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 (F _1,35 = 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.     

The Effect of Sham Controlled Continuous Theta Burst Stimulation and Low Frequency Repetitive Transcranial Magnetic Stimulation on Upper Extremity Spasticity and Functional Recovery in Chronic Ischemic Stroke Patients

ObjectiveThis randomized controlled study examined the effect of continuous theta burst stimulation (cTBS) and low frequency repetitive transcranial magnetic stimulation (rTMS) on upper extremity spasticity and functional recovery in chronic ischemic stroke patients.Materials and MethodsTwenty chronic ischemic stroke patients were randomized into three groups as real rTMS group (n = 7), real cTBS group (n = 7) and sham cTBS group (n = 6), in which real rTMS with physical therapy (PT), real cTBS with PT and sham cTBS with PT were applied in 10 sessions, respectively. The evaluation parameters were assessed at pre-treatment, post-treatment and follow up at 4 weeks.ResultsTen sessions of real rTMS or real cTBS combined with PT were found beneficial in motor functional recovery and daily living activities both at post-treatment and follow up at 4 weeks (p ? 0.05). In the sham cTBS group, functional improvement was not significant (p > 0.05). In addition, in the real rTMS group, elbow flexor, pronator, wrist flexor and finger flexor spasticity were significantly decreased; in the real cTBS group, significant decrease was observed in the elbow flexor and wrist flexor spasticity (p ? 0.05). In comparison with sham cTBS group, only in the real cTBS group, significant improvement was observed in the level of wrist flexor spasticity at follow up at 4 weeks (p ? 0.017).ConclusionsIn this study, it was observed that real cTBS or real rTMS combined with PT provided improvement on upper extremity motor functions and daily living activities in chronic ischemic stroke patients, but improvement in spasticity was limited.     

Probing the role of the right inferior frontal gyrus during Pain‐Related empathy processing: Evidence from fMRI and TMS

Recent studies have suggested that the right inferior frontal gyrus (rIFG) may be involved in pain‐related empathy. To verify the role of the rIFG, we performed a functional magnetic resonance imaging (fMRI) experiment to replicate previous research and further designed a noninvasive repetitive transcranial magnetic stimulation (rTMS) experiment to probe the causal role of the rIFG in pain‐related empathy processing. We assigned 74 volunteers (37 females) to three groups. Group 1 (n = 26) performed a task in which participants were required to perceive pain in others (task of pain: TP) and we used fMRI to observe the activity of the rIFG during pain‐related empathy processing. Then, we applied online rTMS to the rIFG and the vertex site (as reference site) to observe the performance of Group 2 (n = 24; performing TP) and Group 3 (n = 24; performing a control task of identifying body parts; task of body: TB). fMRI experiment demonstrated stronger activation in the rIFG than in the vertex during the perception of pain in others (p < .0001, Bonferroni‐corrected). rTMS experiment indicated that when the rIFG was temporarily disrupted, participants perceived pain in others significantly more slowly (p < .0001, Bonferroni‐corrected) than when the vertex was disrupted. Our results provide evidence that the rIFG is involved in pain‐related empathy processing, which yields insights into how the brain perceives pain in others.     

Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature

Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta‐analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short‐term follow‐up) and 1‐month post stimulation (long‐term follow‐up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short‐term follow‐up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long‐term follow‐up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3‐point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion. © 2015 International Parkinson and Movement Disorder Society     

The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: A randomized,double‐blind,placebo‐controlled study

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. © 2010 Movement Disorder Society     

High‐frequency rTMS over the supplementary motor area for treatment of Parkinson's disease

Dysfunction of the basal ganglia‐thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson's disease (PD). Using high‐frequency repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA), we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD. In this double‐blind placebo‐controlled study, 99 patients were enrolled and assigned randomly to SMA‐stimulation and sham‐stimulation groups. For SMA stimulation, 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110% active motor threshold for leg muscles in one session. The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS. Each session of intervention was carried out once a week for the first 8 weeks. The SMA stimulation, in contrast to the sham stimulation, engendered significant improvements in total scores and motor scores of the Unified Parkinson's Disease Rating Scale. Mean improvements in motor scores were 4.5 points in the SMA‐stimulation group and ?0.1 points in the sham‐stimulation group. Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients; SMA is a potential stimulation site for PD treatment. © 2008 Movement Disorder Society     

The default mode network and cognition in Parkinson's disease: A multimodal resting‐state network approach

Involvement of the default mode network (DMN) in cognitive symptoms of Parkinson''s disease (PD) has been reported by resting‐state functional MRI (rsfMRI) studies. However, the relation to metabolic measures obtained by [18F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET) is largely unknown. We applied multimodal resting‐state network analysis to clarify the association between intrinsic metabolic and functional connectivity abnormalities within the DMN and their significance for cognitive symptoms in PD. PD patients were classified into normal cognition (n = 36) and mild cognitive impairment (MCI; n = 12). The DMN was identified by applying an independent component analysis to FDG‐PET and rsfMRI data of a matched subset (16 controls and 16 PD patients) of the total cohort. Besides metabolic activity, metabolic and functional connectivity within the DMN were compared between the patients'' groups and healthy controls (n = 16). Glucose metabolism was significantly reduced in all DMN nodes in both patient groups compared to controls, with the lowest uptake in PD‐MCI (p < .05). Increased metabolic and functional connectivity along fronto‐parietal connections was identified in PD‐MCI patients compared to controls and unimpaired patients. Functional connectivity negatively correlated with cognitive composite z‐scores in patients (r = −.43, p = .005). The current study clarifies the commonalities of metabolic and hemodynamic measures of brain network activity and their individual significance for cognitive symptoms in PD, highlighting the added value of multimodal resting‐state network approaches for identifying prospective biomarkers.     

Neural oscillatory responses to performance monitoring differ between high‐ and low‐impulsive individuals,but are unaffected by TMS

Higher impulsivity may arise from neurophysiological deficits of cognitive control in the prefrontal cortex. Cognitive control can be assessed by time‐frequency decompositions of electrophysiological data. We aimed to clarify neuroelectric mechanisms of performance monitoring in connection with impulsiveness during a modified Eriksen flanker task in high‐ (n = 24) and low‐impulsive subjects (n = 21) and whether these are modulated by double‐blind, sham‐controlled intermittent theta burst stimulation (iTBS). We found a larger error‐specific peri‐response beta power decrease over fronto‐central sites in high‐impulsive compared to low‐impulsive participants, presumably indexing less effective motor execution processes. Lower parieto‐occipital theta intertrial phase coherence (ITPC) preceding correct responses predicted higher reaction time (RT) and higher RT variability, potentially reflecting efficacy of cognitive control or general attention. Single‐trial preresponse theta phase clustering was coupled to RT in correct trials (weighted ITPC), reflecting oscillatory dynamics that predict trial‐specific behavior. iTBS did not modulate behavior or EEG time‐frequency power. Performance monitoring was associated with time‐frequency patterns reflecting cognitive control (parieto‐occipital theta ITPC, theta weighted ITPC) as well as differential action planning/execution processes linked to trait impulsivity (frontal low beta power). Beyond that, results suggest no stimulation effect related to response‐locked time‐frequency dynamics with the current stimulation protocol. Neural oscillatory responses to performance monitoring differ between high‐ and low‐impulsive individuals, but are unaffected by iTBS.     

0.2-Hz repetitive transcranial magnetic stimulation has no add-on effects as compared to a realistic sham stimulation in Parkinson's disease.

To study the efficacy of 0.2-Hz repetitive transcranial magnetic stimulation (rTMS) on Parkinson's disease (PD), 85 patients with PD were enrolled into three groups: 1). motor cortical, 2). occipital, and 3). sham stimulation. A round coil was centered over the vertex in motor cortical stimulation, and over the inion in occipital stimulation. In one session, 100 stimuli of 0.2-Hz rTMS at an intensity of 1.1 times active motor threshold (AMT) were given. In sham stimulation, electric currents were given with electrodes fixed on the head to mimic the sensation in real stimulation. Each session was carried out once a week for the first 8 weeks. The Unified Parkinson Disease Rating Scale (UPDRS), Hamilton Rating Scale for Depression (HRSD) and subjective score (visual analogue scale) were assessed. There were no significant differences in clinical features among the three groups. Total and motor score of UPDRS were improved to the same extent by rTMS over Cz, inion, and sham stimulation. HRSD was improved by rTMS over Cz and sham stimulation in the same manner. Subjective score was not significantly improved by any methods of stimulation. 0.2-Hz rTMS at an intensity of 1.1 x AMT has only a placebo effect on PD. Our realistic sham stimulation maneuver must produce powerful placebo effects as a real stimulation.     

Repetitive transcranial magnetic stimulation for levodopa‐induced dyskinesias in Parkinson's disease

In a placebo‐controlled, single‐blinded, crossover study, we assessed the effect of “real” repetitive transcranial magnetic stimulation (rTMS) versus “sham” rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician‐assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low‐frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses. © 2008 Movement Disorder Society     

Cortical network organization reflects clinical response to subthalamic nucleus deep brain stimulation in Parkinson's disease

The degree of response to subthalamic nucleus deep brain stimulation (STN‐DBS) is individual and hardly predictable. We hypothesized that DBS‐related changes in cortical network organization are related to the clinical effect. Network analysis based on graph theory was used to evaluate the high‐density electroencephalography (HDEEG) recorded during a visual three‐stimuli paradigm in 32 Parkinson''s disease (PD) patients treated by STN‐DBS in stimulation “off” and “on” states. Preprocessed scalp data were reconstructed into the source space and correlated to the behavioral parameters. In the majority of patients (n = 26), STN‐DBS did not lead to changes in global network organization in large‐scale brain networks. In a subgroup of suboptimal responders (n = 6), identified according to reaction times (RT) and clinical parameters (lower Unified Parkinson''s Disease Rating Scale [UPDRS] score improvement after DBS and worse performance in memory tests), decreased global connectivity in the 1–8 Hz frequency range and regional node strength in frontal areas were detected. The important role of the supplementary motor area for the optimal DBS response was demonstrated by the increased node strength and eigenvector centrality in good responders. This response was missing in the suboptimal responders. Cortical topologic architecture is modified by the response to STN‐DBS leading to a dysfunction of the large‐scale networks in suboptimal responders.     

Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson's disease and concurrent depression.

Previous studies show that cognitive functions are more impaired in patients with Parkinson's disease (PD) and depression than in nondepressed PD patients. We compared the cognitive effects of two types of antidepressant treatments in PD patients: fluoxetine (20 mg/day) versus repetitive transcranial magnetic stimulation (rTMS, 15 Hz, 110% above motor threshold, 10 daily sessions) of the left dorsolateral prefrontal cortex. Twenty-five patients with PD and depression were randomly assigned either to Group 1 (active rTMS and placebo medication) or to Group 2 (sham rTMS and fluoxetine). A neuropsychological battery was assessed by a rater blind to treatment arm at baseline and 2 and 8 weeks after treatment. Patients in both groups had a significant improvement of Stroop (colored words and interference card) and Hooper and Wisconsin (perseverative errors) test performances after both treatments. Furthermore, there were no adverse effects after either rTMS or fluoxetine in any neuropsychological test of the cognitive test battery. The results show that rTMS could improve some aspects of cognition in PD patients similar to that of fluoxetine. The mechanisms for this cognitive improvement are unclear, but it is in the context of mood improvement.     

Personalized connectivity‐guided DLPFC‐TMS for depression: Advancing computational feasibility,precision and reproducibility

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory depression, however, therapeutic outcomes vary. Mounting evidence suggests that clinical response relates to functional connectivity with the subgenual cingulate cortex (SGC) at the precise DLPFC stimulation site. Critically, SGC‐related network architecture shows considerable interindividual variation across the spatial extent of the DLPFC, indicating that connectivity‐based target personalization could potentially be necessary to improve treatment outcomes. However, to date accurate personalization has not appeared feasible, with recent work indicating that the intraindividual reproducibility of optimal targets is limited to 3.5 cm. Here we developed reliable and accurate methodologies to compute individualized connectivity‐guided stimulation targets. In resting‐state functional MRI scans acquired across 1,000 healthy adults, we demonstrate that, using this approach, personalized targets can be reliably and robustly pinpointed, with a median accuracy of ~2 mm between scans repeated across separate days. These targets remained highly stable, even after 1 year, with a median intraindividual distance between coordinates of only 2.7 mm. Interindividual spatial variation in personalized targets exceeded intraindividual variation by a factor of up to 6.85, suggesting that personalized targets did not trivially converge to a group‐average site. Moreover, personalized targets were heritable, suggesting that connectivity‐guided rTMS personalization is stable over time and under genetic control. This computational framework provides capacity for personalized connectivity‐guided TMS targets to be robustly computed with high precision and has the flexibly to advance research in other basic research and clinical applications.     

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD.ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD.MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing.ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD.ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.     

Low-frequency repetitive transcranial magnetic stimulation for dyskinesia and motor performance in Parkinson’s disease

Dyskinesias are one of the most frequent and disabling complications of the long-term treatment of Parkinson’s disease (PD). Although the cause is not completely understood, it appears that an imbalance between excitatory and inhibitory inputs from the basal ganglia to the motor cortex leads to overactivation of motor and premotor areas. Overactivation of the supplementary motor area (SMA) has been observed in neuroimaging studies in dyskinetic PD patients. We investigated the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the SMA on levodopa-induced dyskinesias (LID) and motor performance in PD. We tested whether longer duration (10 days) and higher number of total pulses (1800 pulses) would enhance the beneficial effect. Seventeen dyskinetic PD patients were randomly assigned to real rTMS or sham (placebo) rTMS, and 1 Hz rTMS or sham rTMS was applied over the SMA for 10 consecutive days. Patients were assessed at baseline and 1 day after the last rTMS with a levodopa challenge test, and video recordings were taken. Dyskinesias and motor performance were rated off-line by two blinded raters using video recordings. After 10 days of treatment with rTMS, we observed that 1 Hz rTMS delivered over the SMA had decreased LID lasting for 24 hours without a change in motor performance, whereas sham rTMS induced no significant change in dyskinesia scores. These results support a possible therapeutic effect of low-frequency rTMS in LID. However, in order to suggest rTMS as an effective treatment, long-term observations and further investigations with a larger patient population are essential.     

高低频重复经颅磁刺激治疗卒中后上肢痉挛的对照研究

目的 探讨高、低频重复经颅磁刺激（repetitive transcranial magnetic stimulation,rTMS）大脑初级运动皮层（M1区）治疗卒中后上肢痉挛的临床疗效及差异。      

Deep‐learning based fully automatic segmentation of the globus pallidus interna and externa using ultra‐high 7 Tesla MRI

Deep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson''s disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this study, we present a deep‐learning based neural network, which we term GP‐net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP‐net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP‐net performs 3D inference in a patient‐specific manner, alleviating the need for atlas‐based segmentation. GP‐net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state‐of‐the‐art atlas‐based segmentations. We also demonstrate a postoperative lead location assessment with respect to a segmented globus pallidus obtained by GP‐net.     

Treatment of articulatory dysfunction in Parkinson's disease using repetitive transcranial magnetic stimulation

Background and purpose: Neuroimaging has demonstrated that improved speech outcomes in Parkinson’s Disease (PD) subsequent to behavioural treatment approaches are associated with increased activity in the motor and pre‐motor cortex. High‐frequency repetitive transcranial magnetic stimulation (rTMS) is capable of modulating cortical activity and has been reported to have significant benefit to general motor function in PD. It is possible that high‐frequency rTMS may also have beneficial outcomes on speech production in PD. Methods: High‐frequency (5 Hz) rTMS was applied to 10 active stimulation and 10 sham placebo patients for 10 min/day (3000 pulses), for 10 days and speech outcome measures and lingual kinematic parameters recorded at baseline and 1 week, 2 and 12 months post‐stimulation. Results: The findings demonstrated positive treatment‐related changes observed in the active rTMS group when compared to the sham placebo control group at 2 and 12 months post‐stimulation in speech intelligibility, communication efficiency ratio, maximum velocity of tongue movements and distance of tongue movements. Conclusion: The results support the use of high‐frequency rTMS as a therapeutic tool for the treatment of articulatory dysfunction in PD.     

Basal ganglia atrophy–associated causal structural network degeneration in Parkinson's disease

Parkinson''s disease (PD) is a progressive neurodegenerative disease characterized by both motor and non‐motor symptoms. A convergent pathophysiological hallmark of PD is an early selective vulnerability within the basal ganglia circuit. However, the causal interactions between basal ganglia atrophy and progressive structural network alterations in PD remain unaddressed. Here, we adopted voxel‐based morphometry method to measure gray matter (GM) volume for each participant (n = 84 PD patients and n = 70 matched healthy controls). Patients were first divided into three stages according to the Hoehn and Yahr (H&Y) and the Part III of Unified Parkinson''s Disease Rating Scale scores respectively to analyze the stage‐specific GM atrophy patterns. Then, the modulation of early caudate atrophy over other brain structures was evaluated using the whole‐brain voxel‐wise and region‐of‐interest‐wise causal structural covariance network approaches. We found that GM atrophy progressively expands from the basal ganglia to the angular gyrus, temporal areas, and eventually spreads through the subcortical–cortical networks as PD progresses. Notably, we identified a shared caudate‐associated degeneration network including the basal ganglia, thalamus, cerebellum, sensorimotor cortex, and cortical association areas with the PD progressive factors. These findings suggest that the early structural vulnerability of basal ganglia in PD may play a pivotal role in the modulation of motor and non‐motor circuits at the structural level. Our work provides evidence for a novel mechanism of network degeneration that underlies the pathology of PD and may have potential clinical applications in the development of early predictors of PD onset and progress.     

Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment: a double-blind randomized sham-controlled trial

Individuals with amnestic mild cognitive impairment(aMCI) have a high risk of developing Alzheimer's disease. Although repetitive transcranial magnetic stimulation(rTMS) is considered a potentially effective treatment for cognitive impairment in patients with aMCI, the neuroimaging mechanisms are poorly understood. Therefore, we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University, China. Twenty-four patients with aMCI were randomly assigned to receive true rTMS(treatment group, n = 12, 6 men and 6 women; age 65.08 ± 4.89 years) or sham stimulation(sham group, n = 12, 5 men and 7 women; age 64.67 ± 4.77 years). rTMS parameters included a stimulation frequency of 10 Hz, stimulation duration of 2 seconds, stimulation interval of 8 seconds, 20 repetitions at 80% of the motor threshold, and 400 pulses per session. rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks. Our results showed that compared with baseline, Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation(ALFF) was significantly increased at the end of treatment and 1 month after treatment. Compared with the sham group, the ALFF values in the right inferior frontal gyrus, triangular part of the inferior frontal gyrus, right precuneus, left angular gyrus, and right supramarginal gyrus were significantly increased, and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group. These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas. This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University, China(approval No. BYL20190901) on September 3, 2019 and registered in the Chinese Clinical Trials Registry(registration No. ChiCTR1900028180) on December 14, 2019.