Stereo-Electroencephalography-Guided Network Neuromodulation for Psychiatric Disorders: The Neurophysiology Monitoring Unit.

BACKGROUND AND OBJECTIVES: Recent advances in stereotactic and functional neurosurgery have brought forth the stereo-electroencephalography approach which allows deeper interrogation and characterization of the contributions of deep structures to neural and affective functioning. We argue that this approach can and should be brought to bear on the notoriously intractable issue of defining the pathophysiology of refractory psychiatric disorders and developing patient-specific optimized stimulation therapies. METHODS: We have developed a suite of methods for maximally leveraging the stereo-electroencephalography approach for an innovative application to understand affective disorders, with high translatability across the broader range of refractory neuropsychiatric conditions. RESULTS: This article provides a roadmap for determining desired electrode coverage, tracking high-resolution research recordings across a large number of electrodes, synchronizing intracranial signals with ongoing research tasks and other data streams, applying intracranial stimulation during recording, and design choices for patient comfort and safety. CONCLUSION: These methods can be implemented across other neuropsychiatric conditions needing intensive electrophysiological characterization to define biomarkers and more effectively guide therapeutic decision-making in cases of severe and treatment-refractory disease.

Intracranial stimulation and EEG feature analysis reveal affective salience network specialization.

Emotion is represented in limbic and prefrontal brain areas, herein termed the affective salience network (ASN). Within the ASN, there are substantial unknowns about how valence and emotional intensity are processed-specifically, which nodes are associated with affective bias (a phenomenon in which participants interpret emotions in a manner consistent with their own mood). A recently developed feature detection approach ('specparam') was used to select dominant spectral features from human intracranial electrophysiological data, revealing affective specialization within specific nodes of the ASN. Spectral analysis of dominant features at the channel level suggests that dorsal anterior cingulate (dACC), anterior insula and ventral-medial prefrontal cortex (vmPFC) are sensitive to valence and intensity, while the amygdala is primarily sensitive to intensity. Akaike information criterion model comparisons corroborated the spectral analysis findings, suggesting all four nodes are more sensitive to intensity compared to valence. The data also revealed that activity in dACC and vmPFC were predictive of the extent of affective bias in the ratings of facial expressions-a proxy measure of instantaneous mood. To examine causality of the dACC in affective experience, 130 Hz continuous stimulation was applied to dACC while patients viewed and rated emotional faces. Faces were rated significantly happier during stimulation, even after accounting for differences in baseline ratings. Together the data suggest a causal role for dACC during the processing of external affective stimuli.

Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain.

Genetic predisposition and environmental stress are known etiologies of stress-related psychiatric disorders. Environmental stress during adolescence is assumed to be particularly detrimental for adult affective behaviors. To investigate how genetic stress-reactivity differences modify the effects of stress during adolescence on adult affective behaviors we employed two inbred strains with differing stress reactivity. The Wistar Kyoto More Immobile (WMI) rat strain show increased stress-reactivity and despair-like behaviors as well as passive coping compared to the nearly isogenic control strain, the Wistar Kyoto Less Immobile (WLI). Males and females of these strains were exposed to contextual fear conditioning (CFC) during early adolescence (EA), between 32 and 34 postnatal days (PND), and were tested for the consequences of this mild EA stress in adulthood. Early adolescent stress significantly decreased anxiety-like behavior, measured in the open field test (OFT) and increased social interaction and recognition in adult males of both strains compared to controls. In contrast, no significant effects of EA stress were observed in adult females in these behaviors. Both males and females of the genetically less stress-reactive WLI strain showed significantly increased immobility in the forced swim test (FST) after EA stress compared to controls. In contrast, immobility was significantly attenuated by EA stress in adult WMI females compared to controls. Transcriptomic changes of the glucocorticoid receptor (Nr3c1, GR) and the brain-derived neurotrophic factor (Bdnf) illuminate primarily strain and stress-dependent changes, respectively, in the prefrontal cortex and hippocampus of adults. These results suggest that contrary to expectations, limited adolescent stress is beneficial to males thru decreasing anxiety and enhancing social behaviors, and to the stress more-reactive WMI females by way of decreasing passive coping.