Immediate and long-term electrophysiological biomarkers of antidepressant-like behavioral effects after subanesthetic ketamine and medial prefrontal cortex deep brain stimulation treatment.

Introduction: Both ketamine (KET) and medial prefrontal cortex (mPFC) deep brain stimulation (DBS) are emerging therapies for treatment-resistant depression, yet our understanding of their electrophysiological mechanisms and biomarkers is incomplete. This study investigates aperiodic and periodic spectral parameters, and the signal complexity measure sample entropy, within mPFC local field potentials (LFP) in a chronic corticosterone (CORT) depression model after ketamine and/or mPFC DBS. Methods: Male rats were intraperitoneally administered CORT or vehicle for 21 days. Over the last 7 days, animals receiving CORT were treated with mPFC DBS, KET, both, or neither; then tested across an array of behavioral tasks for 9 days. Results: We found that the depression-like behavioral and weight effects of CORT correlated with a decrease in aperiodic-adjusted theta power (5-10 Hz) and an increase in sample entropy during the administration phase, and an increase in theta peak frequency and a decrease in the aperiodic exponent once the depression-like phenotype had been induced. The remission-like behavioral effects of ketamine alone correlated with a post-treatment increase in the offset and exponent, and decrease in sample entropy, both immediately and up to eight days post-treatment. The remission-like behavioral effects of mPFC DBS alone correlated with an immediate decrease in sample entropy, an immediate and sustained increase in low gamma (20-50 Hz) peak width and aperiodic offset, and sustained improvements in cognitive function. Failure to fully induce remission-like behavior in the combinatorial treatment group correlated with a failure to suppress an increase in sample entropy immediately after treatment. Conclusion: Our findings therefore support the potential of periodic theta parameters as biomarkers of depression-severity; and periodic low gamma parameters and cognitive measures as biomarkers of mPFC DBS treatment efficacy. They also support sample entropy and the aperiodic spectral parameters as potential cross-modal biomarkers of depression severity and the therapeutic efficacy of mPFC DBS and/or ketamine. Study of these biomarkers is important as objective measures of disease severity and predictive measures of therapeutic efficacy can be used to personalize care and promote the translatability of research across studies, modalities, and species.

Theta-frequency medial septal nucleus deep brain stimulation increases neurovascular activity in MK-801-treated mice.

Introduction: Deep brain stimulation (DBS) has shown remarkable success treating neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, epilepsy, and obsessive-compulsive disorder. DBS is now being explored to improve cognitive and functional outcomes in other psychiatric conditions, such as those characterized by reduced N-methyl-D-aspartate (NMDA) function (i.e., schizophrenia). While DBS for movement disorders generally involves high-frequency (>100 Hz) stimulation, there is evidence that low-frequency stimulation may have beneficial and persisting effects when applied to cognitive brain networks. Methods: In this study, we utilize a novel technology, functional ultrasound imaging (fUSI), to characterize the cerebrovascular impact of medial septal nucleus (MSN) DBS under conditions of NMDA antagonism (pharmacologically using Dizocilpine [MK-801]) in anesthetized male mice. Results: Imaging from a sagittal plane across a variety of brain regions within and outside of the septohippocampal circuit, we find that MSN theta-frequency (7.7 Hz) DBS increases hippocampal cerebral blood volume (CBV) during and after stimulation. This effect was not present using standard high-frequency stimulation parameters [i.e., gamma (100 Hz)]. Discussion: These results indicate the MSN DBS increases circuit-specific hippocampal neurovascular activity in a frequency-dependent manner and does so in a way that continues beyond the period of electrical stimulation.

Cilostazol for the management of moyamoya disease: a systematic review of the early evidence, efficacy, safety, and future directions.

Surgical revascularization remains the standard treatment for symptomatic moyamoya disease (MMD). As with any major surgical treatment, revascularization is associated with risks and limitations, denoting the need for noninvasive treatments to improve ischemic symptoms and prevent strokes. Cilostazol is a selective phosphodiesterase III inhibitor with antiplatelet, antithrombotic, and vasodilatory effects commonly used in peripheral vascular disease. Clinical studies assessing the efficacy of cilostazol in the management of stroke and MMD were recently reported, although a comprehensive assessment of the overall evidence is lacking. A systematic scoping review was conducted to assess the early evidence on cilostazol administration in patients with MMD. The inclusion criteria encompassed original human studies primarily focused on cilostazol's safety, efficacy, or utilization in managing MMD patients. A search of the PubMed database was conducted in June 2023, yielding 5 peer-reviewed publications that satisfied the inclusion criteria and were subjected to narrative synthesis. Risk of bias assessment was not applicable due to the scoping nature of this review. East Asian studies demonstrate increasing rates of cilostazol prescriptions for patients with MMD. In a large population-based study, cilostazol was compared to other antiplatelet medications and yielded the largest decrease in mortality among patients with newly diagnosed MMD. Other studies reported significant improvements in cerebral blood flow and cognitive function, which were deemed to be independent of one another. There are limited data on the safety profile of cilostazol in the MMD population, although the evidence derived from various studies performed in the general stroke population can likely provide insights into its potential utility in MMD patients. Cilostazol targets several critical pathways involved in the pathophysiology of MMD. The evidence corroborates the potential benefits of cilostazol for the management of MMD, although these findings should be interpreted with caution due to the small number of studies and lack of randomized trials. Subgroups of patients need to be identified who can safely undergo medical management in lieu of revascularization surgery or to improve surgical outcomes. Additional studies are needed to assess the efficacy and safety of cilostazol therapy, especially in Western populations.

Neuromodulation of OCD: A review of invasive and non-invasive methods.

Early research into neural correlates of obsessive compulsive disorder (OCD) has focused on individual components, several network-based models have emerged from more recent data on dysfunction within brain networks, including the the lateral orbitofrontal cortex (lOFC)-ventromedial caudate, limbic, salience, and default mode networks. Moreover, the interplay between multiple brain networks has been increasingly recognized. As the understanding of the neural circuitry underlying the pathophysiology of OCD continues to evolve, so will too our ability to specifically target these networks using invasive and noninvasive methods. This review discusses the rationale for and theory behind neuromodulation in the treatment of OCD.

Pathophysiological Mechanisms Underlying Idiopathic Normal Pressure Hydrocephalus: A Review of Recent Insights.

The pathophysiologic mechanisms underpinning idiopathic normal pressure hydrocephalus (iNPH), a clinically diagnosed dementia-causing disorder, continue to be explored. An increasing body of evidence implicates multiple systems in the pathogenesis of this condition, though a unifying causative etiology remains elusive. Increased knowledge of the aberrations involved has shed light on the iNPH phenotype and has helped to guide prognostication for treatment with cerebrospinal fluid diversion. In this review, we highlight the central role of the cerebrovasculature in pathogenesis, from hydrocephalus formation to cerebral blood flow derangements, blood-brain barrier breakdown, and glymphatic pathway dysfunction. We offer potential avenues for increasing our understanding of how this disease occurs.

Frequency-specific medial septal nucleus deep brain stimulation improves spatial memory in MK-801-treated male rats.

BACKGROUND: Few treatments exist for the cognitive symptoms of schizophrenia. Pharmacological agents resulting in glutamate N-methyl-d-aspartate (NMDA) receptor hypofunction, such as MK-801, mimic many of these symptoms and disrupt neural activity. Recent evidence suggests that deep brain stimulation (DBS) of the medial septal nucleus (MSN) can modulate medial prefrontal cortex (mPFC) and hippocampal activity and improve spatial memory. OBJECTIVE: Here, we examine the effects of acute MK-801 administration on oscillatory activity within the septohippocampal circuit and behavior. We also evaluate the potential for MSN stimulation to improve cognitive behavioral measures following MK-801 administration. METHODS: 59 Sprague Dawley male rats received either acute intraperitoneal (IP) saline vehicle injections or MK-801 (0.1 mg/kg). Theta (5-12 Hz), low gamma (30-50 Hz) and high frequency oscillatory (HFO) power were analyzed in the mPFC, MSN, thalamus and hippocampus. Rats underwent MSN theta (7.7 Hz), gamma (100 Hz) or no stimulation during behavioral tasks (Novel object recognition (NOR), elevated plus maze, Barnes maze (BM)). RESULTS: Injection of MK-801 resulted in frequency-specific changes in oscillatory activity, decreasing theta while increasing HFO power. Theta, but not gamma, stimulation enhanced the anxiolytic effects of MK-801 on the elevated plus maze. While MK-801 treated rats exhibited spatial memory deficits on the Barnes maze, those that also received MSN theta, but not gamma, stimulation found the escape hole sooner. CONCLUSIONS: These findings demonstrate that acute MK-801 administration leads to altered neural activity in the septohippocampal circuit and impaired spatial memory. Further, these findings suggest that MSN theta-frequency stimulation improves specific spatial memory deficits and may be a possible treatment for cognitive impairments caused by NMDA hypofunction.

A Review of Medical and Surgical Options for the Treatment of Facial Pain.

Facial pain is a common medical complaint that is easily misdiagnosed. As a result, this pain often goes mistreated. Despite this, there are a variety of pharmacologic, surgical, and neuromodulatory options for the treatment of facial pain. In this review, the authors detail the forms of facial pain and their treatment options. They discuss the common medications used in the first-line treatment of facial pain and the second-line surgical and neuromodulatory options available to patients when pharmacologic options fail.

On the Design of a Novel Underactuated Robotic Finger Prosthesis for Partial Hand Amputation.

This paper presents a novel robotic finger prosthesis for partially amputated patients who have lost a thumb and index finger. The challenging issues were to design i) a three-degree-of-freedom (DOF) underactuated mechanism that mimics intact finger movements including motion profiles and self-adaptation for unknown constraints, ii) an attachment socket for everyday life that allows ease of donning and doffing, and comfortable wearability, and iii) a shape to pack the selected components including an actuator, linkages, and sensors into a limited space avoiding motion interference with other intact fingers and wrist. This paper reports our effort to solve the challenging issues. The proposed three-DOF prosthetic finger can generate 4.6N pinch force and 99.4°/s angular velocity at the MCP joints. For command signals, surface-electromyogram (sEMG) sensors were used. This enables users to operate the fingers with certain configuration and grasping force. The performance of the proposed design was verified through the box-and-block test and bottle opening test with a patient who has a partially amputated hand.