship between fear-relevant stimuli and aversive consequences, a so called covariation bias, might contribute to the maintenance of anxiety disorders. In a recent fMRI study, we confronted spider phobia and healthy participants with pictures of spiders, mushrooms and puppies, randomly followed by painful electric stimuli (US). Spider phobics overestimated the spider-US association and displayed enhanced activity in US-related sensorimotor cortex (paracentral lobule, PCL). Here, we report results from an additional functional connectivity analysis. Within spider phobics but not in healthy controls, USs after spiders led to enhanced connectivity between PCL and left prefrontal cortex (PFC). Most importantly, covariation bias in spider phobia was predicted by connectivity between PCL and visual cortex, insula, primary sensorimotor cortex and secondary somatosensory cortex. Reduced covariation bias was predicted by connectivity between PCL and PFC. In response to spider pictures, the amygdala was functionally connected to somatosensory and visual areas. These results suggest that synchronous activity of sensory cortices may promote fear-sustaining associative memory bias, while right PFC might help to reduce bias.

Objective The relationship between preoperative functional findings, derived from functional magnetic resonance imaging and diffusion tensor imaging, and surgical outcomes in patients with motor cortical arteriovenous malformations (AVMs) has not been determined. The aim of this study was to determine the relationship between preoperative functional findings and surgical outcomes in patients with motor cortical AVM. Methods Fifteen patients with AVM involving the precentral knob and/or paracentral lobule were reviewed. Each motor function involved was examined as an independent object. Preoperative functional findings included cortical reorganization, activation around the nidus, corticospinal tract (CST) reorganization, nidus involving the CST, and the level of the CST involved. The relationship between preoperative functional findings and surgical outcomes was analyzed statistically. A muscle strength of grade 3 or less was defined as a poor outcome after surgery, and a muscle strength of grade 4 or greater was defined as a good outcome. Results Eighteen objects were created and analyzed. Cortical reorganization ( P = 1.000) was not correlated with surgical outcomes. However, nidus involving the CST was significantly associated with poor short-term outcomes (1 week after surgery) ( P = 0.028) and permanent deficit in muscle strength ( P = 0.042). Most of the objects had good outcomes (16/18, 88.9%) at 6 months after surgery (long-term outcomes). Only 1 patient with CST ruptured at the corona radiata level and 1 patient who had postoperative hemorrhage obtained poor long-term outcomes. Conclusions Nidus involving the CST and the level of the CST involved, rather than cortical reorganization, may be associated with surgical outcomes in patients with motor cortical AVM.

A study on ASD detection in females using MRI is presented using the ABIDE dataset.VBM is used to study differences in gray matter composition.Different regions within the motor cortex area are affected for female ASD patients.Age-specific approach improves accuracy (by 2.5% for adolescents, 15% for adults).Proposed EMcRBFN classifier achieves higher accuracy than SVM and PBL-McRBFN. In this paper, we present an accurate detection of Autism Spectrum Disorder (ASD) from structural MRI using an Extended Metacognitive Radial Basis Function Neural Classifier (EMcRBFN). An automatic whole brain Voxel Based Morphometry (VBM) approach is used to identify gray matter composition in the brain from structural Magnetic Resonance Imaging (MRI) and an improved q-Gaussian classifier and its metacognitive learning algorithm has been proposed to approximate the functional relationship between the high dimensional VBM features and the true class labels. Recent genetic studies indicate that ASD manifests in different ways between males and females and also between adolescents and adults. Accordingly, the proposed EMcRBFN classifier has been evaluated using the publicly available Autism Brain Imaging Data Exchange dataset with a comprehensive study on both males and females and also between adolescents and adults in both categories. EMcRBFN classifier performance is compared with currently existing results for ASD classification in the literature and also with well known standard classifiers. The results clearly indicate that the performance of the EMcRBFN classifier is better than that of the other classifiers considered in this study. Further, the comprehensive study also indicates that the following subregions in the brain viz., premotor cortex and supplementary motor cortex are affected for adult-females while the somatosensory cortex subregion is affected for adolescent-females with ASD. Similar results indicate that the precentral gyrus, motor cortex, medial frontal gyrus and the paracentral lobule areas are affected for adolescent males while the superior frontal gyrus and the frontal eye fields areas are affected for adult males with ASD.

Background: Tract-tracing studies in cats and rats demonstrated that the auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus solitarii (NTS); it has remained unclear as to whether or not the ABVN projects to the NTS in humans. Objective: To ascertain whether non-invasive electrical stimulation of the cymba conchae, a region of the external ear exclusively innervated by the ABVN, activates the NTS and the “classical” central vagal projections in humans. Methods: Twelve healthy adults underwent two fMRI scans in the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was applied to the earlobe (control, scan #1) and left cymba conchae (scan #2). Statistical analyses were performed with FSL. Two region-of-interest analyses were performed to test the effects of cymba conchae stimulation (compared to baseline and control, earlobe, stimulation) on the central vagal projections (corrected; brainstem P

Model-oriented therapies of aphasic word production have been shown to be effective, with item-specific therapy effects being larger than generalisation effects for untrained items. However, it remains unclear whether semantic versus phonological therapy lead to differential effects, depending on type of lexical impairment. Functional imaging studies revealed that mainly left-hemisphere, perisylvian brain areas were involved in successful therapy-induced recovery of aphasic word production. However, the neural underpinnings for model-oriented therapy effects have not received much attention yet.We aimed at identifying brain areas indicating (1) general therapy effects using a naming task measured by functional magnetic resonance imaging (fMRI) in 14 patients before and after a 4-week naming therapy, which comprised increasing semantic and phonological cueing-hierarchies. We also intended to reveal differential effects (2) of training versus generalisation, (3) of therapy methods, and (4) of type of impairment as assessed by the connectionist Dell model.Training effects were stronger than generalisation effects, even though both were significant. Furthermore, significant impairment-specific therapy effects were observed for patients with phonological disorders (P-patients). (1) Left inferior frontal gyrus, pars opercularis (IFGoper), was a positive predictor of therapy gains while the right caudate was a negative predictor. Moreover, less activation decrease due to therapy in left-hemisphere temporo-parietal language areas was positively correlated with therapy gains. (2) Naming of trained compared to untrained words yielded less activation decrease in left superior temporal gyrus (STG) and precuneus, bilateral thalamus, and right caudate due to therapy. (3) Differential therapy effects could be detected in the right superior parietal lobule for the semantic method, and in regions involving bilateral anterior and mid cingulate, right precuneus, and left middle/superior frontal gyrus for the phonological method. (4) Impairment-specific changes of activation were found for P-patients in left IFGoper. Patients with semantic disorders (S-patients) relied on right frontal areas involving IFG, pars triangularis. After therapy, they revealed less activation decrease in areas involving left STG, caudate, paracentral lobule, and right rolandic operculum.Regarding naming performance, the present study corroborates previous findings on training and generalisation effects and reveals differential therapy effects for P-patients. Moreover, brain imaging results confirm a predominance of (1) general effects in the left brain hemisphere. (2) Brain regions related to visual strategy, monitoring/feedback, and articulatory patterns were characteristic for the familiar trained items. (3) Distinct regions associated with strategies, monitoring capacities, and linguistic information indicate the specific therapeutic influence on word retrieval. (4) While P-patients relied more on preserved phonological functions in the left hemisphere, S-patients revealed right-sided compensation of semantic processing as well as increased strategic efforts in both hemispheres.

Purpose The regional quantification of amyloid burden is crucial for the clinical diagnosis of Alzheimer’s disease [1]. The best method to evaluate regional amyloid deposition in PET is through the use MR imaging for brain space normalization. However, since MR imaging is not always available in the clinical practice, a MR-less methodology is needed in order to compute semi-quantitative and analyze regional amyloid burden. Methods Forty-four patients with clinical evidence of dementia, underwent 18F-Florbetaben PET (FBB-PET), FDG-PET, neuropsychological assessment and cerebrospinal fluid analysis. We implemented a methodology that uses SPM12 to import and normalize the FBB-PET images in Montreal Neurological Institute (MNI) space without MRI, and the Automated Anatomical Labeling (AAL) atlas [2] in order to extract regional uptake from normalized FBB-PET. SUVR has been computed by using cerebellum as control region (‘ Cerebelum _ 4 _ 5 ’ of AAL atlas). We then computed Receiver Operating Characteristic (ROC) curve in order to find best thresholds for identifying clinical subgroups in our patients. Results Semi-quantitative evaluation of FBB-PET images and ROC analysis stated that SUVR value of 1,006 in the bilateral inferior frontal cortex and a SUVR of 1.03 in the precuneus region were the best cutoff (AUC 0.883 and 0.826, respectively). Box-Plot analysis showed a trend distribution of elevated SUVR levels in bilateral frontal cortex, angular girus, occipital, parietal, precuneus and paracentral lobule, among AD patients. Conclusion MR-less methodology based on Tissue Probability Map and AAL atlas provide regional quantification of amyloid burden. The ROC analysis is able to retrieve useful thresholds for the classification of AD versus non-AD thus providing a tool in clinical practice. We will perform the study on a larger sample in order to confirm the results.

Background: White matter hyperintensities (WMH) represent ischemic white matter damage in late-life depression (LLD) and are associated with cognitive control dysfunction. Understanding the impact of WMH on the structural connectivity of gray matter and the cognitive control correlates of WMH-related structural dysconnectivity can provide insight into the pathophysiology of LLD. Methods: We compared WMH burden and performance on clinical measures of cognitive control in patients with LLD (N = 44) and a control group of non-depressed older adults (N = 59). We used the Network Modification (NeMo) Tool to investigate the impact of WMH on structural dysconnectivity in specific gray matter regions, and how such connectivity was related to cognitive control functions. Results: Compared to the control group, LLD participants had greater WMH burden, poorer performance on Trail Making Test (TMT) A & B, and greater self-reported dysexecutive behavior on the Frosntal Systems Behavior Scale-Executive Function subscale (FrSBe-EF). Within the LLD group, disrupted connectivity in the left supramarginal gyrus, paracentral lobule, thalamus, and pallidum was associated with psychomotor slowing (TMT-A). Altered connectivity in the left supramarginal gyrus, paracentral lobule, precentral gyrus, postcentral gyrus, thalamus, and pallidum was associated with poor attentional set-shifting (TMT-B). A follow-up analysis that isolated set-shifting ability (TMT-B/A ratio) confirmed the association with dysconnectivity in the bilateral paracentral lobule, right thalamus, left precentral gyrus, postcentral gyrus, and pallidum; additionally, it revealed associations with dysconnectivity in the right posterior cingulate, and left anterior cingulate, middle frontal cortex, and putamen. Conclusions: In LLD, WMH are associated with region-specific disruptions in cortical and subcortical gray matter areas involved in attentional aspects of cognitive control systems and sensorimotor processing, which in turn are associated with slower processing speed, and reduced attentional set-shifting. Clinical trials registration: https://clinicaltrials.gov/ct2/show/NCT01728194 Keywords: Late life depression, cognitive control, executive functions, White matter hyperintensities, Structural connectivity, MRI

Objective An epileptic seizure is the most common clinical manifestation of a primary brain tumor. Due to modern neuroimaging, detailed anatomical information on a brain tumor is available early in the diagnostic process and therefore carries considerable potential in clinical decision making. The goal of this study was to gain a better understanding of the relevance of anatomical tumor characteristics on seizure prevalence and semiology. Methods We reviewed prospectively collected clinical and imaging data of all patients operated on a supratentorial intraparenchymal primary brain tumor at our department between January 2009 and December 2016. The effect of tumor histology, anatomical location and white matter infiltration on seizure prevalence and semiology were assessed using uni- and multivariate analyses. Results Of 678 included patients, 311 (45.9%) presented with epileptic seizures. Tumor location within the central lobe was associated with higher seizure prevalence (OR 4.67, 95% CI: 1.90–13.3, p = .002), especially within the precentral gyrus or paracentral lobule (100%). Bilateral extension, location within subcortical structures and invasion of deeper white matter sectors were associated with a lower risk (OR 0.45, 95% CI: 0.25–0.78; OR 0.10, 95% CI: 0.04–0.21 and OR 0.39, 95% CI: 0.14–0.96, respectively). Multivariate analysis revealed the impact of a location within the central lobe on seizure risk to be highly significant and more relevant than histopathology (OR: 4.79, 95% CI: 1.82–14.52, p = .003). Seizures due to tumors within the central lobe differed from those of other locations by lower risk of secondary generalization (p, Graphical abstract Unlabelled Image, Highlights • Brain tumor location affects seizure prevalence and semiology. • Central lobe location is the strongest independent pro-epileptogenic factor. • The precentral gyrus and paracentral lobule are most epileptogenic. • Central lobe tumors rarely cause bilateral tonic-clonic seizures. • Tumor location and white matter infiltration may guide antiepileptic therapy.

Hoarding Disorder (HD) is a common and chronic condition that is associated with distinct abnormalities in neural function. The impact of treatment on these abnormalities is not known. Six patients with HD and 6 healthy control (HC) participants underwent a functional magnetic resonance imaging (fMRI) task in which they made simulated decisions about whether to acquire or discard a variety of objects. The HD patients then received 16 sessions of manualized group cognitive behavioral therapy (CBT) for HD. After treatment, the HD patients completed the same fMRI decision-making tasks to identify changes in brain function elicited by decision-making. During acquiring decisions, reductions in HD patients' hemodynamic activity were observed in medial frontal gyrus, anterior and posterior cingulate, left insular cortex/postcentral gyrus, right caudate and putamen, paracentral lobule, bilateral posterior parietal lobe regions, right superior temporal gyrus, left hippocampus/parahippocampus, occipital cortex, and anterior cerebellum. During discarding decisions, reduced activity was observed in right superior/medial frontal gyri, left insula/putamen, posterior cingulate, precuneus, right posterior hippocampus, lingual/cuneus and right putamen. Prior to treatment, activity in these regions differed significantly between HD patients and HC participants. However, after CBT, most of these differences were no longer significant, suggesting normalization of neural function.

Objective: To investigate whether there are differences in brain connectivity in late-life depression (LLD) and nondepressed subjects using the left and right heads of caudate nuclei (hCN) as the seed regions. Design: Resting-state functional magnetic resonance imaging (fMRI) data were collected using a 3-Tesla MRI System. Setting: Subjects were recruited from primary or secondary care services in the Newcastle area. Participants: Thirty-three subjects aged 65 years and older; 16 who had a recent episode of LLD and 17 nondepressed subjects. Measurements: Functional connectivity was analyzed by extracting the temporal signal variation from the left and right hCN and cross correlating with the rest of the brain. Results: Significant connectivity between the hCN and frontal areas was observed in the nondepressed group, whereas in LLD, connectivity was seen over a much wider area. Regions showing significantly greater connectivity (p ≤0.05) in LLD compared with the nondepressed group were frontal (precentral, subgyral, middle frontal, and paracentral lobule), sublobar (thalamus and insula), limbic (cingulate), parietal (postcentral gyrus, precuneus, inferior parietal lobule, and supramarginal gyrus), and temporal (superior temporal gyrus). Conversely, no brain regions showed greater connectivity in the nondepressed group than LLD. In both groups, the right hCN showed significantly greater connectivity than the left in numerous brain regions, but connectivity for the left hCN did not exceed the right in any brain regions. Conclusions: This resting-state study showed increased connectivity in specific brain regions in LLD compared with the nondepressed group, which supports the view that functional connectivity is altered in depression.

Introduction To describe the feasibility, safety and seizure outcome of patients with medically intractable rolandic epilepsy(RE) who underwent staged resections guided by multimodal extra and intraoperative SEEG recordings. Methods We retrospectively studied and analyzed patients, who underwent extra and intraoperative intracranial invasive stereoEEG monitoring, data related to semiology, non-invasive electrophysiology, imaging, type of resection, complications, surgical pathology results and seizure outcome from January 2015 through September 2017, under Cleveland Clinic IRB. Results Five patients were identified as having intractable RE based on analysis of pre-surgical evaluation using 3T magnetic resonance imaging (MRI), magnetoencephalography(MEG) and positron emission tomography (PET). Preoperative magnetic resonance imaging were considered nonlesional in all five patients but after the pre-surgical evaluation, there were abnormal sulcation pattern or increased signal in white matter were noticed which are of unknown significance. All five patients were underwent sEEG implantation with hypothesis of peri-rolandic or paracentral lobule regions being epileptogenic. Extra-operative sEEG data in all patients showed ictal onset zone involving rolandic cortex (hand knob and paracentral lobule), premotor and/or supplementary motor area (SMA). In two patients, hand knob rolandic cortex was the region of interest The other three being paracentral lobule (leg motor). Given all the data (semiology, sEEG data and pre-sugical evaluation), the conclusion of epileptogenic zone (EZ) being close proximity to eloquent cortex. Given the semiology, staged resection approach with continuous sEEG recording was performed in the operating room. Resection of interictally active non-eloquent cortex electrodes was performed first guided by real-time intraoperative sEEG (electrophysiology) data. The resection was also guided by the sEEG electrode in three dimensions. Resolution of rolandic hand motor spike activities was documented after resection of SMA in three patients, cingulate and pre-motor areas in one patient. In the last patient, hand sensory area was resected sparing motor cortex. Three out of five patients did not have any deficit but two had mild foot drop. Pathology showed focal cortical dysplasia type (IB, IIA, and IIB) and a possible vascular malformation in another. All patients were reported to be seizure free at follow up period of 6–28 months. Conclusion Taken into account of hyper-synchronous connectivity in frontal and parietal rolandic regions, we present a case series of patients who underwent staged resections guided by a novel multimodal method of invasive monitoring. The results of this highly selected group of patients testify for the feasibility and safety of a novel multimodal method of invasive monitoring, combining the benefits of both intra and extra-operative SEEG recording, especially operating around the central lobule near hand knob regions.

Loss of bladder control (urge incontinence) is common in elderly; the cause is usually unknown. Functional imaging has revealed the brain network controlling responses to bladder filling. Age-related changes in this network might predispose to urge incontinence. We sought such changes in 10 continent, healthy women aged 30-79 years who underwent fMRI while fluid (approximately 20 ml) was repeatedly infused into and withdrawn from the bladder. Data were collected in 4 measurement blocks with progressively increasing bladder volumes and were analyzed by SPM2, using the contrast infuse-withdraw to quantify response to bladder infusion. Effective connectivity was examined by physiophysiological interaction (PhPI; see interpretation in Supplementary Material), with right insula (RI) and dorsal anterior cingulate cortex (dACC) as seed regions. Dependence on age and bladder volume (= block number) was assessed. Bladder infusion evoked expected activations. Activation decreased with age in bilateral insula and dACC. PhPI revealed connectivity with RI and dACC in regions that included bilateral putamen and R pontine micturition center. Interaction (connectivity) tended to increase with age in regions including L insula, L paracentral lobule and PAG. Consistent with a special role in maintaining continence, medial prefrontal cortex (mPFC) showed a trend to deactivation on bladder infusion that became more prominent in old age, and a trend to negative interaction (connectivity) that weakened significantly with age. Thus, with increasing age, weaker signals in the bladder control network as a whole and/or changes in mPFC function or connecting pathways may be responsible for the development of urge incontinence.

This study describes the use of a novel magnetic resonance imaging (MRI) compatible system capable of measuring isometric ankle, knee and hip joint torques in real-time during functional MRI (fMRI) testing in healthy volunteers. The motor representations of three isometric torques – ankle dorsiflexion, ankle plantarflexion and knee extension – were studied at two time points. The reliability of motor performance and fMRI-derived measures of brain activity across sessions was examined. Reproducible motor performance was observed for each of the tasks; torques of the requested amplitude, assisted by visual feedback, were generated at the relevant joint with good accuracy, both within and across the two sessions. Significant blood oxygen level dependent (BOLD) signal increases were observed in the left primary sensorimotor cortex (SM1) in the paracentral lobule and in secondary motor areas for all tasks. Within these areas there was substantial overlap of the motor representations though differential activation was observed in SM1, with greater activation of inferior paracentral lobule during knee extension than for either ankle task. Also, BOLD signal decreases were observed bilaterally within SM1 in the hand knob region for all tasks. No major session-related effects were identified at the group level. High intraclass correlation coefficients were observed for t-values of voxels in cortical motor areas for each contraction type for individuals, suggesting that fMRI-derived activity across time points was reliable. These findings support the use of this apparatus in serial studies of lower limb function.

Neither GM (ASD: 0.66±0.0 liters; Control 0.65±0.06 liters; Z=-0.18, P=0.78) nor WM (ASD: 0.41±0.04 liters; Control 0.43±0.04 liters; Z =-0.18, P =1.62) volume showed global differences between groups. The total intracranial volume of the ASD subjects (1.07±0.07 liters) was similar to that of the controls (1.08±0.09 liters) (Z =-0.67, P = 0.65). The gray-white absolute volume ratio was 1.60 for ASD and 1.53 for controls respectively. Regional Gray Matter Volume Difference Between Two Groups The exploratory analysis revealed individuals with ASD exhibited smaller GM volume in the right inferior frontal gyrus, precentral gyrus, postcentral gyrus, cuneus, right superior temporal gyrus and lingual gyrus. The regions that exhibited larger volumes in ASD were the cerebellum, paracentral lobule, superior parietal lobule, medial prefrontal gyrus, fusiform gyrus, middle frontal gyrus and subcallosal gyrus. Interaction of Age by Groups The right inferior parietal lobule and posterior cingulate of the adolescents with ASD showed a negative correlation with age whereas the controls displayed the opposite pattern. For the right inferior parietal lobule, the GM content with age had a significantly positive correlation in the control (r = 0.652, P = 0.001) but a negative correlation in the ASD (r = -0.434, P = 0.034). Additionally, the posterior cingulate had a significant interaction (controls: r = 0.672, P = 0.001; ASD: r = 0.021, P = 0.921). Conclusions In terms of global comparison, the present findings pointed out that the brain enlargement early in ASD childhood did not persist into adolescence. Regionally, imbalance GM volumes of participants with ASD appear in line with previous reports [6-7]. Notably, the right inferior parietal lobule and posterior cingulate showed a significant interaction of age throughout adolescence by groups as indicated by an accelerated age-related loss of GM volume in ASD whilst an age-related gain in control. We also found that the medial prefrontal cortex had a larger volume while the lingual cortex had a smaller volume, was in line with previous reports that described the frontal lobe as having the greatest enlargements and the occipital lobes having the least [8]. This may suggest that the cortical areas affected most in ASD are phylogenetically and ontogenetically late-developing regions that are essential to complex human cognitive functions such as executive function and social interaction. The current MRI study with the use of voxel-based morphometry provide evidence on the presence of aberrant development in the social cognition network, including inferior parietal lobule and posterior cingulate, during adolescence in ASD. These findings may lend indirect supports to the social brain hypothesis of autism.

The literature only rarely mention the genital and sexual manifestations occurring in the course of partial seizures in man. The authors presently describe 42 seizures of this type recorded with E.E.G. and Stereo-E.E.G. techniques in 15 patients. The results of this study indicate that the genital and sexual paroxystic manifestations do have a specific semeiology, and there can be related to the initial localization of the electrical discharge which may begin in one of three different regions (perisylvian region, anterior part of the cingular gyrus and the paracentral lobule). Penile erection is observed in only one seizure starting in the central region. Orgasm occurs in the only one female patient in the course of the seizures beginning in the perisylvian region (temporal region). Early sensitive symptomatology characterizes very often the seizures beginning in the perisylvian region but also in the paracentral lobule. Post-ictal or peri-ictal true masturbation occurs at the end of the ictal discharge beginning either in the perisylvian region or in the anterior part of the cingular gyrus. The sexual dyspraxic (i.e. fondling the genitals) characterizes only the post-ictal phase of the seizures beginning in any of the three regions.

Somatosensory evoked potentials following stimulation of the median nerve at the wrist and the tibial nerve at the ankle were recorded in 5 patients with parasagittal tumours, 4 in the fronto-parietal and 1 in the frontal region. Three had intracerebral tumours and 2 parasagittal meningiomas. The extent of each lesion was determined by CT scan, showing a unilateral process involving predominantly the paracentral lobule and adjacent parts of the post- and precentral gyri ("Mantelkante') in 4 patients and a more frontal location of one meningioma affecting mainly the superior frontal gyrus. SEPs recorded from the patients with fronto-parietal tumours showed a uniform pattern with a complete absence of the wave N70 of the tibial SEP elicited by stimulating the nerve contralateral to the lesion. All other waves, including the P40-N50 complex on both sides and the median SEP, were in the normal range. In contrast, the frontal meningioma led to an only slightly altered from of the waves immediately following the initial P40-N50 complex. It is concluded that the tumour abolished the generators of the wave N70 which are apparently located in the cortical somatosensory leg area. Therefore unilateral loss of the wave N70 is indicative of parasagittal lesions. The results may give good evidence that the P40-N50 complex is generated in the thalamus or thalamo-cortical connections.