Transcranial focused ultrasound of the amygdala modulates fear network activation and connectivity.

BACKGROUND: Current noninvasive brain stimulation methods are incapable of directly modulating subcortical brain regions critically involved in psychiatric disorders. Transcranial Focused Ultrasound (tFUS) is a newer form of noninvasive stimulation that could modulate the amygdala, a subcortical region implicated in fear. OBJECTIVE: We investigated the effects of active and sham tFUS of the amygdala on fear circuit activation, skin conductance responses (SCR), and self-reported anxiety during a fear-inducing task. We also investigated amygdala tFUS' effects on amygdala-fear circuit resting-state functional connectivity. METHODS: Thirty healthy individuals were randomized in this double-blinded study to active or sham tFUS of the left amygdala. We collected fMRI scans, SCR, and self-reported anxiety during a fear-inducing task (participants viewed red or green circles which indicated the risk of receiving an aversive stimulus), as well as resting-state scans, before and after tFUS. RESULTS: Compared to sham tFUS, active tFUS was associated with decreased (pre to post tFUS) blood-oxygen-level-dependent fMRI activation in the amygdala (F(1,25) = 4.86, p = 0.04, η2 = 0.16) during the fear task, and lower hippocampal (F(1,27) = 4.41, p = 0.05, η2 = 0.14), and dorsal anterior cingulate cortex (F(1,27) = 6.26, p = 0.02; η2 = 0.19) activation during the post tFUS fear task. The decrease in amygdala activation was correlated with decreased subjective anxiety (r = 0.62, p = 0.03). There was no group effect in SCR changes from pre to post tFUS (F(1,23) = 0.85, p = 0.37). The active tFUS group also showed decreased amygdala-insula (F(1,28) = 4.98, p = 0.03) and amygdala-hippocampal (F(1,28) = 7.14, p = 0.01) rsFC, and increased amygdala-ventromedial prefrontal cortex (F(1,28) = 3.52, p = 0.05) resting-state functional connectivity. CONCLUSIONS: tFUS can change functional connectivity and brain region activation associated with decreased anxiety. Future studies should investigate tFUS' therapeutic potential for individuals with clinical levels of anxiety.

Probabilistic and rich individual working memories revealed by a betting game.

When asked to remember a color, do people remember a point estimate (e.g., a particular shade of red), a point estimate plus an uncertainty estimate, or are memory representations rich probabilistic distributions over feature space? We asked participants to report the color of a circle held in working memory. Rather than collecting a single report per trial, we had participants place multiple bets to create trialwise uncertainty distributions. Bet dispersion correlated with performance, indicating that internal uncertainty guided bet placement. While the first bet was on average the most precisely placed, the later bets systematically shifted the distribution closer to the target, resulting in asymmetrical distributions about the first bet. This resulted in memory performance improvements when averaging across bets, and overall suggests that memory representations contain more information than can be conveyed by a single response. The later bets contained target information even when the first response would generally be classified as a guess or report of an incorrect item, suggesting that such failures are not all-or-none. This paradigm provides multiple pieces of evidence that memory representations are rich and probabilistic. Crucially, standard discrete response paradigms underestimate the amount of information in memory representations.

Case Report of Dual-Site Neurostimulation and Chronic Recording of Cortico-Striatal Circuitry in a Patient With Treatment Refractory Obsessive Compulsive Disorder.

Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of cortico-striatal-thalamo-cortical (CSTC) loops. Deep brain stimulation (DBS) and lesions of CSTC structures have shown promise for treating both OCD and related disorders involving over-expression of automatic/habitual behaviors. Physiologically, we propose that this CSTC hyper-connectivity may be reflected in high synchrony of neural firing between loop structures, which could be measured as coherent oscillations in the local field potential (LFP). Here we report the results from the pilot patient in an Early Feasibility study (https://clinicaltrials.gov/ct2/show/NCT03184454) in which we use the Medtronic Activa PC+ S device to simultaneously record and stimulate in the supplementary motor area (SMA) and ventral capsule/ventral striatum (VC/VS). We hypothesized that frequency-mismatched stimulation should disrupt coherence and reduce compulsive symptoms. The patient reported subjective improvement in OCD symptoms and showed evidence of improved cognitive control with the addition of cortical stimulation, but these changes were not reflected in primary rating scales specific to OCD and depression, or during blinded cortical stimulation. This subjective improvement was correlated with increased SMA and VC/VS coherence in the alpha, beta, and gamma bands, signals which persisted after correcting for stimulation artifacts. We discuss the implications of this research, and propose future directions for research in network modulation in OCD and more broadly across psychiatric disorders.

Strategic trade-offs between quantity and quality in working memory.

Is working memory capacity determined by an immutable limit-for example, 4 memory storage slots? The fact that performance is typically unaffected by task instructions has been taken as support for such structural models of memory. Here, we modified a standard working memory task to incentivize participants to remember more items. Participants were asked to remember a set of colors over a short retention interval. In 1 condition, participants reported a random item's color using a color wheel. In the modified task, participants responded to all items and their response was only considered correct if all responses were on the correct half of the color wheel. We looked for a trade-off between quantity and quality-participants storing more items, but less precisely, when required to report them all. This trade-off was observed when tasks were blocked and when task-type was cued after encoding, but not when task-type was cued during the response, suggesting that task differences changed how items were actively encoded and maintained. This strategic control over the contents of working memory challenges models that assume inflexible limits on memory storage. (PsycINFO Database Record