Abnormal interhemispheric functional cooperation in schizophrenia follows the neurotransmitter profiles.

BACKGROUND: Interhemispheric cooperation is one of the most prominent functional architectures of the human brain. In patients with schizophrenia, interhemispheric cooperation deficits have been reported using increasingly powerful neurobehavioural and neuroimaging measures. However, these methods rely in part on the assumption of anatomic symmetry between hemispheres. In the present study, we explored interhemispheric cooperation deficits in schizophrenia using a newly developed index, connectivity between functionally homotopic voxels (CFH), which is unbiased by hemispheric asymmetry. METHODS: Patients with schizophrenia and age- and sexmatched healthy controls underwent multimodal MRI, and whole-brain CFH maps were constructed for comparison between groups. We examined the correlations of differing CFH values between the schizophrenia and control groups using various neurotransmitter receptor and transporter densities. RESULTS: We included 86 patients with schizophrenia and 86 matched controls in our analysis. Patients with schizophrenia showed significantly lower CFH values in the frontal lobes, left postcentral gyrus and right inferior temporal gyrus, and significantly greater CFH values in the right caudate nucleus than healthy controls. Moreover, the differing CFH values in patients with schizophrenia were significantly correlated with positive symptom score and illness duration. Functional connectivity within frontal lobes was significantly reduced at the voxel cluster level compared with healthy controls. Finally, the abnormal CFH map of patients with schizophrenia was spatially associated with the densities of the dopamine D1 and D2 receptors, fluorodopa, dopamine transporter, serotonin transporter and acetylcholine transporter. CONCLUSION: Regional abnormalities in interhemispheric cooperation may contribute to the clinical symptoms of schizophrenia. These CFH abnormalities may be associated with dysfunction in neurotransmitter systems strongly implicated in schizophrenia.

A Controlled Clinical Study of Accelerated High-Dose Theta Burst Stimulation in Patients with Obsessive-Compulsive Disorder.

Background: Obsessive-compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method: Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results: After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups (p < 0.001), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90, p=0.18). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion: Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.

Longitudinal changes in mental health among medical students in China during the COVID-19 epidemic: depression, anxiety and stress at 1-year follow -up.

This study aimed to evaluate the influence of COVID-19 on the mental health of Chinese medical students at 1-year of follow-up. From 2 February 2020 to 23 February 2021, we conducted three waves of research online (T1 = during outbreak, T2 = controlling period, T3 = 1 year after outbreak). The survey collected demographic data and several self reporting questionnaires to measure the depressive, anxiety and stress symptoms. A total of 4002 participants complete the whole research phases. The study major, grade level and gender were the main factors related to psychological distress caused by the COVID-19 crisis. Importantly, medical knowledge has a protective effect on medical students' psychological distress during the COVID-19 period.

Functional and structural alterations in the pain-related circuit in major depressive disorder induced by electroconvulsive therapy.

Approximately two-thirds of major depressive disorder (MDD) patients have pain, which exacerbates the severity of depression. Electroconvulsive therapy (ECT) is an efficacious treatment that can alleviate depressive symptoms; however, treatment for pain and the underlying neural substrate is elusive. We enrolled 34 patients with MDD and 33 matched healthy controls to complete clinical assessments and neuroimaging scans. MDD patients underwent second assessments and scans after ECT. We defined a pain-related network with a published meta-analysis and calculated topological patterns to reveal topologic alterations induced by ECT. Using the amplitude of low-frequency fluctuations (ALFFs), we probed local function aberrations of pain-related circuits in MDD patients. Subsequently, we applied gray matter volume (GMV) to reveal structural alterations of ECT relieving pain. The relationships between functional and structural aberrations and pain were determined. ECT significantly alleviated pain. The neural mechanism based on pain-related circuits indicated that ECT weakened the circuit function (ALFF: left amygdala and right supplementary motor area), while augmenting the structure (GMV: bilateral amygdala/insula/hippocampus and anterior cingulate cortex). The topologic patterns became less efficient after ECT. Correlation analysis between the change in pain and GMV had negative results in bilateral amygdala/insula/hippocampus. Similarity, there was a positive correlation between a change in ALFF in the left amygdala and improved clinical symptoms. ECT improved pain by decreasing brain local function and global network patterns, while increasing structure in pain-related circuits. Functional and structural alterations were associated with improvement in pain.

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior.

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world's population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA-mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.

Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with great potential in the treatment of Parkinson's disease (PD). This study aimed to investigate the clinical efficacy of accelerated rTMS and to understand the underlying neural mechanism. In a double-blinded way, a total of 42 patients with PD were randomized to receive real (n = 22) or sham (n = 20) continuous theta-burst stimulation (cTBS) on the left supplementary motor area (SMA) for 14 consecutive days. Patients treated with real cTBS, but not with sham cTBS, showed a significant improvement in Part III of the Unified PD Rating Scale (p < .0001). This improvement was observed as early as 1 week after the start of cTBS treatment, and maintained 8 weeks after the end of the treatment. These findings indicated that the treatment response was swift with a long-lasting effect. Imaging analyses showed that volume of the left globus pallidus (GP) increased after cTBS treatment. Furthermore, the volume change of GP was mildly correlated with symptom improvement and associated with the baseline fractional anisotropy of SMA-GP tracts. Together, these findings implicated that the accelerated cTBS could effectively alleviate motor symptoms of PD, maybe by modulating the motor circuitry involving the SMA-GP pathway.

Pre-supplementary motor network connectivity and clinical outcome of magnetic stimulation in obsessive-compulsive disorder.

A large proportion of patients with obsessive-compulsive disorder (OCD) respond unsatisfactorily to pharmacological and psychological treatments. An alternative novel treatment for these patients is repetitive transcranial magnetic stimulation (rTMS). This study aimed to investigate the underlying neural mechanism of rTMS treatment in OCD patients. A total of 37 patients with OCD were randomized to receive real or sham 1-Hz rTMS (14 days, 30 min/day) over the right pre-supplementary motor area (preSMA). Resting-state functional magnetic resonance imaging data were collected before and after rTMS treatment. The individualized target was defined by a personalized functional connectivity map of the subthalamic nucleus. After treatment, patients in the real group showed a better improvement in the Yale-Brown Obsessive Compulsive Scale than the sham group (F1,35  = 6.0, p = .019). To show the neural mechanism involved, we identified an "ideal target connectivity" before treatment. Leave-one-out cross-validation indicated that this connectivity pattern can significantly predict patients' symptom improvements (r = .60, p = .009). After real treatment, the average connectivity strength of the target network significantly decreased in the real but not in the sham group. This network-level change was cross-validated in three independent datasets. Altogether, these findings suggest that personalized magnetic stimulation on preSMA may alleviate obsessive-compulsive symptoms by decreasing the connectivity strength of the target network.

Dynamic brain connectome and high risk of mental problem in clinical nurses.

With the growing population and rapid change in the social environment, nurses in China are suffering from high rates of stress; however, the neural mechanism underlying this occupation related stress is largely unknown. In this study, mental status was determined for 81 nurses and 61 controls using the Symptom Checklist 90 (SCL-90) scale. A subgroup (n = 57) was further scanned by resting-state functional MRI with two sessions. Based on the SCL-90 scale, "somatic complaints" and "diet/sleeping" exhibited the most prominent difference between nurses and controls. This mental health change in nurses was further supported by the spatial independent component analysis on functional MRI data. First, dynamic functional connectome analysis identified two discrete connectivity configurations (States I and II). Controls had more time in the State I than II, while the nurses had more time in the State II than I. Second, nurses showed a similar static network topology as controls, but altered dynamic properties. Third, the symptom-imaging correlation analysis suggested the functional alterations in nurses as potential imaging biomarkers indicating a high risk for "diet/sleeping" problems. In summary, this study emphasized the high risk of mental deficits in nurses and explored the underlying neural mechanism using dynamic brain connectome, which provided valuable information for future psychological intervention.

Better modulation for risk decision-making after optimized magnetic stimulation.

Traditional repetitive transcranial magnetic stimulation can only produce a significant but weak effect on the cortex while theta burst stimulation (TBS), a patterned accelerated form of stimulation, can produce a stronger poststimulation effect, which may improve decision-making abilities. We designed a comparative assessment of the effect of intermittent TBS (iTBS), 20 Hz, in two risk decision-making tasks on healthy controls. Participants were randomized and assigned to the iTBS (n = 29), 20 Hz (n = 29), or sham (n = 29) groups. The effects of the different methods of left dorsolateral prefrontal cortex stimulation on risk decision-making functions were compared based on subjects' performance in the Game of Dice Task (GDT) and Risky Gains Task (RGT). The main indicators were positive and negative feedback utilization rates of GDT and RGT. Both iTBS and 20 Hz stimulation resulted in significant improvements upon negative feedback in the GDT, with increases in safe options and reductions in risky options; iTBS stimulation increased subjects' use of positive feedback in the GDT and RGT (all p < 0.05). Furthermore, the iTBS group had a stronger feedback risk reduction effect than the 20 Hz or sham group following RGT negative feedback (p < 0.05). Individuals would integrate positive and negative information more efficiently, leading to them making rational choices after excitatory transcranial magnetic stimulation. Moreover, iTBS has a stronger risk reduction effect following negative feedback than the 20Hz stimulation did. In summary, iTBS might have clinical value in decision promotion.

Therapeutic efficacy of connectivity-directed transcranial magnetic stimulation on anticipatory anhedonia.

BACKGROUND: There are currently no effective treatments specifically targeting anticipatory anhedonia, a major symptom of severe depression which is associated with poor outcomes. The present study investigated the efficacy of individualized repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (lDLPFC)-nucleus accumbens (NAcc) network on anticipatory anhedonia in depression. METHODS: This randomized, double-blind, sham-controlled clinical trial (NCT03991572) enrolled 56 depression patients with anhedonia symptoms. Each participant received 15 once-daily sessions of rTMS at 10 Hz and 100% motor threshold. Stimulation was localized to the site of strongest IDLPFC-NAcc connectivity by functional magnetic resonance imaging. The Hamilton depression rating scale (HAMD) was used to measure depression severity, the temporal experience pleasure scale (TEPS) to measure anticipatory and consummatory anhedonia to specifically measure anticipatory/motivational anhedonia. Event-related potentials during the monetary incentive delay (MID) task were recorded to evaluate the electrophysiological correlates of reward anticipation and response. RESULTS: Patients in the Real group showed significant improvements in anticipatory anhedonia and general depression symptoms posttreatment compared to the Sham group. The Real group also demonstrated more positive going cue-N2 and cue-P3 amplitude during MID reward trials after treatment. The change in cue-P3 posttreatment was positive correlated with improved TEPS-anti score. CONCLUSION: Individualized rTMS of the lDLPFC-NAcc network can effectively alleviate anticipatory anhedonia and improved the reward seeking as evidenced by enhanced MID behavioral performance and more positive going cue-N2 and cue-P3. The lDLPFC-NAcc network plays a critical role in anticipatory reward and motivation processing.

Aberrant brain network topology in the frontoparietal-limbic circuit in bipolar disorder: a graph-theory study.

Characterizing the properties of brain networks across mood states seen in bipolar disorder (BP) can provide a deeper insight into the mechanisms involved in this type of affective disorder. In this study, graph theoretical methods were used to examine global, modular and nodal brain network topology in the resting state using functional magnetic resonance imaging data acquired from 95 participants, including those with bipolar depression (BPD; n = 30) and bipolar mania (BPM; n = 39) and healthy control (HC) subjects (n = 26). The threshold value of the individual subjects' connectivity matrix varied from 0.15 to 0.30 with steps of 0.01. We found that: (1) at the global level, BP patients showed a significantly increased global efficiency and synchronization and a decreased path length; (2) at the nodal level, BP patients showed impaired nodal parameters, predominantly within the frontoparietal and limbic sub-network; (3) at the module level, BP patients were characterized by denser FCs (edges) between Module III (the front-parietal system) and Module V (limbic/paralimbic systems); (4) at the nodal level, the BPD and BPM groups showed state-specific differences in the orbital part of the left superior-frontal gyrus, right putamen, right parahippocampal gyrus and left fusiform gyrus. These results revealed abnormalities in topological organization in the whole brain, especially in the frontoparietal-limbic circuit in both BPD and BPM. These deficits may reflect the pathophysiological processes occurring in BP. In addition, state-specific regional nodal alterations in BP could potentially provide biomarkers of conversion across different mood states.

Finger Tapping Task Activation vs. TMS Hotspot: Different Locations and Networks.

Both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have been used to non-invasively localize the human motor functional area. These locations can be clinically used as stimulation target of TMS treatment. However, it has been reported that the finger tapping fMRI activation and TMS hotspot were not well-overlapped. The aim of the current study was to measure the distance between the finger tapping fMRI activation and the TMS hotspot, and more importantly, to compare the network difference by using resting-state fMRI. Thirty healthy participants underwent resting-state fMRI, task fMRI, and then TMS hotspot localization. We found significant difference of locations between finger tapping fMRI activation and TMS hotspot. Specifically, the finger tapping fMRI activation was more lateral than the TMS hotspot in the premotor area. The fMRI activation peak and TMS hotspot were taken as seeds for resting-state functional connectivity analyses. Compared with TMS hotspot, finger tapping fMRI activation peak showed more intensive functional connectivity with, e.g., the bilateral premotor, insula, putamen, and right globus pallidus. The findings more intensive networks of finger tapping activation than TMS hotspot suggest that TMS treatment targeting on the fMRI activation area might result in more remote effects and would be more helpful for TMS treatment on movement disorders.

A common variant of the NOTCH4 gene modulates functional connectivity of the occipital cortex and its relationship with schizotypal traits.

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.

Increased Accuracy of Emotion Recognition in Individuals with Autism-Like Traits after Five Days of Magnetic Stimulations.

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.

Regional and network properties of white matter function in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder with dysfunction in cortices as well as white matter (WM) tracts. While the changes to WM structure have been extensively investigated in PD, the nature of the functional changes to WM remains unknown. In this study, the regional activity and functional connectivity of WM were compared between PD patients (n = 57) and matched healthy controls (n = 52), based on multimodel magnetic resonance imaging data sets. By tract-based spatial statistical analyses of regional activity, patients showed decreased structural-functional coupling in the left corticospinal tract compared to controls. This tract also displayed abnormally increased functional connectivity within the left post-central gyrus and left putamen in PD patients. At the network level, the WM functional network showed small-worldness in both controls and PD patients, yet it was abnormally increased in the latter group. Based on the features of the WM functional connectome, previously un-evaluated individuals could be classified with fair accuracy (73%) and area under the curve of the receiver operating characteristics (75%). These neuroimaging findings provide direct evidence for WM functional changes in PD, which is crucial to understand the functional role of fiber tracts in the pathology of neural circuits.

Classification of schizophrenia by intersubject correlation in functional connectome.

Functional connectomes have been suggested as fingerprinting for individual identification. Accordingly, we hypothesized that subjects in the same phenotypic group have similar functional connectome features, which could help to discriminate schizophrenia (SCH) patients from healthy controls (HCs) and from depression patients. To this end, we included resting-state functional magnetic resonance imaging data of SCH, depression patients, and HCs from three centers. We first investigated the characteristics of connectome similarity between individuals, and found higher similarity between subjects belonging to the same group (i.e., SCH-SCH) than different groups (i.e., HC-SCH). These findings suggest that the average connectome within group (termed as group-specific functional connectome [GFC]) may help in individual classification. Consistently, significant accuracy (75-77%) and area under curve (81-86%) were found in discriminating SCH from HC or depression patients by GFC-based leave-one-out cross-validation. Cross-center classification further suggests a good generalizability of the GFC classification. We additionally included normal aging data (255 young and 242 old subjects with different scanning sequences) to show factors could be improved for better classification performance, and the findings emphasized the importance of increasing sample size but not temporal resolution during scanning. In conclusion, our findings suggest that the average functional connectome across subjects contained group-specific biological features and may be helpful in clinical diagnosis for schizophrenia.

Hippocampal-subregion functional alterations associated with antidepressant effects and cognitive impairments of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT), an effective antidepressive treatment, is frequently accompanied by cognitive impairment (predominantly memory), usually transient and self-limited. The hippocampus is a key region involved in memory and emotion processing, and in particular, the anterior-posterior hippocampal subregions has been shown to be associated with emotion and memory. However, less is known about the relationship between hippocampal-subregion alterations following ECT and antidepressant effects or cognitive impairments. METHODS: Resting-state functional connectivity (RSFC) based on the seeds of hippocampal subregions were investigated in 45 pre- and post-ECT depressed patients. Structural connectivity between hippocampal subregions and corresponding functionally abnormal regions was also conducted using probabilistic tractography. Antidepressant effects and cognitive impairments were measured by the Hamilton Depressive Rating Scale (HDRS) and the Category Verbal Fluency Test (CVFT), respectively. Their relationships with hippocampal-subregions alterations were examined. RESULTS: After ECT, patients showed increased RSFC in the hippocampal emotional subregion (HIPe) with the left middle occipital gyrus (LMOG) and right medial temporal gyrus (RMTG). Decreased HDRS was associated with increased HIPe-RMTG RSFC (r = -0.316, p = 0.035) significantly and increased HIPe-LMOG RSFC at trend level (r = -0.283, p = 0.060). In contrast, the hippocampal cognitive subregion showed decreased RSFC with the bilateral angular gyrus, and was correlated with decreased CVFT (r = 0.418, p = 0.015 for left; r = 0.356, p = 0.042 for right). No significant changes were found in structural connectivity. CONCLUSION: The hippocampal-subregions functional alterations may be specially associated with the antidepressant and cognitive effects of ECT.

Functional Connectivity of the Corticobasal Ganglia-Thalamocortical Network in Parkinson Disease: A Systematic Review and Meta-Analysis with Cross-Validation.

Purpose To quantitatively summarize the functional connectivity (FC) feature of the corticobasal ganglia-thalamocortical (CBTC) network in patients with Parkinson disease (PD) by means of a meta-analysis with cross-validation. Materials and Methods For this prospective study, a systematic literature search in the PubMed and EMBASE databases was performed for resting-state functional magnetic resonance (MR) imaging studies of PD published between January 2000 and May 2017. Then, a coordinate-based meta-analysis was conducted by Effect Size-Signed Differential Mapping. A cross-validation analysis was performed by using an independent resting-state functional MR imaging data set that contained 25 patients with PD and 19 age-, sex-, and education-matched healthy control participants. Two-sample t test was performed on FC maps between PD and control groups. Results Thirty studies with 854 patients with PD and 831 control participants were included in this meta-analysis. The main meta-analysis found increased FC in the left pre- and postcentral gyrus in patients with PD compared with healthy control participants (z = 2.6; P < .001). The abnormality of the postcentral gyrus was further confirmed by subgroup meta-analyses on medication-naive (n = 25; z = 2.2; P < .001) and medication-off (n = 11; z = 1.5; P < .001) experiments, which suggested that the finding was unaffected by medication. The abnormality of the postcentral gyrus was cross-validated by the independent data set (t = 5.0; P < .05), which suggested a high reproducibility and generalizability. Conclusion This meta-analysis emphasizes the left postcentral gyrus as a critical region in PD, which may become a potential target for clinical intervention. © RSNA, 2018 Online supplemental material is available for this article.

Dynamic aftereffects in supplementary motor network following inhibitory transcranial magnetic stimulation protocols.

The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or "protocol" main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies.

Decreased Network Efficiency in Benign Epilepsy with Centrotemporal Spikes.

Purpose To investigate the functional connectome alterations in benign epilepsy with centrotemporal spikes with respect to the occurrence of interictal epileptic discharges (IEDs) during functional magnetic resonance (MR) imaging. Materials and Methods This prospective study was approved by the local institutional review board and was HIPAA compliant. All participants were consecutively enrolled with written informed consent. Forty-three right-handed patients were classified into IED (n = 20, 13 girls and seven boys; mean age ± standard deviation, 9.00 years ± 1.95) and non-IED (n = 23, 11 girls and 12 boys; mean age, 10.22 years ± 2.13) groups on the basis of electroencephalographic data simultaneously recorded during resting-state functional MR imaging at 3.0 T. The functional connectome features (estimated with graph theoretical analysis) in patient groups and control subjects who were matched for sex, age, and education level (n = 28, all right-handed, 13 girls and 15 boys; mean age, 10.00 years ± 2.31) were compared by using one-way analysis of variance. Results Patients with IEDs and those without IEDs showed consistently abnormal global topology in their functional networks (ie, decreased global efficiency; P < .05) relative to that of control subjects, with no differences between the two patient groups (P > .05). Decreased regional efficiency and connectivity strength were observed in the patients with IEDs and those without (mainly in the perirolandic and frontal areas) relative to control subjects (P < .05). Moreover, the altered functional features significantly correlated with clinical characteristics (ie, disease duration and age at symptom onset, P < .05). Conclusion These findings suggest that decreased global and regional efficiency are prominent functional deficits in children with benign epilepsy with centrotemporal spikes and can be readily identified with resting-state functional MR imaging, irrespective of IEDs. © RSNA, 2016 Online supplemental material is available for this article.