Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette’s syndrome, the supplementary motor area in Parkinson’s disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.

Parkinson’s disease (PD) is an incurable neurological disorder that often begins insidiously with sleep disturbances and somatic symptoms, progressing to whole-body motor and cognitive symptoms^1,2,3,4,5. Dysfunction of the somato-cognitive action network (SCAN)—which is thought to control action execution^6,7 by coordinating arousal, organ physiology and whole-body motor plans with behavioural motivation—is a potential contributor to the diverse clinical manifestations of PD. To investigate the role of the SCAN in PD pathophysiology and treatments (medications, deep-brain stimulation (DBS), transcranial magnetic stimulation (TMS) and MRI-guided focused ultrasound stimulation (MRgFUS)), we built a large (n = 863), multimodal, multi-intervention clinical imaging dataset. Resting-state functional connectivity revealed that the substantia nigra and all PD DBS targets (subthalamic nucleus, globus pallidus and ventral intermediate thalamus) are selectively connected to the SCAN rather than to effector-specific motor regions. Importantly, PD was characterized by specific hyperconnectivity between the SCAN and the subcortex. We therefore followed six PD cohorts undergoing DBS, TMS, MRgFUS and levodopa therapy using precision resting-state functional connectivity and electrocorticography recording. Efficacious treatments reduced SCAN-to-subcortex hyperconnectivity. Targeting the SCAN instead of effector regions doubled the efficacy of TMS treatments. Focused ultrasound treatment benefits increased when the target was closer to the thalamic SCAN sweet spot. Thus, SCAN hyperconnectivity is central to PD pathophysiology and its alleviation is a hallmark of successful neuromodulation. Targeting functionally defined subcortical SCAN nodes may improve existing therapies (DBS, MRgFUS), whereas cortical SCAN targets offer effective non-invasive or minimally invasive neuromodulation for PD.

Automated assessment of patients with Parkinson's disease (PD) is urgently required in clinical practice to improve the diagnostic efficiency and objectivity and to remotely monitor the motor disorder symptoms and general health of these patients, especially in view of the travel restrictions due to the recent coronavirus epidemic. Gait motor disorder is one of the critical manifestations of PD, and automated assessment of gait is vital to realize automated assessment of PD patients. To this end, we propose a novel two-stream spatial-temporal attention graph convolutional network (2s-ST-AGCN) for video assessment of PD gait motor disorder. Specifically, the skeleton sequence of human body is extracted from videos to construct spatial-temporal graphs of joints and bones, and a two-stream spatial-temporal graph convolutional network is then built to simultaneously model the static spatial information and dynamic temporal variations. The multi-scale spatial-temporal attention-aware mechanism is also designed to effectively extract the discriminative spatial-temporal features. The deep supervision strategy is then embedded to minimize classification errors, thereby guiding the weight update process of the hidden layer to promote significant discriminative features. Besides, two model-driven terms are integrated into this deep learning framework to strengthen multi-scale similarity in the deep supervision and realize sparsification of discriminative features. Extensive experiments on the clinical video dataset show that the proposed model exhibits good performance with an accuracy of 65.66% and an acceptable accuracy of 98.90%, which is much better than that of the existing sensor- and vision-based methods for Parkinsonian gait assessment. Thus, the proposed method is potentially useful for assessing PD gait motor disorder in clinical practice.