IntroductionMajor depressive disorder with suicidal ideation (MDD/SI+) is characterized by high prevalence, high recurrence rate, high disability rate and low response rate. There is an urgent need for clarifying the pathogenesis and developing novel treatment methods.MethodsSubjects were recruited for the collection of Magnetic Resonance Imaging data and clinical scales. Individual target-transcranial magnetic stimulation (IT-TMS) using Stanford Neuromodulation Therapy over individualized left dorsolateral prefrontal cortex was performed to treat MDD/SI+ with the ethical approval (KY20212218-C-1). GRETNA software was used to analyze brain network characteristics according to graph theory.ResultsA total of 32 patients (aged 18-55) and 28 healthy controls (aged 20-51) had been recruited. Patients after IT-TMS treatment had significant reduction in suicidal ideation and depressive symptom. The functional network of all three groups conformed to small-world topology. There was a renormalization in topology structure after IT-TMS treatment. Decreased functional connectivity between right insula and left anterior cingulate gyrus correlated with improvement in Beck Scale for Suicide Ideation scores.DiscussionThe current study highlights that MDD/SI+ patients in this cohort showed abnormal brain network connections compared to healthy controls, and that IT-TMS may exert its treatment effects by reducing spontaneous hyper-connectivity in the salience network and insula.

Dear Editor, The resection of intracranial tumors, such as acoustic neuroma, often causes facial paralysis.1 Injury to the facial nerve is the immediate cause of this paralysis. Nerve anastomosis, including hypoglossal–facial2 and masseteric–facial nerve anastomosis (MFA),3 is an effective method to remodel the injured nerve and establish a nerve regeneration pathway.4, 5 However, regaining normal facial function and good symmetry takes more than 12 months.6 Repetitive transcranial magnetic stimulation (rTMS) applies a continuously adjustable magnetic field to the central nervous system (CNS), achieving cumulative curative results. However, whether rTMS can be used to promote recovery from facial paralysis is known. Here, we report accelerated facial recovery with a novel form of rTMS, individual-target TMS (IT-TMS). The patient's recovery period was reduced to approximately 6 months with a corresponding improvement in House–Brackmann (HB) scale results. The patient was a 33-year-old woman who had surgery for the removal of a left acoustic neuroma on June 15, 2021. Then she gradually developed facial paralysis on the left side, evaluated as grade VI using the HB scale. The paralysis was initially complicated by loss of control of the left facial muscles, deviation of the mouth to the right side, facial asymmetry, and incomplete eyelid closure. Symptoms progressed to left facial dystonia and stiffness, loss of control of the angulus oris on the lesioned side, an expanded area of unclosed eyelid, and self-reported insomnia. Four months later, the patient underwent MFA (Figure 1A,B) on October 16, 2021. During the following 1 month prior to IT-TMS treatment, the patient received daily traditional Chinese medicine treatment. She was also prescribed nerve growth factor and vitamin B12. However, her facial function did not improve and the facial grade VI persisted. The patient denied a history of facial trauma or other tumor surgery, and she had had a normal facial function before the removal of the acoustic neuroma. The possibility of epilepsy, magnetic resonance imaging (MRI) contraindications, and other diseases were excluded (Table S1). The patient provided written informed consent. This study was approved by the Ethics Committee of Xijing Hospital and conducted under the Declaration of Helsinki. IT-TMS (Figure 1C) was initiated at the Department of Neurosurgery, Xijing Hospital, on November 15, 2021. IT-TMS was performed under established safety guidelines and protocols,7 using a stimulator with a figure-8 coil and a neuronavigational system, the Black Dolphin Navigation Robot (S-50, Solide Company, Xi'an, China), with a coupled three-dimensional individualized facial tracer and infrared cameras that guided the precise and repetitive targeting over the same site across different sessions. The specific anatomical sites are in the precentral gyrus that are corresponding to masseteric muscles (Figure 1D). Briefly, the predefined targets, based on individual MRI brain images collected prior to treatment, were integrated into the operation system, in which a three-dimensional restoration of brain images and targets was visualized (Figure 1C). This process allowed the visual operation for target selection and monitoring. The patient received 10 Hz stimulation at 120% of the resting motor threshold delivering 18 trains with an inter-train interval of 8 s (1800 pulses per session, 2 sessions/3600 pulses per day, 5 days/10 sessions per week, 1 week interval after 1 week stimulation). The intersession interval was 50 min, and the treatment lasted 6 months. The schematic signal transduction evoked by IT-TMS is shown in Figure 1E. The patient was instructed by a professional physiotherapist to perform 30 min of facial exercises daily (as shown in Video S1 and S2) immediately after IT-TMS. She was also encouraged to do the daily exercises during the weekly interval as well. The clinical information is summarized in Table S1. The HB results are shown in Table 1 for baseline, timepoint 1 (T1), and timepoint 2 (T2). The records for three facial actions are shown. Before IT-TMS treatment (baseline), the patient had obvious facial asymmetry at rest (Figure 1F), a disfigured face when attempting to use mimetic musculature (Figure 1G), and a broad eyelid gap (Figure 1H). After the first month of treatment (T1), her symptoms were partially improved, as indicated by less asymmetry, oral improvement, and more closure of the eyelid. Six months later (T2), the patient had complete facial symmetry, restored facial expression, and almost complete closure of the eyelid. The movement ability and stiffness were significantly improved after 6 months of IT-TMS treatment. The patient also reported good sleep and recovery from dry eyes. Her treatment was terminated on May 15, 2022. No significant adverse effects were reported during or after treatment. Patients with facial paralysis have been reported to have a reduced area of the brain cortex corresponding to facial function on the lesioned side, and the remodeling of facial representations is closely correlated with a better prognosis.8 In our study, IT-TMS targeting masseteric muscle representations successfully improved facial stiffness, strength, and symmetry. Compared with previously published results,6 the addition of IT-TMS shortened the time needed for rehabilitation, from more than 12 months to approximately 6 months. The significantly accelerated process allowed better recovery within a shorter period of time and allowed the patient a quicker return to normal life. The effects could be attributed to the projections of neural impulses activated by IT-TMS from the CNS into the facial nerve (Figure 1E), helping to strengthen masseteric–facial nerve transfer and remodel cortical representations. IT-TMS, combined with facial exercises, led to excitatory after-effects and improved recovery. Moreover, IT-TMS guaranteed the precise stimulation over the masseteric hotspot and therefore offered significant efficacy, notably improving the clinical treatment of facial paralysis. In conclusion, IT-TMS could be a promising means of neurostimulation to accelerate facial recovery for patients who would otherwise undergo a longer period of rehabilitation. A larger-sample trial is going on to verify the effects demonstrated in this case study and to optimize the parameters. In addition, it would be worthwhile to study whether a higher dose of stimulation could lead to a shorter recovery period. Comparison with a sham group and an exercise-only group are also warranted. This work was supported by Academic Discipline Boosting Program of Xijing Hospital (grant number XJZT19Ml13). The authors declare that they have no conflict of interest. Facial exercises-facial movement Facial exercises-muscle massage Supplementary Table 1-An overview of clinical information of this patient Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

目的 产后抑郁症(postpartum depression,PPD)属于抑郁症的一种亚型,不但严重影响家庭及工作的正常运行,甚至会产生自杀意念.随着神经成像技术的发展让我们更深一步了解了PPD脑损伤的机制,即前额叶-脑岛-杏仁核环路的异常代谢活动可能介导了PPD的发病.最近斯坦福加速智能神经调节疗法对耐药性抑郁症具有较高的缓解率,可能是临床快速治疗PPD的有效疗法.本研究拟明确个体化靶向(transcranial magnetic stimulation,TMS)治疗PPD的临床疗效与脑影响变化的关系.方法 收集32例个体化经颅磁治疗前后的PPD患者(functional magnetic resonance imaging,fMRI)数据,并与32名健康对照的脑影响进行比较,并基于体素的镜像同伦连接性分析(voxel-mirrored homotopic connectivity,VMHC)治疗前后患者大脑半球功能连接的变化.结果 发现经过TMS治疗后患者的汉密尔顿抑郁症量表(hamilton depression scale,HAMD-17)、爱丁堡产后抑郁量表(edinburgh postnatal depression Scale,EPDS)等与大脑半球间/内的功能连接均发生变化,特别是PPD患者在经过rTMS治疗后额叶、脑岛、杏仁核等脑区减少的镜像同伦连接性在治疗后表现出重组.此外,在rTMS治疗后左右脑岛之间连接性的增加与EPDS得分的降低显著相关.结论 我们的结果揭示了人类大脑半球间/内的功能连接异常可能是导致PPD的关键因素,并为rTMS高效缓解PPD的病理机制和临床应用提供了证据.

Background Efforts to resection of glioma lesions located in brain-eloquent areas must balance the extent of resection (EOR) and functional preservation. Currently, intraoperative direct electrical stimulation (DES) is the gold standard for achieving the maximum EOR while preserving as much functionality as possible. However, intraoperative DES inevitably involves risks of infection and epilepsy. The aim of this study was to verify the reliability of individual-target transcranial magnetic stimulation (IT-TMS) in preoperative mapping relative to DES and evaluate its effectiveness based on postsurgical outcomes. Methods Sixteen language-eloquent glioma patients were enrolled. Nine of them underwent preoperative nTMS mapping (n=9, nTMS group), and the other seven were assigned to the non-nTMS group and did not undergo preoperative nTMS mapping (n=7). Before surgery, online IT-TMS was performed during a language task in the nTMS group. Sites in the cortex at which this task was disturbed in three consecutive trials were recorded and regarded as positive and designated nTMS hotspots (HS nTMS ). Both groups then underwent awake surgery and intraoperative DES mapping. DES hotspots (HS DES ) were also determined in a manner analogous to HS nTMS . The spatial distribution of HS nTMS and HS DES in the nTMS group was recorded, registered in a single brain template, and compared. The center of gravity (CoG) of HS nTMS (HS nTMS-CoG )-based and HS DES-CoG -based diffusion tensor imaging-fiber tracking (DTI-FT) was performed. The electromagnetic simulation was conducted, and the values were then compared between the nTMS and DES groups, as were the Western Aphasia Battery (WAB) scale and fiber-tracking values. Results HS nTMS and HS DES showed similar distributions (mean distance 6.32 ± 2.6 mm, distance range 2.2-9.3 mm, 95% CI 3.9-8.7 mm). A higher fractional anisotropy (FA) value in nTMS mapping ( P =0.0373) and an analogous fiber tract length ( P =0.2290) were observed. A similar distribution of the electric field within the brain tissues induced by nTMS and DES was noted. Compared with the non-nTMS group, the integration of nTMS led to a significant improvement in language performance (WAB scores averaging 78.4 in the nTMS group compared with 59.5 in the non-nTMS group, P =0.0321 < 0.05) as well as in brain-structure preservation (FA value, P =0.0156; tract length, P =0.0166). Conclusion Preoperative IT-TMS provides data equally crucial to DES and thus facilitates precise brain mapping and the preservation of linguistic function.

OBJECTIVE:To analyze the changes of brain small-world and node function network properties in patients with insomnia following radiotherapy for cervical cancer based on graph theory analysis and explore the correlation between functional networks and the clinical efficacy of individual-target transcranial magnetic stimulation (IT-TMS) for treatment of insomnia.METHODS:The resting state functional magnetic resonance imaging (rs-fMRI) data were collected from 30 patients with insomnia following radiotherapy for cervical cancer and 30 matched healthy individuals. All the patients received accelerated intelligent neuromodulation TMS therapy. Using graph theory analysis and GRETNA software, the functional connectivity matrices were constructed and the attribute features were extracted. The scores on the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) of the participants were collected before and after IT-TMS, and the correlation between improvement in insomnia and the functional network was investigated.RESULTS:The two groups matched for age, gender, and education level (P>0.05) showed significant differences in PSQI, ISI, SAS and SDS scores (P<0.05). Both groups showed attributes of the small-world network. Compared with the healthy individuals, the patients showed significantly decreased σ, EI, Cp and Lp (P<0.05) and increased Eg (P<0.05) at baseline, which, along with insomnia symptoms, were all improved after IT-TMS treatment. The patients showed reduced functional connections of the node network at follow-up compared with the baseline, and the low functional connectivity between the right insula and left superior frontal gyrus was correlated with the improvement of ISI scores.CONCLUSION:The patients with insomnia following radiotherapy for cervical cancer have impaired information integration ability of the brain network, IT-TMS can significantly improve insomnia symptoms by reducing the hyperconnectivity between the default mode network and the salience network.

Stroke is the leading cause of disability globally in need of novel and effective methods of rehabilitation. Intermittent theta burst stimulation (iTBS) has been adopted as a Level B recommendation for lower limb spasticity in guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Nonetheless, the methodological differences and deficits of existing work bring about heterogenous results and therefore limit the universal clinical use of rTMS in lower extremity (LE) rehabilitation. The variation of stimulated targets across motor cortex contributes mainly to these heterogeneities. This narrative review includes studies of rTMS on LE motor function rehabilitation in patients after stroke until now. Some analyses of brain imaging and electromagnetic simulation and quantification through computational modeling were also performed. rTMS appears capable of fostering LE motor rehabilitation after stroke, but the actually stimulated targets are considerably bias making it difficult to confirm effectiveness. The main reason for this phenomenon is probably inaccurate targeting of motor cortical leg representation. An underlying updated method is proposed as Individual-Target TMS (IT-TMS) combined with brain imaging. rTMS is a promising validated method for LE function regaining. Future studies should systematically compare the effects of IT-TMS with traditional rTMS using large samples in random clinical trials. This article is categorized under: Neuroscience > Clinical Neuroscience.

Primary insomnia (PI) is among the most prevalent sleep-related disorders and has a far-reaching impact on daytime functioning. Repetitive transcranial magnetic stimulation (rTMS) has drawn attention because of its effectiveness and safety. The purpose of the current study was to detect changes in the topological organization of whole-brain functional networks and to determine their associations with the clinical treatment effects of rTMS. Resting-state functional magnetic resonance imaging (rsfMRI) data from 32 patients with PI were collected and compared with findings from 32 age- and gender-matched healthy controls (HCs). The patients were treated with Stanford accelerated intelligent neuromodulation therapy, which is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation protocol. Graph theoretical analysis was used to construct functional connectivity matrices and to extract the attribute features of small-world networks in insomnia. Scores on the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the associations between these clinical characteristics and functional metrics, were the primary outcomes. At baseline, the patients with PI showed inefficient small-world property and aberrant functional segregation and functional integration compared with the HCs. These properties showed renormalization after individualized rTMS treatment. Furthermore, low functional connectivity between the right insula and left medial frontal gyrus correlated with improvement in ISI scores. We highlight functional network dysfunctions in PI patients and provide evidence into the pathophysiological mechanisms involved and the possible mode of action of rTMS.

Postpartum depression (PPD) is a depressive condition that is associated with a high risk of stressful life events, poor marital relationships, and even suicide. Neuroimaging techniques have enriched our understanding of cerebral mechanisms underlying PPD; namely, abnormalities in the amygdala-insula-frontal circuit might contribute to the pathogenesis of PPD. Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation repetitive transcranial magnetic stimulation (rTMS) protocol. It has been shown to be effective, safe, tolerable, and rapid acting for treating treatment-resistant depression, and may be a valuable tool in the treatment of PPD. The purpose of the current study was to detect inter-hemispheric connectivity changes and their relationship with the clinical treatment effects of rTMS. Resting-state fMRI data from 32 patients with PPD treated with SAINT were collected and compared with findings from 32 age matched healthy controls. Voxel-mirrored homotopic connectivity (VMHC) was used to analyze the patterns of interhemispheric intrinsic functional connectivity in patients with PPD. Scores on the 17-item Hamilton Depression Rating Scale, Edinburgh Postnatal Depression Scale (EPDS) scores, and the relationships between these clinical characteristics and VMHC were the primary outcomes. Patients with PPD at baseline showed reduced VMHC in the amygdala, insula, and medial frontal gyrus compared with the HCs. These properties showed a renormalization after individualized rTMS treatment. Furthermore, increased connectivity between the left and right insula after SAINT was significantly correlated with the improvement of EPDS scores. Our results reveal the disruptions in the intrinsic functional architecture of interhemispheric communication in patients with PPD, and provide evidence for the pathophysiological mechanisms and the effects of rTMS.

Objective:To explore the efficacy, safety and possible brain network mechanisms of individualized targeted robot assisted Stanford accelerated intelligent neuromodulation therapy (SAINT).Methods:This was a small-sample, open-label study including 15 depressed patients with suicidal ideation. All participants were treated with SAINT in combination with SNRIs. The stimulation target was localized to the region of the left dorsolateral prefrontal cortex (DLPFC) that showed the most negative functional connectivity with the subgenual anterior cingulate cortex (sgACC) based on fMRI data. Stimulation sessions were delivered hourly. Ten sessions were applied per day (18, 000 pulses/day) for 5 consecutive days (90, 000 pulses in total). Stimulation was delivered at 90% resting motor threshold. The changes of functional connectivity of brain networks in various brain regions before and after treatment were compared and analyzed by rest software and functional connectivity analysis based on seed points. The Beck Suicidal Ideation Scale Chinese Version (BSI-CV), HAMD 17, and MADRS were used to assess the suicidal ideation and depressive symptoms at baseline, post treatment, 15 days after treatment, and 30 days after treatment. Statistical analysis was performed using repeated measurements of ANOVA and paired t-tests. Results:(1) After 5-day treatment, individual′s BSI-CV score decreased significantly ( F=38.77, P<0.01), and their average score decreased by 11.80±1.17 (95 %CI=8.19-15.41), with a response rate of 86.67%. SAINT was well tolerated, and there were no significant side effects on individual′s cognitive function. (2) After treatment, patient′s MADRS score decreased significantly at all follow-up assessments ( F=306.97, P<0.01), and the average score decreased by 22.53±1.10 (95 %CI=19.15-25.91) after 5-day treatment, with a response rate of 93.33%. After 15 days and 30 days, the remission and response rates of treatment were 53.33%, 100.00%, 93.33% and 100.00%, respectively. (3) The functional network connectivity after individualized targeted robot assisted SAINT therapy showed significant improvement between sgACC, frontal lobe, temporal lobe, and parietal lobe. Conclusion:Individualized targeted robot assisted SAINT therapy showed satisfactory efficacy and safety in the reduction of suicidal ideation and depressive symptoms, and also improve the functional network connectivity of the injured brain network. Meanwhile, large-sample, randomized, and double-blind controlled studies are warranted to confirm the findings of the current study.

Suicidal ideation increases precipitously in patients with depression, contributing to the risk of suicidal attempts. Despite the recent advancement in transcranial magnetic stimulation, its effectiveness in depression disorder and its wide acceptance, the network mechanisms of the clinical response to suicidal ideation in major depressive disorder remain unclear. Independent component analysis for neuroimaging data allows the identification of functional network connectivity which may help to explore the neural basis of suicidal ideation in major depressive disorder. Resting-state functional magnetic resonance imaging data and clinical scales were collected from 30 participants (15 major depressive patients with suicidal ideation and 15 healthy subjects). Individual target-transcranial magnetic stimulation (IT-TMS) was then used to decrease the subgenual anterior cingulate cortex activity through the left dorsolateral prefrontal cortex. Thirty days post IT-TMS therapy, seven of 15 patients (46.67%) met suicidal remission criteria, and 12 patients (80.00%) met depression remission criteria. We found that IT-TMS could restore the abnormal functional network connectivity between default mode network and precuneus network, left executive control network and sensory-motor network. Furthermore, the changes in functional network connectivity between the default mode network and precuneus network were associated with suicidal ideation, and depressive symptoms were related to connectivity between left executive control network and sensory-motor network. These findings illustrate that IT-TMS is an effective protocol for the accurate restoration of impaired brain networks, which is consistent with clinical symptoms.

Mild traumatic brain injury (mTBI) initiating long-term effects on white matter integrity resembles brain-aging changes, implying an aging process accelerated by mTBI. This longitudinal study aims to investigate the mTBI-induced acceleration of the brain-aging process by developing a neuroimaging model to predict brain age. The brain-age prediction model was defined using relevance vector regression based on fractional anisotropy from diffusion-tensor imaging of 523 healthy individuals. The model was used to estimate the brain-predicted age difference (brain-PAD) between the chronological and estimated brain age in 116 acute mTBI patients and 63 healthy controls. Fifty patients were followed 6~12 months to evaluate the longitudinal changes in brain-PAD. We investigated whether brain-PAD was greater in patients with elderly age, post-concussion complaints, and apolipoprotein E (APOE) ε4 genotype, and whether it had the potential to predict neuropsychological outcomes. The brain-age prediction model predicted brain age accurately (r = 0.96). The brains of mTBI in the acute phase were estimated to be "older", with greater brain-PAD (2.59 ± 5.97 years) than the healthy controls (0.12 ± 3.19 years) (P < 0.05), and remained stable 6-12 month post-injury (2.50 ± 4.54 years). Patients with older age or post-concussion complaints, rather than APOE ε4 genotype, had greater brain-PADs (P < 0.001, P = 0.024). Additionally, brain-PAD in the acute phase predicted information processing speed at the 6~12 month follow-up (r = -0.36, P = 0.01). In conclusion, mTBI accelerates the brain-aging process, and brain-PAD may be capable of evaluating aging-associated issues post-injury, like increased risks of neurodegeneration.

The present study examined dynamic interhemispheric structural and functional connectivity in mild traumatic brain injury (mTBI) patients with longitudinal observations from early subacute to chronic stages within 1 year of injury. Forty-two mTBI patients and 42 matched healthy controls underwent clinical and neuropsychological evaluations, diffusion tensor imaging, and resting-state functional magnetic resonance imaging. All mTBI patients were initially evaluated within 14 d post-injury (T-1) and at 3 months (T-2) and 6-12 months (T-3) follow-ups. Separate transcallosal fiber tracts in the corpus callosum (CC) with respect to their specific interhemispheric cortical projections were derived with fiber tracking and voxel-mirrored homotopic connectivity analyses. With diffusion tensor imaging-based tractography, five vertical segments of the CC (I-V) were distinguished. Correlation analyses were performed to evaluate relationships between structural and functional imaging measures as well as imaging indices and neuropsychological measures. The loss of integrity in the CC demonstrated saliently persistent and time-dependent regional specificity after mTBI. The impairment spanned multiple segments from CC II at T-1 and CC I, II, VI, and V at T-2 to all subregions at T-3. Moreover, loss of interhemispheric structural connectivity through the CC corresponded well to regions presenting altered interhemispheric functional connectivity. Decreased functional connectivity in the dorsolateral prefrontal cortex thereafter contributed to poor executive function in mTBI patients. The current study provides further evidence that the CC is a sign to interhemispheric highways underpinning the widespread cerebral pathology typifying mTBI syndrome.

OBJECTIVE:To investigate regional white matter fibers loss in Leukoaraiosis (LA) and its relationship with cognitive impairments.METHODS:Fifty-six participants with LA and 38 healthy controls underwent clinical evaluations and MR scans. Participants with LA were classified as cognitively normal (LA-NC, n = 18), vascular cognitive impairment of none dementia (LA-VCIND, n = 24), and vascular dementia (LA-VaD, n = 14) by Mini-Mental State Examination and Clinical Dementia Rating. Cognitive domains including visual-spatial, naming, attention, language, abstraction, memory, and orientation were assessed. With the use of Tract-based spatial statistics, mean fractional anisotropy (FA) of major white matter fiber tracts were compared between LA and controls and among LA groups with varying levels of cognitive impairments. Regression analyses were performed to evaluate relationships between FA values and cognitive performance.RESULTS:Participants showed significant FA reduction in the corpus callosum (CC), bilateral corona radiata, anterior limb of the internal capsule, external capsule, posterior thalamic radiation, and superior longitudinal fasciculus compared to controls and across LA groups. The LA-VaD group showed consistent damage in the body and genu of CC compared to the LA-NC and LA-VCIND groups. A positive correlation between visual-spatial and FA reduction in right anterior corona radiates in LA-VCIND and body of CC in LA- VaD.INTERPRETATION:We found regional fiber loss in the CC across the cognitive spectrum in patients with LA and correlations between FA and visuospatial impairment in the anterior corona radiata in patients with LA-VCIND and in the body of CC in patients with LA-VaD.

Stroke is a leading cause of motor disability. Acupuncture is an effective therapeutic strategy for poststroke motor impairment. However, its mechanism is still elusive. Twenty-two stroke patients having a right-hemispheric subcortical infarct and 22 matched healthy controls were recruited to undergo diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) scanning. The resting-state fMRI was implemented before and after needling at GB34 (Yanglingquan). The stroke patients presented a substantially reduced fractional anisotropy value in the right superior longitudinal fasciculus (SLF), corticospinal tract, and corpus callosum. The structural integrity of the frontoparietal part of the SLF (SLF-FP) correlated with the motor scores of lower limbs in stroke patients. This corticocortical association bundle originated from the premotor cortex (PM) and the adjacent supplementary motor area (SMA), known as secondary motor areas, and terminated in the supramarginal gyrus (SMG). After acupuncture intervention, the corresponding functional connectivity between the PM/SMA and SMG was enhanced in stroke patients compared with healthy controls. These findings suggested that the integrity of the SLF is a potential neuroimaging biomarker for motor disability of lower limbs following a stroke. Acupuncture could increase the communication between the cortices connected by the impaired white matter tracts, implying the neural mechanism underlying the acupuncture intervention.

Mild traumatic brain injury (mTBI) is the most common neurological insult and leads to long-lasting cognitive impairments. The immune system modulates brain functions and plays a key role in cognitive deficits, however, the relationship between TBI-induced changes in inflammation-related cytokine levels and cognitive consequences is unclear. This was investigated in the present study in two cohorts of individuals within 1 week of mTBI (n = 52, n = 43) and 54 matched healthy control subjects. Patients with mTBI were also followed up at 1 and 3 months post-injury. Measures included cognitive assessments and a 9-plex panel of serum cytokines including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-12, chemokine ligand 2 (CCL2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). The contribution of cytokine levels to cognitive function was evaluated by multivariate linear regression analysis. The results showed that serum levels of IL-1β, IL-6, and CCL2 were acutely elevated in mTBI patients relative to controls; CCL2 level was remained high over 3 months whereas IL-1β and IL-6 levels were declined by 3 months post-injury. A high level of CCL2 was associated with greater severity of post-concussion symptoms (which survived in the multiple testing correction); elevated IL-1β was associated with worse working memory in acute phase (which failed in correction); and acute high CCL2 level predicted higher information processing speed at 3 months post-injury (which failed in correction). Thus, acute serum cytokine levels are useful for evaluating post-concussion symptoms and predicting cognitive outcome in participants with mTBI.

Acupuncture at pericardium 6 (PC6) shows a consistently positive efficacy in nausea response suggested by consensus expert guidelines. Nausea encompasses aversive symptom as well as strong emotional components. Disgust is a subjective emotion of uneasy commonly accompanying with a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Understanding the brain circuitry by which acupuncture influences the disgust emotion may further elucidate the modulation effect of acupuncture on aversive experience. In the present study, a well-established aversive conditioning model on healthy subjects was combined with acupuncture intervention at PC6, as well as different acupoints (both local PC7 and distant GB37) as separate controls, to investigate the brain network involved aversive regulation with acupuncture; 48 healthy subjects were enrolled and randomized into four parallel groups: group 1 received disgust-induced (DI) stimuli only; groups 2, 3, and 4 received acupuncture at three single acupoints separately prior to the DI. Disgust sensations were rated at baseline and following disgust stimuli. Acupuncture PC6 can induce significant attenuations in disgust sensations than that of no intervention and acupuncture at other acupoints. Neuroimaging further showed that increased causal interaction strength between the cerebellum (nodulus) and insula can predict greater attenuations in aversive experiences. We also found evidence for radical reorganizations of local stronger casual interaction patterns to disgust-induced brain responses targeted by acupuncture at different acupoints. This study provided the brain substrate for acupuncture on aversion modulation. The coupling between the cerebellum (nodulus) and insula supported interoception system and vestibular control which provided the specific neural basis.

Patients with mild traumatic brain injury (mTBI) may suffer from a widespread spectrum of symptoms that arise from the damage of long-distance white matter connections in distributed brain networks. In brain networks, an increasing attention has been devoted to assessing the functional roles of regions by estimating the spatial layout of their connections among different modules, using the participation coefficient. In the present study, we aimed to investigate the role of hubs in inter-subnetwork information coordination and integration by using participation coefficients after mTBI. 74 patients after mTBI within 7 days post-injury and 51 matched healthy controls enrolled in this study. Our results presented that hubs for mTBI patients distributed in more extensive networks such as the default mode network (DMN), ventral attention network (VAN) and frontoparietal network (FPN), somatomotor network (SMN) and visual network (VN), compared with healthy controls limited to the first three. Participation coefficients for mTBI presented significantly decreased in the DMN (P=0.015) and FPN (P=0.02), while increased in the VN (P=0.035). SVM trained with participation coefficient metrics were able to identify mTBI patients from controls with 78% accuracy, providing for its diagnose potential in clinical settings. From our point of view, difference between two groups could be related with functional network reorganization in mTBI groups.

The main objective of this study was to evaluate sex differences in cortical thickness after acute mild traumatic brain injury (mTBI) and its associations with clinical outcomes. Thirty-two patients with mTBI at acute phase (2.4 ± 1.3 days post-injury) and 30 healthy controls were enrolled. All the participants underwent comprehensive neurocognitive assessments and MRI to assess cortical thickness. Significant sex differences were determined by using variance analysis of factorial design. Relations between the cortical thickness and clinical assessments were measured with the Spearman Correlation. Results revealed that patients with mTBI had significantly reduced cortical thickness in the left entorhinal cortex while increased cortical thickness in the left precuneus cortex and right lateral occipital cortex, compared with healthy controls. The interaction effect of the group × sex on cortical thickness was significant. Female patients had significant thicker cortical thickness in the left caudal anterior cingulate cortex (ACC) than male patients and had higher scores on Posttraumatic stress disorder Checklist—Civilian Version (PCL-C). Spearman correlational analysis showed a significantly positive correlations between the cortical thickness of the left caudal ACC and PCL-C ratings in female patients. Sex differences in cortical thickness support its potential as a neuroimaging phenotype for investigating the differences in clinical profiles of mild TBI between women and men.

Traumatic brain injury (TBI) is a substantial public health problem. Differences in the progress of recovery make it a heterogeneous injury and limit effective diagnostic tools that depend on patients’ clinical manifestation. Neuroimaging methods have been widely applied in published reports, especially advanced neuroimaging techniques such as diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). fMRI is a widely used diagnostic imaging method for task-related dysfunction after TBI and in the assessment of cognitive. It can measure the fluctuations that exist in human brains during either active task states or a resting state. DTI, a relatively new MRI technique that is sensitive to microstructural abnormalities shows great advantages on visualizing axonal injury and major pathology in white matter tracts following TBI. It can be a significant early indicator for TBI, providing prognostics for later injury.

OBJECTIVE:Post-traumatic headache (PTH) is one of the most frequent and persistent physical symptoms following mild traumatic brain injury (mTBI) and develop in more than 50% of this population. This study aimed to investigate the periaqueductal grey (PAG)-seeded functional connectivity (FC) in patients with mTBI with acute post-traumatic headache (APTH) and further examine whether the FC can be used as a neural biomarker to identify patients developing chronic pain 3 months postinjury.METHODS:70 patients with mTBI underwent neuropsychological measurements and MRI scans within 7 days postinjury and 56 (80%) of patients were followed up at 3 months. 46 healthy controls completed the same protocol on recruitment to the study. PAG-seeded resting-state FC analysis was measured in 54 patients with mTBI with APTH, in comparison with 46 healthy volunteers.RESULTS:The mTBI+APTH group presented significantly reduced PAG-seeded FC within the default mode network (DMN), compared with healthy volunteers group. The connectivity strength can also predict patients' complaints on the impact of headache on their lives. Crucially, the initial FC strength between the PAG-right precuneus as well as the PAG-right inferior parietal lobule became the important predictor to identify patients with mTBI developing persistent PTH 3 months postinjury.CONCLUSIONS:Patients with mTBI+APTH exhibited significant PAG-related FC differences mainly within the DMN. These regions extended beyond traditional pain processing areas and may reflect the diminished top-down attention regulation of pain perception through antinociceptive descending modulation network. The disrupted PAG-DMN FC may be used as an early imaging biomarker to identify patients at risk of developing persistent PTH.