Brain Stimulation最新文献

Background: Posttraumatic stress disorder (PTSD) is common and debilitating, and many individuals do not respond to existing therapies. We developed a fundamentally novel neuromodulation-based therapy for treatment-resistant PTSD. This approach is premised on coupling prolonged exposure therapy, a first-line evidence-based cognitive behavioral therapy that directs changes within fear networks, with concurrent delivery of short bursts of vagus nerve stimulation (VNS), which enhance synaptic plasticity.

Methods: We performed a first-in-human prospective open-label early feasibility study (EFS) using a next-generation miniaturized system to deliver VNS therapy in nine individuals with moderate to severe treatment-resistant PTSD. All individuals received a standard 12-session course of prolonged exposure therapy combined with VNS. Assessments were performed before, 1 week after, and 1, 3, and 6 months after the completion of therapy.

Clinicaltrials: gov registration: NCT04064762.

Results: VNS therapy resulted in significant, clinically-meaningful improvements in multiple metrics of PTSD symptoms and severity compared to baseline (CAPS-5, PCL-5, and HADS all p < 0.001 after therapy). These benefits persisted at 6 months after the cessation of therapy, suggesting lasting improvements. All participants showed loss of PTSD diagnosis after completing treatment. No serious or unexpected device-related adverse events were observed.

Conclusions: These findings provide a demonstration of the safety and feasibility of VNS therapy for PTSD and highlight the potential of this approach. Collectively, these support the validation of VNS therapy for PTSD in a rigorous randomized controlled trial.

Optogenetic techniques are often employed to dissect neural pathways with presumed specificity for targeted projections. In this study, we used optogenetic fMRI to investigate the effective landscape of stimulating the cell bodies versus one of its projection terminals. Specifically, we selected a long-range unidirectional projection from the ventral subiculum (vSUB) to the nucleus accumbens shell (NAcSh) and placed two stimulating fibers-one at the vSUB cell bodies and the other at the vSUB terminals in the NAcSh. Contrary to the conventional view that terminal stimulation confines activity to the feedforward stimulated pathway, our findings reveal that terminal stimulation induces brain activity and connectivity patterns remarkably similar to those of vSUB cell body stimulation. This observation suggests that the specificity of optogenetic terminal stimulation may induce antidromic activation, leading to broader network involvement than previously acknowledged.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) effectively alleviates motor fluctuations in Parkinson's disease (PD). Optimal electrode placement and effective programming significantly influence outcomes. From a patient's perspective, DBS should relieve motor symptoms while avoiding side effects. However, there is a lack of programming routines that consider patients' subjective feedback for parameter adjustment.

Objective: This study assessed the usefulness of patients' subjective ratings as feedback for DBS programming.

Methods: We analyzed 260 DBS settings from 11 STN-DBS patients, pairing each volume of tissue activated (VTA) with a subjective rating measured by a visual analogue scale (VAS). We performed sweet spot mapping and connectivity analyses, utilizing voxel-wise and nonparametric permutation statistics to identify neuroanatomical regions and connectivity profiles associated with the highest VAS ratings. To validate our findings, we cross-validated the results in an independent test dataset of 6 patients (189 settings) to determine if the sweet spot and connectivity profile could predict the subjective patient perception.

Results: VTAs with the highest VAS scores were localized to the dorsolateral STN, consistent with published sweet spots derived from clinical data. Connectivity with the supplementary motor area (SMA) and primary motor cortex (M1) was associated with a more positive subjective perception. Connectivity profiles derived from one dataset successfully predicted outcomes in an independent dataset, as validated through leave-one-cohort-out cross-validation.

Conclusions: Mapping patients' subjective perceptions using VAS yields conclusive anatomical results that align with objective clinical and imaging measures. VAS-guided programming could provide an additional feedback mechanism for both acute and chronic DBS parameter adjustments.

Transcranial ultrasonic stimulation (TUS) has the potential to usher in a new era for human neuroscience by allowing spatially precise and high-resolution non-invasive targeting of both deep and superficial brain regions. Currently, fundamental research on the mechanisms of interaction between ultrasound and neural tissues is progressing in parallel with application-focused research. However, a major hurdle in the wider use of TUS is the selection of optimal parameters to enable safe and effective neuromodulation in humans. In this paper, we will discuss the major factors that determine the efficacy of TUS. We will discuss the thermal and mechanical biophysical effects of ultrasound, which underlie its biological effects, in the context of their relationships with tunable parameters. Based on this knowledge of biophysical effects, and drawing on concepts from radiotherapy, we propose a framework for conceptualising TUS dose.

Background: Low-frequency sinusoidal galvanic vestibular stimulation (sGVS) can induce perceptions of sway and nausea through entraining vestibular afferent firing to the sinusoidal stimulus. As recently shown, concurrent dorsolateral prefrontal cortex (dlPFC) stimulation via transcranial alternating current stimulation (tACS) greatly attenuates these vestibular perceptions.

Objective: Given that both vestibular afferents and dlPFC efferents project to the insular cortex, it was reasoned that the insula is the most likely area for the top-down inhibitory interaction to take place.

Methods: To identify the sites of this interaction, blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was collected whilst simultaneously delivering sinusoidal electrical stimulation (±2 mA, 0.2 Hz, 60 cycles) to 20 participants. These stimuli were randomly applied as follows: (i) bilateral sGVS alone via the mastoid processes; (ii) tACS of the dlPFC alone at electroencephalogram site F4; and (iii) sGVS and tACS together.

Results: Altered BOLD signal-intensity patterns were identified in the parieto-insular vestibular cortex and thalamus when comparing both sGVS and dlPFC stimulation to concurrent stimulation. Within the brainstem, signal-intensity increased in the inferior olivary nucleus and decreased in the nucleus of the solitary tract during concurrent stimulation, when analysed relative to single stimuli. Because concurrent stimulation elicited different activation patterns in each of these regions compared to the single stimuli, they were considered to be key for the interaction.

Conclusion: Given the role each plays in dlPFC and vestibular pathways, the inhibitory function exerted by the dlPFC on vestibular processing likely involves ongoing modulation of one or several of these cortical centres.