Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans.

Background: Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively. Objective/Hypothesis: We sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional functioning as well as learning and memory. We hypothesized that tFUS would result in significant longitudinal changes in perfusion in the targeted brain region as well as selective modulation of BOLD activity and BOLD-based functional connectivity of the target region. Methods: In this study, we collected MRI before, simultaneously during, and after tFUS of two deep brain structures on different days in sixteen healthy adults each serving as their own control. Using longitudinal arterial spin labeling (ASL) MRI and simultaneous blood oxygen level dependent (BOLD) functional MRI, we found changes in cerebral perfusion, regional brain activity and functional connectivity specific to the targeted regions of the amygdala and entorhinal cortex (ErC). Results: tFUS selectively increased perfusion in the targeted brain region and not in the contralateral homolog or either bilateral control region. Additionally, tFUS directly affected BOLD activity in a target specific fashion without engaging auditory cortex in any analysis. Finally, tFUS resulted in selective modulation of the targeted functional network connectivity. Conclusion: We demonstrate that tFUS can selectively modulate perfusion, neural activity and connectivity in deep brain structures and connected networks. Lack of auditory cortex findings suggests that the mechanism of tFUS action is not due to auditory or acoustic startle response but rather a direct neuromodulatory process. Our findings suggest that tFUS has the potential for future application as a novel therapy in a wide range of neurological and psychiatric disorders associated with subcortical pathology.

Neural and behavioral effects of modification of visual attention in body dysmorphic disorder.

In individuals with body dysmorphic disorder (BDD), perceptual appearance distortions may be related to selective attention biases and aberrant visual scanning, contributing to imbalances in global vs. detailed visual processing. Treatments for the core symptom of perceptual distortions are underexplored in BDD; yet understanding their mechanistic effects on brain function is critical for rational treatment development. This study tested a behavioral strategy of visual-attention modification on visual system brain connectivity and eye behaviors. We acquired fMRI data in 37 unmedicated adults with BDD and 30 healthy controls. Participants viewed their faces naturalistically (naturalistic viewing), and holding their gaze on the image center (modulated viewing), monitored with an eye-tracking camera. We analyzed dynamic effective connectivity and visual fixation duration. Modulated viewing resulted in longer mean visual fixation duration compared to during naturalistic viewing, across groups. Further, modulated viewing resulted in stronger connectivity from occipital to parietal dorsal visual stream regions, also evident during the subsequent naturalistic viewing, compared with the initial naturalistic viewing, in BDD. Longer fixation duration was associated with a trend for stronger connectivity during modulated viewing. Those with more severe BDD symptoms had weaker dorsal visual stream connectivity during naturalistic viewing, and those with more negative appearance evaluations had weaker connectivity during modulated viewing. In sum, holding a constant gaze on a non-concerning area of one's face may confer increased communication in the occipital/parietal dorsal visual stream, facilitating global/holistic visual processing. This effect shows persistence during subsequent naturalistic viewing. Results have implications for perceptual retraining treatment designs.

Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS. METHODS: Medications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks. RESULTS: Use of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02). CONCLUSIONS: Concomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome.