A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum.

OBJECTIVES: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. MATERIALS AND METHODS: Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). RESULTS: VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. CONCLUSIONS: This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Behavioral and neural sensitivity to uncertain threat in individuals with alcohol use disorder: Associations with drinking behaviors and motives.

A developing theory is that individuals with alcohol use disorder (AUD) display exaggerated reactivity to threats that are uncertain (U-threat), which facilitates excessive drinking as a means of avoidance-based coping. There is a promising initial behavioral evidence supporting this theory; however, the neural bases of reactivity to U-threat in individuals with AUD have not been examined. The extent to which biomarkers of U-threat reactivity map onto drinking behaviors and coping motives for alcohol use is also unknown. The current study therefore examined group differences in behavioral and neural reactivity to U-threat in adults with and without AUD. The study also tested whether behavior and brain responses to U-threat correlate with problematic drinking and coping motivated drinking. Volunteers (n = 65) with and without a history of AUD (38 AUD, 27 controls) were included and completed a well-validated threat-of-shock task to probe responses to U-threat and predictable threat (P-threat) while startle eyeblink potentiation was collected. Individuals also completed a newly designed, analogous version of the task during functional magnetic resonance imaging (fMRI). Results indicated that individuals with AUD displayed greater startle magnitude during U-threat, but not P-threat, and greater right insula and dorsal anterior cingulate cortex (dACC) activation during both forms of threat compared with controls. Startle magnitude and insula activation during U-threat positively correlated with self-reported problem drinking and coping motives for alcohol use. Findings demonstrate that individuals with AUD display exaggerated sensitivity to U-threat at the behavioral and neural level and that these multimethod biomarkers tap into negative reinforcement processes of alcohol abuse.

Fibromyalgia predicts increased odds of pain-related addiction exacerbation among individuals with pain and opioid use disorder.

ABSTRACT: Fibromyalgia and opioid use disorder (OUD) are highly impactful chronic illnesses with substantially overlapping psychosocial, biological, and clinical features. Little previous research has examined interactions between fibromyalgia and OUD. Limiting such research has been the previous requirement of a clinical examination to diagnose fibromyalgia. The 2011 American College of Rheumatology Fibromyalgia Survey (ACR-FMS) is a validated self-report instrument with high sensitivity and specificity for fibromyalgia intended to enable fibromyalgia research in settings where a clinical examination is impractical. The present observational study uses the ACR-FMS to determine whether fibromyalgia affects odds of acknowledging pain-related OUD exacerbations among a sample of participants with pain and OUD. Participants with pain and OUD (n = 125) were recruited from an academic substance use treatment facility. The ACR-FMS, along with an original scale measuring pain-related OUD exacerbation-the Pain-related OUD Exacerbation Scale-was administered through an electronic survey. The factor structure, internal consistency, and construct validity of Pain-related OUD Exacerbation Scale were tested. In addition, descriptive analyses, multiple hierarchical linear regression, ordinal logistic regression, and multinomial logistic regression analyses were performed. Although all participants had pain, those with fibromyalgia demonstrated significantly greater odds of acknowledging pain-related OUD exacerbations. Pain-related OUD Exacerbation Scale was found to have a single-factor solution, strong internal consistency, and construct validity. This study provides first evidence of fibromyalgia as a risk factor for pain-related exacerbation of OUD and introduces a new scale with promising psychometric properties to measure pain-related OUD exacerbation.

Aberrant pulvinar effective connectivity in generalized social anxiety disorder.

Recent neuroimaging findings in general social anxiety disorder (gSAD) have extended our understanding of the neural mechanisms of gSAD beyond an amygdala-centric fear-based hyperactivity model to include other brain regions and networks relevant to salient cues. In particular, higher order areas compromising visual networks that process emotional and social information have been implicated. The pulvinar anchors this network and is a key regulatory node that mediates complex sensory inputs and the integration between limbic and frontal brain systems. However, the role of the pulvinar and specifically alteration of its effective connectivity with the rest of the brain has not been examined in the pathophysiology of gSAD, a disorder characterized by aberrant socio-emotional processing. The main aim of this study was to examine the pulvinar network effective connectivity in gSAD. In this study, we recruited 21 individuals with gSAD and 19 demographically matched healthy controls (HC), who performed an emotional face processing task while brain activity was recorded using functional magnetic resonance imaging (fMRI). To examine pulvinar-based network dynamics, Granger causality (GC) based effective connectivity (EC) analysis was applied on fMRI data to compare gSAD and HC. The EC analysis revealed heightened casual influential dynamics between pulvinar in higher order visual and frontal regions in gSAD. In conclusion, these preliminary data suggest a novel network-based cortico-pulvino-cortical neural mechanism in the pathophysiology of gSAD.

Neural response to errors in combat-exposed returning veterans with and without post-traumatic stress disorder: a preliminary event-related potential study.

Post-traumatic stress disorder (PTSD) is characterized by sustained anxiety, hypervigilance for potential threat, and hyperarousal. These symptoms may enhance self-perception of one's actions, particularly the detection of errors, which may threaten safety. The error-related negativity (ERN) is an electrocortical response to the commission of errors, and previous studies have shown that other anxiety disorders associated with exaggerated anxiety and enhanced action monitoring exhibit an enhanced ERN. However, little is known about how traumatic experience and PTSD would affect the ERN. To address this gap, we measured the ERN in returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with combat-related PTSD (PTSD group), combat-exposed OEF/OIF veterans without PTSD [combat-exposed control (CEC) group], and non-traumatized healthy participants [healthy control (HC) group]. Event-related potential and behavioral measures were recorded while 16 PTSD patients, 18 CEC, and 16 HC participants completed an arrow version of the flanker task. No difference in the magnitude of the ERN was observed between the PTSD and HC groups; however, in comparison with the PTSD and HC groups, the CEC group displayed a blunted ERN response. These findings suggest that (1) combat trauma itself does not affect the ERN response; (2) PTSD is not associated with an abnormal ERN response; and (3) an attenuated ERN in those previously exposed to combat trauma but who have not developed PTSD may reflect resilience to the disorder, less motivation to do the task, or a decrease in the significance or meaningfulness of 'errors,' which could be related to combat experience.