Acute effects of deep brain stimulation on brain function in obsessive-compulsive disorder.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD) yet neural markers of optimized stimulation parameters are largely unknown. We aimed to describe (sub-)cortical electrophysiological responses to acute DBS at various voltages in OCD. METHODS: We explored how DBS doses between 3-5 V delivered to the ventral anterior limb of the internal capsule of five OCD patients affected electroencephalograms and intracranial local field potentials (LFPs). We focused on theta power/ phase-stability, given their previously established role in DBS for OCD. RESULTS: Cortical theta power and theta phase-stability did not increase significantly with DBS voltage. DBS-induced theta power peaks were seen at the previously defined individualized therapeutic voltage. Although LFP power generally increased with DBS voltages, this occurred mostly in frequency peaks that overlapped with stimulation artifacts limiting its interpretability. Though highly idiosyncratic, three subjects showed significant acute DBS effects on electroencephalogram theta power and four subjects showed significant carry-over effects (pre-vs post DBS, unstimulated) on LFP and electroencephalogram theta power. CONCLUSIONS: Our findings challenge the presence of a consistent dose-response relationship between stimulation voltage and brain activity. SIGNIFICANCE: Theta power may be investigated further as a neurophysiological marker to aid personalized DBS voltage optimization in OCD.

Patient specific intracranial neural signatures of obsessions and compulsions in the ventral striatum.

Objective. Deep brain stimulation is a treatment option for patients with refractory obsessive-compulsive disorder. A new generation of stimulators hold promise for closed loop stimulation, with adaptive stimulation in response to biologic signals. Here we aimed to discover a suitable biomarker in the ventral striatum in patients with obsessive compulsive disorder using local field potentials.Approach.We induced obsessions and compulsions in 11 patients undergoing deep brain stimulation treatment using a symptom provocation task. Then we trained machine learning models to predict symptoms using the recorded intracranial signal from the deep brain stimulation electrodes.Main results.Average areas under the receiver operating characteristics curve were 62.1% for obsessions and 78.2% for compulsions for patient specific models. For obsessions it reached over 85% in one patient, whereas performance was near chance level when the model was trained across patients. Optimal performances for obsessions and compulsions was obtained at different recording sites.Significance. The results from this study suggest that closed loop stimulation may be a viable option for obsessive-compulsive disorder, but that intracranial biomarkers are patient and not disorder specific.Clinical Trial:Netherlands trial registry NL7486.

White matter abnormalities in misophonia.

Misophonia is a condition in which specific ordinary sounds provoke disproportionately strong negative affect and physiological arousal. Evidence for neurobiological abnormalities underlying misophonia is scarce. Since many psychiatric disorders show white matter (WM) abnormalities, we tested for both macro and micro-structural WM differences between misophonia patients and healthy controls. We collected T1-weighted and diffusion-weighted magnetic resonance images from 24 patients and 25 matched controls. We tested for group differences in WM volume using whole-brain voxel-based morphometry and used the significant voxels from this analysis as seeds for probabilistic tractography. After calculation of diffusion tensors, we compared group means for fractional anisotropy, mean diffusivity, and directional diffusivities, and applied tract-based spatial statistics for voxel-wise comparison. Compared to controls, patients had greater left-hemispheric WM volumes in the inferior fronto-occipital fasciculus, anterior thalamic radiation, and body of the corpus callosum connecting bilateral superior frontal gyri. Patients also had lower averaged radial and mean diffusivities and voxel-wise comparison indicated large and widespread clusters of lower mean diffusivity. We found both macro and microstructural WM abnormalities in our misophonia sample, suggesting misophonia symptomatology is associated with WM alterations. These biological alterations may be related to differences in social-emotional processing, particularly recognition of facial affect, and to attention for affective information.

Structural and functional brain abnormalities in misophonia.

Misophonia is a newly described condition in which specific ordinary sounds provoke disproportionately strong negative affect. Since evidence for neurobiological abnormalities underlying misophonia is scarce, we tested whether misophonia patients differed from healthy controls in grey matter volumes and resting-state functional connectivity. We collected structural magnetic resonance imaging and resting-state functional magnetic resonance imaging data from 24 misophonia patients and 25 matched controls. Compared to controls, voxel-based morphometry showed larger right amygdala volume in misophonia patients. Follow-up seed-based functional connectivity analysis of the amygdala showed a different pattern of connectivity with the cerebellum, driven by greater connectivity with the left amygdala. Additional data-driven independent component analysis showed greater connectivity within lateral occipital cortices and fusiform gyri in the ventral attention network. We propose that the amygdala enlargement may be associated with heightened emotional reactivity in misophonia. The higher connectivity between left amygdala and cerebellum might be linked to a tendency to exhibit reflex-like physical reactions to triggers. Higher attention network connectivity may reflect sensory enhancement of visual triggers or visual imagery related to trigger sounds. In sum, we found structural and functional abnormalities which implicate dysfunction of emotional and attentional systems in misophonia.

Exploring the Role of the Nucleus Accumbens in Adaptive Behavior Using Concurrent Intracranial and Extracranial Electrophysiological Recordings in Humans.

Recent human electrophysiological evidence implicated θ-band communication between the nucleus accumbens (NAc) and frontal and parietal cortex in cognitive flexibility. Since the NAc is connected with the motor system, we tested whether phase and amplitude-based NAc-cortical connectivity and power modulation likewise underlie flexibility in motor action control. We combined concurrently recorded intracranial and extracranial electroencephalograms from seven psychiatric patients implanted with deep brain stimulation (DBS) electrodes who performed a stop signal task (SST). Inhibition success, as opposed to failure, was associated with greater prestimulus information flow from right NAc to medial frontal cortex through phase coupling of θ oscillations. Inhibition failure evoked θ power increases in the left NAc and medial frontal cortex, whereas parieto-occipital cortex showed an α power decrease. We conclude that NAc-to-frontal θ connectivity, possibly facilitating processing of task-relevant information, and α and θ power modulations, possibly reflecting post-error engagement of cognitive control, contribute to adaptive behavior pertaining motor control.

Publisher Correction: Misophonia is associated with altered brain activity in the auditory cortex and salience network.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Neural Basis of Response Bias on the Stop Signal Task in Misophonia.

Objective: Misophonia is a newly described condition in which specific ordinary sounds provoke disproportionately strong negative affect. Since evidence for psychobiological dysfunction underlying misophonia is scarce, we tested whether misophonia patients, like many patients with impulse control or obsessive-compulsive spectrum disorders, show impaired ability to inhibit an ongoing motor response. Methods: We collected functional magnetic resonance imaging data during a stop signal task in 22 misophonia patients and 21 matched healthy controls. Results: Compared to controls, patients tended to show longer stop signal delays, which is the time between stimuli signaling response initiation and inhibition. Additionally, patients tended to activate left dorsolateral prefrontal cortex more during responding rather than successful inhibition, as was seen in controls. Furthermore, patients lacked inhibition success-related activity in posterior cingulate cortices and activated the superior medial frontal gyri less during inhibition success compared to failure, a feature correlated with stop signal delays over the sample. Conclusions: Misophonia patients did not show impaired response inhibition. However, they tended to show a response bias on the stop signal task, favoring accuracy over speed. This implies perfectionism and compulsive, rather than impulsive, behavior. Moreover, brain activations were in line with patients, compared to controls, engaging more cognitive control for slowing responses, while employing more attentional resources for successful inhibition.

Misophonia is associated with altered brain activity in the auditory cortex and salience network.

Misophonia is characterized by intense rage and disgust provoked by hearing specific human sounds resulting in social isolation due to avoidance. We exposed patients with symptom provoking audiovisual stimuli to investigate brain activity of emotional responses. 21 patients with misophonia and 23 matched healthy controls were recruited at the psychiatry department of the Amsterdam UMC. Participants were presented with three different conditions, misophonia related cues (video clips with e.g. lip smacking and loud breathing), aversive cues (violent or disgusting clips from movies), and neutral cues (video clips of e.g. someone meditating) during fMRI. Electrocardiography was recorded to determine physiological changes and self-report measures were used to assess emotional changes. Misophonic cues elicited anger, disgust and sadness in patients compared to controls. Emotional changes were associated with increases in heart rate. The neuroimaging data revealed increased activation of the right insula, right anterior cingulate cortex and right superior temporal cortex during viewing of the misophonic video clips compared to neutral clips. Our results demonstrate that audiovisual stimuli trigger anger and physiological arousal in patients with misophonia, associated with activation of the auditory cortex and salience network.