Neuromodulation For Treatment Research Articles

Educating the next generation of psychiatrists in the use of clinical neuromodulation therapies: what should all psychiatry residents know?

A variety of neuromodulation treatments are available today and more are on the way, but are tomorrow’s psychiatrists prepared to incorporate these tools into their patients’ care plans? This article addresses the need for training in clinical neuromodulation for general psychiatry trainees. To ensure patient access to neuromodulation treatments, we believe that general psychiatrists should receive adequate education in a spectrum of neuromodulation modalities to identify potential candidates and integrate neuromodulation into their multidisciplinary care plans. We propose curricular development across the four FDA-cleared modalities currently available in psychiatric practice: electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). With a focus on psychiatry residency training, the article delineates core learning components for each neuromodulation technique. For each modality, we review the clinical training status, the respective FDA-cleared indications, mechanisms of action, clinical indications and contraindications, adverse effects, informed consent process, dosing considerations, and clinical management guidelines. The approach outlined in this article aims to contribute to the development of a well-rounded generation of psychiatry trainees with the capacity to navigate the growing field of neuromodulation. Whether or not a psychiatrist specializes in delivering neuromodulation therapies themselves, it is incumbent on all psychiatrists to be able to identify patients who should be referred to neuromodulation therapies, and to provide comprehensive patient care before, during and after clinical neuromodulation interventions to optimize outcomes and prevent relapse.

Edge-Community Entropy is a Novel Neural Correlate of Aging and Moderator of Fluid Cognition.

Decreased neuronal specificity of the brain in response to cognitive demands (i.e., neural dedifferentiation) has been implicated in age-related cognitive decline. Investigations into functional connectivity analogues of these processes have focused primarily on measuring segregation of nonoverlapping networks at rest. Here, we used an edge-centric network approach to derive entropy, a measure of specialization, from spatially overlapping communities during cognitive task fMRI. Using Human Connectome Project Lifespan data (713 participants, 36-100 years old, 55.7% female), we characterized a pattern of nodal despecialization differentially affecting the medial temporal lobe and limbic, visual, and subcortical systems. At the whole-brain level, global entropy moderated declines in fluid cognition across the lifespan and uniquely covaried with age when controlling for the network segregation metric modularity. Importantly, relationships between both metrics (entropy and modularity) and fluid cognition were age-dependent, although entropy's relationship with cognition was specific to older adults. These results suggest entropy is a potentially important metric for examining how neurological processes in aging affect functional specialization at the nodal, network, and whole-brain level.Significant Statement Many potential clinical applications of fMRI necessitate examining localized function to assess and guide behavioral, pharmacological, surgical, and neuromodulatory interventions. Edge-community entropy offers the mathematical and conceptual advantage of calculating the functional specialization of individual nodes within an overlapping and interdependent system of communities using whole-brain, temporally-informed data. We suggest entropy during cognitive tasks may be a more conceptually appropriate functional connectivity analogue of age-related neural dedifferentiation than network segregation metrics, and demonstrate entropy strongly correlates with age and moderates cognition. Notably, entropy was strongly related to age at the whole-brain level and more strongly related than participation coefficient at the nodal level, offering greater potential to interrogate how local age-related dysfunction influences distributed systems supporting cognition and behavior.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

Effects of the motor cortical theta‐burst transcranial‐focused ultrasound stimulation on the contralateral motor cortex

AbstractTheta‐burst transcranial ultrasound stimulation (tbTUS) increases primary motor cortex (M1) excitability for at least 30 min. However, the remote effects of focal M1 tbTUS on the excitability of other cortical areas are unknown. Here, we examined the effects of left M1 tbTUS on right M1 excitability. An 80 s train of active or sham tbTUS was delivered to the left M1 in 20 healthy subjects. Before and after the tbTUS, we measured: (1) corticospinal excitability using motor‐evoked potential (MEP) amplitudes from single‐pulse transcranial magnetic stimulation (TMS) of left and right M1; (2) interhemispheric inhibition (IHI) from left to right M1 and from right to left M1 using a dual‐site paired‐pulse TMS paradigm; and (3) intracortical circuits of the right M1 with short‐interval intracortical inhibition and intracortical facilitation (ICF) using paired‐pulse TMS. Left M1 tbTUS decreased right M1 excitability as shown by decreased MEP amplitudes, increased right M1 ICF and decreased short‐interval IHI from left to right hemisphere at interstimulus interval (ISI) of 10 ms but not long‐interval IHI at interstimulus interval of 40 ms. The study showed that left M1 tbTUS can change the excitability of remote cortical areas with decreased right M1 excitability and interhemispheric inhibition. The remote effects of tbTUS should be considered when it is used in neuroscience research and as a potential neuromodulation treatment for brain disorders. imageKey points Transcranial ultrasound stimulation (TUS) is a novel non‐invasive brain stimulation technique for neuromodulation with the advantages of being able to achieve high spatial resolution and target deep brain structures. A repetitive TUS protocol, with an 80 s train of theta burst patterned TUS (tbTUS), has been shown to increase primary motor cortex (M1) excitability, as well as increase alpha and beta movement‐related spectral power in distinct brain regions. In this study, we examined on the effects of the motor cortical tbTUS on the excitability of contralateral M1 measured with MEPs elicited by transcranial magnetic stimulation. We showed that left M1 tbTUS decreased right M1 excitability and left‐to‐right M1 interhemispheric inhibition, and increased intracortical facilitation of right M1. These results lead to better understand the effects of tbTUS and can help the development of tbTUS for the treatment of neurological and psychiatric disorders and in neuroscience research.

Intracranial Neuromodulation for Neurologic Recovery

Neurologic insults (traumatic brain injuries, strokes, and spinal cord injuries) profoundly influence motor, cognitive, and psychological functions. Current medical and surgical therapies are often insufficient to address the functional deficits from these injuries. Intracranial neuromodulation, specifically deep brain stimulation (DBS) and motor cortex stimulation (MCS), has been studied to improve these deficits. Preclinical results demonstrate that DBS and MCS effectively potentiate the sequalae of neurologic insult. Clinical evidence is limited, but existing reports and clinical trials show the promising therapeutic potential of intracranial neuromodulation. Further study of intracranial neuromodulation treatment is warranted, with greater attention to confounding variables and methodology.

A modified neural circuit framework for semantic memory retrieval with implications for circuit modulation to treat verbal retrieval deficits.

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart etal., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto-polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co-activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre-SMA (e.g., frontal aslant tract and fronto-striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits.

Food-related inhibitory control deficits in young male adults with obesity: Behavioral and ERP evidence from a food-related go/no-go task

PurposeObesity poses a pervasive challenge to global public health, which is linked to adverse physical health outcomes and cognitive decline. Cognitive function, particularly food-related cognitive function, plays a critical role in sustaining a healthy weight and mitigating the progression of obesity. The aim of this study was to investigate the behavioral and neuroelectronic aspects of food-related inhibitory functions in young adult males with obesity. MethodsForty-nine participants with obesity and healthy-weight were recruited (BMI = 35.83 ± 5.06 kg/m2 vs. 22.55 ± 1.73 kg/m2, age = 24.23 ± 4.55 years vs. 26.00 ± 3.97 years). A food-related Go/No-go task which included 6 distinct blocks in a randomized order was conducted to investigate the general and food-related inhibitory control. 180 stimulus images from the Food Picture Database encompassing high-calorie food, low-calorie food, and neutral images were selected. Behavioral (Go RT, Go ACC, No-go ACC) and event-related potential measures (N2 and P3 amplitude) during the food-related Go/No-go task were measured. ResultsThe main findings indicated that the group with obesity exhibited lower No-go accuracy, slower go reaction times, and smaller P3 amplitudes in high-calorie, low-calorie foods, and neutral picture, compared to the normal-weight group, but with no group difference in N2. Additionally, high-calorie food induced larger N2 and P3 amplitude than the neutral stimuli. ConclusionsYoung male adults with obesity exhibit poorer inhibitory control in both food and non-food domains, specifically in slower reaction time and reduced accuracy, featuring difficulties in neural resource recruitment during the inhibitory control process. Additionally, the P3 component could serve as sensitive indicators to reveal the neural mechanisms of inhibitory control deficits in obesity, while the N2 and P3 components may differentiate the neural differences between high-calorie foods and non-foods in inhibitory control processing. Food, especially high-calorie food, induces more neural resources and may exacerbate the poor inhibitory ability towards food in obesity. Targeted interventions such as exercise interventions, cognitive training as well as neuromodulation interventions are warranted in the future to improve impaired general and food-related inhibitory functions in the obese populations, offering both theoretical and practical frameworks for obesity prevention and treatment.

Uncovering spatiotemporal dynamics of the corticothalamic network at ictal onset.

Although the clinical efficacy of deep brain stimulation targeting the anterior nucleus (AN) and centromedian nucleus (CM) of the thalamus has been actively investigated for the treatment of medication-resistant epilepsy, few studies have investigated dynamic ictal changes in corticothalamic connectivity in human electroencephalographic (EEG) recording. This study aims to establish the complex spatiotemporal dynamics of the ictal corticothalamic network associated with various seizure foci. We analyzed 10 patients (aged 2.7-28.1 years) with medication-resistant focal epilepsy who underwent stereotactic EEG evaluation with thalamic sampling. We examined both undirected and directed connectivity, incorporating coherence and spectral Granger causality analysis (GCA) between the diverse seizure foci and thalamic nuclei (AN and CM) at ictal onset. In our analysis of 36 seizures, coherence between seizure onset and thalamic nuclei increased across all frequencies, especially in slower bands (delta, theta, alpha). GCA showed increased information flow from seizure onset to the thalamus across all frequency bands, but outflows from the thalamus were mainly in slower frequencies, particularly delta. In the subgroup analysis based on various seizure foci, the delta coherence showed a more pronounced increase at CM than at AN during frontal lobe seizures. Conversely, in limbic seizures, the delta coherence increase was greater at AN compared to CM. It appears that the delta frequency plays a pivotal role in modulating the corticothalamic network during seizures. Our results underscore the significance of comprehending the spatiotemporal dynamics of the corticothalamic network at ictal onset, and this knowledge could guide personalized responsive neuromodulation treatment strategies.

Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

A large normative connectome for exploring the tractographic correlates of focal brain interventions

Diffusion-weighted MRI (dMRI) is a widely used neuroimaging modality that permits the in vivo exploration of white matter connections in the human brain. Normative structural connectomics – the application of large-scale, group-derived dMRI datasets to out-of-sample cohorts – have increasingly been leveraged to study the network correlates of focal brain interventions, insults, and other regions-of-interest (ROIs). Here, we provide a normative, whole-brain connectome in MNI space that enables researchers to interrogate fiber streamlines that are likely perturbed by given ROIs, even in the absence of subject-specific dMRI data. Assembled from multi-shell dMRI data of 985 healthy Human Connectome Project subjects using generalized Q-sampling imaging and multispectral normalization techniques, this connectome comprises ~12 million unique streamlines, the largest to date. It has already been utilized in at least 18 peer-reviewed publications, most frequently in the context of neuromodulatory interventions like deep brain stimulation and focused ultrasound. Now publicly available, this connectome will constitute a useful tool for understanding the wider impact of focal brain perturbations on white matter architecture going forward.

The Efficacy of Neuromodulation Interventions for Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

To determine the efficacy and safety of a neuromodulation intervention regimen in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Systematic searches were conducted in seven English databases. Randomized controlled trials of all neuromodulation interventions (both invasive and non-invasive) for the treatment of CIPN were selected. Group comparisons of differences between interventions and controls were also made. We divided the outcomes into immediate-term effect (≤3 weeks), short-term effect (3 weeks to ≤3 months), and long-term effect (>3 months). Sixteen studies and 946 patients with CIPN were included. Among immediate-term effects, neuromodulation interventions were superior to usual care for improving pain (SMD=-0.77, 95% CI -1.07~ 0.47), FACT-Ntx (MD = 5.35, 95% CI 2.84~ 7.87), and QOL (SMD = 0.44, 95% CI 0.09~ 0.79) (moderate certainty); neuromodulation loaded with usual care was superior to usual care for improving pain (SMD=-0.47, 95% CI -0.71 ~ -0.23), and QOL (SMD = 0.40, 95% CI 0.12 ~ 0.69) (moderate certainty). There were no statistically significant differences between the neuromodulation interventions regimen vs usual care in short- and long-term outcomes and neuromodulation vs sham stimulation from any outcome measure. There were mild adverse events such as pain at the site of stimulation and bruising, and no serious adverse events were reported. Neuromodulation interventions had significant immediate-term efficacy in CIPN but had not been shown to be superior to sham stimulation; short-term and long-term efficacy could not be determined because there were too few original RCTs. Moreover, there are no serious adverse effects of this therapy.

147 Medial Septal Nucleus Theta Stimulation Improves Spatial Working Memory and Increases Hippocampal Neurovascular Activity in a Mouse Model of Alzheimers Disease (5xFAD)

INTRODUCTION: Alzheimer’s disease (AD) remains among the most prolific neurodegenerative disorders. The pathogenesis is the result, in part, of aberrant cerebral circuitry; in particular, the mesolimbic-septohippocampal circuit and its associated medial septal nucleus (MSN). Interestingly, the administration of theta stimulation via deep brain stimulation (DBS) to the MSN has been demonstrated to increase hippocampal theta oscillations, which are critical to the role of the hippocampus in learning and memory. Recently, functional ultrasound imaging (fUSI) has emerged as a method of evaluating large-scale neural activity with both high spatiotemporal resolution (∼100 μm3) and sensitivity to slow blood flow (∼1 mm/s). fUSI allows for the in-vivo analyses of neurovascular changes secondary to our theta-burst neuromodulatory intervention. METHODS: 12 male 5xFAD mice were partitioned into two groups, one received theta-burst stimulation targeting the MSN (n = 4) and the other acted as controls (n = 8). Following stimulation, spatial working memory was assessed via the Barnes maze task. An additional 44 C57BL/6 mice were partitioned into three groups: one receiving theta (7.7 Hz) stimulation to the MSN (n = 16), one receiving gamma stimulation to the MSN (100 Hz, n = 14), and the remaining group acting as the control (n = 14). RESULTS: The MSN theta stimulation group of 5xFAD mice demonstrated decreased latency compared to controls (p = 0.003). CBF volumes in the hippocampus were relatively increased in the theta-burst group when compared to both control and gamma stimulation groups. CONCLUSIONS: Our results demonstrate significant improvement in cognitive performance secondary to MSN theta-burst stimulation. Additionally, these changes were mirrored by CBF volume increases in the hippocampus in a frequency-dependent manner. These findings provide evidence for the therapeutic role of theta MSN stimulation in the treatment of AD and furthers fUSI’s role in evaluating in-vivo CBF.

892 Pain Intensity Is Characterized by Theta Band Dynamics and Opioid Pain Medication Effect at Gamma Band Dynamics Within the Human Subcortical Structures

INTRODUCTION: Chronic pain is a multifaceted condition that involves processes of sensation, cognition, and emotion. Given its complexity, characterizing the dynamic changes in pain intensity for patients with chronic pain has remained a challenge. Several EEG studies have shown chronic pain patients to exhibit an increased theta and alpha band power, and acute pain to induce an increased gamma power. However, these do not inform the dynamical changes in pain fluctuations, and critically at the subcortical hubs that modulate the processes of sensation, cognition, and emotion. METHODS: The patients continuously rated their pain level for approximately 10 minutes, and we characterized the pain reduction that occurred spontaneously and that occurred via opioid pain medication. We used a novel method coined variance of auto-information (VAI), that would parameterize the stochasticity (i.e., randomness) of the theta and gamma bandpass filtered LFP. RESULTS: In all four patients, the theta VAI (randomness) was found to be lower as pain was relieved both spontaneously (p = 0.01) and via fentanyl (p = 0.03). The gamma VAI was higher when pain was relieved via fentanyl (p = 0.03). CONCLUSIONS: The results demonstrate characterizing pain intensity using the human neuronal oscillatory activity from the subcortical structures. We also introduce the VAI method that consistently characterize pain relief among chronic pain patients. These findings may help to identify biomarkers for pain intensity, and potentially guide stimulation targets for closed-loop neuromodulatory treatment.

414 Post-stroke Cognitive deficits are associated with reduced cognitive conflict evoked mid-frontal EEG theta oscillations and can be potentially improved with prefrontal transcranial electrical stimulation

OBJECTIVES/GOALS: Cognitive dysfunction and/or depressionfollowing ischemic stroke results in loss of independence in daily functioning. The objective of this work is to assess neural correlates of post-stroke cognitive deficits and the effect of left frontal transcranial electrical stimulation on cognitive control and associated brain rhythms. METHODS/STUDY POPULATION: We recorded midfrontal scalp EEG from 15 healthy and 13 participants with stroke while they performed a multi-source interference task (MSIT). The stroke cohort also performed additional MSIT sessions where they received active and sham transcranial direct current stimulation (tDCS) on the left prefrontal cortex (PFC). The EEG was pre-processed to get rid of eye movement and other channel noise artifacts and filtered to retain 0.5-55 Hz components. A Morlet wavelet was used to estimate power in theta (4-8 Hz), alpha (8-15 Hz) and gamma (35-50 Hz) frequency bands over a period of 2 seconds following MSIT image presentation. A generalized linear mixed effects model was used to find effect of group on behavior and EEG oscillations. A GLME was also used to find effects of active tDCS on behavior and EEG. RESULTS/ANTICIPATED RESULTS: We found Group (healthy v stroke) as a significant predictor of both response time (behavior) and conflict evoked theta power in the frontal channels (F1-Fz, F2-Fz). We also found that active tDCS significantly improved MSIT performance as compared to sham, after accounting for cognitive load. Active tDCS also induced low frequency oscillations in frontal EEG channels compared to sham. Preliminary results indicate that mid-frontal theta oscillations are a potential neural correlate of post-stroke cognitive deficit and tDCS of the left PFC might be a promising therapeutic intervention to ameliorate this. DISCUSSION/SIGNIFICANCE: Current therapeutic approaches often do not alleviate post stroke executive dysfunction, hence a better understanding of the brain network changes underlying such deficit can elucidate neural correlates of post stroke cognitive deficit to inform the development of neuromodulation interventions.

State-dependent effects of repetitive transcranial magnetic stimulation on symptom dimensions of obsessive-compulsive disorder: A case report

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation procedure that is FDA-cleared for treating obsessive-compulsive disorder (OCD). Evidence suggests that controlling brain state during rTMS treatment can influence treatment outcomes. We present the case of a patient with refractory OCD who received symptom provocation immediately preceding rTMS treatment sessions. The patient experienced more subjective and objective improvement in OCD symptoms targeted by provocations than in other symptom domains. These results suggest the importance of brain state during rTMS and could be used to guide and optimize neuromodulation treatment for OCD.

Radiological and clinical biomarkers in patients with central post stroke pain

Background. Central post-stroke pain (CPSP) occurs following cerebrovascular accidents and is a neuropathic pain syndrome that is characterized by stimulation-independent pain; shooting, burning, or electric shock-like sensation and paresthesia. Multiple pathogenetic theories have been proposed for the CPSP including disinhibition, central sensitization, thalamic changes, and altered function of spinothalamic tract (STT). Investigations such as MRI DTI can help to understand the pathogenesis of CPSP. Objective. To determine the radiological and clinical biomarkers in cases with CPSP. Methods. This case-control study was retrospectively conducted upon 60 persons divided into 20 CPSP cases (group 1), 20 cases with no CPSP (group 2) and 20 healthy controls (group 3). All subjects had Routine MRI and complete neurological examination including “Sensory testing but stroke patients were evaluated by quantitative assessment of neuropathic pain, the National Institutes of Health Stroke Scale (NIHSS), Ashworth scale, Modified Rankin Scale (MRS) and Hamilton depression rating scale (HAM-D scale). Results. Significant differences existed among studied groups as regard motor examination, sensory examination, NIHSS score and Hamilton depression score. A non-significant difference was detected among the groups regarding MRS findings. A significant difference existed between groups 1 and 2, between groups 1 and 3 while no significant difference was detected between groups 2 and 3 for all FA readings and all ADC readings in ipsilateral affected side assessed at internal capsule, midbrain, and pons. No significant difference existed between groups 1 and 2, between groups 1 and 3 and between groups 2 and 3 as regard FA readings and ADC readings in contralateral side assessed at internal capsule, midbrain, and pons. Conclusion. Our study highlighted the significance of white matter tracts (WMT) other than the conventional pain pathways in CPSP and can thus serve as a predictive marker for CPSP onset or a prognostic marker after any drug therapy or neuromodulatory treatment.

AxoDetect: an automated nerve image segmentation and quantification workflow for computational nerve modeling

Objective. Bioelectronic treatments targeting near-organ innervation have unprecedented clinical applications. Particularly in the spleen, the inhibition of the cholinergic inflammatory response by near-organ nerve stimulation has potential to replace pharmacological treatments in chronic and autoimmune diseases. A caveat is that the optimization of therapeutic stimulation parameters relies on in vivo experimentation, which becomes challenging due to the small nerve diameters (2 μ m), complex anatomy, and mixed axon type composition of the autonomic nerves. Effective development of in silico models requires tools which allow for fast and efficient quantification of axonal composition of specific nerves. Current approaches to generate such information rely on manual image segmentation and quantification. Approach. We developed a combined image-segmentation and model-generation software called AxoDetect: a target- and format-agnostic computer vision algorithm which can segment myelin, endo/epineurium, and both myelinated and unmyelinated fibers from a nerve image without training. Main results. AxoDetect is over 10 times faster on average when compared with current automatic methods while maintaining flexibility through the use of tunable pixel threshold filters to detect different types of tissue. When compared to a distribution-based and a manually segmented model of the splenic nerve terminal branch 1, the model generated with AxoDetect had comparable threshold prediction and was able to accurately detect an increase in activation threshold caused by the addition of surrounding fat tissue to the modeled nerve. Significance. AxoDetect contributes to the acceleration of neuromodulation treatment development through faster model design and iteration without requiring training. Furthermore, the computer vision approach and tunable nature of the filters in our method allow for its use in a variety of histological applications. Our approach will impact not only the study of nerves but also the design of implantable neural interfaces to enhance bioelectronic therapeutic options.

Increases in functional connectivity between the default mode network and sensorimotor network correlate with symptomatic improvement after transcranial direct current stimulation for obsessive-compulsive disorder

BackgroundNon-invasive neuromodulation is a promising intervention for obsessive-compulsive disorder (OCD), although its neurobiological mechanisms of action are still poorly understood. Recent evidence suggests that abnormalities in the connectivity of the default mode network (DMN) and the supplementary motor area (SMA) with other brain regions and networks are involved in OCD pathophysiology. We examined if transcranial direct current stimulation (tDCS) alters these connectivity patterns and if they correlate with symptom improvement in treatment-resistant OCD. MethodsIn 23 patients from a larger clinical trial (comparing active tDCS to sham) who underwent pre- and post-treatment MRI scans, we assessed resting-state functional MRI (rs-fMRI) data. The treatment involved 30-minute daily tDCS sessions for four weeks (weekdays only), with the cathode over the SMA and the anode over the left deltoid. We conducted whole-brain connectivity analysis comparing active tDCS-treated to sham-treated patients. ResultsWe found that active tDCS, but not sham, led to connectivity increasing between the DMN and the bilateral pre/postcentral gyri (p = 0.004, FDR corrected) and temporal-auditory areas plus the SMA (p = 0.028, FDR corrected). Also, symptom improvement was directly associated with connectivity increasing between the left lateral sensorimotor network and the left precuneus (r = 0.589, p = 0.034). LimitationsLimited sample size (23 participants with resting-state neuroimaging), inability to analyze specific OCD symptom dimensions (e.g., harm, sexual/religious, symmetry/checking, cleaning/contamination). ConclusionsThese data offer novel information concerning functional connectivity changes associated with non-invasive neuromodulation interventions in OCD and can guide new brain stimulation interventions in the framework of personalized interventions.

The neurorehabilitation of post-stroke dysphagia: Physiology and pathophysiology.

Swallowing is a complex process involving the precise contractions of numerous muscles of the head and neck, which act to process and shepherd ingested material from the oral cavity to its eventual destination, the stomach. Over the past five decades, information from animal and human studies has laid bare the complex network of neurones in the brainstem, cortex and cerebellum that are responsible for orchestrating each normal swallow. Amidst this complexity, problems can and often do occur that result in dysphagia, defined as impaired or disordered swallowing. Dysphagia is common, arising from multiple varied disease processes that can affect any of the neuromuscular structures involved in swallowing. Post-stroke dysphagia (PSD) remains the most prevalent and most commonly studied form of dysphagia and, as such, provides an important disease model to assess dysphagia physiology and pathophysiology. In this review, we explore the complex neuroanatomical processes that occur during normal swallowing and PSD. This includes how strokes cause dysphagia, the mechanisms through which natural neuroplastic recovery occurs, current treatments for patients with persistent dysphagia and emerging neuromodulatory treatments.

Functional ultrasound imaging of the human spinal cord

Utilizing the first in-human functional ultrasound imaging (fUSI) of the spinal cord, we demonstrate the integration of spinal functional responses to electrical stimulation. We record and characterize the hemodynamic responses of the spinal cord to a neuromodulatory intervention commonly used for treating pain and increasingly used for the restoration of sensorimotor and autonomic function. We found that the hemodynamic response to stimulation reflects a spatiotemporal modulation of the spinal cord circuitry not previously recognized. Our analytical capability offers a mechanism to assess blood flow changes with a new level of spatial and temporal precision invivo and demonstrates that fUSI can decode the functional state of spinal networks in a single trial, which is of fundamental importance for developing real-time closed-loop neuromodulation systems. This work is a critical step toward developing a vital technique to study spinal cord function and effects of clinical neuromodulation.