Racial disparities in access to DBS: results of a real-world U.S. claims data analysis

IntroductionDeep brain stimulation (DBS) is an effective and standard-of-care therapy for Parkinson’s Disease and other movement disorders when symptoms are inadequately controlled with conventional medications. It requires expert care for patient selection, surgical targeting, and therapy titration. Despite the known benefits, racial/ethnic disparities in access have been reported. Technological advancements with smartphone-enabled devices may influence racial disparities. Real-world evidence investigations can shed further light on barriers to access and demographic disparities for DBS patients.MethodsA retrospective cross-sectional study was performed using Medicare claims linked with manufacturer patient data tracking to analyze 3,869 patients who received DBS. Patients were divided into two categories: traditional omnidirectional DBS systems with dedicated proprietary controllers (“traditional”; n = 3,256) and directional DBS systems with smart controllers (“smartphone-enabled”; n = 613). Demographics including age, sex, and self-identified race/ethnicity were compared. Categorical demographics, including race/ethnicity and distance from implanting facility, were analyzed for the entire population.ResultsA significant disparity in DBS utilization was evident. White individuals comprised 91.4 and 89.9% of traditional and smartphone-enabled DBS groups, respectively. Non-White patients were significantly more likely to live closer to implanting facilities compared with White patients.ConclusionThere is great racial disparity in utilization of DBS therapy. Smartphone-enabled systems did not significantly impact racial disparities in receiving DBS. Minoritized patients were more likely to live closer to their implanting facility than White patients. Further research is warranted to identify barriers to access for minoritized patients to receive DBS. Technological advancements should consider the racial discrepancy of DBS utilization in future developments

Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway

Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.National Institutes of Health (U.S.) (Grant AG047661)National Institutes of Health (U.S.) (Grant NS051874)JPB FoundationSwiss National Science Foundation (Grant for Prospective Researchers)Human Frontier Science Program (Strasbourg, France) (Long-Term Postdoctoral Fellowship

Racial Disparities in Access to DBS: Results of a Real-World U.S. Claims Data Analysis

INTRODUCTION: Deep brain stimulation (DBS) is an effective and standard-of-care therapy for Parkinson\u27s Disease and other movement disorders when symptoms are inadequately controlled with conventional medications. It requires expert care for patient selection, surgical targeting, and therapy titration. Despite the known benefits, racial/ethnic disparities in access have been reported. Technological advancements with smartphone-enabled devices may influence racial disparities. Real-world evidence investigations can shed further light on barriers to access and demographic disparities for DBS patients. METHODS: A retrospective cross-sectional study was performed using Medicare claims linked with manufacturer patient data tracking to analyze 3,869 patients who received DBS. Patients were divided into two categories: traditional omnidirectional DBS systems with dedicated proprietary controllers ( traditional ; RESULTS: A significant disparity in DBS utilization was evident. White individuals comprised 91.4 and 89.9% of traditional and smartphone-enabled DBS groups, respectively. Non-White patients were significantly more likely to live closer to implanting facilities compared with White patients. CONCLUSION: There is great racial disparity in utilization of DBS therapy. Smartphone-enabled systems did not significantly impact racial disparities in receiving DBS. Minoritized patients were more likely to live closer to their implanting facility than White patients. Further research is warranted to identify barriers to access for minoritized patients to receive DBS. Technological advancements should consider the racial discrepancy of DBS utilization in future developments

Neural Circuit Mechanisms Underlying the Exacerbation of Alzheimer’s Disease by Chronic Stress

Both epidemiological and animal studies have demonstrated a strong association between Alzheimer’s disease (AD), neuropsychiatric symptoms such as depression and anxiety, and chronic psychological stress. The neurophysiological basis of fear, anxiety, and stress has been well studied and is thought to involve the basolateral amygdala (BLA) – a structure of the anterior temporal lobe, which interprets fearful stimuli and outputs a behavioral fear response. To determine if increased BLA activity could act to accelerate the progression of AD, we manipulated a direct BLA-to-hippocampus circuit using optogenetic (ChR2) and pharmacogenetic (GiDREADD) technologies, and subsequently examined hippocampal AD-related pathology, synaptic density, histone-deacetylase-2 expression, and hippocampus-dependent learning and memory abilities. We found that in wild-type mice, activation of glutamatergic BLA neurons was both necessary and sufficient to produce the molecular and cognitive effects of chronic stress. Terminal photostimulation of direct BLA afferents within the hippocampus was also sufficient. Chronic activation of BLA glutamatergic neurons in the 5xFAD model of AD accelerated the neuropathological and cognitive AD-like phenotype, while chronic BLA inactivation had opposite effects. Overall our results suggest that neuropsychiatric disease and chronic stress may act through enhanced BLA activation to accelerate the progression of AD

Double-dissociation of the catecholaminergic modulation of synaptic transmission in the oval bed nucleus of the stria terminalis.

International audienceThe bed nucleus of the stria terminalis (BST) is a cluster of nuclei within the extended amygdala, a forebrain macrostructure with extensive projection to motor nuclei of the hindbrain. The subnuclei of the BST coordinate autonomic, neuroendocrine, and somato-motor functions and receive robust neuromodulatory monoaminergic afferents, including 5-HT-, noradrenaline (NA)-, and dopamine (DA)-containing terminals. In contrast to 5-HT and NA, little is known about how DA modulates neuronal activity or synaptic transmission in the BST. DA-containing afferents to the BST originate in the ventral tegmental area, the periaqueducal gray, and the retrorubral field. They form a fairly diffuse input to the dorsolateral BST with dense terminal fields in the oval (ovBST) and juxtacapsular (jxBST) nuclei. The efferent-afferent connectivity of the BST suggests that it may play a key role in motivated behaviors, consistent with recent evidence that the dorsolateral BST is a target for drugs of abuse. This study describes the effects of DA on synaptic transmission in the ovBST. Whole cell voltage clamp recordings were performed on ovBST neurons in brain slices from adult rats in the presence or absence of exogenous DA and receptor-targeted agonists and antagonists. The results showed that DA selectively and exclusively reduced inhibitory synaptic transmission in the ovBST in a dose-dependent and D2-like dopamine receptor-dependent manner. DA also modulated excitatory synaptic transmission in a dose-dependent dependent manner. However, this effect was mediated by α2-noradrenergic receptors. Thus these data reveal a double dissociation in catecholaminergic regulation of excitatory and inhibitory synaptic transmission in the ovBST and may shed light on the mechanisms involved in neuropathological behaviors such as stress-induced relapse to consumption of drugs of abuse