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.

Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy.

OBJECTIVE: Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing. METHODS: Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others. RESULTS: With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS. SIGNIFICANCE: This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.

Stress and anxiety: counterpart elements of the stress/anxiety complex.

The relationship between stress and anxiety is complicated. Stress initially arises from one's environment; anxiety overlays physiological arousal, cognitive appraisals, emotional states, and behavioral responses. Both are components of a stress-anxiety complex, which has evolved to enable individuals to adapt to their environment and achieve equilibrium. Anxiety disorders, which result when this mechanism goes awry, occur along a spectrum. One of the main variables affecting anxiety disorders is the extent of stress. Each anxiety disorder should be evaluated along a stress axis, leading to improved case conceptualization and intervention strategies.

A non-linear dynamical approach to belief revision in cognitive behavioral therapy.

Belief revision is the key change mechanism underlying the psychological intervention known as cognitive behavioral therapy (CBT). It both motivates and reinforces new behavior. In this review we analyze and apply a novel approach to this process based on AGM theory of belief revision, named after its proponents, Carlos Alchourrón, Peter Gärdenfors and David Makinson. AGM is a set-theoretical model. We reconceptualize it as describing a non-linear, dynamical system that occurs within a semantic space, which can be represented as a phase plane comprising all of the brain's attentional, cognitive, affective and physiological resources. Triggering events, such as anxiety-producing or depressing situations in the real world, or their imaginal equivalents, mobilize these assets so they converge on an equilibrium point. A preference function then evaluates and integrates evidentiary data associated with individual beliefs, selecting some of them and comprising them into a belief set, which is a metastable state. Belief sets evolve in time from one metastable state to another. In the phase space, this evolution creates a heteroclinic channel. AGM regulates this process and characterizes the outcome at each equilibrium point. Its objective is to define the necessary and sufficient conditions for belief revision by simultaneously minimizing the set of new beliefs that have to be adopted, and the set of old beliefs that have to be discarded or reformulated. Using AGM, belief revision can be modeled using three (and only three) fundamental syntactical operations performed on belief sets, which are expansion; revision; and contraction. Expansion is like adding a new belief without changing any old ones. Revision is like adding a new belief and changing old, inconsistent ones. Contraction is like changing an old belief without adding any new ones. We provide operationalized examples of this process in action.

Interactions between diabetes and anxiety and depression: implications for treatment.

Anxiety or depression may be a risk factor for the development of diabetes. This relationship may occur through a combination of genetic predispositions; epigenetic contingencies; exacerbating conditions such as metabolic syndrome (a precursor to diabetes); and other serious medical conditions. Medications used to treat anxiety and depression have significant side effects, such as weight gain, further increasing the possibility of developing diabetes. These components combine, interact, and reassemble to create a precarious system for persons with, or predisposed to, diabetes. Clinicians must be aware of these interrelationships to adequately treat the disease.