A brief demonstration of frontostriatal connectivity in OCD patients with intracranial electrodes.

Closed-loop neuromodulation is presumed to be the logical evolution for improving the effectiveness of deep brain stimulation (DBS) treatment protocols (Widge et al., 2018). Identifying symptom-relevant biomarkers that provide meaningful feedback to stimulator devices is an important initial step in this direction. This report demonstrates a technique for assaying neural circuitry hypothesized to contribute to OCD and DBS treatment outcomes. We computed phase-lag connectivity between LFPs and EEGs in thirteen treatment-refractory OCD patients. Simultaneous recordings from scalp EEG and externalized DBS electrodes in the ventral capsule/ventral striatum (VC/VS) were collected at rest during the perioperative treatment stage. Connectivity strength between midfrontal EEG sensors and VC/VS electrodes correlated with baseline OCD symptoms and 12-month posttreatment OCD symptoms. Results are qualified by a relatively small sample size, and limitations regarding the conclusiveness of VS and mPFC as neural generators given some concerns about volume conduction. Nonetheless, findings are consistent with treatment-relevant tractography findings and theories that link frontostriatal hyperconnectivity to the etiopathogenesis of OCD. Findings support the continued investigation of connectivity-based assays for aiding in determination of optimal stimulation location, and are an initial step towards the identification of biomarkers that can guide closed-loop neuromodulation systems.

Inhibition of midfrontal theta with transcranial ultrasound explains greater approach versus withdrawal behavior in humans.

Recent reviews highlighted low-intensity transcranial focused ultrasound (TUS) as a promising new tool for non-invasive neuromodulation in basic and applied sciences. Our preregistered double-blind within-subjects study (N = 152) utilized TUS targeting the right prefrontal cortex, which, in earlier work, was found to positively enhance self-reported global mood, decrease negative states of self-reported emotional conflict (anxiety/worrying), and modulate related midfrontal functional magnetic resonance imaging activity in affect regulation brain networks. To further explore TUS effects on objective physiological and behavioral variables, we used a virtual T-maze task that has been established in prior studies to measure motivational conflicts regarding whether participants execute approach versus withdrawal behavior (with free-choice responses via continuous joystick movements) while allowing to record related electroencephalographic data such as midfrontal theta activity (MFT). MFT, a reliable marker of conflict representation on a neuronal level, was of particular interest to us since it has repeatedly been shown to explain related behavior, with relatively low MFT typically preceding approach-like risky behavior and relatively high MFT typically preceding withdrawal-like risk aversion. Our central hypothesis is that TUS decreases MFT in T-maze conflict situations and thereby increases approach and reduces withdrawal. Results indicate that TUS led to significant MFT decreases, which significantly explained increases in approach behavior and decreases in withdrawal behavior. This study expands TUS evidence on a physiological and behavioral level with a large sample size of human subjects, suggesting the promise of further research based on this distinct TUS-MFT-behavior link to influence conflict monitoring and its behavioral consequences. Ultimately, this can serve as a foundation for future clinical work to establish TUS interventions for emotional and motivational mental health.

Investigating the role of the right inferior frontal gyrus in control perception: A double-blind cross-over study using ultrasonic neuromodulation.

Being able to control inner and environmental states is a basic need of living creatures. The perception of such control is based on the perceived ratio of outcome probabilities given the presence and the absence of agentic behavior. If an organism believes that options exist to change the probability of a given outcome, control perception (CP) may emerge. Nonetheless, regarding this model, not much is known about how the brain processes CP from this information. This study uses low-intensity transcranial focused ultrasound neuromodulation in a randomized-controlled double blind cross-over design to investigate the impact of the right inferior frontal gyrus of the lateral prefrontal cortex (lPFC) on this process. 39 healthy participants visited the laboratory twice (once in a sham, once in a neuromodulation condition) and rated their control perception regarding a classical control illusion task. EEG alpha and theta power density were analyzed in a hierarchical single trial-based mixed modeling approach. Results indicate that the litFUS neuromodulation changed the processing of stimulus probability without changing CP. Furthermore, neuromodulation of the right lPFC was found to modulate mid-frontal theta by altering its relationship with self-reported effort and worrying. While these data indicate lateral prefrontal sensitivity to stimulus probability, no evidence emerged for the dependency of CP on this processing.