A Pilot Randomized Trial of Combined Cognitive-Behavioral Therapy and Exercise Training Versus Exercise Training Alone for the Management of Chronic Insomnia in Obstructive Sleep Apnea.

Insomnia treatment among individuals with comorbid insomnia and obstructive sleep apnea is suboptimal. In a pilot randomized controlled trial, 19 individuals with comorbid insomnia and obstructive sleep apnea were allocated to one of two arms: EX + EX, consisting of two 8-week phases of exercise training (EX), or RE + CBTiEX, encompassing 8 weeks of relaxation training (RE) followed by 8 weeks of combined cognitive-behavioral therapy and exercise (CBTiEX). Outcomes included Insomnia Severity Index (ISI), polysomnography, and cardiorespiratory fitness measures. A mixed-model analysis of variance revealed a Group × Time interaction on peak oxygen consumption change, F(1, 14) = 10.1, p = .007, and EX increased peak oxygen consumption (p = .03, g' = -0.41) and reduced ISI (p = .001, g' = 0.82) compared with RE (p = .49, g = 0.16) post-8 weeks. Post-16 weeks, there was a significant Group × Time interaction (p = .014) driven by RE + CBTiEX yielding a larger improvement in ISI (p = .023, g' = 1.48) than EX + EX (p = .88, g' < 0.1). Objective sleep was unchanged. This study showed promising effects of regular EX alone and combined with cognitive-behavioral therapy for insomnia on ISI in comorbid insomnia and obstructive sleep apnea.

The Role of Diet in Parkinson's Disease.

The aim of this review is to examine the intersection of Parkinson's disease (PD) with nutrition, to identify best nutritional practices based on current evidence, and to identify gaps in the evidence and suggest future directions. Epidemiological work has linked various dietary patterns and food groups to changes in PD risk; however, fewer studies have evaluated the role of various diets, dietary components, and supplements in the management of established PD. There is substantial interest in exploring the role of diet-related interventions in both symptomatic management and potential disease modification. In this paper, we evaluate the utility of several dietary patterns, including the Mediterranean (MeDi), Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), Alternative Healthy Eating Index (AHEI), vegan/vegetarian, and ketogenic diet in persons with PD. Additionally, we provide an overview of the evidence relating several individual food groups and nutritional supplements to PD risk, symptoms and progression.

Therapeutic Potentials of Localized Blood-Brain Barrier Disruption by Noninvasive Transcranial Focused Ultrasound: A Technical Review.

The demands for region-specific, noninvasive therapies for neurologic/psychiatric conditions are growing. The rise of transcranial focused ultrasound technology has witnessed temporary and reversible disruptions of the blood-brain barrier in the brain with exceptional control over the spatial precisions and depth, all in a noninvasive manner. Starting with small animal studies about a decade ago, the technique is now being explored in nonhuman primates and humans for the assessment of its efficacy and safety. The ability to transfer exogenous/endogenous therapeutic agents, cells, and biomolecules across the blood-brain barrier opens up new therapeutic avenues for various neurologic conditions, with a possibility to modulate the excitability of regional brain function. This review addresses the technical fundamentals, sonication parameters, experimental protocols, and monitoring techniques to examine the efficacy/safety in focused ultrasound-mediated blood-brain barrier disruption and discuss its potential translations to clinical use.

Localized Blood-Brain Barrier Opening in Ovine Model Using Image-Guided Transcranial Focused Ultrasound.

Transcranial application of focused ultrasound (FUS) combined with vascular introduction of microbubble contrast agents (MBs) has emerged as a non-invasive technique that can temporarily create a localized opening in the blood-brain barrier (BBB). Under image-guidance, we administered FUS to sheep brain after intravenous injection of microbubbles. BBB opening was confirmed by performing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to detect the extravasated gadolinium-based magnetic resonance contrast agents. Through pharmacokinetic analysis as well as independent component analysis of the DCE-MRI data, we observed localized enhancement in BBB permeability at the area that subjected to acoustic pressure of 0.48 MPa (mechanical index = 0.96). On the other hand, application of a higher pressure at 0.58 MPa resulted in localized, minor cerebral hemorrhage. No animals exhibited abnormal behavior during the post-FUS survival periods up to 2 mo. Our data suggest that monitoring for excessive BBB disruption is important for safe translation of the method to humans.

Basal Ganglia: Striosomes and the Link between Motivation and Action.

The basal ganglia integrate motivation and action across their circuits; neurons in anatomical modules called striosomes could contribute strongly to this merger. A new method focusing on network interconnections will allow a better understanding of the functional role of striosomes.

Transcranial focused ultrasound stimulation of motor cortical areas in freely-moving awake rats.

BACKGROUND: Low-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia. RESULTS: We developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague-Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions. CONCLUSIONS: The wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.

Focused ultrasound brain stimulation to anesthetized rats induces long-term changes in somatosensory evoked potentials.

Low-intensity transcranial focused ultrasound (FUS) has emerged as a non-invasive brain stimulation modality that can reach deep brain areas with high spatial specificity. Previous studies have identified transient effects of FUS on the brain excitability and accompanying physiological responses. Yet the presence of long-lasting effects of FUS, which extend on the order of half an hour or more, has not been probed. We transcranially applied FUS to the somatosensory areas of the anesthetized rats for 10 min at a low duty cycle (5%) and intensity, far below the level that could alter the tissue temperature. Concurrently, we measured electroencephalographic (EEG) somatosensory evoked potentials (SEP) induced by the unilateral electrical stimulation of the hind limb before and after the sonication. Compared to the control sham condition that did not involve sonication, differential SEP features were evident and persisted beyond 35 min after the administration of FUS. The presence of this non-transient neuromodulatory effect may provide early evidence that FUS-mediated brain stimulation has the potential to induce neuroplasticity.

Multi-resolution simulation of focused ultrasound propagation through ovine skull from a single-element transducer.

Transcranial focused ultrasound (tFUS) is emerging as a non-invasive brain stimulation modality. Complicated interactions between acoustic pressure waves and osseous tissue introduce many challenges in the accurate targeting of an acoustic focus through the cranium. Image-guidance accompanied by a numerical simulation is desired to predict the intracranial acoustic propagation through the skull; however, such simulations typically demand heavy computation, which warrants an expedited processing method to provide on-site feedback for the user in guiding the acoustic focus to a particular brain region. In this paper, we present a multi-resolution simulation method based on the finite-difference time-domain formulation to model the transcranial propagation of acoustic waves from a single-element transducer (250 kHz). The multi-resolution approach improved computational efficiency by providing the flexibility in adjusting the spatial resolution. The simulation was also accelerated by utilizing parallelized computation through the graphic processing unit. To evaluate the accuracy of the method, we measured the actual acoustic fields through ex vivo sheep skulls with different sonication incident angles. The measured acoustic fields were compared to the simulation results in terms of focal location, dimensions, and pressure levels. The computational efficiency of the presented method was also assessed by comparing simulation speeds at various combinations of resolution grid settings. The multi-resolution grids consisting of 0.5 and 1.0 mm resolutions gave acceptable accuracy (under 3 mm in terms of focal position and dimension, less than 5% difference in peak pressure ratio) with a speed compatible with semi real-time user feedback (within 30 s). The proposed multi-resolution approach may serve as a novel tool for simulation-based guidance for tFUS applications.