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Background: Default mode network (DMN) is recognized to be involved in generation and propagation of epileptic activities in various epilepsies. Converging evidence has suggested disturbed functional connectivity (FC) in epilepsies, which was inferred to be related to underlying pathological mechanisms. However, abnormal changes of FC in DMN revealed by different studies are controversial, which obscures the role of DMN in distinct epilepsies. Objective: The present work aims to investigate the voxel-wise FC in DMN across epilepsies. Methods: A systematic review was conducted on 22 published articles before October 2020 indexed in PubMed and Web of Science. A meta-analysis with a random-effect model was performed using the effect-size signed differential mapping approach. Subgroup analyses were performed in three groups: idiopathic generalized epilepsy (IGE), mixed temporal lobe epilepsy (TLE), and mixed focal epilepsy (FE) with different foci. Results: The meta-analysis suggested common decreased FC in mesial prefrontal cortices across different epilepsies. Additional decreased FC in posterior DMN was observed in IGE. The TLE showed decreased FC in temporal lobe regions and increased FC in dorsal posterior cingulate cortex. Interestingly, an opposite finding in ventral and dorsal middle frontal gyrus was observed in TLE. The FE demonstrated increased FC in cuneus. Conclusion: The current findings revealed both common and specific alterations of FC in DMN across different epilepsies, highlighting the contribution of these dysfunctions to epileptic activities and cognitive behaviors in patients. Furthermore, the current study provided powerful evidence to support DMN as a potential candidate for effective intervention in epilepsy.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently identified autoimmune disorder with heterogeneous neurological, psychiatric, and cognitive manifestations. The NMDAR is a key signaling node for neurovascular coupling, the mechanism by which cerebral blood perfusion is enhanced to meet local metabolic requirements from increased neuronal activity. Therefore, anti-NMDAR encephalitis may disrupt neurovascular coupling and induce cognitive deficits. This study examined neurovascular coupling and cognitive function in anti-NMDAR encephalitis patients to identify prognostic biomarkers, reveal potential pathogenic mechanisms, and provide clues to possible therapeutic strategies. In this study, twenty-three anti-NMDAR encephalitis patients and thirty healthy controls received neuropsychological testing and multimodal magnetic resonance imaging (MRI). Cerebral blood flow (CBF) was calculated from arterial spin labeling, and regional homogeneity (ReHo) was computed from functional MRI. Pearson's correlation coefficients between CBF and ReHo were calculated to obtain neurovascular coupling. At the whole gray matter level, CBF‒ReHo coupling was reduced in patients compared to healthy controls. At the regional level, CBF‒ReHo was significantly lower among patients in the precentral gyrus, frontal gyrus, insula, cuneus, inferior parietal lobe, supramarginal gyrus, angular gyrus, precuneus, temporal gyrus, and temporal pole. Reduced CBF‒ReHo in the left superior medial frontal gyrus of patients was significantly correlated with a deficit in verbal inhibition control, and the reduced CBF‒ReHo in the left insula was significantly correlated with impaired executive function. In conclusion, anti-NMDAR encephalitis is associated with both global and regional disruptions in neurovascular coupling that may in turn lead to deficits in specific cognitive domains.

Background: Cannabis is one of the most commonly used substances in the United States. Prior literature using task-based functional magnetic resonance imaging (fMRI) has identified that individuals with Cannabis use disorder (CUD) show impairments in emotion processing circuitry. However, whether the functional networks involving these regions are also altered in CUD remains poorly understood. Aims: Investigate changes in resting-state functional connectivity (rsFC) in regions related to emotional processing in CUD. Methods: Sixty-two participants completed resting-state fMRI, including 21 with CUD, 20 with histories of illicit substance use but no current CUD diagnosis, and 21 with no history of illicit substance use. Whole-brain seed-based connectivity analyses were performed and one-way analyses of covariance (ANCOVAs) were conducted to detect group differences in the bilateral amygdalae, hippocampi, and the anterior and posterior cingulate cortices. Results: The CUD group exhibited significant reductions in rsFC between the amygdala and the cuneus, paracentral lobule, and supplementary motor area, and between the cingulate cortices and the occipital and temporal lobes. There were no significant group differences in hippocampal functional connectivity. In addition, CUD symptom counts based on the Structured Clinical Interview for DSM-5 (SCID) and the Cannabis Use Disorders Identification Test (CUDIT) significantly correlated with multiple connectivity metrics. Conclusion: These data expand on emerging literature indicating that CUD is associated with dysfunction in the neural circuits underlying emotion processing. Dysfunction in emotion processing circuits may play a role in the behavioral impairments seen in emotion processing tasks in individuals with CUD, and the severity of CUD symptoms appears to be directly related to the degree of dysfunction in these circuits.

Identifying treatment options for patients with alcohol dependence is challenging. This study investigates the application of real-time functional MRI (rtfMRI) neurofeedback (NF) to foster resistance towards craving-related neural activation in alcohol dependence. We report a double-blind, placebo-controlled rtfMRI study with three NF sessions using alcohol-associated cues as an add-on therapy to the standard treatment. Fifty-two patients (45 male; 7 female) diagnosed with alcohol dependence were recruited in Munich, Germany. RtfMRI data were acquired in three sessions and clinical abstinence was evaluated 3 months after the last NF session. Before the NF training, BOLD responses and clinical data did not differ between groups, apart from anger and impulsiveness. During NF training, BOLD responses of the active group were decreased in medial frontal areas/caudate nucleus, and increased, e.g. in the cuneus/precuneus and occipital cortex. Within the active group, the down-regulation of neuronal responses was more pronounced in patients who remained abstinent for at least 3 months after the intervention compared to patients with a relapse. As BOLD responses were comparable between groups before the NF training, functional variations during NF cannot be attributed to preexisting distinctions. We could not demonstrate that rtfMRI as an add-on treatment in patients with alcohol dependence leads to clinically superior abstinence for the active NF group after 3 months. However, the study provides evidence for a targeted modulation of addiction-associated brain responses in alcohol dependence using rtfMRI.

Background Major depressive disorder and bipolar disorder in adolescents are prevalent and are associated with cognitive impairment, executive dysfunction, and increased mortality. Early intervention in the initial stages of major depressive disorder and bipolar disorder can significantly improve personal health. Methods We collected 309 samples from the Adolescent Brain Cognitive Development study, including 116 adolescents with bipolar disorder, 64 adolescents with major depressive disorder, and 129 healthy adolescents, and employed a support vector machine to develop classification models for identification. We developed a multimodal model, which combined functional connectivity of resting-state functional magnetic resonance imaging and four anatomical measures of structural magnetic resonance imaging (cortical thickness, area, volume, and sulcal depth). We measured the performances of both multimodal and single modality classifiers. Results The multimodal classifiers showed outstanding performance compared with all five single modalities, and they are 100% for major depressive disorder versus healthy controls, 100% for bipolar disorder versus healthy control, 98.5% (95% CI: 95.4–100%) for major depressive disorder versus bipolar disorder, 100% for major depressive disorder versus depressed bipolar disorder and the leave-one-site-out analysis results are 77.4%, 63.3%, 79.4%, and 81.7%, separately. Conclusions The study shows that multimodal classifiers show high classification performances. Moreover, cuneus may be a potential biomarker to differentiate major depressive disorder, bipolar disorder, and healthy adolescents. Overall, this study can form multimodal diagnostic prediction workflows for clinically feasible to make more precise diagnose at the early stage and potentially reduce loss of personal pain and public society.

The aim of the study is to explore interhemispheric homotopic functional connectivity alterations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric lupus (NPSLE and non-NPSLE, respectively) and their potential correlations with clinical characteristics and neuropsychological performance. Based on resting-state functional MRI (rs-fMRI) data collected from SLE patients and matched healthy controls (HCs), the voxel-mirrored homotopic connectivity (VMHC) analysis was conducted to measure functional homotopy. Subsequently, correlations between altered functional homotopy and clinical/neuropsychological data were analyzed. Compared with the HC group, both NPSLE and non-NPSLE groups showed attenuated homotopic connectivity in middle temporal gyrus (MTG), cuneus (CUN), middle occipital gyrus (MOG), angular gyrus (ANG), and postcentral gyrus (PoCG). NPSLE patients also exhibited decreased homotopic connectivity in inferior parietal gyrus (IPG) and middle frontal gyrus (MFG). Compared with non-NPSLE patients, NPSLE patients showed weaker interhemispheric homotopic functional connectivity in MOG. Decreased homotopic functional connectivity in PoCG, IPG, and MOG were associated with the anxiety state of SLE patients. Our findings revealed attenuated functional homotopy in both NPSLE and non-NPSLE groups compared to the HC group, which appeared to be more severe in patients with comorbid neuropsychiatric lupus. Interhemispheric homotopy dysconnectivity may participate in the neuropathology of anxiety symptoms in SLE.

The secondary prevention trials of Alzheimer’s disease (AD) require an enrichment strategy to recruit individuals with imminent cognitive decline at the preclinical stage. Previously, we demonstrated a variant neural correlates of episodic memory (EM) function in apolipoprotein E (APOE) e4 carriers. Herein, we investigated whether this variation was associated with longitudinal EM performance. This 3-year longitudinal study included 88 normal elderly subjects with EM assessment and resting-state functional MRI data at baseline; 48 subjects (27 e3 homozygotes and 21 e4 carriers) underwent follow-up EM assessment. In the identified EM neural correlates, multivariable regression models examined the association between hippocampal functional connectivity (HFC) and longitudinal EM change. Independent validation was performed using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. At baseline, the EM neural correlates were characterized in the Papez circuit regions in the e3 homozygotes, but in the sensorimotor cortex and cuneus in the e4 carriers. Longitudinally, the e4 carriers exhibited a negative association of the baseline HFC strength in the EM neural correlates with annual rate of EM change (R2 = 0.25, p = 0.05). This association also showed a trend in the ADNI dataset (R2 = 0.42, p = 0.06). These results indicate that hippocampal hyperconnectivity in the variant EM neural correlates is associated with imminent EM decline in e4 carriers, which may serve as a promising enrichment strategy for secondary prevention trials of AD.

BACKGROUND The striatum has been reported to be implicated in various neurological diseases, including lifelong premature ejaculation (LPE). Altered striatum-related functional connectivity was investigated in LPE patients in previous studies; however, structural abnormalities in the striatum have been less studied in LPE. PURPOSE To identify the gray matter volume (GMV) and structural covariance patterns of the striatum between LPE patients and healthy controls (HCs). STUDY TYPE Prospective. SUBJECTS Forty-three LPE patients and 31 male HCs. FIELD STRENGTH/SEQUENCE 3.0 T magnetic resonance imaging (MRI) scanner; T1-weighted imaging using a spoiled gradient recalled echo sequence. ASSESSMENT Preprocessing of structural MRI data and the striatum-seeded GMV computation were conducted using SPM12. STATISTICAL TESTS Two sample t-test was used to compare differences in GMV of the striatum between patients and HCs. Regions showing altered between-group GMV were considered as seeds for structural covariance analysis in two groups. Additionally, correlations between GMV findings and clinical features were assessed with age and total intracranial volume (TIV) as covariates and with age, TIV, anxiety, and depression scores as covariates in the patient group, P

Suicidal ideation (SI) is a direct risk factor for suicide in patients with depression. Regarding the emergence of SI, previous studies have discovered many risk factors, including childhood abuse as the major public problem. Previous imaging studies have demonstrated that SI or childhood abuse has effects on brain structure and function, respectively, but the interaction effects between them have not been fully studied. To explore the interaction effect between SI and childhood abuse, 215 patients with major depressive disorder completed the Childhood Trauma Questionnaire to evaluate childhood abuse and Beck’s Scale for Suicidal Ideation to evaluate SI. Then, they completed magnetic resonance imaging (MRI) within one week after completing questionnaires. Respectively, we preprocessed the structural and functional images and analyzed gray matter volumes (GMV) and mean fractional amplitude of low-frequency fluctuation (mfALFF) values. Results showed that the changes of GMV in the cuneus, precuneus, paracentric lobule, inferior frontal gyrus, and caudate nucleus and local activity in cuneal and middle temporal gyrus are in relation with SI and childhood abuse. And in left caudate, SI and childhood abuse interact with each other on the influence of GMV. That is, the influence of SI in GMV was related to childhood abuse, and the influence of childhood abuse in GMV was also related to SI. Therefore, the combination of SI and childhood abuse based on imaging should help us better understand the suicide ideation developing mechanism and propose more effective targeted prevention strategies for suicide prevention.

ObjectivesWe aimed to investigate changes in regional cerebral blood flow (rCBF) using arterial spin labelling (ASL) in patients with visual snow syndrome (VSS), in order to understand more about the underlying neurobiology of the condition, which remains mostly unknown.MethodsWe performed an MRI study in which whole-brain maps of rCBF were obtained using pseudo-continuous ASL. Twenty-four patients with VSS and an equal number of gender and age-matched healthy volunteers took part in the study. All subjects were examined with both a visual paradigm consisting of a visual-snow like stimulus, simulating key features of the snow, and a blank screen at rest, randomly presented.ResultsPatients with VSS had higher rCBF than controls over an extensive brain network, including the bilateral cuneus, precuneus, supplementary motor cortex, premotor cortex and posterior cingulate cortex, as well as the left primary auditory cortex, fusiform gyrus and cerebellum. These areas were largely analogous comparing patients either at rest, or when looking at a ‘snow-like’ visual stimulus. This widespread, similar pattern of perfusion differences in either condition suggests a neurophysiological signature of visual snow. Furthermore, right insula rCBF was increased in VSS subjects compared with controls during visual stimulation, reflecting a greater task-related change and suggesting a difference in interoceptive processing with constant perception of altered visual input.ConclusionThe data suggest VSS patients have marked differences in brain processing of visual stimuli, validating its neurobiological basis.

Background The medial occipital lobe, composed of the lingual gyrus and cuneus, is necessary for both basic and higher level visual processing. It is also known to facilitate cross-modal, nonvisual functions, such as linguistic processing and verbal memory, after the loss of the visual senses. A detailed cortical model elucidating the white matter connectivity associated with this area could improve our understanding of the interacting brain networks that underlie complex human processes and postoperative outcomes related to vision and language. Methods Generalized q-sampling imaging tractography, validated by gross anatomic dissection for qualitative visual agreement, was performed on 10 healthy adult controls obtained from the Human Connectome Project. Results Major white matter connections were identified by tractography and validated by gross dissection, which connected the medial occipital lobe with itself and the adjacent cortices, especially the temporal lobe. The short- and long-range connections identified consisted mainly of U-shaped association fibers, intracuneal fibers, and inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, middle longitudinal fasciculus, and lingual–fusiform connections. Conclusions The medial occipital lobe is an extremely interconnected system, supporting its ability to perform coordinated basic visual processing, but also serves as a center for many long-range association fibers, supporting its importance in nonvisual functions, such as language and memory. The presented data represent clinically actionable anatomic information that can be used in multimodal navigation of white matter lesions in the medial occipital lobe to prevent neurologic deficits and improve patients' quality of life after cerebral surgery.

Objectives Many studies on various meditation types have reported regional gray matter volume changes using voxel-based morphometric analysis of structural MRI, but there are no studies done on structural MRI of Rajyoga meditators. The objective of the present study is to analyze and compare gray matter volume changes of brain regions in meditators and non-meditators and further study the effects of meditation experience on alterations in various brain regions. These regions were then correlated and compared to positive thought scores of participants. Methods Forty participants in each group (closely matched for age, gender, and handedness) were selected after obtaining their informed consent, and voxel-based morphometric analysis was carried out using their structural MRI scans. Results On voxel-wise comparison of the brain scans, meditators were observed to have significantly higher global gray matter volume and significant regional gray matter volume increases in the right superior frontal gyrus, left inferior orbitofrontal cortex, left inferior parietal gyrus, left posterior cerebellum, left middle temporal gyrus, bilateral precuneus, and cuneus. Additionally, long-term meditators particularly had significantly higher positive thinking scores compared to non-meditators. On multiple regression analysis, gray matter volume of the left superior parietal gyrus and left inferior parietal gyrus had a positive association, whereas the left posterior cerebellum had a negative association with hours of meditation experience. With the positive thoughts score, a significant relationship was found in the right superior temporal gyrus in meditators. Conclusions These findings indicate that Rajyoga meditation experience/practice enhances gray matter volume of specific brain regions and positive thoughts.

Working memory is a basic human cognitive function. However, the genetic signatures and their biological pathway remain poorly understood. In the present study, we tried to clarify this issue by exploring the potential associations and pathways among genetic variants, brain morphometry and working memory performance. We first carried out association analyses between 2‐back accuracy and 212 image‐derived phenotypes from 1141 Human Connectome Project (HCP) subjects using a linear mixed model (LMM). We found a significantly positive correlation between the left cuneus volume and 2‐back accuracy (T = 3.615, p = 3.150e−4, Cohen's d = 0.226, corrected using family‐wise error [FWE] method). Based on the LMM‐based genome‐wide association study (GWAS) on the HCP dataset and UK Biobank 33 k GWAS summary statistics, we identified eight independent single nucleotide polymorphisms (SNPs) that were reliably associated with left cuneus volume in both UKB and HCP dataset. Within the eight SNPs, we found a negative correlation between the rs76119478 polymorphism and 2‐back accuracy accuracy (T = −2.045, p = .041, Cohen's d = −0.129). Finally, an LMM‐based mediation analysis elucidated a significant effect of left cuneus volume in mediating rs76119478 polymorphism on the 2‐back accuracy (indirect effect = −0.007, 95% BCa CI = [−0.045, −0.003]). These results were also replicated in a subgroup of Caucasians in the HCP population. Further fine mapping demonstrated that rs76119478 maps on intergene CTD‐2315A10.2 adjacent to protein‐encoding gene DAAM1, and is significantly associated with L3HYPDH mRNA expression. Our study suggested this new variant rs76119478 may regulate the working memory through exerting influence on the left cuneus volume., Working memory's genetic signatures and biological pathways remain poorly understood. Using the UK Biobank GWAS summary statistic and the HCP dataset, new variant rs76119478 may regulate the working memory through exerting influence on the left cuneus volume.

Speakers regulate vocal motor behaviors in a compensatory manner when perceiving errors in auditory feedback. Little is known, however, about the source of interindividual variability that exists in the degree to which speakers compensate for perceived errors. The present study included 40 young adults to investigate whether individual differences in auditory integration for vocal pitch regulation, as indexed by vocal compensations for pitch perturbations in auditory feedback, can be predicted by cortical morphology as assessed by gray-matter volume, cortical thickness, and surface area in a whole-brain manner. The results showed that greater gray-matter volume in the left inferior parietal lobule and greater cortical thickness and surface area in the left superior/middle temporal gyrus, temporal pole, inferior/superior parietal lobule, and precuneus predicted larger vocal responses. Greater cortical thickness in the right inferior frontal gyrus and superior parietal lobule and surface area in the left precuneus and cuneus were significantly correlated with smaller magnitudes of vocal responses. These findings provide the first evidence that vocal compensations for feedback errors are predicted by the structural morphology of the frontal and tempo-parietal regions, and further our understanding of the neural basis that underlies interindividual variability in auditory–motor control of vocal production.

Our study aimed to investigate whether changes in brain function measured with functional magnetic resonance imaging (fMRI) can be detected among individuals with depressive disorders and suicidal ideation. The association between depression severity and brain images is also discussed. Our study recruited 111 participants in three groups: 35 depressive patients with suicidal ideation (SI), 32 depressive patients without suicidal ideation (NS), and 44 healthy controls (HCs). All participants were scanned using 3T MRI to obtain resting-state functional images, and functional connectivity (FC), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and graph theoretical analysis (GTA) were performed. We found functional activity differences, such as the hippocampus and thalamus, in the SI group compared with the NS group. We also concluded lower activity in the thalamus and cuneus regions were related to suicidal ideation. We also found several functional connectivity of the brain areas, such as hippocampus, cuneus, and frontal regions, in the SI group correlated with Hamilton Depression Rating Scale (HAM-D) and Hospital Anxiety and Depression Scale (HADS). A graph theoretical analysis (GTA) and network-based statistical (NBS) analysis revealed different topological organization and slightly better local segregation of the brain network in healthy participants compared with those in depressive patients with suicidal ideation. We suggest that brain functional connectivity may be affected in depressive patients with suicidal ideation.

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.

IntroductionLisdexamfetamine (LDX) is a drug used to treat ADHD/impulsive patients. Impulsivity is known to affect inhibitory, emotional and cognitive function. On the other hand, smell and odor processing are known to be affected by neurological disorders, as they are modulators of addictive and impulsive behaviors specifically. We hypothesize that, after LDX ingestion, inhibitory pathways of the brain would change, and complementary behavioral regulation mechanisms would appear to regulate decision-making and impulsivity.Methods20 children were studied in an aleatory crossover study. Imaging of BOLD-fMRI activity, elicited by olfactory stimulation in impulsive children, was performed after either LDX or placebo ingestion.ResultsFindings showed that all subjects that underwent odor stimulation presented activations of similar intensities in the olfactory centers of the brain. This contrasted with inhibitory regions of the brain such as the cingulate cortex and frontal lobe regions, which demonstrated changed activity patterns and intensities. While some differences between the placebo and medicated states were found in motor areas, precuneus, cuneus, calcarine, supramarginal, cerebellum and posterior cingulate cortex, the main changes were found in frontal, temporal and parietal cortices. When comparing olfactory cues separately, pleasant food smells like chocolate seemed not to present large differences between the medicated and placebo scenarios, when compared to non-food-related smells.ConclusionsWe demonstrated that LDX, first, altered the inhibitory pathways of the brain, second, increased activity in large amounts of brain regions which were not activated by smell in drug-naïve patients, third, facilitated a complementary behavioral regulation mechanism, run by the cerebellum, which regulated decision-making and impulsivity in motor and frontal structures.

Despite advances in understanding the consequences of age-related episodic memory decline for future simulation, much remains unknown regarding changes in the neural underpinnings of future thinking with age. We used a repetition suppression paradigm to explore age-related changes in the neural correlates of emotional future simulation. Younger and older adults simulated positive, negative, and neutral future events either two or five times. Reductions in neural activity for events simulated five versus two times (i.e., repetition suppression) identifies brain regions responsive to the specific emotion of simulated events. Critically, older adults showed greater repetition suppression than younger adults in the temporal pole for negative simulations, and the cuneus for positive simulations. These findings suggest that older adults distance themselves from negative future possibilities by thinking about them in a more semantic way, consistent with the view that older adults down-regulate negative affect and up-regulate positive affect. More broadly this study increases our understanding of the impact of aging on the neural underpinnings of episodic future simulation.

Purpose Temporal lobe epilepsy is increasingly being recognized as a disorder associated with brain networks extending outside the seizure onset zone. In the current study, we aim to clarify regional functional changes using a regional homogeneity method. Methods We retrospectively included resting-state fMRI data from 14 left and 18 right temporal lobe epilepsy patients. Data from the control group were acquired from an open dataset. Regional homogeneity was calculated, and a two-sample t-test was performed to compare the left and right temporal lobe epilepsy groups with the control group. Results Compared with the healthy control group, the left temporal lobe epilepsy group showed increased regional homogeneity in the left anterior and middle cingulate cortex, and putamen; right inferior frontal gyrus; bilateral temporal lobe and precentral gyrus and decreased regional homogeneity in the left superior parietal gyrus, cuneus and inferior occipital gyrus; right inferior parietal lobule and bilateral rectus. The right temporal lobe epilepsy group showed increased regional homogeneity in the left middle cingulate cortex, precuneus, precentral and postcentral gyrus; right insula and bilateral temporal lobe and decreased regional homogeneity in the left cuneus and superior occipital gyrus; right supramarginal gyrus, fusiform gyrus, lingual gyrus, inferior occipital gyrus and putamen; and the bilateral rectus. Conclusion Regional homogeneity measurements provide evidence supporting that temporal lobe epilepsy is a complex network disease. Functional disruption of temporal lobe epilepsy at the brain region level was revealed, which may provide novel insights for any potential diagnostic and therapeutic approaches.

Objective Using functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients. Methods Twenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients. Results The group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A. Conclusion Our results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.

OBJECTIVE To understand the changes in functional connectivity between brain areas of potential importance in migraine during different phases of the attack. BACKGROUND Migraine is a symptomatically heterogeneous disorder. Understanding the possible changes in brain function and, therefore, neurobiology during different phases of the migraine attack is important in developing disease biomarkers and advancing therapeutics. DESIGN Randomized, double-blind, placebo-controlled, multi-visit experimental study. METHODS Subjects aged 18-50 years with migraine with and without aura (≤22 headache days per month) were recruited from across the UK using advertising, from both population and hospital clinic samples (n = 53). Consented subjects were randomized to a 0.5 µg/kg/min nitroglycerin infusion or to placebo over 20 minutes across different study visits, during the period February 2015-July 2017.* All subjects were exposed to a nitroglycerin infusion at least on 1 occasion at screening.** For those subjects who consented to participate in imaging visits (n = 25), structural T1, T2 and FLAIR sequences and resting state blood oxygen level dependant contrast (rsBOLD) time series, using a multiecho EPI sequence, were conducted over 30-40 minutes at baseline and rsBOLD during premonitory symptoms and migraine headache on a 3T General Electric MR750 MRI scanner. For the placebo visit, the imaging was conducted at the same times following infusion in the absence of symptoms. RESULTS Montreal Neurological Institute (MNI) coordinates were used to characterize identified brain areas of connectivity change. Using repeated measures ANOVA models with time (visit number) and trigger substance (nitroglycerin/placebo) as factors, significant positive functional coupling was found between the thalami bilaterally and the right precuneus and cuneus regions during the nitroglycerin-triggered premonitory phase (T = 3.23, peak connectivity change at [-6, -68, 40] for left thalamus, P = 0.012 and [-4, -68, 40] for right thalamus, P = 0.019). The nitroglycerin-triggered premonitory phase was associated with a change in the direction of connectivity from positive to negative between the pons and the limbic lobe (T = 3.47, peak connectivity change at [2, 8, 50], P

Background To measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity. Methods In this cross-sectional, case-control study, vascular volume fraction, effective diffusion, parenchymal diffusion, and blood flow parameters were regionally compared in cSLE patients and matched healthy controls. These markers of microvascular and microstructural integrity were derived by diffusion-weighted brain MRI and intravoxel incoherent motion (IVIM) modeling. Formal neurocognitive testing was completed focused on the domains of attention, visuoconstructional ability, working memory, and psychomotor speed. Test scores and measures of disease severity were regressed against regional microvascular integrity parameters among cSLE patients. Results Formal cognitive testing confirmed normal cognitive ability among all cSLE patients included in the analysis (n = 11). Nevertheless, reduction in blood volume fraction coincided with increased effective diffusion and flow parameters in cSLE patients vs. controls in posterior brain regions including the cuneus and precuneus. Regional microvascular measures correlated (|r| = 0.54–0.66) with neuropsychiatric scores and disease activity among cSLE patients. Conclusions There is imaging evidence, using IVIM, of degraded microvascular integrity in cSLE patients with normal cognitive ability. The observed regional changes correspond with posterior vascular border zones. These outcomes appear consistent with regional gray matter volume loss previously observed in cSLE patients with overt neurocognitive deficits, supporting the notion that adverse vascular changes precede loss of cognitive ability in cSLE. Longitudinal studies are needed to confirm the findings of this initial study.

Objective Multimodal magnetic resonance imaging (MRI) was used to detect whether 6 months after pain relieving, the structural and functional abnormalities in the brain of postherpetic neuralgia (PHN) patients are changeable. Methods Fifteen successfully treated PHN patients were enrolled ; the brain activity and structural abnormalities were detected and compared before and 6 months after treatment. The functional parameters were evaluated with resting-state functional MRI technique, i.e., the regional homogeneity (ReHo) and fractional amp litude of low-frequency fluctuation (fALFF). Structural changes were detected with voxel-based morphometry (VBM) and diffusion kurtosis imaging (DKI). Results Six months after pain relieving, PHN brain showed different ReHo and fALFF values in the frontal lobe, caudate, supramarginal gyrus, anterior cingulate cortex (ACC), cuneus, middle temporal gyrus, and cerebellum. In addition, VBM intensity in the cerebellum increased; DKI values decreased in the thalamus and increased in the temporal lobe after successful treatment. Conclusion Six months after pain relieving, functional and structural changes exist in PHN brain. Changes in some differential areas in PHN brain, such as ACC, frontal lobe, thalamus, and temporal lobe indicate that the central plasticity may be reversible after chronic pain relieving.

The apolipoprotein E (APOE) e4 allele is a genetic risk factor for Alzheimer's disease, whereas educational attainments have protective effects against cognitive decline in aging and patients with Alzheimer's disease. We examined the possible effects of years of education and APOE genotype on the topological properties of the functional network in normal aging, mild cognitive impairment and Alzheimer's disease. The years of education showed a significant, negative association with the local efficiency, clustering coefficient and small-worldness of functional networks in APOE e4 noncarriers but not in e4 carriers. These associations were mainly observed in normal aging and were reduced in mild cognitive impairment and Alzheimer's disease. Moreover, regions of the inferior frontal gyrus, temporal pole, and cuneus also showed correlations between education and nodal degree. Our findings demonstrated that the protective effects of education persist in APOE e4 noncarriers but diminish in e4 carriers. In addition, the protective effects of education were attenuated or reduced in the progression of Alzheimer's disease.

OBJECTIVE Cervical spondylotic myelopathy is regarded as a chronic, special incomplete spinal cord injury, so the sensory components transmitted to thalamus decreased after distal spinal cord injury, which lead the disturbance of thalamus-cortex circuits, which might explain the alterations of clinical function of cervical spondylotic myelopathy patients. However, for lack of effective methods to evaluate the disturbance circuits and how the relative mechanism adapt to the recovery of cervical spondylotic myelopathy patients after decompression. Therefore, this study aim to explore how the possible mechanism of thalamus-cortex circuits reorganization adapt to the recovery of clinical function. METHODS Regard thalamus as the interest area, we evaluate the brain functional connectivity within 43 pre-operative cervical spondylotic myelopathy patients, 21 post-operative (after 3 months) cervical spondylotic myelopathy patients and 43 healthy controls. Functional connectivity difference between pre-/post-operative cervical spondylotic myelopathy group and healthy controls group were obtained by two independent samples t-test, and difference between pre-operative cervical spondylotic myelopathy and post-operative cervical spondylotic myelopathy group were obtained by paired t-test. Clinical function was measured via Neck Disability Index and Japanese Orthopaedic Association scores. Furthermore, Pearson correlation were used to analyse the correlation between functional connectivity values and clinical scores. RESULTS Compared with healthy controls group, pre-operative cervical spondylotic myelopathy group showed increased functional connectivity between left thalamus and bilateral lingual gyrus/cuneus/right cerebellum posterior lobe (Voxel P-value

Cerebral palsy is a neurodevelopmental movement disorder that affects coordination and balance. Therapeutic treatments for balance deficiencies in this population primarily focus on the musculoskeletal system, whereas the neural basis of balance impairment is often overlooked. Magnetic resonance elastography (MRE) is an emerging technique that has the ability to sensitively assess microstructural brain health through in vivo measurements of neural tissue stiffness. Using magnetic resonance elastography, we have previously measured significantly softer grey matter in children with cerebral palsy as compared with typically developing children. To further allow magnetic resonance elastography to be a clinically useful tool in rehabilitation, we aim to understand how brain stiffness in children with cerebral palsy is related to dynamic balance reaction performance as measured through anterior and posterior single-stepping thresholds, defined as the standing perturbation magnitudes that elicit anterior or posterior recovery steps. We found that global brain stiffness is significantly correlated with posterior stepping thresholds ( P = .024) such that higher brain stiffness was related to better balance recovery. We further identified specific regions of the brain where stiffness was correlated with stepping thresholds, including the precentral and postcentral gyri, the precuneus and cuneus, and the superior temporal gyrus. Identifying brain regions affected in cerebral palsy and related to balance impairment can help inform rehabilitation strategies targeting neuroplasticity to improve motor function.

This study aimed to identify to resting-state cerebral blood flow (CBF) connectivity alterations in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Three-dimensional pseudo-continuous arterial spin labeling (pcASL) imaging was performed to measure the resting-state CBF in 23 patients with anti-NMDAR encephalitis at the peak stage of the disease and 32 healthy subjects. CBF was normalized to reduce variations among subjects. CBF was compared between the groups, and the correlations between the CBF alterations and clinical parameters were assessed. Differences in CBF connectivity in specific brain regions were also compared between groups. Compared with the healthy subjects, the patients with anti-NMDAR encephalitis exhibited increased CBF in the left insula (L_insula), left superior temporal lobe (L_STL), L_hippocampus, L_pallidum, bilateral putamen (Bi_putamen), and Bi_caudate, and decreased CBF in the bilateral precuneus (Bi_Pc) and bilateral occipital lobe (Bi_OL) (P

Background The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month). Methods We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥50% reduction of baseline headache days and poor outcome was defined as reduction Results Among 56 patients with HFM, 37 had good outcome and 19 poor outcome. Compared to the healthy controls (n = 37), patients with poor outcome had decreased GMV over the left posterior cingulate gyrus, and increased GMV over the bilateral cerebellum and the right precentral gyrus. Further, patients with poor outcome had greater GMV over the right and the left cerebella compared to patients with good outcome, and the GMVs of the cerebella were correlated to 2-year headache frequencies (right: r = 0.38, P = 0.005; left: r = 0.35, P = 0.009). Structural connectivity were increased between the cerebellum and the cuneus, the calcarine cortex, and the temporal lobe, respectively, in patients with poor outcome, and was decreased between the cerebellum and the prefrontal cortex in patients with poor outcome. The structural covariance integrities between the right cerebellum and the right cuneus were correlated to 2-year headache frequencies (r = 0.36, P = 0.008). Conclusions Structural volume and connectivity changes of the cerebellum may underlie headache persistence in patients with HFM.

Objective To identify important clinical or imaging features predictive of an individual's response to electroconvulsive therapy (ECT) by utilizing a machine learning approach. Methods Twenty-seven depressed patients who received ECT were recruited. Clinical demographics and pretreatment structural magnetic resonance imaging (MRI) data were used as candidate features to build models to predict remission and post-ECT Hamilton Depression Rating Scale scores. Support vector machine and support vector regression with elastic-net regularization were used to build models using (i) only clinical features, (ii) only MRI features, and (iii) both clinical and MRI features. Consistently selected features across all individuals were identified through leave-one-out cross-validation. Results Compared with models that include only clinical variables, the models including MRI data improved the prediction of ECT remission: the prediction accuracy improved from 70% to 93%. Features selected consistently across all individuals included volumes in the gyrus rectus, the right anterior lateral temporal lobe, the cuneus, and the third ventricle, as well as 2 clinical features: psychotic features and family history of mood disorder. Conclusions Pretreatment structural MRI data improved the individual predictive accuracy of ECT remission, and only a small subset of features was important for prediction.

Background Recently, a biologically-driven psychosis classification (B-SNIP Biotypes) was derived using brain-based cognitive and electrophysiological markers. Here, we characterized a local functional-connectivity measure, regional homogeneity (ReHo), as a biomarker across Biotypes and conventional DSM diagnoses. Methods Whole-brain ReHo measures of resting-state functional MRI were examined in psychosis patients and healthy controls organized by Biotype and by DSM-IV-TR diagnosis (n = 737). Group-level ANOVA and individual-level prediction models using support vector machines (SVM) were employed to evaluate the discriminative characteristics in comparisons of 1) DSM diagnostic groups, 2) Biotypes, to controls, and 3) within-proband subgroups with each other. Results Probands grouped by Biotype versus controls showed a unique abnormality pattern: Biotype-1 displayed bidirectional ReHo differences in more widespread areas, with higher ReHo in para-hippocampus, fusiform, inferior temporal, cerebellum, thalamus and caudate, plus lower ReHo in the postcentral gyrus, middle temporal, cuneus, and middle occipital cortex; Biotype-2 and Biotype-3 showed lesser and unidirectional ReHo changes. Among diagnostic groups, only schizophrenia showed higher ReHo versus control values in the inferior/middle temporal area and fusiform gyrus. For within-patient comparisons, Biotype-1 showed characteristic ReHo when compared to Biotype-2 and Biotype-3. SVM results more accurately identified Biotypes than DSM diagnoses. Conclusion We characterized patterns of ReHo abnormalities across both Biotypes and DSM sub-groups. Both group-level statistical and machine-learning methods were more sensitive in capturing ReHo deficits in Biotypes than DSM. Overall ReHo is a robust psychosis biomarker.

Yuan-Yuan Wu,* Shui-Feng Wang,* Pei-Wen Zhu, Qing Yuan, Wen-Qing Shi, Qi Lin, Biao Li, You-Lan Min, Qiong Zhou, Yi Shao Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong Zhou; Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Donghu, Nanchang, Jiangxi 330006, People’s Republic of ChinaEmail 1357483244@qq.com; freebee99@163.comPurpose: The purpose was to investigate the differences in spontaneous functional connectivity (FC) of the primary visual cortex (V1) between patients with neovascular glaucoma (NVG) and healthy controls (HCs) using resting-state functional magnetic resonance imaging data.Methods: A total of 18 patients with NVG (nine males and nine females) and 18 HCs with similar age and sex background were enrolled in the study and inspected using resting-state functional magnetic resonance imaging. The differences in FC of the V1 between the two groups were compared using the independent samples t-test. We used the receiver operating characteristic (ROC) curve to compare the average FC values of NVG subjects with those of HCs.Results: FC in the left V1 and right fusiform gyrus, bilateral cuneus, and left precuneus was significantly decreased in the NVG group compared with that reported in the HC group. Meanwhile, patients with NVG presented increased FC between the right V1 and bilateral middle frontal gyrus. However, they also exhibited declining FC between the right V1 and left precuneus, and bilateral cuneus. The ROC curve analysis of each brain region indicated that the accuracy of the area under the ROC curves regarding NVG was excellent.Conclusion: NVG involves aberrant FC in the V1 in different brain areas, including the visual-related and cognitive-related regions. These findings may assist in unveiling the underlying neural mechanisms of impaired visual function in NVG.Keywords: neovascular glaucoma, functional connectivity, spontaneous brain activity, primary visual cortex

Background: A single-nucleotide polymorphism (SNP) of the LHPP gene (rs35936514) has been reported to be associated with major depressive disorder (MDD) in genome-wide association studies. However, the systems-level neural effects of rs35936514 that mediate the association are unknown. We hypothesized that variations in rs35936514 would be associated with structural and functional changes in gray matter (GM) at rest in MDD patients. Methods: A total of 50 MDD patients and 113 healthy controls (HCs) were studied. Functional connectivity (FC) was analyzed by defining the bilateral hippocampus as the seed region. Voxel-based morphometry (VBM) was performed to assess the patterns of GM volume. The subjects were further divided into two groups: a CC homozygous group (CC; 24 MDD and 56 HC) and a risk T-allele carrier group (CT/ TT genotypes; 26 MDD and 57 HC). A 2×2 analysis of variance (ANOVA: diagnosis × genotype) was used to determine the interaction effects and main effect (P Results: Significant diagnosis × genotype interaction effects on brain morphology and FC were noted. Compared to other subgroups, the MDD patients with the T allele showed an increased hippocampal FC in the bilateral calcarine cortex and cuneus and a decreased hippocampal FC in the right dorsolateral prefrontal cortex (DLPFC), bilateral anterior cingulate cortex (ACC), and medial prefrontal cortex (MPFC), in addition to reduced GM volume in the right DLPFC, bilateral temporal cortex, and posterior cingulate cortex (PCC). Conclusions: LHPP gene polymorphisms may affect functional and structural changes in the GM at rest and may play an important role in the pathophysiological mechanisms of MDD.

Most of our knowledge on the human neural bases of spatial updating comes from functional magnetic resonance imaging (fMRI) studies in which recumbent participants moved in virtual environments. As a result, little is known about the dynamic of spatial updating during real body motion. Here, we exploited the high temporal resolution of electroencephalography (EEG) to investigate the dynamics of cortical activation in a spatial updating task where participants had to remember their initial orientation while they were passively rotated about their vertical axis in the dark. After the rotations, the participants pointed toward their initial orientation. We contrasted the EEG signals with those recorded in a control condition in which participants had no cognitive task to perform during body rotations. We found that the amplitude of the P1N1 complex of the rotation-evoked potential (RotEPs) (recorded over the vertex) was significantly greater in the Updating task. The analyses of the cortical current in the source space revealed that the main significant task-related cortical activities started during the N1P2 interval (136–303 ms after rotation onset). They were essentially localized in the temporal and frontal (supplementary motor complex, dorsolateral prefrontal cortex, anterior prefrontal cortex) regions. During this time-window, the right superior posterior parietal cortex (PPC) also showed significant task-related activities. The increased activation of the PPC became bilateral over the P2N2 component (303–470 ms after rotation onset). In this late interval, the cuneus and precuneus started to show significant task-related activities. Together, the present results are consistent with the general scheme that the first task-related cortical activities during spatial updating are related to the encoding of spatial goals and to the storing of spatial information in working memory. These activities would precede those involved in higher order processes also relevant for updating body orientation during rotations linked to the egocentric and visual representations of the environment.

BackgroundThe neurobiological mechanisms underlying the effects of delta-9-tetrahydrocannabinol (THC) remain unclear. Here, we examined the spatial acute effect of THC on human on regional brain activation or blood flow (hereafter called ‘activation signal’) in a ‘core’ network of brain regions that subserve a multitude of processes. We also investigated whether the neuromodulatory effects of THC are related to the local expression of its key molecular target, cannabinoid-type-1 (CB1R) but not type-2 (CB2R) receptor.MethodsA systematic search was conducted of acute THC-challenge studies using fMRI, PET, and arterial spin labelling in accordance with established guidelines. Using pooled summary data from 372 participants, tested using a within-subject repeated measures design under experimental conditions, we investigated the effects of a single dose (6-42mg) of THC, compared to placebo, on brain signal.FindingsAs predicted, THC augmented the activation signal, relative to placebo, in the anterior cingulate, superior frontal cortices, middle temporal and middle and inferior occipital gyri, striatum, amygdala, thalamus, and cerebellum crus II and attenuated it in the middle temporal gyrus (spatially distinct from the cluster with THC-induced increase in activation signal), superior temporal gyrus, angular gyrus, precuneus, cuneus, inferior parietal lobule, and the cerebellum lobule IV/V. Using post-mortem gene expression data from an independent cohort from the Allen Human Brain atlas, we found a direct relationship between the magnitude of THC-induced brain signal change, indexed using pooled effect-size estimates, and CB1R gene expression, a proxy measure of CB1R protein distribution, but not CB2R expression. A dose-response relationship was observed with THC dose in certain brain regions.InterpretationThese meta-analytic findings shed new light on the localisation of the effects of THC in the human brain, suggesting that THC has neuromodulatory effects in regions central to many cognitive tasks and processes, with greater effects in regions with higher levels of CB1R expression.