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Abstract The prevalence of autism spectrum disorders (ASDs) differs substantially between males and females, suggesting that sex-related neurodevelopmental factors are central to ASD pathogenesis. Numerous studies have suggested that abnormal brain specialization patterns and poor regional cooperation contribute to ASD pathogenesis, but relatively little is known about the related sex differences. Therefore, this study examined sex differences in brain functional specialization and cooperation among children with ASD. The autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) derived from resting-state functional magnetic resonance imaging (rs-fMRI) were compared between 58 male and 13 female children with ASD. In addition, correlations were examined between regional CFH values showing significant sex differences and symptom scores on the autism behavior checklist (ABC) and childhood autism rating scale (CARS). Male children with ASD demonstrated significantly greater CFH in the left fusiform gyrus (FG) and right opercular part of the inferior frontal gyrus (IFGoperc) than female children with ASD. In addition, the CFH value of the left FG in male children with ASD was negatively correlated with total ABC score and subscale scores for sensory and social abilities. In contrast, no sex differences were detected in brain specialization. These regional abnormalities in interhemispheric cooperation among male children with ASD may provide clues to the neural mechanisms underlying sex differences in ASD symptomatology and prevalence. Autism spectrum disorders, sex, resting-state functional magnetic resonance imaging, cerebral specialization, interhemispheric cooperation.

Abstract Background Cerebral specialization and interhemispheric cooperation are two vital features of the human brain. Their dysfunction may be associated with disease progression in patients with Alzheimer's disease (AD), which is featured as progressive cognitive degeneration and asymmetric neuropathology. Objective This study aimed to examine and define two inherent properties of hemispheric function in patients with AD by utilizing resting‐state functional magnetic resonance imaging (rs‐fMRI). Methods Sixty‐four clinically diagnosed AD patients and 52 age‐ and sex‐matched cognitively normal subjects were recruited and underwent MRI and clinical evaluation. We calculated and compared brain specialization (autonomy index, AI) and interhemispheric cooperation (connectivity between functionally homotopic voxels, CFH). Results In comparison to healthy controls, patients with AD exhibited enhanced AI in the left middle occipital gyrus. This increase in specialization can be attributed to reduced functional connectivity in the contralateral region, such as the right temporal lobe. The CFH of the bilateral precuneus and prefrontal areas was significantly decreased in AD patients compared to controls. Imaging‐cognitive correlation analysis indicated that the CFH of the right prefrontal cortex was marginally positively related to the Montreal Cognitive Assessment score in patients and the Auditory Verbal Learning Test score. Moreover, taking abnormal AI and CFH values as features, support vector machine‐based classification achieved good accuracy, sensitivity, specificity, and area under the curve by leave‐one‐out cross‐validation. Conclusion This study suggests that individuals with AD have abnormal cerebral specialization and interhemispheric cooperation. This provides new insights for further elucidation of the pathological mechanisms of AD.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective noninvasive neuromodulation technique for Parkinson's disease (PD). However, the efficacy of rTMS varies widely between individuals. This study aimed to investigate the factors related to the response to rTMS in PD patients. Methods: We retrospectively analyzed the response of 70 idiopathic PD patients who underwent rTMS for 14 consecutive days targeting the supplementary motor area (SMA) in either an open-label trail (n = 31) or a randomized, double-blind, placebo-controlled trial (RCT) (n = 39). The motor symptoms of PD patients were assessed by the United Parkinson's Disease Rating Scale Part III (UPDRSIII). Based on previous studies, the UPDRSIII were divided into six symptom clusters: axial dysfunction, resting tremor, rigidity, bradykinesia affecting right and left extremities, and postural tremor. Subsequently, the efficacy of rTMS to different motor symptom clusters and clinical predictors were analyzed in these two trails. Results: After 14 days of treatment, only the total UPDRSIII scores and rigidity scores improved in both the open-label trial and the RCT. The results of multiple linear regression analysis indicated that baseline rigidity scores (β = 0.37, p = 0.047) and RMT (β = 0.30, P = 0.02) positively predicted the improvement of UPDRSIII. The baseline rigidity score (β = 0.55, P

Background: Deficits in associative memory (AM) are the earliest and most prominent feature of Alzheimer's disease (AD) and demonstrate a clear cause of distress for patients and their families. Objective: The present study aimed to determine AM enhancements following accelerated intermittent theta-burst stimulation (iTBS) in patients with AD. Methods: In a randomized, double-blind, sham-controlled design, iTBS was administered to the left dorsolateral prefrontal cortex (DLPFC) of patients with AD for 14 days. Measurements included AM (primary outcome) and a comprehensive neuropsychological battery. Patients were evaluated at baseline, following the intervention (week 2), and 8 weeks after treatment cessation (week 10). Results: Sixty patients with AD were initially enrolled; 47 completed the trial. The active group displayed greater AM improvements compared with the sham group at week 2 (P = 0.003), which was sustained at week 10. Furthermore, higher Mini-Mental State Examination (MMSE) scores at baseline were associated with greater AM improvements at weeks 2 and 10. For the independent iTBS group, this correlation predicted improvements in AM (P

ObjectivesSeveral studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM.MethodsIn this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS).ResultsThere was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction.ConclusionOur prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis.

ObjectiveTwo subregions of the dorsolateral prefrontal cortex have been identified as effective repetitive transcranial magnetic stimulation (rTMS) targets for the “anxiosomatic” and “dysphoric” symptoms, respectively. We aimed to develop a convenient approach to locate these targets on the scalp.Materials and methodsIn a discovery experiment, the two personalized targets were precisely identified on 24 subjects using a neuronavigation system. Then, a localized approach was developed based on individual scalp landmarks. This “landmark-based approach” was replicated and validated in an independent cohort (N = 25). Reliability of the approach was tested by calculating the correlation of both the inter-rater and intra-rater results. Validity was tested by comparing the mean distance between the personalized and landmark-based targets to the TMS spatial resolution (i.e., 5 mm). We further conducted a total of 24 sham rTMS sessions to estimate the misplacement between the coil center and target during a 10-min stimulation without neuronavigation.ResultsThe parameters of the “landmark-based approach” in the discovery experiment were replicated well in an independent cohort. Using discovery parameters, we successfully identified the symptom-specific targets in the independent cohort. Specifically, the mean distance between the personalized and landmark-based targets on the cortex was not significantly larger than 5 mm. However, the personalized and landmark-based targets distance exceeded 5 mm in more than 50% of subjects. During the 10-min sham rTMS session, the average coil misplacement was significantly larger than 5 mm.ConclusionThe “landmark-based approach” can conveniently and reliably locate the two symptom-specific targets at group level. However, the accuracy was highly varied at individual level and further improvement is needed.

The correlation between brain structural changes in major depressive disorder (MDD) and gene expression is unclear. Here, the authors explore the correlation between cell type-specific gene expression changes and cortical structural difference in individuals with major depressive disorder.

Abstract Background Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. Methods In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image(rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). Results Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype. Conclusion Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.

White matter hyperintensities (WMHs) are commonly observed in older adults and are associated with cognitive impairment. Although previous studies have found abnormal functional connectivities in patients with WMHs based on static functional magnetic resonance imaging (fMRI), the topological properties in the context of brain dynamics remain relatively unexplored. Herein, we explored disrupted dynamic topological properties of functional network connectivity in patients with WMHs and its relationship with cognitive impairment. We included 36 healthy controls (HC) and 104 patients with mild WMHs (n = 39), moderate WMHs (n = 37), and severe (n = 28) WMHs. The fMRI data of all participants were analyzed using Anatomical Automatic Labeling (AAL) and a sliding-window approach to generate dynamic functional connectivity matrics. Then, graph theory methods were applied to calculate the topological properties. Comprehensive neuropsychological scales were used to assess cognitive functions. Relationships between cognitive functions and abnormal dynamic topological properties were evaluated by Pearson’s correlation. We found that the patients with WMHs had higher temporal variability in regional properties, including betweenness centrality, nodal efficiencies, and nodal clustering coefficient. Furthermore, we found that the degree of centrality was related to executive function and memory, and the local coefficient correlated to executive function. Our results indicate that patients with WMHs have higher temporal variabilities in regional properties and are associated with executive and memory function.

Objective: People with schizophrenia have serious impairments in social function, especially in decision-making ability. Transcranial magnetic stimulation modified intermittent theta burst transcranial magnetic stimulation (iTBS) has been shown to regulate the functional connection of brain networks. Our study explored the therapeutic effect of iTBS on decision-making disorders in schizophrenia.Methods: Participants were pseudorandomized and assigned to iTBS (n = 16) or sham (n = 16) group. iTBS group was administered 1,800 pulses on the target of the left dorsol lateral prefrontal cortex (L-DLPFC) per day for 14 consecutive days. We compared Iowa gambling task performance and associated event-related spectral perturbation results (ERSP) among two groups.Results: The results show that participants' performance in the high-lose in the iTBS group had stronger stimulation of theta spectral power than those in the sham group. Specifically, we found that under high-risk conditions, compared with the control group, the iTBS group showed significant activation of the theta spectrum power in the FPZ, FZ, FCZ, and CZ regions after treatment.Conclusions: Our results provide evidence that long-term iTBS stimulation effectively improves the decision-making ability of schizophrenia. After receiving negative feedback, patients can turn to safety options. These findings support that iTBS may be a potential treatment for clinical decision-making disorders.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder with onset during childhood. Because of its complex spectrum of phenotypes, the underlying pathophysiology of TS is still unclear. Resting-state functional magnetic resonance imaging demonstrated aberrant spontaneous neural synchronization in conventional frequency band (0.01–0.08 Hz) in TS. No published studies have reported abnormalities of local synchronization across different frequency bands. We estimated the alterations of local synchronization across five bands ranging from 0 to 0.25 Hz. Seventy-nine children with TS and 63 age-, sex-, and handedness-matched healthy children were recruited. Frequency-specific regional homogeneity (ReHo) and independent component analysis were used to identify functional alterations between TS and healthy children. TS patients showed significantly increased ReHo in the left precentral gyrus and decreased ReHo in the right operculum. Abnormal ReHo alterations of the superior frontal gyrus, superior parietal gyrus, anterior cingulate gyrus, putamen, superior temporal gyrus, and operculum were observed in different frequency bands. TS patients showed increased connectivity of the right superior frontal gyrus within the left executive control network. In addition, a significantly negative correlation was found between Yale Global Tic Severity Scale (YGTSS) vocal score and ReHo values of the right operculum in the highest frequency bands (0.198–0.25 Hz), while a significant positive correlation was found between YGTSS motor score and altered connectivity of the right superior frontal gyrus. The present study revealed frequency-specific abnormal alterations of ReHo in the whole brain and altered connectivity within the executive control network of TS children. Its neural importance and clinical practicability require further investigation.

Linguistic deficits are frequent symptoms among stroke survivors. The neural mechanism of post-stroke aphasia (PSA) was incompletely understood. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) was widely used among several neuropsychological disorders. However, previous rs-fMRI studies of PSA were limited to very small sample size and the absence of reproducibility with different neuroimaging indexes. The present study performed comparisons with static and dynamic amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) based on modest sample size (40 PSA and 37 healthy controls). Compared with controls, PSA showed significantly increased static ALFF predominantly in the bilateral supplementary motor area (SMA) and right hippocampus-parahippocampus (R HIP-ParaHip) and decreased static ALFF in right cerebellum. The increased dynamic ALFF in SMA and decreased dynamic ALFF in right cerebellum were also found in PSA. The static and dynamic ALFF in right cerebellum was positively correlated with spontaneous speech. The FC between the SMA and R HIP-ParaHip was significantly stronger in patients than controls and positively correlated with ALFF in bilateral SMA. In addition, the FC between the R HIP-ParaHip and the right temporal was also enhanced in patients and negatively correlated with repetition, naming, and comprehension score. These findings revealed consistently abnormal intrinsic neural activity in SMA and cerebellum, which may underlie linguistic deficits in PSA.

ObjectiveAsymmetry is a subtle but pervasive aspect of the human brain, which may be altered in several neuropsychiatric conditions. Magnetic resonance imaging (MRI) studies have reported that cerebral structural asymmetries are altered in Alzheimer’s disease (AD), but most of these studies were conducted at the region-of-interest level. At the functional level, there are few reports of resting-state functional asymmetries based on functional MRI. In this study, we investigated lateral differences in structural volumes and strengths of functional connectivity between individuals with AD and healthy controls (HCs) at the voxel level.MethodsForty-eight patients with AD and 32 matched HCs were assessed. An analysis of voxel-based morphometry (VBM) of gray matter volume was performed at the whole-brain level to explore anatomical cerebral asymmetries in AD. We then performed a seed-to-whole-brain functional connectivity (FC) analysis to reveal FC asymmetries in AD. An asymmetry index (AI) was used to measure these changes, and the relationship between the structural and functional AIs and the clinical symptoms of AD was explored.ResultsA VBM analysis revealed a rightward and a leftward lateralization in the amygdala and the thalamus, respectively, in patients with AD. FC between the amygdala and the precuneus showed a rightward lateralization in AD, which was the opposite of the lateralization in the HCs. The asymmetric changes in structure and function were associated with disease severity and functional impairment in AD.ConclusionOur study highlights the value of considering asymmetries in the amygdala and the thalamus in clinical evaluations and their relevance to clinical measures.

To understand the neural mechanism of repetitive transcranial magnetic stimulation (rTMS), the after-effects following one session or multiple days of stimulation have been widely investigated. However, the relation between the short-term effect (STE) and long-term effect (LTE) of rTMS is largely unknown. This study aims to explore whether the after-effects of 5-day rTMS on supplementary motor area (SMA) network could be predicted by one-session response. A primary cohort of 38 healthy participants underwent five daily sessions of real or sham continuous theta-burst stimulation (cTBS) on the left SMA. Resting-state functional magnetic resonance imaging (fMRI) data were acquired at the first (before and after the first stimulation) and sixth experimental day. The SMA connectivity changes after the first cTBS and after 5 days of stimulation were defined as STE and LTE, respectively. Compared to the baseline, significant STE and LTE were found in the bilateral paracentral gyrus (ParaCG) after real stimulation, suggesting shared neural correlates of short- and long-term stimulations. Region-of-interest analysis indicated that the resting-state functional connectivity between SMA and ParaCG increased after real stimulation, while no significant change was found after sham stimulation. Leave-one-out cross-validation indicated that the LTE in ParaCG could be predicted by the STE after real but not sham stimulations. In an independent cohort, the after-effects of rTMS on ParaCG and short- to long-term prediction were reproduced at the region-of-interest level. These imaging evidences indicate that one-session rTMS can aid to predict the regions responsive to long-term stimulation and the individualized response degree.

The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent (BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxel's ALFF by the global mean ALFF, named mALFF. Although fractional ALFF (fALFF), a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. The current study borrowed the percent signal change in task fMRI studies and proposed percent amplitude of fluctuation (PerAF) for RS-fMRI. We firstly applied PerAF and mPerAF (i.e., divided by global mean PerAF) to eyes open (EO) vs. eyes closed (EC) RS-fMRI data. PerAF and mPerAF yielded prominently difference between EO and EC, being well consistent with previous studies. We secondly performed test-retest reliability analysis and found that (PerAF ≈ mPerAF ≈ mALFF) > (fALFF ≈ mfALFF). Head motion regression (Friston-24) increased the reliability of PerAF, but decreased all other metrics (e.g. mPerAF, mALFF, fALFF, and mfALFF). The above results suggest that mPerAF is a valid, more reliable, more straightforward, and hence a promising metric for voxel-level RS-fMRI studies. Future study could use both PerAF and mPerAF metrics. For prompting future application of PerAF, we implemented PerAF in a new version of REST package named RESTplus.

Individuals with autism-like traits (ALT) belong to a subclinical group with similar social deficits as autism spectrum disorders (ASD). Their main social deficits include atypical eye contact and difficulty in understanding facial expressions, both of which are associated with an abnormality of the right posterior superior temporal sulcus (rpSTS). It is still undetermined whether it is possible to improve the social function of ALT individuals through noninvasive neural modulation. To this end, we randomly assigned ALT individuals into the real (n=16) and sham (n=16) stimulation groups. All subjects received five consecutive days of intermittent theta burst stimulation (iTBS) on the rpSTS. Eye tracking data and functional magnetic resonance imaging (fMRI) data were acquired on the first and sixth days. The real group showed significant improvement in emotion recognition accuracy after iTBS, but the change was not significantly larger than that in the sham group. Resting-state functional connectivity (rsFC) between the rpSTS and the left cerebellum significantly decreased in the real group than the sham group after iTBS. At baseline, rsFC in the left cerebellum was negatively correlated with emotion recognition accuracy. Our findings indicated that iTBS of the rpSTS could improve emotion perception of ALT individuals by modulating associated neural networks. This stimulation protocol could be a vital therapeutic strategy for the treatment of ASD.

A number of repetitive transcranial magnetic stimulation (rTMS) protocols have been developed for modulating brain function non-invasively. To identify the most powerful one, these protocols have been compared in the context of the motor system. However, to what extent the conclusions could be generalized to high-level functions is largely unknown. In this study, we compared the modulatory effect of three excitatory rTMS protocols on high-level cognition represented by response inhibition ability. Our first experiment revealed that intermittent theta-burst stimulation (iTBS) could significantly improve reaction time in a stop signal task, while 5-Hz and 25-Hz stimuli were ineffective. This iTBS effect was significantly higher than that for the sham simulation and only occurred in the second session of the stop signal task after iTBS in the first experiment. However, this aftereffect of iTBS was not reproduced in the second experiment, indicating high variability across subjects. Thus, on the one hand, our findings indicate that iTBS on the pre-SMA could improve inhibitory control, but on the other hand, the reliability and reproducibility of this effect needs further investigation.

Alzheimer’s disease (AD) is a common memory-impairment disorder frequently accompanied by olfactory identification (OI) impairments. In fact, OI is a valuable marker for distinguishing AD from normal age-related cognitive impairment and may predict the risk of mild cognitive impairment (MCI)-to-AD transition. However, current olfactory tests were developed based on Western social and cultural conditions, and are not very suitable for Chinese patients. Moreover, the neural substrate of OI in AD is still unknown. The present study investigated the utility of a newly developed Chinese smell identification test (CSIT) for OI assessment in Chinese AD and MCI patients. We then performed a correlation analysis of gray matter volume (GMV) at the voxel and region-of-interest (ROI) levels to reveal the neural substrates of OI in AD. Thirty-seven AD, 27 MCI, and 30 normal controls (NCs) completed the CSIT and MRI scans. Patients (combined AD plus MCI) scored significantly lower on the CSIT compared to NCs [F(2,91) = 62.597, p < 0.001)]. Voxel-level GMV analysis revealed strong relationships between CSIT score and volumes of the left precentral gyrus and left inferior frontal gyrus (L-IFG). In addition, ROI-level GMV analysis revealed associations between CSIT score and left amygdala volumes. Our results suggest the following: (1) OI, as measured by the CSIT, is impaired in AD and MCI patients compared with healthy controls in the Chinese population; (2) the severity of OI dysfunction can distinguish patients with cognitive impairment from controls and AD from MCI patients; and (3) the left-precentral cortex and L-IFG may be involved in the processing of olfactory cues.

Empathy, including cognitive and emotional empathy, refers to the ability to infer the mental states of others and to the capacity to share emotions. The neural mechanisms involved in empathy are complex and not yet fully understood, and previous studies have shown that both cognitive and emotional empathy are closely associated with the inferior frontal gyrus (IFG). In this study, we examined whether empathy can be modulated by high-definition transcranial direct current stimulation (HD-tDCS) of the right IFG. Twenty-three healthy participants took part in all three experimental conditions (i.e., anodal, cathodal and sham stimulation) in a randomized order. Participants then completed the Chinese version of the Multifaceted Empathy Test (MET), which assesses both cognitive and emotional empathy. The results show that scores obtained for cognitive empathy following cathodal stimulation are significantly lower than those obtained following sham stimulation. In addition, scores obtained for cognitive empathy following anodal stimulation are higher than those obtained following sham stimulation, though the difference is only marginally significant. However, the results fail to show whether the stimulation of the right IFG via HD-tDCS plays a role in emotional empathy. Our results suggest that the right IFG plays a key role in cognitive empathy and indicate that HD-tDCS can regulate cognitive empathy by inducing excitability changes in the right IFG.

Despite decades of research on depression, the underlying pathophysiology of depression remains incompletely understood. Emerging evidence from task-based studies suggests that the abnormal reward-related processing contribute to the development of depression. It is unclear about the function pattern of reward-related circuit during resting state in depressive patients. In present study, seed-based functional connectivity was used to evaluate the functional pattern of reward-related circuit during resting state. Selected seeds were two key nodes in reward processing, medial orbitofrontal cortex (mOFC) and nucleus accumbens (NAcc). Fifty depressive patients and 57 healthy participants were included in present study. Clinical severity of participants was assessed with Hamilton depression scale and Hamilton anxiety scale. We found that compared with healthy participants, depressive patients showed decreased connectivity of right mOFC with left temporal pole (TP_L), right insula extending to superior temporal gyrus (INS_R/STG) and increased connectivity of right mOFC with left precuneus. Similarly, decreased connectivity of left mOFC with TP_L and increased connectivity with cuneus were found in depressive patients. There is also decreased connectivity of right NAcc with bilateral temporal pole, as well as decreased connectivity of left NAcc with INS_R/STG. In addition, the functional connectivity of right nucleus accumbens with right temporal pole (TP_R) was negatively correlated with clinical severity. Our results emphasize the role of communication deficits between reward systems and paralimbic cortex in the pathophysiology of depression.

Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and limbic networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, medial temporal lobe, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (hand knob area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS.

The aim of the current study was to localize the epileptic focus and characterize its causal relation with other brain regions, to understand the cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 37 children with BECTS and 25 children matched for age, sex and educational achievement. We identified the potential epileptogenic zone (EZ) by comparing the amplitude of low frequency fluctuation (ALFF) of spontaneous blood oxygenation level dependent fMRI signals between the groups. Granger causality analysis was applied to explore the causal effect between EZ and the whole brain. Compared with controls, children with BECTS had significantly increased ALFF in the right postcentral gyrus and bilateral calcarine, and decreased ALFF in the left anterior cingulate cortex, bilateral putaman/caudate, and left cerebellum. ALFF values in the putaman/caudate were positively correlated with verbal IQ scores in patients. The ALFF values in cerebellum and performance IQ scores were negatively correlated in patients. These results suggest that ALFF disturbances in the putaman/caudate and cerebellum play an important role in BECTS cognitive dysfunction. Compared with controls, the patients showed increased driving effect from the EZ to the right medial frontal cortex and posterior cingulate cortex and decreased causal effects from the EZ to left inferior frontal gyrus. The causal effect of the left inferior frontal gyrus negatively correlated with disease duration, which suggests a relation between the epileptiform activity and language impairment. All together, these findings provide additional insight into the neurophysiological mechanisms of epilepitogenisis and cognitive dysfunction associated with BECTS.

Although mesial temporal lobe epilepsy (mTLE) is characterized by the pathological changes in mesial temporal lobe, function alteration was also found in extratemporal regions. Our aim is to investigate the information flow between the epileptogenic zone (EZ) and other brain regions. Resting-state functional magnetic resonance imaging (RS-fMRI) data were recorded from 23 patients with left mTLE and matched controls. We first identified the potential EZ using the amplitude of low-frequency fluctuation (ALFF) of RS-fMRI signal, then performed voxel-wise Granger causality analysis between EZ and the whole brain. Relative to controls, patients demonstrated decreased driving effect from EZ to thalamus and basal ganglia, and increased feedback. Additionally, we found an altered causal relation between EZ and cortical networks (default mode network, limbic system, visual network and executive control network). The influence from EZ to right precuneus and brainstem negatively correlated with disease duration, whereas that from the right hippocampus, fusiform cortex, and lentiform nucleus to EZ showed positive correlation. These findings demonstrate widespread brain regions showing abnormal functional interaction with EZ. In addition, increased ALFF in EZ was positively correlated with the increased driving effect on EZ in patients, but not in controls. This finding suggests that the initiation of epileptic activity depends not only on EZ itself, but also on the activity emerging in large-scale macroscopic brain networks. Overall, this study suggests that the causal topological organization is disrupted in mTLE, providing valuable information to understand the pathophysiology of this disorder.