Target For Neuromodulation Research Articles

Lateral Occipital Cortex as a Novel Target for Neuromodulation to Attenuate Auditory and Visual Hallucinations in a Patient with Ultra-treatment-resistant Schizophrenia: A Case Report

Lateral Occipital Cortex as a Novel Target for Neuromodulation to Attenuate Auditory and Visual Hallucinations in a Patient with Ultra-treatment-resistant Schizophrenia: A Case Report

Human Astrocytes Synchronize Neural Organoid Networks.

Biological neural networks exhibit synchronized activity within and across interconnected regions of the central nervous system. Understanding how these coordinated networks are established and maintained may reveal therapeutic targets for neurodegeneration and neuromodulation. Here, we tested the influence of astrocytes upon synchronous network activity using human pluripotent stem cell-derived bioengineered neural organoids. This study revealed that astrocytes significantly increase activity within individual organoids and across long distances among numerous rapidly merged organoids via influencing synapses and bioenergetics. Treatment of amyloid protein inhibited synchronous activity during neurodegeneration, yet this can be rescued by propagating activity from neighboring networks. Altogether, this study identifies critical contributions of human astrocytes to biological neural networks and delivers a rapid, reproducible, and scalable model to investigate long-range functional communication of the nervous system in healthy and disease states.

Mapping lesion-related human aggression to a common brain network

BackgroundAggression exacts a significant toll on human societies and is highly prevalent among neuropsychiatric patients for which neural mechanisms are unclear and treatment options are limited. MethodsUsing recently validated lesion network mapping technique, we derived an aggression associated network by analyzing 182 patients who had suffered penetrating head injuries during their service in the Vietnam War. To test whether damage to this lesion-derived network would increase the risk of aggression related neuropsychiatric symptoms, we used the Harvard Lesion Repository (N = 928). To explore potential therapeutic relevance of this network, we used an independent Deep brain stimulation dataset of 25 patients with epilepsy, in which irritability and aggression are known potential side effects. ResultsWe found that lesions associated with aggression occurred in many different brain locations but were characterized by a specific brain network defined by functional connectivity to a hub region in the right prefrontal cortex (PFC). This network involves positive connectivity to the ventromedial PFC, dorsolateral PFC, frontal pole, posterior cingulate cortex, anterior cingulate cortex, temporal-parietal junction, and lateral temporal lobe and negative connectivity to the amygdala, hippocampus, insula, and visual cortex. Among all 25 neuropsychiatric symptoms included in the Harvard Lesion Repository, criminality demonstrated the most alignment with our aggression associated network. DBS site connectivity to this same network was associated with increased irritability. ConclusionsWe conclude that brain lesions associated with aggression map to a specific human brain circuit, and the functionally connected regions in this circuit provide testable targets for therapeutic neuromodulation.

MRI textural plasticity in limbic gray matter associated with clinical response to electroconvulsive therapy for psychosis.

Electroconvulsive therapy (ECT) is effective against treatment-resistant psychosis, but its mechanisms remain unclear. Conventional volumetry studies have revealed plasticity in limbic structures following ECT but with inconsistent clinical relevance, as they potentially overlook subtle histological alterations. Our study analyzed microstructural changes in limbic structures after ECT using MRI texture analysis and demonstrated a correlation with clinical response. 36 schizophrenia or schizoaffective patients treated with ECT and medication, 27 patients treated with medication only, and 70 healthy controls (HCs) were included in this study. Structural MRI data were acquired before and after ECT for the ECT group and at equivalent intervals for the medication-only group. The gray matter volume and MRI texture, calculated from the gray level size zone matrix (GLSZM), were extracted from limbic structures. After normalizing texture features to HC data, group-time interactions were estimated with repeated-measures mixed models. Repeated-measures correlations between clinical variables and texture were analyzed. Volumetric group-time interactions were observed in seven of fourteen limbic structures. Group-time interactions of the normalized GLSZM large area emphasis of the left hippocampus and the right amygdala reached statistical significance. Changes in these texture features were correlated with changes in psychotic symptoms in the ECT group but not in the medication-only group. These findings provide in vivo evidence that microstructural changes in key limbic structures, hypothetically reflected by MRI texture, are associated with clinical response to ECT for psychosis. These findings support the neuroplasticity hypothesis of ECT and highlight the hippocampus and amygdala as potential targets for neuromodulation in psychosis.

A potential target for noninvasive neuromodulation of PTSD symptoms derived from focal brain lesions in veterans.

Neuromodulation trials for the treatment of posttraumatic stress disorder (PTSD) have yielded mixed results, and the optimal neuroanatomical target remains unclear. Here we analyzed three datasets to study brain circuitry causally linked to PTSD in military veterans. In veterans with penetrating traumatic brain injury, lesion locations that reduced probability of PTSD were preferentially connected to a circuit including the medial prefrontal cortex, amygdala and anterolateral temporal lobe. In veterans without lesions, PTSD was specifically associated with increased connectivity within this circuit. Reduced functional connectivity within this circuit after transcranial magnetic stimulation correlated with symptom reduction, even though the circuit was not directly targeted. This lesion-based 'PTSD circuit' may serve as a target for clinical trials of neuromodulation in veterans with PTSD.

Beyond Pallidal or Subthalamic Deep Brain Stimulation to Treat Dystonia.

Deep brain stimulation of the subthalamic nucleus and globus pallidus internus is approved by the Food and Drug Administration for treating dystonia. Both targets have shown effectiveness in improving symptoms, but post-operative outcomes can vary significantly among patients. This variability has led researchers to explore alternative neuromodulation targets that might offer more consistent results. Emerging research has highlighted several promising new targets for DBS in dystonia. This review examines pre-clinical and clinical data on novel DBS targets for dystonia and explores non-invasive neuromodulation studies that shed light on the disease's underlying pathological circuitry.

Detecting rhythmic spiking through the power spectra of point process model residuals.

Objective. Oscillations figure prominently as neurological disease hallmarks and neuromodulation targets. To detect oscillations in a neuron's spiking, one might attempt to seek peaks in the spike train's power spectral density (PSD) which exceed a flat baseline. Yet for a non-oscillating neuron, the PSD is not flat: The recovery period ('RP', the post-spike drop in spike probability, starting with the refractory period) introduces global spectral distortion. An established 'shuffling' procedure corrects for RP distortion by removing the spectral component explained by the inter-spike interval (ISI) distribution. However, this procedure sacrifices oscillation-related information present in the ISIs, and therefore in the PSD. We asked whether point process models (PPMs) might achieve more selective RP distortion removal, thereby enabling improved oscillation detection.Approach. In a novel 'residuals' method, we first estimate the RP duration (nr) from the ISI distribution. We then fit the spike train with a PPM that predicts spike likelihood based on the time elapsed since the most recent of any spikes falling within the precedingnrmilliseconds. Finally, we compute the PSD of the model's residuals.Main results. We compared the residuals and shuffling methods' ability to enable accurate oscillation detection with flat baseline-assuming tests. Over synthetic data, the residuals method generally outperformed the shuffling method in classification of true- versus false-positive oscillatory power, principally due to enhanced sensitivity in sparse spike trains. In single-unit data from the internal globus pallidus (GPi) and ventrolateral anterior thalamus (VLa) of a parkinsonian monkey-in which alpha-beta oscillations (8-30 Hz) were anticipated-the residuals method reported the greatest incidence of significant alpha-beta power, with low firing rates predicting residuals-selective oscillation detection.Significance. These results encourage continued development of the residuals approach, to support more accurate oscillation detection. Improved identification of oscillations could promote improved disease models and therapeutic technologies.

Non-invasive prehabilitation to foster widespread fMRI cortical reorganization before brain tumor surgery: lessons from a case series.

The objective of this prospective, single-centre case series was to investigate feasibility, clinical outcomes, and neural correlates of non-invasive Neuromodulation-Induced Cortical Prehabilitation (NICP) before brain tumor surgery. Previous studies have shown that gross total resection is paramount to increase life expectancy but is counterbalanced by the need of preserving critical functional areas. NICP aims at expanding functional margins for extensive tumor resection without functional sequelae. Invasive NICP (intracranial neuromodulation) was effective but characterized by elevated costs and high rate of adverse events. Non-invasive NICP (transcranial neuromodulation) may represent a more feasible alternative. Nonetheless, up to this point, non-invasive NICP has been examined in only two case reports, yielding inconclusive findings. Treatment sessions consisted of non-invasive neuromodulation, to transiently deactivate critical areas adjacent to the lesion, coupled with intensive functional training, to activate alternative nodes within the same functional network. Patients were evaluated pre-NICP, post-NICP, and at follow-up post-surgery. Ten patients performed the intervention. Feasibility criteria were met (retention, adherence, safety, and patient's satisfaction). Clinical outcomes showed overall stability and improvements in motor and executive function from pre- to post-NICP, and at follow-up. Relevant plasticity changes (increase in the distance between tumor and critical area) were observed when the neuromodulation target was guided by functional neuroimaging data. This is the first case series demonstrating feasibility of non-invasive NICP. Neural correlates indicate that neuroimaging-guided target selection may represent a valid strategy to leverage neuroplastic changes before neurosurgery. Further investigations are needed to confirm such preliminary findings.

Dysfunction of motor cortices in Parkinson's disease.

The cerebral cortex has long been thought to be involved in the pathophysiology of motor symptoms of Parkinson's disease. The impaired cortical function is believed to be a direct and immediate effect of pathologically patterned basal ganglia output, mediated to the cerebral cortex by way of the ventral motor thalamus. However, recent studies in humans with Parkinson's disease and in animal models of the disease have provided strong evidence suggesting that the involvement of the cerebral cortex is much broader than merely serving as a passive conduit for subcortical disturbances. In the present review, we discuss Parkinson's disease-related changes in frontal cortical motor regions, focusing on neuropathology, plasticity, changes in neurotransmission, and altered network interactions. We will also examine recent studies exploring the cortical circuits as potential targets for neuromodulation to treat Parkinson's disease.

Disrupted hemodynamic response within dorsolateral prefrontal cortex during cognitive tasks among people with multiple sclerosis-related fatigue.

Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls. We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score). In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks. Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.

The influence of subclavian ansae stimulation on cardiac hemodynamics and electrophysiology in atrial fibrillation- exploring a novel target for neuromodulation in atrial fibrillation (SAS-AF study)

Abstract Background Sympathetic nervous system activation plays a significant role in arrhythmia development and maintenance.Neuromodulation techniques such as stellate ganglion block and sympathectomy, are limited by off-target side effects and complex targeting.The Subclavian Ansae (SA,a nerve cord encircling the subclavian artery) may be an intravascular site allowing specific targeting of the cardiac afferent sympathetic system.Preclinical studies have revealed increased sympathetic tone upon selective SA stimulation. Objective We sought to define for the first time in Humans the functional anatomy and physiology of Subclavian Ansae via a percutaneous approach. Methods A prior cadaveric study defined the anatomical course of the subclavian ansae, encircling the subclavian arteries and connecting the middle cervical ganglia to inferior cervical ganglia/stellate.Patients undergoing catheter ablation for paroxysmal atrial fibrillation(pAF) under general anesthesia were prospectively recruited for the study. Subclavian Ansae stimulation (SAS) was performed on the left and/or the right (L/SAS ± R/SAS) within the subclavian artery using the TactiCath Ablation Catheter introduced via a femoral arterial sheath. Stimulation parameters included up to 70 V output, 10 Hz frequency, and pulse width of 2-4ms for 20-30s. Test pulses ensured no cardiac capture during stimulation. Participants discontinued antiarrhythmic agents at least 4-5 half-lives prior to the procedure. Invasive arterial blood pressure(BP), heart rate (HR), and electrophysiological parameters were recorded in response to selective stimulation. An increase of ten percent or more in either arterial blood pressure(BP) or heart rate(HR) from the initial baseline measurements was deemed a positive response. Results 15 patients (62±11 years, 9 males, pAF duration 51±24 months) underwent the simulation protocol prior to their clinical AF ablation procedure. A positive hemodynamic response was observed in nine patients, and among them, arrhythmia was inducible in 3 patients (atrial fibrillation in 2 patients and repeated runs of atrial ectopy in 1 patient) in response to SAS. Mean sinus cycle length(CL) decreased(chronotropic) after stimulation,particularly with a significant change observed in response to R/SAS. Additionally,L/SAS led to a notable increase in mean systolic (SBP) and diastolic(DBP) blood pressure (inotropic). While the mean right atrial effective refractory period (ERP) did not significantly decrease after stimulation, there was a demonstrable difference in interatrial conduction time(dromotropy). Six patients, including the initial 3 subjected to low-energy stimulation (up to 12V), did not exhibit an adrenergic response. Conclusion This study represents the first successful application of selective SAS in humans. A heterogeneity in electrophysiological modulation by SAS exists, including laterality.The SA is a potential important target for targeted autonomic neuromodulation therapy

Tibial Nerve Stimulation for Urge Urinary Incontinence and Overactive Bladder: Narrative Review of Randomized Controlled Trials and Applicability to Implantable Devices.

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI). Technologies are currently available to deliver tibial nerve stimulation (TNS) through percutaneous devices or through implantable devices. The benefits and safety of percutaneous TNS have led to it as a guideline-recommended therapy. However, patient compliance is limited by the burden of weekly office visits and the need for maintenance treatments. Further, insurance often only covers a limited number of lifetime visits for percutaneous TNS. These factors and others have led to the development, study, and utilization of implantable TNS devices. Implantable TNS devices deliver the same therapeutic mechanism of action for nerve stimulation with a permanent implanted device that provides at-home stimulation rather than in-office therapy delivery. Additionally, there is an added potential for dynamic and patient-centered stimulation. There is a large body of high-quality evidence published for TNS, including numerous randomized controlled trials published on percutaneous TNS which have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Percutaneous TNS also performs better than conservative therapy including pelvic floor muscle training. The percutaneous and implantable approaches deliver nerve stimulation to the same target nerve, using the same mechanism of action. Therefore, data from randomized trials of percutaneous TNS are informative for implantable TNS devices. At the time of this article's publication, at least two implantable TNS devices have received marketing authorization from the Food and Drug Administration (FDA). The objective of this review is to discuss the mechanism of action for TNS and summarize the published literature from clinical trials of percutaneous TNS as a foundation of high-quality evidence for implantable devices targeting the tibial nerve.

Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

Early auditory processing abnormalities alter individual learning trajectories and sensitivity to computerized cognitive training in schizophrenia.

Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a 'bottom up' intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown. Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10-12 weeks later. SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ. TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.

Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia.

The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

Prior-guided individualized thalamic parcellation based on local diffusion characteristics.

Comprising numerous subnuclei, the thalamus intricately interconnects the cortex and subcortex, orchestrating various facets of brain functions. Extracting personalized parcellation patterns for these subnuclei is crucial, as different thalamic nuclei play varying roles in cognition and serve as therapeutic targets for neuromodulation. However, accurately delineating the thalamic nuclei boundary at the individual level is challenging due to intersubject variability. In this study, we proposed a prior-guided parcellation (PG-par) method to achieve robust individualized thalamic parcellation based on a central-boundary prior. We first constructed probabilistic atlas of thalamic nuclei using high-quality diffusion MRI datasets based on the local diffusion characteristics. Subsequently, high-probability voxels in the probabilistic atlas were utilized as prior guidance to train unique multiple classification models for each subject based on a multilayer perceptron. Finally, we employed the trained model to predict the parcellation labels for thalamic voxels and construct individualized thalamic parcellation. Through a test-retest assessment, the proposed prior-guided individualized thalamic parcellation exhibited excellent reproducibility and the capacity to detect individual variability. Compared with group atlas registration and individual clustering parcellation, the proposed PG-par demonstrated superior parcellation performance under different scanning protocols and clinic settings. Furthermore, the prior-guided individualized parcellation exhibited better correspondence with the histological staining atlas. The proposed prior-guided individualized thalamic parcellation method contributes to the personalized modeling of brain parcellation.

Network Localization of State and Trait of Auditory Verbal Hallucinations in Schizophrenia.

Neuroimaging studies investigating the neural substrates of auditory verbal hallucinations (AVH) in schizophrenia have yielded mixed results, which may be reconciled by network localization. We sought to examine whether AVH-state and AVH-trait brain alterations in schizophrenia localize to common or distinct networks. We initially identified AVH-state and AVH-trait brain alterations in schizophrenia reported in 48 previous studies. By integrating these affected brain locations with large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we then leveraged novel functional connectivity network mapping to construct AVH-state and AVH-trait dysfunctional networks. The neuroanatomically heterogeneous AVH-state and AVH-trait brain alterations in schizophrenia localized to distinct and specific networks. The AVH-state dysfunctional network comprised a broadly distributed set of brain regions mainly involving the auditory, salience, basal ganglia, language, and sensorimotor networks. Contrastingly, the AVH-trait dysfunctional network manifested as a pattern of circumscribed brain regions principally implicating the caudate and inferior frontal gyrus. Additionally, the AVH-state dysfunctional network aligned with the neuromodulation targets for effective treatment of AVH, indicating possible clinical relevance. Apart from unifying the seemingly irreproducible neuroimaging results across prior AVH studies, our findings suggest different neural mechanisms underlying AVH state and trait in schizophrenia from a network perspective and more broadly may inform future neuromodulation treatment for AVH.

Colonic Electrical Stimulation for Chronic Constipation: A Perspective Review.

Chronic constipation affects around 20% of the population and there is no efficient solution. This perspective review explores the potential of colonic electric stimulation (CES) using neural implants and methods of bioelectronic medicine as a therapeutic way to treat chronic constipation. The review covers the neurophysiology of colonic peristaltic function, the pathophysiology of chronic constipation, the technical aspects of CES, including stimulation parameters, electrode placement, and neuromodulation target selection, as well as a comprehensive analysis of various animal models highlighting their advantages and limitations in elucidating the mechanistic insights and translational relevance for CES. Finally, the main challenges and trends in CES are discussed.

Variation in brain connectivity during motor imagery and motor execution in stroke patients based on electroencephalography.

The objective of this study was to analyze the changes in connectivity between motor imagery (MI) and motor execution (ME) in the premotor area (PMA) and primary motor cortex (MA) of the brain, aiming to explore suitable forms of treatment and potential therapeutic targets. Twenty-three inpatients with stroke were selected, and 21 right-handed healthy individuals were recruited. EEG signal during hand MI and ME (synergy and isolated movements) was recorded. Correlations between functional brain areas during MI and ME were compared. PMA and MA were significantly and positively correlated during hand MI in all participants. The power spectral density (PSD) values of PMA EEG signals were greater than those of MA during MI and ME in both groups. The functional connectivity correlation was higher in the stroke group than in healthy people during MI, especially during left-handed MI. During ME, functional connectivity correlation in the brain was more enhanced during synergy movements than during isolated movements. The regions with abnormal functional connectivity were in the 18th lead of the left PMA area. Left-handed MI may be crucial in MI therapy, and the 18th lead may serve as a target for non-invasive neuromodulation to promote further recovery of limb function in patients with stroke. This may provide support for the EEG theory of neuromodulation therapy for hemiplegic patients.

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.