Deep brain stimulation (DBS) of structures in the brain’s reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain’s anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB–DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients’ left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients’ health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB–DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB–DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB–DBS for treatment-refractory mood disorders in a more rigorous fashion.

The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection neuron (PN)-type resolution in real time during behavior. Combining genetic targeting and wide-field imaging, we monitored activity dynamics of subcortical-projecting (PT Fezf2 ) and intratelencephalic-projecting (IT PlxnD1 ) types across dorsal cortex of mice during different brain states and behaviors. IT PlxnD1 and PT Fezf2 neurons showed distinct activation patterns during wakeful resting, spontaneous movements, and upon sensory stimulation. Distinct IT PlxnD1 and PT Fezf2 subnetworks were dynamically tuned to different sensorimotor components of a naturalistic feeding behavior, and optogenetic inhibition of subnetwork nodes disrupted specific components of this behavior. Lastly, IT PlxnD1 and PT Fezf2 projection patterns are consistent with their subnetwork activation patterns. Our results show that, in addition to the concept of columnar organization, dynamic areal and PN typespecific subnetworks are a key feature of cortical functional architecture linking microcircuit components with global brain networks.

OBJECTIVE To provide better postoperative healthcare for patients with Parkinson’s disease (PD) who received deep brain stimulation (DBS) surgery and to allow surgeons improved tracking of surgical outcomes, the authors sought to examine the applicability and feasibility of remote assessment using smartphones. METHODS A disease management mobile application specifically for PD was used to perform the remote assessment of patients with PD who underwent DBS. Connection with patients was first established via a phone call or a social application, and instructions for completing the remote assessment were delivered. During the video-based virtual meeting, three nonmotor assessment scales measuring the quality of life and mental state, and a modified version of the Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRS III) measuring motor abilities were evaluated. After the assessment, a report and the satisfaction questionnaire were sent to the patient. RESULTS Overall, 22 patients were recruited over a 4-week period. Among those, 18 patients completed the assessment on the mobile application. The mean duration was 41.3 minutes for video assessment and 17.5 minutes for nonmotor assessment via telephone. The mean estimated cost was 427.68 Chinese yuan (CNY) for an in-person visit and 20.91 CNY for a virtual visit (p < 0.001). The mean time estimate for an in-person visit was 5.51 hours and 0.68 hours for a virtual visit (p = 0.002). All patients reported satisfaction (77.78% very satisfied and 22.22% satisfied) with the virtual visit and were specifically impressed by the professionalism and great attitude of the physician assistant. The majority of patients agreed that the evaluation time was reasonable (50% totally agree, 44.44% agree, and 5.56% neither agree nor disagree) and all patients expressed interest in future virtual visits (61.11% very willingly and 38.89% willingly). No adverse events were observed during the virtual visit. CONCLUSIONS Innovation in remote assessment technologies was highly feasible for its transforming power in the clinical management of patients with PD who underwent DBS and research. Video-based remote assessment offered considerable time and resource reduction for both patients and doctors. It also increased safety and was a well-accepted, favored tool. Finally, the results of this study have shown there is potential to combine remote assessment tools with real-life clinical visits and other telemedical technologies to collectively benefit the postoperative healthcare of patients with PD undergoing DBS.

Cooperative forelimb and mouth movements during eating contribute to diet selection among vertebrates including the oromanual manipulatory skills in rodents and primates. Whereas spinal and brainstem circuits implement forelimb and orofacial actions, whether there is a specialized cortical circuit that flexibly assembles these to achieve cross-body and oromanual coordination for skilled manipulation remains unclear. Here we discover a cortical region and its cell-type-specific circuitry that orchestrates body postures and oromanual coordination for food manipulation in mice. An optogenetic screen of cortical areas and projection neuron types identified a rostral forelimb-orofacial area (RFO), wherein activation of pyramidal tract (PTFezf2) and intratelencephalic (ITPlxnD1) neurons induced concurrent posture, forelimb and orofacial eating-like movements. In a pasta-eating behavior, RFO PTFezf2and ITPlxnD1activity were closely correlated with picking up the pasta, adopting a sitting posture, oromanual manipulation, and hand-assisted biting. RFO inactivation and inhibition of RFO PTsFezf2and ITsPlxnD1impaired posture and oromanual coordination, leading to deficient pasta manipulation and biting. RFO is reciprocally connected to forelimb and orofacial sensorimotor areas as well as insular and visceral areas. Within this network, ITsPlxnD1project bilaterally to the entire network and the ventrolateral striatum and PTsFezf2project to multiple subcortical areas associated with forelimb and orofacial control. These results suggest that ITsPlxnD1select and coordinate the feeding program involving multiple body parts and PTsFezf2implement the fine details of movements. Our study reveals a neural circuit basis of hand-mouth coordination for object manipulation.