Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity

<p>Abstract</p> <p>Background</p> <p>Epilepsy is a common neurological disorder, which is attributed to uncontrollable abnormal hyper-excitability of neurons. We investigated the feasibility of using low-intensity, pulsed radiation of focused ultrasound (FUS) to non-invasively suppress epileptic activity in an animal model (rat), which was induced by the intraperitonial injection of pentylenetetrazol (PTZ).</p> <p>Results</p> <p>After the onset of induced seizures, FUS was transcranially administered to the brain twice for three minutes each while undergoing electroencephalographic (EEG) monitoring. An air-backed, spherical segment ultrasound transducer (diameter: 6 cm; radius-of-curvature: 7 cm) operating at a fundamental frequency of 690 KHz was used to deliver a train of 0.5 msec-long pulses of sonication at a repetitive rate of 100 Hz to the thalamic areas of the brain. The acoustic intensity (130 mW/cm²) used in the experiment was sufficiently within the range of safety guidelines for the clinical ultrasound imaging. The occurrence of epileptic EEG bursts from epilepsy-induced rats significantly decreased after sonication when it was compared to the pre-sonication epileptic state. The PTZ-induced control group that did not receive any sonication showed a sustained number of epileptic EEG signal bursts. The animals that underwent sonication also showed less severe epileptic behavior, as assessed by the Racine score. Histological analysis confirmed that the sonication did not cause any damage to the brain tissue.</p> <p>Conclusions</p> <p>These results revealed that low-intensity, pulsed FUS sonication suppressed the number of epileptic signal bursts using acute epilepsy model in animal. Due to its non-invasiveness and spatial selectivity, FUS may offer new perspectives for a possible non-invasive treatment of epilepsy.</p

New Strategies for Combining Mindfulness with Integrative Cognitive Behavioral Therapy for the Treatment of Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) severely impacts social functioning, distress levels, and utilization of medical care compared with that of other major psychiatric disorders. Neither pharmacological nor psychotherapy interventions have adequately controlled cardinal symptoms of GAD: pervasive excessive anxiety and uncontrollable worry. Research has established cognitive behavioral therapy (CBT) as the most effective psychotherapy for controlling GAD; however, outcomes remain at only 50% reduction, with high relapse rates. Mindfulness has been integrated with CBT to treat people suffering from numerous psychiatric disorders, with mindfulness based stress reduction (MBSR) being the most researched. Preliminary evidence supports MBSR’s potential for controlling GAD symptoms and key researchers suggest mindfulness practices possess key elements for treating GAD. Classical mindfulness (CM) differs significantly from MBSR and possesses unique potentials for directly targeting process and state GAD symptoms inadequately treated by CBT. This article introduces the theory and practice of CM, its differences from MBSR, and a critical review of MBSR and CBT treatments for GAD. CM strategies designed to complement CBT targeting cardinal GAD symptoms are outlined with a case study illustrating its use

Dynamical Principles of Emotion-Cognition Interaction: Mathematical Images of Mental Disorders

The key contribution of this work is to introduce a mathematical framework to understand self-organized dynamics in the brain that can explain certain aspects of itinerant behavior. Specifically, we introduce a model based upon the coupling of generalized Lotka-Volterra systems. This coupling is based upon competition for common resources. The system can be regarded as a normal or canonical form for any distributed system that shows self-organized dynamics that entail winnerless competition. Crucially, we will show that some of the fundamental instabilities that arise in these coupled systems are remarkably similar to endogenous activity seen in the brain (using EEG and fMRI). Furthermore, by changing a small subset of the system's parameters we can produce bifurcations and metastable sequential dynamics changing, which bear a remarkable similarity to pathological brain states seen in psychiatry. In what follows, we will consider the coupling of two macroscopic modes of brain activity, which, in a purely descriptive fashion, we will label as cognitive and emotional modes. Our aim is to examine the dynamical structures that emerge when coupling these two modes and relate them tentatively to brain activity in normal and non-normal states

Low-intensity focused ultrasound pulsation device used during magnetic resonance imaging: evaluation of magnetic resonance imaging-related heating at 3 Tesla/128 MHz.

ObjectiveThe objective of this study was to determine magnetic resonance imaging (MRI)-related heating for a low-intensity focused ultrasound pulsation (LIFUP) device used during MRI performed at 3 T/128 MHz.Materials and methodsA special phantom was constructed to mimic the thermal properties of the human brain, and a piece of human temporal bone (skull) was embedded on top. Four fluoroptic thermometry probes, placed above and below the skull, were used to measure temperature changes during MRI (3 T/128 MHz; scanner-reported head average specific absorption rate 1.1-2 W/kg) with and without concurrent LIFUP sonication. LIFUP sonication was applied using a focused ultrasound device (BXPulsar 1001, Brainsonix, Inc., Los Angeles, CA, USA) at a derated spatial-peak temporal-average intensity of 3870 mW/cm(2) .ResultsMRI performed at relatively high specific absorption rate (SAR) caused a slight elevation in temperature (≤0.6°C). Concurrent use of MRI at a medium-strength SAR and LIFUP sonication resulted in maximum temperature rise of 3.1°C after 8 min of continuous use.ConclusionsUnder the specific conditions utilized for this investigation, LIFUP sonication does not appear to present significant heating risks when used concurrently with MRI. This information has important implications for the use of the LIFUP sonication in human subjects undergoing MRI at 3 T/128 MHz

Low-intensity focused ultrasound pulsation device used during magnetic resonance imaging: evaluation of magnetic resonance imaging-related heating at 3 Tesla/128 MHz.

ObjectiveThe objective of this study was to determine magnetic resonance imaging (MRI)-related heating for a low-intensity focused ultrasound pulsation (LIFUP) device used during MRI performed at 3 T/128 MHz.Materials and methodsA special phantom was constructed to mimic the thermal properties of the human brain, and a piece of human temporal bone (skull) was embedded on top. Four fluoroptic thermometry probes, placed above and below the skull, were used to measure temperature changes during MRI (3 T/128 MHz; scanner-reported head average specific absorption rate 1.1-2 W/kg) with and without concurrent LIFUP sonication. LIFUP sonication was applied using a focused ultrasound device (BXPulsar 1001, Brainsonix, Inc., Los Angeles, CA, USA) at a derated spatial-peak temporal-average intensity of 3870 mW/cm(2) .ResultsMRI performed at relatively high specific absorption rate (SAR) caused a slight elevation in temperature (≤0.6°C). Concurrent use of MRI at a medium-strength SAR and LIFUP sonication resulted in maximum temperature rise of 3.1°C after 8 min of continuous use.ConclusionsUnder the specific conditions utilized for this investigation, LIFUP sonication does not appear to present significant heating risks when used concurrently with MRI. This information has important implications for the use of the LIFUP sonication in human subjects undergoing MRI at 3 T/128 MHz

Effective Deepening of Meditative-States with Focused Ultrasound Stimulation and its Moderation by Prior-Experience

This study explores the intersection of meditation and neurostimulation, focusing on Focused Ultrasound Stimulation (FUS) as a potential aid in achieving meditative states. We compared the effects of FUS to sham stimulation in experienced and novice meditators, targeting three specific brain regions: the posterior cingulate cortex (PCC), the caudate nucleus (CN), and the insular cortex (Iav). Our investigation is particularly relevant given the growing evidence of meditation's positive impact on mental health and well-being, and the challenges many face in maintaining regular meditative practice. The chosen targets are backed by empirical and theoretical support, reflecting their roles in meditative states and related cognitive functions. This study not only contributes to understanding the neural mechanisms of meditation but also explores the potential of FUS in enhancing meditative practices, especially for those who struggle to achieve these states independently

Synergistic application of cardiac sympathetic decentralization and comprehensive psychiatric treatment in the management of anxiety and electrical storm.

We report here, for the first time, two cases demonstrating a synergistic application of bilateral cardiac sympathetic decentralization and multimodal psychiatric treatment for the assessment and management of anxiety following recurrent Implantable Cardioverter Defibrillator (ICD) shocks. In a first case the combination of bilateral cardiac sympathetic decentralization (BCSD), cognitive behavioral psychotherapy and anxiolytic medication was sufficient to attenuate the patients symptoms and maladaptive behaviors, with a maintained benefit at 1 year. Among the more prominent subjective changes in the post-lesion state we observed a decrease in aversive interoceptive sensations, particularly of the heartbeat. The patient continued to experience cognitive threat appraisals on a frequent basis, although these were no longer incapacitating. In a second case, we report the effect of BCSD on autonomic tone and subjective state. In the post-lesion state we observed attenuated sympathetic responses to the valsalva maneuver, isometric handgrip and mental arithmetic stressor, including decreased systolic and diastolic blood pressure and, decreased skin conductance. Collectively, these preliminary findings suggest that an integrative, multidisciplinary approach to treating anxiety disorders in the setting of ventricular arrhythmias and recurrent ICD shocks can result in sustained improvements in physical, psychological, and functional status. These findings raise the possibility of a potential role for the stellate ganglion in the modulation of emotional experience and afferent transmission of interoceptive information to the central nervous system