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BACKGROUND Adolescence is a critical period for neural development and has been associated with high rates of alcohol abuse. This research examined potential long-term brain and behavioral effects of early versus late-onset adolescent binge drinking in an adult sample of post-9/11 Veterans. METHODS We compared cortical thickness measures in Veterans with a history of binge drinking that began before the age of 15 (n = 50; mean age = 32.1 years) to those with a history of binge drinking with onset after the age of 15 (n = 300; mean age = 32.1 years). Data processing was conducted with FreeSurfer. A targeted neuropsychological battery (Digit Span test, Delis-Kaplan Executive Function System Color-Word Interference Test, California Verbal Learning Test-II) was used to examine the relationships between cortical thickness and attention, memory, and inhibition. A reference group of social drinkers with no history of early binge drinking (n = 31) was used to provide normative data. RESULTS Early-onset adolescent binge drinkers (EBD) had greater cortical thickness in several regions than late-onset adolescent binge drinkers (LBD); both binge-drinking groups had greater cortical thickness than the reference group. There was a stronger negative association between cortical thickness and age in EBDs than LBDs in the (i) lateral orbitofrontal cortex, (ii) supramarginal gyrus, (iii) paracentral lobule, and (iv) anterior caudal cingulate. Poorer performance on the attention and inhibition tasks in the EBDs was also associated with thicker cortices. CONCLUSIONS This study demonstrates greater cortical thickness across frontoparietal regions in adults who began binge drinking in early versus late adolescence. A stronger negative association between cortical thickness and age in the EBDs suggests that early-onset adolescent binge drinking may be associated with accelerated cortical thinning. Thicker cortex in these regions, which are known to mediate inhibitory control, may increase impulsive behavior and contribute to the risk of alcohol addiction.

Background It has been proposed that individuals with generalized anxiety disorder (GAD) show dysfunctional computations related to approach-avoidance decision-making. However, few studies have examined the neural basis of this impairment, particularly in adolescents with GAD. The goal of the current study was to address this gap in the literature. Method The study involved 51 adolescents with GAD and 51 typically developing (TD) comparison individuals matched on age (16.10 and 15.75 respective means), gender (30 F/21 M and 24 F/27 M), and IQ (103.20 and 103.18 respective means). Participants underwent functional magnetic resonance imaging during a passive avoidance task. Results We found a significant Group-by-Reinforcement interaction within reward-related brain regions including the caudate, putamen, mid cingulate/paracentral lobule, and superior and middle frontal gyrus. TD adolescents showed a greater differential response to reward versus punishment feedback within these regions relative to adolescents with GAD. In particular, this reflected reduced responses to rewards in the adolescents with GAD. There were no group differences in neural responses when making approach/avoidance responses. Conclusion The results of this study suggest reduced differential responsiveness to reinforcement as a component of the pathophysiology seen in adolescents with GAD. This dysfunction likely underpins decision-making impairments that may exacerbate the participants' worry.

The cingulate gyrus is part of the limbic system with extensive connectivity to different anatomical and functional areas. The traditional transcortical approach for a cingulate gyrus glioma contains high risk of transient or even irreversible postoperative hemiplegia. We present a case of gravity-assisted, fully endoscopic resection of a cingulate gyrus glioma with improvement of motor dysfunction while preserving the paracentral lobule, corticospinal tracts, and supplementary motor area. This case demonstrates the value of gravity-assisted endoscopic resection in the dominant cingulate gyrus tumor which is surrounded by eloquent parenchyma.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by chronic pain in pelvic area and lower urinary tract symptoms (LUTS). Previous neuroimaging studies demonstrated that chronic pain was associated with the altered brain activity. However, the pathological mechanisms associated with altered brain control of CP/CPPS are not well-understood. Therefore, we sought to investigate the topological properties of white matter brain networks in patients with CP/CPPS and whether the topological configuration of frontal-parietal control network was disrupted. We collected 19 patients with CP/CPPS and 32 matched healthy controls (HCs). Diffusion tensor imaging data of all participates were used to map the white matter structural networks. Graph theoretical method was applied to investigate the alterations of topological properties of brain network in patients. Moreover, we also investigated whether the alerted brain regions might be correlated with any clinical features of patients by the method of Pearson correlation analysis. Both CP/CPPS patients and HCs exhibited a 'small-world' behavior or economical small-world architecture of the white matter brain networks. In addition, CP/CPPS had a lower global efficiency in the right middle frontal gyrus (orbital part) and a higher global efficiency in the left middle cingulate and paracingulate gyri. CP/CPPS also showed increased local efficiency in the left middle cingulate and paracingulate gyri and paracentral lobule. Moreover, the local efficiency of the left middle cingulate gyrus was positively correlated with the scores of the influence of symptoms on the quality of life. The local efficiency of the left precuneus and right supplementary motor area were positively correlated with the total scores of NIH-CPSI and the scores of pain and discomfort symptoms, respectively. Together, we found that patients with CP/CPPS had alterations of connections within the frontal-parietal control network, which suggested that the altered connectivity involved in the executive control processing procedures might contribute to the pathogenesis of the pelvic pain and LUTS in CP/CPPS. Thus these results provided new insights into the understanding of CP/CPPS.

Object. To explore the specific effect of the international standard scalp acupuncture (ISSA) on patients with brain dysfunction after acute ischemic stroke (AIS) based on resting-state functional magnetic resonance imaging (Rs-fMRI). Design. A parallel-group randomized controlled trial. Participants. 30 hemiplegic patients with middle cerebral artery acute infarction of the dominant hemisphere. Interventions. 30 patients were divided into 2 groups randomly. 15 patients in the treatment group (TG) were treated with ISSA, needling at the parietal midline (MS5) and left anterior/posterior parietal-temporal oblique lines (MS6 and MS7), combined with western routine treatment. While another 15 patients in the control group (CG) received routine treatment only. Main Outcome Measures. (1) Functional connectivity (FC): patients received brain scan using 3.0 T MRI after the treatment for 1 week. Based on the Matlab2012a platform, SPM12 software and DPABI software were used to process the scanning data and finally the functional connectivity of the brain was obtained. (2) National Institute of Health Stroke Scale (NIHSS) score. Results. The difference in the NIHSS score between the two groups of patients before and after treatment was statistically significant (tNIHSS = 2.225; PNIHSS = 0.038), indicating that TG had a better effect. Centered to the seed region of the left supplementary motor area (SMA) (−5.32, 4.85, 61.38), FC increased at the left middle cerebellar peduncle, left cerebellum posterior lobe (uvula and declive), vermis, fusiform gyrus, lingual gyrus, inferior occipital gyrus, calcarine, cuneus, precuneus, BA7, BA18 and BA19, etc. Centered to the seed region of the left parahippocampal gyrus (PG) (−21.17, −15.95, −20.70), FC increased at the left precuneus, inside-paracingulate, inferior parietal gyrus, paracentral lobule, BA5, BA6, BA7, and BA40, right median cingulate, precuneus, BA19, BA23, and BA31, etc. Conclusions. It is indicated that ISSA can regulate the brain functional connection in patients with middle cerebral artery acute infarction in the dominant hemisphere and specifically strengthen the connections between visual, cognitive, motor control, and planning-related brain regions, which may be related to the recovery of movement in the mechanism. This trial is registered with ChiCTR-IOR-15007672.

Multiple reports for brain functional and structural alterations in patients with Crohn's disease (CD) were published. The current study aimed to meta-analyze the existing neuroimaging data and hence produce a brain map revealing areas with functional and structural differences between patients with CD and healthy controls. Original studies published until 2019 were identified from Scopus, Web of Science and PubMed databases, and included into the analysis if they reported relevant results from task-related or resting state functional magnetic resonance imaging (fMRI or rsfMRI) or voxel-based morphometry (VBM), in the form of standardized brain coordinates based on whole-brain analysis. The brain coordinates and sample size of significant results were extracted from eligible studies to be meta-analyzed with the activation likelihood estimation method using the GingerALE software. Sixteen original studies comprised of a total of 865 participants fulfilled the inclusion criteria. Compared to healthy controls, patients with CD had reduced resting state brain connectivity in the paracentral lobule and cingulate gyrus as well as reduced grey matter volume in the medial frontal gyrus. No significant results were found vice versa. These neural correlates allow a better understanding on the effects of CD on the pain expectation, emotion, and quality of life of patients and potentially serve as useful biomarkers for evaluating treatment efficacy.

OBJECTIVEThe aim of this study was to investigate the anatomical consistency, morphology, axonal connectivity, and correlative topography of the dorsal component of the superior longitudinal fasciculus (SLF-I) since the current literature is limited and ambiguous.METHODSFifteen normal, adult, formalin-fixed cerebral hemispheres were studied through a medial to lateral fiber microdissection technique. In 5 specimens, the authors performed stepwise focused dissections of the lateral cerebral aspect to delineate the correlative anatomy between the SLF-I and the other two SLF subcomponents, namely the SLF-II and SLF-III.RESULTSThe SLF-I was readily identified as a distinct fiber tract running within the cingulate or paracingulate gyrus and connecting the anterior cingulate cortex, the medial aspect of the superior frontal gyrus, the pre–supplementary motor area (pre-SMA), the SMA proper, the paracentral lobule, and the precuneus. With regard to the morphology of the SLF-I, two discrete segments were consistently recorded: an anterior and a posterior segment. A clear cleavage plane could be developed between the SLF-I and the cingulum, thus proving their structural integrity. Interestingly, no anatomical connection was revealed between the SLF-I and the SLF-II/SLF-III complex.CONCLUSIONSStudy results provide novel and robust anatomical evidence on the topography, morphology, and subcortical architecture of the SLF-I. This fiber tract was consistently recorded as a distinct anatomical entity of the medial cerebral aspect, participating in the axonal connectivity of high-order paralimbic areas.

Introduction The projection of the human male urogenital system onto the paracentral lobule has not previously been mapped comprehensively. Aim To map specific urogenital structures onto the primary somatosensory cortex toward a better understanding of sexual response in men. Methods Using functional magnetic resonance imaging, we mapped primary somatosensory cortical responses to self-stimulation of the penis shaft, glans, testicles, scrotum, rectum, urethra, prostate, perineum, and nipple. We further compared neural response with erotic and prosaic touch of the penile shaft. Main Outcome Measure We identified the primary mapping site of urogenital structures on the paracentral lobule and identified networks involved in perceiving touch as erotic. Results We mapped sites on the primary somatosensory cortex to which components of the urogenital structures project in men. Evidence is provided that penile cutaneous projection is different from deep penile projection. Similar to a prior report in women, we show that the nipple projects to the same somatosensory cortical region as the genitals. Evidence of differential representation of erotic and nonerotic genital self-stimulation is also provided, the former activating sensory networks other than the primary sensory cortex, indicating a role of “top-down” activity in erotic response. Clinical Implications We map primary sites of projection of urogenital structures to the primary somatosensory cortex and differentiate cortical sites of erotic from nonerotic genital self-stimulation. Strength & Limitations To our knowledge, this is the first comprehensive mapping onto the primary somatosensory cortex of the projection of the components of the urogenital system in men and the difference in cortical activation in response to erotic vs nonerotic self-stimulation. The nipple was found to project to the same cortical region as the genitals. Evidence is provided that superficial and deep penile stimulation project differentially to the cortex, suggesting that sensory innervation of the penis is provided by more than the (pudendal) dorsal nerve. Conclusion This study reconciles prior apparently conflicting findings and offers a comprehensive mapping of male genital components to the paracentral lobule. We provide evidence of differential projection of light touch vs pressure applied to the penile shaft, suggesting differential innervation of its superficial, vs deep structure. Similar to the response in women, we found nipple projection to genital areas of the paracentral lobule. We also provide evidence of differential representation of erotic and nonerotic genital self-stimulation, the former activating sensory networks other than the primary sensory cortex, indicating a role of top-down activity in erotic response.

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.

Psychosis disorders share overlapping symptoms and are characterized by a wide-spread breakdown in functional brain integration. Although neuroimaging studies have identified numerous connectivity abnormalities in affective and non-affective psychoses, whether they have specific or unique connectivity abnormalities, especially within the early stage is still poorly understood. The early phase of psychosis is a critical period with fewer chronic confounds and when treatment intervention may be most effective. In this work, we examined whole-brain functional network connectivity (FNC) from both static and dynamic perspectives in patients with affective psychosis (PAP) or with non-affective psychosis (PnAP) and healthy controls (HCs). A fully automated independent component analysis (ICA) pipeline called “Neuromark” was applied to high-quality functional magnetic resonance imaging (fMRI) data with 113 early-phase psychosis patients (32 PAP and 81 PnAP) and 52 HCs. Relative to the HCs, both psychosis groups showed common abnormalities in static FNC (sFNC) between the thalamus and sensorimotor domain, and between subcortical regions and the cerebellum. PAP had specifically decreased sFNC between the superior temporal gyrus and the paracentral lobule, and between the cerebellum and the middle temporal gyrus/inferior parietal lobule. On the other hand, PnAP showed increased sFNC between the fusiform gyrus and the superior medial frontal gyrus. Dynamic FNC (dFNC) was investigated using a combination of a sliding window approach, clustering analysis, and graph analysis. Three reoccurring brain states were identified, among which both psychosis groups had fewer occurrences in one antagonism state (state 2) and showed decreased network efficiency within an intermediate state (state 1). Compared with HCs and PnAP, PAP also showed a significantly increased number of state transitions, indicating more unstable brain connections in affective psychosis. We further found that the identified connectivity features were associated with the overall positive and negative syndrome scale, an assessment instrument for general psychopathology and positive symptoms. Our findings support the view that subcortical-cortical information processing is disrupted within five years of the initial onset of psychosis and provide new evidence that abnormalities in both static and dynamic connectivity consist of shared and unique features for the early affective and non-affective psychoses.

Clinical effects of anti-cholinergic drugs implicate cholinergic systems alterations in the pathophysiology of some cardinal motor impairments in Parkinson’s disease. The topography of affected cholinergic systems deficits and motor domain specificity are poorly understood. Parkinson's disease patients (n = 108) underwent clinical and motor assessment and vesicular acetylcholine transporter [18F]-fluoroethoxybenzovesamicol PET imaging. Volumes-of-interest-based analyses included detailed thalamic and cerebellar parcellations. Successful PET sampling for most of the small-sized parcellations was available in 88 patients. A data-driven approach, stepwise regression using the forward selection method, was used to identify cholinergic brain regions associating with cardinal domain-specific motor ratings. Regressions with motor domain scores for model-selected regions followed by confounder analysis for effects of age of onset, duration of motor disease and levodopa equivalent dose were performed. Among 7 model-derived regions associating with postural instability and gait difficulties domain scores three retained significance in confounder variable analysis: medial geniculate nucleus (standardized β = −0.34, t = −3.78, P = 0.0003), lateral geniculate nucleus (β = −0.32, t = −3.4, P = 0.001) and entorhinal cortex (β = −0.23, t = −2.6, P = 0.011). A sub-analysis of non-episodic postural instability and gait difficulties scores demonstrated significant effects of the medial geniculate nucleus, entorhinal cortex and globus pallidus pars interna. Among 6 tremor domain model-selected regions two regions retained significance in confounder variable analysis: cerebellar vermis section of lobule VIIIb (β = −0.22, t = −2.4, P = 0.021) and the putamen (β = −0.23, t = −2.3, P = 0.024). None of the three model-selected variables for the rigidity domain survived confounder analysis. Two out of the four model-selected regions for the distal limb bradykinesia domain survived confounder analysis: globus pallidus pars externa (β = 0.36, t = 3.9, P = 0.0097) and the paracentral lobule (β = 0.26, t = 2.5, P = 0.013). Emphasizing the utility of a systems-network conception of the pathophysiology of Parkinson's disease cardinal motor features, our results are consistent with specific deficits in basal forebrain corticopetal, peduncupontine-laterodorsal tegmental complex, and medial vestibular nucleus cholinergic pathways, against the background of nigrostriatal dopaminergic deficits, contributing significantly to postural instability, gait difficulties, tremor and distal limb bradykinesia cardinal motor features of Parkinson’s disease. Our results suggest significant and distinct consequences of degeneration of cholinergic peduncupontine-laterodorsal tegmental complex afferents to both segments of the globus pallidus. Non-specific regional cholinergic nerve terminal associations with rigidity scores likely reflect more complex multifactorial signalling mechanisms with smaller contributions from cholinergic pathways., Bohnen et al. investigated cholinergic PET correlates of cardinal motor symptoms in Parkinson's disease using complementary analysis approaches. Axial motor and tremor scores significantly associated with different and system-wide cholinergic pathways but evidence for distal limb bradykinesia scores was limited. No specific cholinergic transporter associations were found for rigidity scores., Graphical Abstract Graphical Abstract

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.

The precuneus is a functionally heterogeneous area located on the medial face of the parietal cortex, wedged between the occipital cortex and the paracentral lobule. In view of its topological positioning, this associative cortex is well-placed to play an important role in multisensory integration, specific aspects of which participate to bodily awareness. However, this potential implication remains unestablished. We assessed bodily awareness longitudinally in 14 rare patients who underwent a surgery for a low-grade glioma mainly infiltrating the precuneus. To determine the brain locus the most frequently affected in patients showing bodily awareness disorders, we first contrasted the resection cavity distributions of patients with versus without bodily awareness disorders. We next applied ‘lesion network mapping’ to identify the networks functionally coupled with lesion locations causing bodily awareness disorder. Bodily awareness disorders were observed in half of patients after surgery, especially alien hand, macrosomatognosia and fading limb. Importantly, a dissociation was revealed between the antero-dorsal precuneus (bodily awareness disorders) and postero-dorsal precuneus (no bodily awareness disorders). Furthermore, bodily awareness disorder-related regions were specifically connected to a network of sensorimotor regions while others were connected with the default network. Altogether, the present findings indicate a critical role of the antero-dorsal precuneus in specific aspects of bodily awareness and in the maintenance of body schema.

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which cerebral structural impairment is a consistent feature. Purpose To investigate cerebral microstructural changes in ALS using diffusion kurtosis imaging (DKI) for the first time. Study type Prospective. Subjects Eighteen ALS patients and 20 healthy controls. Field strength/sequence DKI images were obtained by a spin-echo echo-planar imaging sequence on a 3T MRI scanner, with three b-values (0, 1000, and 2000 s/mm2 ) and 64 diffusion encoding directions. Assessment The revised ALS Functional Rating Scale (ALSFRS-R) was administered to assess disease severity, and the symptom duration and disease progression rate were also recorded. Voxel-based analysis was applied to examine the alteration of DKI metrics (ie, mean kurtosis metrics [MK], axial kurtosis [AK], and radial kurtosis [RK]) and the conventional diffusion metrics (ie, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). Statistical tests Student's t-test, chi-square test, and Pearson correlation analysis. Results ALS patients showed MK reductions in gray matter areas, including the bilateral precentral gyrus, bilateral paracentral lobule, and left anterior cingulate gyrus; they also showed decreased MK values in white matter (WM) in the bilateral precentral gyrus, bilateral corona radiata, bilateral middle corpus callosum, left occipital lobe, and right superior parietal lobule. The spatial distribution of the regions with reduced RK was similar to those with decreased MK. No significant AK difference was found between groups. The correlation analysis revealed significant associations between DKI metrics and clinical assessments such as ALSFRS-R score and disease duration. Additionally, several WM regions showed between-group differences in conventional diffusion metrics; but the spatial extent was smaller than that with reduced DKI metrics. Data conclusion The reduction in DKI metrics indicates decreased microstructural complexity in ALS, involving both motor-related areas and extramotor regions. DKI metrics can serve as potential biomarkers for assessing disease severity. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:554-562.

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.

Objective: In this study, we investigate the brain lateralization in ADHD patients. Furthermore, we also explore the difference between male and female patients, and the difference among distinct ADHD subtypes, that is, ADHD–inattentive (ADHD-IA) and ADHD–combined (ADHD-C). Method: We employed the standard deviation to quantify the variability of resting-state functional magnetic resonance imaging (fMRI) signal and measure the lateralization index (LI). Results: ADHD patients showed significantly increased rightward lateralization in the inferior frontal gyrus (opercular), precuneus, and paracentral lobule, and decreased rightward lateralization in the insula. Compared with male patients, female patients showed significantly rightward lateralization in the putamen and lobule VII of cerebellar hemisphere. ADHD-C patients exhibited increased rightward lateralization in the inferior frontal gyrus (opercular), and decreased rightward lateralization in the inferior temporal gyrus, as compared with ADHD-IA. The LI was also found to be related to inattentive and hyper/impulsive scores. Conclusion: These key findings may aid in understanding the pathology of ADHD.

Introduction: Bilateral spastic cerebral palsy (BSCP) is the most common subtype of cerebral palsy (CP), which is characterized by various motor and cognitive impairments, as well as emotional instability. However, the neural basis of these problems and how repetitive transcranial magnetic stimulation (rTMS) can make potential impacts on the disrupted structural brain network in BSCP remain unclear. This study was aimed to explore the topological characteristics of the structural brain network in BSCP following the treatment of rTMS.Methods: Fourteen children with BSCP underwent 4 weeks of TMS and 15 matched healthy children (HC) were enrolled. Diffusion tensor imaging (DTI) data were acquired from children with bilateral spastic cerebral palsy before treatment (CP1), children with bilateral spastic cerebral palsy following treatment (CP2) and HC. The graph theory analysis was applied to construct the structural brain network. Then nodal clustering coefficient (Ci) and shortest path length (Li) were measured and compared among groups.Results: Brain regions with significant group differences in Ci were located in the left precental gyrus, middle frontal gyrus, calcarine fissure, cuneus, lingual gyrus, postcentral gyrus, inferior parietal gyri, angular gyrus, precuneus, paracentral lobule and the right inferior frontal gyrus (triangular part), insula, posterior cingulate gyrus, precuneus, paracentral lobule, pallidum. In addition, significant differences were detected in the Li of the left precental gyrus, lingual gyrus, superior occipital gyrus, middle occipital gyrus, superior parietal gyrus, precuneus and the right median cingulate gyrus, posterior cingulate gyrus, hippocampus, putamen, thalamus. Post hoc t-test revealed that the CP2 group exhibited increased Ci in the right inferior frontal gyrus, pallidum and decreased Li in the right putamen, thalamus when compared with the CP1 group.Conclusion: Significant differences of node-level metrics were found in various brain regions of BSCP, which indicated a disruption in structural brain connectivity in BSCP. The alterations of the structural brain network provided a basis for understanding of the pathophysiological mechanisms of motor and cognitive impairments in BSCP. Moreover, the right inferior frontal gyrus, putamen, thalamus could potentially be biomarkers for predicting the efficacy of TMS.

BackgroundCognitive abilities are impaired by sleep deprivation and can be recovered when sufficient sleep is obtained. Changes in alpha-band oscillations are considered to be highly related to sleep deprivation. The effect of sleep deprivation on brain activation and functional connectivity in the resting-state alpha band remains unclear. The purpose of this study was to investigate how sleep deprivation and recovery sleep could change resting-state alpha-band neural oscillations.MethodsIn this study, thirty young, healthy participants obtained approximately 8 h of normal sleep, followed by 36 h of sleep deprivation. On the following recovery night, subjects underwent recovery sleep. Resting-state EEG after normal sleep, sleep deprivation and recovery sleep was recorded. Power spectrum, source localization and functional connectivity analyses were used to investigate the changes in resting-state alpha-band activity after normal sleep, sleep deprivation and recovery sleep.ResultsThe results showed that the global alpha power spectrum decreased and source activation was notably reduced in the precuneus, posterior cingulate cortex, cingulate gyrus, and paracentral lobule after sleep deprivation. Functional connectivity analysis after sleep deprivation showed a weakened functional connectivity pattern in a widespread network with the precuneus and posterior cingulate cortex as the key nodes. Furthermore, the changes caused by sleep deprivation were reversed to a certain extent but not significantly after one night of sleep recovery, which may be due to inadequate time for recovery sleep.ConclusionsIn conclusion, large-scale resting-state alpha-band activation and functional connectivity were weakened after sleep deprivation, and the inhibition of default mode network function with the precuneus and posterior cingulate cortex as the pivotal nodes may be an important cause of cognitive impairment. These findings provide new insight into the physiological response of sleep deprivation and determine how sleep deprivation disrupts brain alpha-band oscillations.

Mood disorder patients have greater suicide risk than members of the general population, but how suicidal behavior relates to brain functions has not been fully elucidated. This study investigated how functional connectivity (FC) values between the right/left amygdala and the whole brain relate to suicidal behavior in patients with mood disorder. The participants in this study were 100 mood disorder patients with suicidal behavior (SB group), 120 mood disorder patients with non-suicidal behavior (NSB group), and 138 age- and gender-matched healthy controls (HC group). Whole-brain FC values among the three groups were compared using an analysis of covariance (ANCOVA). Compared to the NSB and HC groups, increased FC values in the right amygdala-bilateral paracentral lobule/precuneus circuit were observed in the SB group (Bonferroni-corrected,p< 0.017). The FC values in the NSB group did not differ significantly from those in the HC group (Bonferroni-corrected,p> 0.017). Moreover, there were no significant differences in FC values between mood disorder patients with suicide attempt (SA group) and mood disorder patients with suicidal ideation (SI group), while the FC values between the right amygdala and bilateral paracentral lobule/precuneus in the SA group were higher than the mean in the SI group. These findings suggest that right amygdala-paracentral lobule/precuneus dysfunction has an important role in patients with mood disorder and suicidal behavior.

Item does not contain fulltext A fundamental question in affective neuroscience is whether there is a common hedonic system for valence processing independent of modality, or there are distinct neural systems for different modalities. To address this question, we used both region of interest and whole-brain representational similarity analyses on functional magnetic resonance imaging data to identify modality-general and modality-specific brain areas involved in valence processing across visual and auditory modalities. First, region of interest analyses showed that the superior temporal cortex was associated with both modality-general and auditory-specific models, while the primary visual cortex was associated with the visual-specific model. Second, the whole-brain searchlight analyses also identified both modality-general and modality-specific representations. The modality-general regions included the superior temporal, medial superior frontal, inferior frontal, precuneus, precentral, postcentral, supramarginal, paracentral lobule and middle cingulate cortices. The modality-specific regions included both perceptual cortices and higher-order brain areas. The valence representations derived from individualized behavioral valence ratings were consistent with these results. Together, these findings suggest both modality-general and modality-specific representations of valence. 11 p.

The central sulcus is an important landmark in the brain. This study aimed to investigate the distinctive signal of the paracentral lobule (PL) on T1-weighted images (T1WIs; the white PL sign) and evaluate its usefulness as a new method of identifying the central sulcus. T1WIs of the brain of 96 participants (age, 58.9 ± 17.9 years; range, 8–87 years) scanned at 3-T MR system were retrospectively reviewed. First, we qualitatively analyzed the signal of the cortex of the PL by comparing it with that of the ipsilateral superior frontal gyrus on a 4-point grading score. Second, we compared the cortical signal intensity and gray/white-matter contrast between the PL and superior frontal gyrus. Third, we evaluated the usefulness of the PL signal for identifying the central sulcus. The PL cortex was either mildly hyperintense (grade 2) or definitely hyperintense (grade 3) in comparison with that of superior frontal cortex in all participants. The signal intensity of the PL cortex was significantly higher than that of the superior frontal cortex (p

Parkinson's disease (PD) is the most universal chronic degenerative neurological dyskinesia and an important threat to elderly health. At present, the researches of PD are mainly based on single-modal data analysis, while the fusion research of multi-modal data may provide more meaningful information in the aspect of comprehending the pathogenesis of PD. In this paper, 104 samples having resting functional magnetic resonance imaging (rfMRI) and gene data are from Parkinson's Progression Markers Initiative (PPMI) and Alzheimer's Disease Neuroimaging Initiative (ADNI) database to predict pathological brain areas and risk genes related to PD. In the experiment, Pearson correlation analysis is adopted to conduct fusion analysis from the data of genes and brain areas as multi-modal sample characteristics, and the clustering evolution random forest (CERF) method is applied to detect the discriminative genes and brain areas. The experimental results indicate that compared with several existing advanced methods, the CERF method can further improve the diagnosis of PD and healthy control, and can achieve a significant effect. More importantly, we find that there are some interesting associations between brain areas and genes in PD patients. Based on these associations, we notice that PD-related brain areas include angular gyrus, thalamus, posterior cingulate gyrus and paracentral lobule, and risk genes mainly include C6orf10, HLA-DPB1 and HLA-DOA. These discoveries have a significant contribution to the early prevention and clinical treatments of PD.

BackgroundDepression is the most common non-motor symptom in patients with Parkinson’s disease (PD) with unknown mechanisms, but the diagnostic criteria of PD with depression (PDD) are not uniform.PurposeThe aim of the study was to investigate interhemispheric interactions between PDD patients and patients with PD without depression (PDND).MethodsThe voxel-mirrored homotopic connectivity (VMHC) combined with the seed-based method was used to investigate intrinsic resting-state functional connectivity (RSFC) in 33 PDD patients, 60 PDND, and 47 healthy controls (HCs).ResultsPDD patients exhibited a decreased VMHC in the bilateral medial frontal gyrus and paracentral lobule (MFG/PCL) than did PDND patients. Parkinson’s disease with depression had a decreased VMHC in the bilateral precentral gyrus than had PDND and HC (p < 0.05). Parkinson’s disease with depression had a decreased homotopic RSFC from the medial frontal gyrus (MFG)/PCL to the contralateral supplementary motor area (SMA) than had PDND (p < 0.05). The decreased homotopic RSFC from the right MFG/PCL to the left SMA was negatively correlated with Hamilton Depression Rating Scale scores (p < 0.05), but not with illness duration, Beck’s Depression Inventory, and Unified Parkinson’s Disease Rating Scale in PD patients.ConclusionsOur findings indicated that the occurrence of depression in Parkinson’s disease is associated with the dysfunctional connectivity from the MFG/PCL to the contralateral SMA, which could be used as potential neuroimaging markers for the diagnosis of depression in PD patients.

Social interaction is critical to emotional well-being. Previous studies have suggested sex differences in the perception of social interaction. However, the findings depend on the nature of interactions and whether it involves facial emotions. Here, we explored sex differences in neural responses to the perception of social interaction using the Human Connectome Project data. Participants (n = 969, 505 women) were engaged in a social cognition task with geometric objects moving and colliding to simulate social interaction. Behaviorally, men relative to women demonstrated higher accuracy in perceiving social vs. random interactions. Men vs. women showed higher activation in the right superior temporal gyrus, bilateral occipital and posterior cingulate cortex and precuneus, and women vs. men showed higher activation in the right inferior frontal cortex, during exposure to social vs. random interactions. In whole-brain regressions, the differences in accuracy rate in identifying social vs. random interactions (AR SOC - AR RAN ) were associated with higher activation in the paracentral lobule (PCL) and lower activation in bilateral anterior insula (AI), pre-supplementary motor area (preSMA), and left middle frontal gyrus (MFG) in men and women combined, lower activation in bilateral AI, preSMA and left MFG in men alone, and higher activation in the PCL and the medial orbitofrontal cortex in women alone. The latter sex differences were confirmed by slope tests. Further, the PCL activity mediated the correlation between an internalizing syndromal score, as assessed by the Achenbach Self-Report, and (AR SOC - AR RAN ) across all subjects. These findings highlighted sex differences in the behavioral and neural processes underlying the perception of social interaction, as well as the influence of internalizing traits on these processes.

Previous studies demonstrated the possible involvement of insula in suicide owing to depression. However, the function of insula in young depressed patients with suicide attempt (SA) remains to be revealed. This study aimed to explore the association between resting-state functional connectivity (FC) of insula and SA in young depressed patients. Fifty-eight adolescents and young adults with major depressive disorder, including 22 with a history of at least one SA (SA group) and 36 without a history of SA (NSA group) were scanned with a 3.0T functional magnetic resonance imaging system, and the resting-state functional magnetic resonance imaging data was extracted. Whole brain resting-state FC of insular subdivisions were compared between the two groups. Significantly increased FC of the left posterior insula with the orbital part of left inferior frontal gyrus, the right supplementary motor area and the bilateral paracentral lobule extending to the bilateral middle cingulate cortex was observed in the SA group compared with the NSA group. In addition, the orbital part of left superior frontal gyrus in the SA group exhibited significantly increased FC with the right posterior insula compared with the NSA group. However, no significant correlation was found between the insular subdivisions FC and different clinical variables in two groups. The present study highlighted the disruptions of the resting-state FC of the posterior insula with the orbitofrontal cortex and a series of motor cortices, and added incremental value to the knowledge of the neural mechanism underlying SA in young depressed patients.

Purpose Functional MRI has played a fundamental role in Parkinson's disease(PD) study. In this paper, we performed an independent component analysis (ICA) based on functional networks to reveal the intricate variations on the morphology and functional properties of brain. Our analysis aims at discovering the differences between PD patients with sensorimotor function impairment and normal controls(NC), thus helping to understand the coordination neurological function degeneration in PD objectively. Method We investigated the blood oxygen level dependent(BOLD) functional MRI obtained at a 3.0 T MRI scanner. 30 PD patients and 28 NC subjects underwent the scan in resting state. The signals of sensory and motor coordinative control areas in the sensorimotor, insula and cerebellum networks acquired by ICA(Independent Component Analysis)were applied to analyze the functional alterations. Specifically, intra-network analysis was performed with signals in local networks, and inter-network analysis was conducted by functional network connectivity (FNC) with signals across different networks. Two sample T test was carried out to detect the significant (p Conclusion We identified an obvious increase in bilateral posterior insula, but decrease in bilateral cerebellum hemisphere, supplementary motor area(SMA) and precentral gyrus paracentral lobule of left postcentral gyrus. Besides, we found a significantly increased connection between independent component (IC) 13 which was located in right postcentral gyrus and cerebellum. Decreased connections were detected between sensory and motor cortex in sensorimotor network and between cerebellum and insula network by FNC analysis in PD patients as well. Discussion Parkinson's disease derives from the degeneration of the dopaminergic neurons in substantia nigra, and results in decreased secretion of inhibitory neurotransmitter. The significant differences between PD and NC groups in our research maybe explain the clinical manifestations of prominent bradykinesia and multiple extrapyramidal symptoms.

As a complex psychiatric disorder, schizophrenia is interpreted as a “dysconnection” syndrome, which is linked to abnormal integrations in between distal brain regions. Recently, neuroimaging has been widely adopted to investigate how schizophrenia affects brain networks. Furthermore, some studies reported frequency dependence of the abnormalities of functional network in schizophrenia, however, dynamic functional connectivity with frequency dependence is rarely used to explore changes in the whole brain of patients with schizophrenia (SZ). Therefore, in the current study, dynamic functional connectivity strength (dFCS) was performed on resting-state functional magnetic resonance data from 96 SZ patients and 121 healthy controls (HCs) at slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz), and slow-2 (0.198–0.25 Hz) frequency bands and further assessed whether the altered dFCS was correlated to clinical symptoms in SZ patients. Results revealed that decreased dFCS of schizophrenia were found in salience, auditory, sensorimotor, visual networks, while increased dFCS in cerebellum, basal ganglia, and prefrontal networks were observed across different frequency bands. Specifically, the thalamus subregion of schizophrenic patients exhibited enhanced dynamic FCS in slow-5 and slow-4, while reduced in slow-3. Moreover, in slow-5 and slow-4, significant interaction effects between frequency and group were observed in the left calcarine cortex, the bilateral inferior orbitofrontal gyrus, and anterior cingulum cortex (ACC). Furthermore, the altered dFCS of insula, thalamus (THA), calcarine cortex, orbitofrontal gyrus, and paracentral lobule were partial correlated with clinical symptoms of SZ patients in slow-5 and slow-4 bands. These results demonstrate the abnormalities of dFCS in schizophrenia patients is rely on different frequency bands and may provide potential implications for exploring the neuropathological mechanism of schizophrenia.

Uncertainty in selecting the appropriate antidepressant for each patient is a major challenge in treatment of major depressive disorder (MDD). No biologically driven markers are currently available to improve precision in treatment selection, thus leading to a trial-and-error process and prolonged morbidity for most patients. This study developed deep learning models that accurately predict treatment outcomes for sertraline, bupropion and placebo. Models were trained on data from the EMBARC study, in which 223 un-medicated subjects with MDD underwent pre-treatment reward task fMRI and received 8 weeks of treatment with sertraline, bupropion, or placebo. These models integrate fMRI and clinical measures and they explain up to 37% of the variance in ΔHAMD, classify remitters with NNT of 2.3-4.3, and classify responders with NNT of 3.2-4.9. Findings reveal new regions predictive of treatment outcome such as the hippocampus and paracentral lobule, while additional regions implicated in existing research are corroborated. Distinct models were identified for each treatment and provide substantial evidence of their potential to improve precision in treatment selection for MDD.

Early life exposure to air pollution poses a significant risk to brain development from direct exposure to toxicants or via indirect mechanisms involving the circulatory, pulmonary or gastrointestinal systems. In children, exposure to traffic related air pollution has been associated with adverse effects on cognitive, behavioral and psychomotor development. We aimed to determine whether childhood exposure to traffic related air pollution is associated with regional differences in brain volume and cortical thickness among children enrolled in a longitudinal cohort study of traffic related air pollution and child health. We used magnetic resonance imaging to obtain anatomical brain images from a nested subset of 12 year old participants characterized with either high or low levels of traffic related air pollution exposure during their first year of life. We employed voxel-based morphometry to examine group differences in regional brain volume, and with separate analyses, changes in cortical thickness. Smaller regional gray matter volumes were determined in the left pre- and post-central gyri, the cerebellum, and inferior parietal lobe of participants in the high traffic related air pollution exposure group relative to participants with low exposure. Reduced cortical thickness was observed in participants with high exposure relative to those with low exposure, primarily in sensorimotor regions of the brain including the pre- and post-central gyri and the paracentral lobule, but also within the frontal and limbic regions. These results suggest that significant childhood exposure to traffic related air pollution is associated with structural alterations in brain.

The right inferior frontal gyrus (rIFG) is a key cortical node in the circuits of emotion and cognitive control, and it has been frequently associated with bipolar disorder (BP); however, a reliable pattern of aberrant rIFG activation and connectivity in bipolar disorder has yet to be established. To further elucidate rIFG abnormalities in different states of bipolar disorder, we examined activation and functional connectivity (FC) in five subregions of rIFG in bipolar disorder. A total of 83 participants, including those with bipolar depression (BPD; n = 25) and bipolar mania (BPM; n = 37) along with healthy control (HC) subjects (n = 26), were examined by resting state functional magnetic resonance imaging (rs-fMRI). Both BPD and BPM groups showed higher values of amplitude of low-frequency fluctuations (ALFF) than healthy control in four of the five rIFG subregions except cluster 2(posterior-ventral rIFG). Using five subregions of rIFG as seeds, the decreased FC in bipolar disorder was mainly between posterior-ventral rIFG(cluster 2) and multiple brain regions including the postcentral gyrus, the precentral gyrus, paracentral lobule, lingual Gyrus, fusiform and cerebellum posterior lobe. These results indicated that local activity and FC were altered within specific subregions of the rIFG in BP. These findings may provide the distinct functional connectivity of rIFG subregions in BP and suggest that the cluster2 (posterior-ventral rIFG) circuitry plays a crucial role in BP. Also, such abnormalities might help define a more precise intervention targets.

Dysfunctional processing of auditory sensory gating has generally been found in schizophrenic patients and ultra-high-risk (UHR) individuals. The aim of the study was to investigate the differences of functional interaction between brain regions and performance during the P50 sensory gating in UHR group compared with those in first-episode schizophrenia patients (FESZ) and healthy controls (HC) groups. The study included 128-channel scalp Electroencephalogram (EEG) recordings during the P50 auditory paradigm for 35 unmedicated FESZ, 30 drug-free UHR, and 40 HC. Cortical sources of scalp electrical activity were recomputed using exact low-resolution electromagnetic tomography (eLORETA), and functional brain networks were built at the source level and compared between the groups (FESZ, UHR, HC). A classifier using decision tree was designed for differentiating the three groups, which uses demographic characteristics, MATRICS Consensus Cognitive Battery parameters, behavioral features in P50 paradigm, and the measures of functional brain networks based on graph theory during P50 sensory gating. The results showed that very few brain connectivities were significantly different between FESZ and UHR groups during P50 sensory gating, and that a large number of brain connectivities were significantly different between FESZ and HC groups and between UHR and HC groups. Furthermore, the FESZ group had a stronger connection in the right superior frontal gyrus and right insula than the HC group. And the UHR group had an enhanced connection in the paracentral lobule and the middle temporal gyrus compared with the HC group. Moreover, comparison of classification analysis results showed that brain network metrics during P50 sensory gating can improve the accuracy of the classification for FESZ, UHR and HC groups. Our findings provide insight into the mechanisms of P50 suppression in schizophrenia and could potentially improve the performance of early identification and diagnosis of schizophrenia for the earliest intervention.

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.

Background Schizophrenia is a clinical syndrome, and its causes have not been well determined. The objective of this study was to investigate the alteration of brain functional connectivity between schizophrenia and healthy control, and present a practical solution for accurately identifying schizophrenia at single-subject level. Methods 24 schizophrenia patients and 21 matched healthy subjects were recruited to undergo the resting-state functional magnetic resonance imaging (rs-fMRI) scanning. First, we constructed the brain network by calculating the Pearson correlation coefficient between each pair of the brain regions. Then, this study proposed a novel non-negative discriminant functional connectivity selection method, i.e. non-negative elastic-net based method (N2EN), to extract the alteration of brain functional connectivity between schizophrenia and healthy control. It ranks the significance of the connectivity with a uniform criterion by introducing the non-negative constraint. Finally, kernel discriminant analysis (KDA) is exploited to classify the subjects with the selected discriminant brain connectivity features. Results The proposed method is applied into schizophrenia classification, and achieves the sensitivity, specificity and accuracy of 100, 90.48 and 95.56%, respectively. Our findings also indicate the alteration of functional network can be used as the biomarks for guiding the schizophrenia diagnosis. The regions of cuneus, superior frontal gyrus, medial, paracentral lobule, calcarine fissure, surrounding cortex, etc. are highly relevant to schizophrenia. Conclusions This study provides a method for accurately identifying schizophrenia, which outperforms several state-of-the-art methods, including conventional brain network classification, multi-threshold brain network based classification, frequent sub-graph based brain network classification and support vector machine. Our investigation suggested that the selected discriminant resting-state functional connectivities are meaningful features for classifying schizophrenia and healthy control.

This study investigated the topological characteristics of brain functional networks in chronic insomnia disorder (CID) patients. The resting-state functional magnetic resonance imaging and graph theory analysis method were applied to investigate the brain functional connectome patterns among 45 CID patients and 32 healthy controls. The brain functional connectome was constructed by thresholding partial correlation matrices of 90 brain regions from an automated anatomical labeling atlas. The topologic properties of brain functional connectomes at both global and nodal levels were tested. The CID patients had decreased number of module (p = .014) and hierarchy (p = .038), and increased assortativity (p = .035). Furthermore, some brain regions located in the default mode network, dorsal attention network, and sensory-motor network in these patients showed altered nodal centralities. Within these areas, the node betweenness of right central paracentral lobule had positive correlation with the Pittsburgh Sleep Quality Index score (R = 0.319, p = .039). The results imply that functional disruptions of CID patients may be related to disruptions in global and regional topological organization of the brain functional connectome, and provide new and important insights to understand the pathophysiological mechanisms of CID., Highlights • Chronic insomnia disorder (CID) patients had disrupted global topological properties. • Many brain regions of CID patients showed altered nodal centralities involving three different resting networks. • Functional disruption of right central paracentral lobule may be a target for therapeutic intervention in pediatric CID. • The disruption of topological organization might be explain the mechanism/reason of functional disruptions of CID.

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.

Late-onset Alzheimer's disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18 months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naïve late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients.

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.

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.

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.

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. Although previous TS studies revealed structural abnormalities in distinct corticobasal ganglia circuits, the topological alterations of the whole-brain white matter (WM) structural networks remain poorly understood. Here, we used diffusion MRI probabilistic tractography and graph theoretical analysis to investigate the topological organization of WM networks in 44 drug-naive TS children and 41 age- and gender-matched healthy children. The WM networks were constructed by estimating inter-regional connectivity probability and the topological properties were characterized using graph theory. We found that both TS and control groups showed an efficient small-world organization in WM networks. However, compared to controls, TS children exhibited decreased global and local efficiency, increased shortest path length and small worldness, indicating a disrupted balance between local specialization and global integration in structural networks. Although both TS and control groups showed highly similar hub distributions, TS children exhibited significant decreased nodal efficiency, mainly distributed in the default mode, language, visual, and sensorimotor systems. Furthermore, two separate networks showing significantly decreased connectivity in TS group were identified using network-based statistical (NBS) analysis, primarily composed of the parieto-occipital cortex, precuneus, and paracentral lobule. Importantly, we combined support vector machine and multiple kernel learning frameworks to fuse multiple levels of network topological features for classification of individuals, achieving high accuracy of 86.47%. Together, our study revealed the disrupted topological organization of structural networks related to pathophysiology of TS, and the discriminative topological features for classification are potential quantitative neuroimaging biomarkers for clinical TS diagnosis. Hum Brain Mapp 38:3988-4008, 2017. © 2017 Wiley Periodicals, Inc.

Shortly after movement termination, there is a strong increase or resynchronization of the beta rhythm (15–30 Hz) across the sensorimotor network of humans, known as the post-movement beta rebound (PMBR). This response has been associated with active inhibition of the motor network following the completion of a movement, sensory afferentation of the sensorimotor cortices, and other functions. However, studies that have directly probed the role of the PMBR in movement execution have reported mixed results, possibly due to differences in the amount of total motor output and/or movement complexity. Herein, we used magnetoencephalography (MEG) during an isometric-force control task to examine whether alterations in the timing of motor termination demands modulate the PMBR, independent of differences in the motor output itself. Briefly, we manipulated the amount of time between the cue to initiate the force and the cue to terminate the force, such that participants were either forced to terminate quickly or slowly. We also performed a control experiment to test for temporal predictability effects. Our results indicated that the PMBR was stronger immediately following movement termination in the prefrontal cortices, supplementary motor area, left postcentral gyrus, paracentral lobule, and parietal cortex when participants were forced to terminate more quickly. These results were not attributable to the temporal predictability of each condition. These findings support the notion that the PMBR response at least partially serves motor inhibition, independent of parameters within the motor output itself, and that particular nodes of the motor network may be differentially modulated by motor termination.

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.

This study aimed to investigate the effects of lesion side and degree of motor recovery on gray matter volume (GMV) difference relative to healthy controls in right-handed subcortical stroke. Structural MRI data were collected in 97 patients with chronic subcortical ischemic stroke and 79 healthy controls. Voxel-wise GMV analysis was used to investigate the effects of lesion side and degree of motor recovery on GMV difference in right-handed chronic subcortical stroke patients. Compared with healthy controls, right-lesion patients demonstrated GMV increase (P, Highlights • There is a lesion-side effect on gray matter volume in subcortical stroke patients. • Right-sided stroke patients show more extensive GMV changes than left-sided ones. • GMV increase in the SMA may facilitate to motor recovery after stroke.

Objective The aim of this study is to investigate the cerebral cortical thickness changes in type 2 diabetes mellitus (T2DM) using a whole brain cortical thickness mapping system based on brain magnetic resonance imaging (MRI).Methods High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 16 patients with T2DM, as well as from 16 normal controls. The whole brain cortical thickness maps were generated, and the cortical thickness of each brain region was calculated according to gyral based regions of interest (ROI) using an automated labeling system by the Freesurfer software. We compared mean cortical thickness at each brain region by the analysis of covariance with age and sex as covariates. The regional difference of the cortical thickness over the whole brain was compared by the analysis of surface-based cortical thickness.Results Mean cortical thicknesses analysis showed bilateral cerebrum in the patients with T2DM (left: 2.52±0.07 mm; right: 2.51±0.08 mm) were significant thinner than those in the normal controls (left: 2.56±0.09 mm; right: 2.56±0.09 mm) (both P

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.

International audience; Glossary : Precuneus: medial part of the posterior parietal cortex, between the occipital (cuneus) and the anterior parietal (paracentral lobule) cortices, well located for visual-somatosensory integration. Body image typically depicts mental representation of one's own body, arising from all sources of sensory and cognitive information, whereas body schema is used to depict the unconscious use of sensory information required by our motor system to maintain body posture and produce accurate movements. Brain lesions may result in deficits for either or both types of body representations.