Central Neural Mechanisms Research Articles

Stellate Ganglia and Cardiac Sympathetic Overactivation in Heart Failure.

Heart failure (HF) is a major public health problem worldwide, especially coronary heart disease (myocardial infarction)-induced HF with reduced ejection fraction (HFrEF), which accounts for over 50% of all HF cases. An estimated 6 million American adults have HF. As a major feature of HF, cardiac sympathetic overactivation triggers arrhythmias and sudden cardiac death, which accounts for nearly 50-60% of mortality in HF patients. Regulation of cardiac sympathetic activation is highly integrated by the regulatory circuitry at multiple levels, including afferent, central, and efferent components of the sympathetic nervous system. Much evidence, from other investigators and us, has confirmed the afferent and central neural mechanisms causing sympathoexcitation in HF. The stellate ganglion is a peripheral sympathetic ganglion formed by the fusion of the 7th cervical and 1st thoracic sympathetic ganglion. As the efferent component of the sympathetic nervous system, cardiac postganglionic sympathetic neurons located in stellate ganglia provide local neural coordination independent of higher brain centers. Structural and functional impairments of cardiac postganglionic sympathetic neurons can be involved in cardiac sympathetic overactivation in HF because normally, many effects of the cardiac sympathetic nervous system on cardiac function are mediated via neurotransmitters (e.g., norepinephrine) released from cardiac postganglionic sympathetic neurons innervating the heart. This review provides an overview of cardiac sympathetic remodeling in stellate ganglia and potential mechanisms and the role of cardiac sympathetic remodeling in cardiac sympathetic overactivation and arrhythmias in HF. Targeting cardiac sympathetic remodeling in stellate ganglia could be a therapeutic strategy against malignant cardiac arrhythmias in HF.

PC002 / #978 ASSESSING THE EFFECT OF TRANSCUTANEOUS VAGUS NERVE STIMULATION ON COGNITION AND ITS POSSIBLE IMPLICATIONS FOR TOURETTE SYNDROME: A PILOT STUDY: E-POSTER VIEWING

In the last years, there has been a growing interest in the application of different non-invasive brain stimulation techniques (such as Transcranial Magnetic Stimulation TMS) to induce functional plastic changes in children and adolescents with neurodevelopmental disorders1, such as in Tourette syndrome TS. Even though the central neural mechanisms of tic generation are still debated, impaired cortico-striato-thalamo-cortical activity, and a general elevation of the sympathetic (over the parasympathetic) tone are important signatures of TS.

Differences in structural connectivity between diabetic and psychological erectile dysfunction revealed by network-based statistic: A diffusion tensor imaging study.

IntroductionType 2 diabetes mellitus (T2DM) has been found to be associated with abnormalities of the central and peripheral vascular nervous system, which were considered to be involved in the development of cognitive impairments and erectile dysfunction (ED). In addition, altered brain function and structure were identified in patients with ED, especially psychological ED (pED). However, the similarities and the differences of the central neural mechanisms underlying pED and T2DM with ED (DM-ED) remained unclear.MethodsDiffusion tensor imaging data were acquired from 30 T2DM, 32 ED, and 31 DM-ED patients and 47 healthy controls (HCs). Then, whole-brain structural networks were constructed, which were mapped by connectivity matrices (90 × 90) representing the white matter between 90 brain regions parcellated by the anatomical automatic labeling template. Finally, the method of network-based statistic (NBS) was applied to assess the group differences of the structural connectivity.ResultsOur NBS analysis demonstrated three subnetworks with reduced structural connectivity in DM, pED, and DM-ED patients when compared to HCs, which were predominantly located in the prefrontal and subcortical areas. Compared with DM patients, DM-ED patients had an impaired subnetwork with increased structural connectivity, which were primarily located in the parietal regions. Compared with pED patients, an altered subnetwork with increased structural connectivity was identified in DM-ED patients, which were mainly located in the prefrontal and cingulate areas.ConclusionThese findings highlighted that the reduced structural connections in the prefrontal and subcortical areas were similar mechanisms to those associated with pED and DM-ED. However, different connectivity patterns were found between pED and DM-ED, and the increased connectivity in the frontal–parietal network might be due to the compensation mechanisms that were devoted to improving erectile function.

Altered Regional Homogeneity in Patients With Diabetic Erectile Dysfunction: A Resting-State fMRI Study.

IntroductionErectile dysfunction (ED) is a common complication of Type-2 Diabetes Mellitus (T2DM) for male patients and it is considered to be associated with different causes including hyperglicemia-induced vascular endothelial cell damages. However, the possible central neural mechanisms shared by these two diseases remain unclear. This study aimed to explore the changes of brain activity and their relationships with the clinical characteristics in patients with diabetic ED.MethodsThe data of resting-state functional magnetic resonance imaging were acquired in 31 T2DM patients with ED (DM-ED) and 31 matched healthy controls (HCs). The whole-brain regional homogeneity (ReHo) values were calculated and compared between groups. In addition, Pearson correlation analysis was performed to evaluate the relationships between brain regions with altered ReHo values and clinical characteristics in the patient group.ResultsThe DM-ED group exhibited increased ReHo values in the right middle frontal gyrus (orbital part) and decreased ReHo values in the left superior frontal gyrus (dorsolateral), paracentral lobule, precuneus and bilateral supplementary motor area when compared with the HCs group. Moreover, significantly negative correlations were found between ReHo values of the left superior frontal gyrus (dorsolateral) and IIEF-5 scores, as well as the level of HbA1c in the DM-ED group.ConclusionThe altered spontaneous brain activity in cognitive-related regions revealed by ReHo values might provide new insights into the neurological pathophysiology underlying DM-ED and serve as potential neuroimaging biomarkers for detecting and evaluating ED in diabetes patients.

Acute intermittent hypercapnic-hypoxia elicits central neural respiratory motor plasticity in humans.

Acute intermittent hypoxia (AIH) elicits long-term facilitation (LTF) of respiration. Although LTF is observed when CO2 is elevated during AIH in awake humans, the influence of CO2 on corticospinal respiratory motor plasticity is unknown. Thus, we tested the hypotheses that acute intermittent hypercapnic-hypoxia (AIHH): (1) enhances cortico-phrenic neurotransmission (reflecting volitional respiratory control); and (2) elicits ventilatory LTF (reflecting automatic respiratory control). Eighteen healthy adults completed four study visits. Day 1 consisted of anthropometry and pulmonary function testing. On Days 2, 3 and 4, in a balanced alternating sequence, participants received: AIHH, poikilocapnic AIH, and normocapnic-normoxia (Sham). Protocols consisted of 15, 60s exposures with 90s normoxic intervals. Transcranial (TMS) and cervical (CMS) magnetic stimulation were used to induce diaphragmatic motor-evoked potentials and compound muscle action potentials, respectively. Respiratory drive was assessed via mouth occlusion pressure (P0.1 ), and minute ventilation measured at rest. Dependent variables were assessed at baseline and 30-60min after exposures. Increases in TMS-evoked diaphragm potential amplitudes were observed following AIHH vs. Sham (+28±41%, P=0.003), but not after AIH. No changes were observed in CMS-evoked diaphragm potential amplitudes. Mouth occlusion pressure also increased after AIHH (+21±34%, P=0.033), but not after AIH. Ventilatory LTF was not observed after any treatment. We demonstrate that AIHH elicits central neural mechanisms of respiratory motor plasticity and increases resting respiratory drive in awake humans. These findings may have important implications for neurorehabilitation after spinal cord injury and other neuromuscular disorders compromising breathing. KEY POINTS: The occurrence of respiratory long-term facilitation following acute exposure to intermittent hypoxia is believed to be dependent upon CO2 regulation - mechanisms governing the critical role of CO2 have seldom been explored. We tested the hypothesis that acute intermittent hypercapnic-hypoxia (AIHH) enhances cortico-phrenic neurotransmission in awake healthy humans. The amplitude of diaphragmatic motor-evoked potentials induced by transcranial magnetic stimulation was increased after AIHH, but not the amplitude of compound muscle action potentials evoked by cervical magnetic stimulation. Mouth occlusion pressure (P0.1 , an indicator of neural respiratory drive) was also increased after AIHH, but not tidal volume or minute ventilation. Thus, moderate AIHH elicits central neural mechanisms of respiratory motor plasticity, without measurable ventilatory long-term facilitation in awake humans.

Title: P2x7 Receptor Activation and Estrogen Status Drive Neuroinflammatory Mechanisms in a Rat Model for Dry Eye.

Dry eye disease (DED) is recognized as a chronic inflammatory condition with an increase in tear osmolarity and loss of tear film integrity. DED is often accompanied by adverse ocular symptoms which are more prevalent in females than males. The basis for ocular hyperalgesia in DED remains uncertain; however, both peripheral and central neural mechanisms are implicated. A model for aqueous deficient DED, exorbital gland excision, was used to determine if activation of the purinergic receptor subtype 7, P2X7R, expressed by non-neural cells in peripheral and central trigeminal nerve pathways, contributed to persistent ocular hyperalgesia. Densitometry of trigeminal brainstem sections revealed increases in P2X7R, the myeloid cell marker Iba1, and the inflammasome, NLRP3, of estradiol-treated DED females compared to estradiol-treated sham females, while expression in DED males and DED females not given estradiol displayed minor changes. No evidence of immune cell infiltration into the trigeminal brainstem was seen in DED rats; however, markers for microglia activation (Iba1) were increased in all groups. Isolated microglia expressed increased levels of P2X7R and P2X4R, IL-1β (Ιnterleukin-1β), NLRP3, and iNOS (nitric oxide synthase). Further, estradiol-treated DED females displayed greater increases in P2X7R, IL-1β and NLRP3 expression compared to untreated DED females. Orbicularis oculi muscle activity (OOemg) evoked by ocular instillation of hypertonic saline (HS) was recorded as a surrogate measure of ocular hyperalgesia and was markedly enhanced in all DED groups compared to sham rats. Systemic minocycline reduced HS-evoked OOemg in all DED groups compared to sham rats. Local microinjection in the caudal trigeminal brainstem of an antagonist for P2X7R (A804598) greatly reduced HS-evoked OOemg activity in all DE groups, while responses in sham groups were not affected. Intra-trigeminal ganglion injection of siRNA for P2X7R significantly reduced HS-evoked OOemg activity in all DED groups, while evoked responses in sham animals were not affected. These results indicated that activation of P2X7R at central and peripheral sites in trigeminal pain pathways contributed to an increase in ocular hyperalgesia and microglia activation in DED males and females. Estrogen treatment in females further amplified ocular hyperalgesia and neuroimmune responses in this model for aqueous deficient DED.

Neural substrates of respiratory sensory gating: A human fMRI study

The involvement of neural substrates in respiratory sensory gating remained unclear. This study aimed to investigate cortical and subcortical activations associated with respiratory sensory gating by using functional magnetic resonance imaging. First, we hypothesized that paired occlusions would induce neural activation in cortical and subcortical areas, including the thalamus and sensorimotor cortices. Secondly, we hypothesized that, in terms of parameter estimates in the general linear model, the activation effect size β ratios (βpaired/βsingle) would be less than 2 due to central neural gating mechanism. Forty-six healthy participants were included in the study. Our analyses showed that the βpaired/βsingle ratios for the supramarginal gyrus, basal ganglia, thalamus, and middle frontal gyrus were less than 2. In conclusion, our results demonstrated a non-linear relationship regarding brain neural activations in response to paired versus single occlusions, suggesting that respiratory sensory information is gated at the subcortical and cortical levels.

Influence of predictability on saccade timing in a head impulse VOR suppression task.

Gaze stabilization performance has been shown to be influenced differently when the head is either passively or actively moved in normal healthy participants. However, for a visual fixation suppression task, it remains unknown if the pattern of coordinated head and eye movement is influenced differently by passive or active head movements. We used a suppression head impulse paradigm (SHIMP), where the subject's goal was to maintain gaze stabilized on a visual target that moved with the head during rapid impulsive head movements, to evaluate gaze fixation performance in three conditions: (1) passive-unpredictable where the examiner applied impulsive head yaw rotations with random timing and direction, (2) passive-predictable where the direction of head rotation was announced and then the examiner repeatedly applied impulses in the same direction, and (3) active where the test subject self-generated their head movements. Thirteen young healthy adults performed all three conditions to assess the percentage of early saccades that initiated the gaze shift toward the final visual target position and the latency of first saccades. Early saccades were defined as those occurring within the duration of the head impulse. Results showed that active head impulses generated the greatest percentage of early saccades, followed by predictable and unpredictable. Among the two passive conditions, predictability shortened the first saccade onset latencies. Active condition onset latencies were shorter than in either of the passive conditions, showing a consistent head-leads-eye pattern defining a specific behavioral pattern that could vary across patient groups leading to insights into central neural mechanisms that control eye-head coordination.

Neurorehabilitation in Adults With Traumatic Upper Extremity Amputation: A Scoping Review

Background Most of the current literature around amputation focuses on lower extremity amputation or engineering aspects of prosthetic devices. There is a need to more clearly understand neurobehavioral mechanisms related to upper extremity amputation and how such mechanisms might influence recovery and utilization of prostheses. Objective This scoping review aims to identify and summarize the current literature on adult traumatic upper limb amputation in regard to recovery and functional outcomes and how neuroplasticity might influence these findings. Methods We identified appropriate articles using Academic Search Complete EBSCO, OVID Medline, and Cochrane databases. The resulting articles were then exported, screened, and reviewed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. Results Eleven (11) studies met the study criteria. Of these studies, 7 focused on sensory involvement, 3 focused on neuroplastic changes post-amputation related to functional impact, and 1 study focused on motor control and learning post-amputation. Overall, these studies revealed an incomplete understanding of the neural mechanisms involved in motor rehabilitation in the central and peripheral nervous systems, while also demonstrating the value of an individualized approach to neurorehabilitation in upper limb loss. Conclusions There is a gap in our understanding of the role of neurorehabilitation following amputation. Overall, focused rehabilitation parameters, demographic information, and clarity around central and peripheral neural mechanisms are needed in future research to address neurobehavioral mechanisms to promote functional recovery following traumatic upper extremity amputation.

Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System.

Age-related hearing loss (ARHL) is a public health problem that has been associated with negative health outcomes ranging from increased frailty to an elevated risk of developing dementia. Significant gaps remain in our knowledge of the underlying central neural mechanisms, especially those related to the efferent auditory pathways. Thus, the aim of this study was to quantify and compare age-related alterations in the cholinergic olivocochlear efferent auditory neurons. We assessed, in young-adult and aged CBA mice, the number of cholinergic olivocochlear neurons, auditory brainstem response (ABR) thresholds in silence and in presence of background noise, and the expression of excitatory and inhibitory proteins in the ventral nucleus of the trapezoid body (VNTB) and in the lateral superior olive (LSO). In association with aging, we found a significant decrease in the number of medial olivocochlear (MOC) cholinergic neurons together with changes in the ratio of excitatory and inhibitory proteins in the VNTB. Furthermore, in old mice we identified a correlation between the number of MOC neurons and ABR thresholds in the presence of background noise. In contrast, the alterations observed in the lateral olivocochlear (LOC) system were less significant. The decrease in the number of LOC cells associated with aging was 2.7-fold lower than in MOC and in the absence of changes in the expression of excitatory and inhibitory proteins in the LSO. These differences suggest that aging alters the medial and lateral olivocochlear efferent pathways in a differential manner and that the changes observed may account for some of the symptoms seen in ARHL.

Increased attentional network activity in premature ejaculation patients with anxiety revealed by resting-state functional magnetic resonance imaging.

Psychological account hypothesizes that premature ejaculation (PE) is a learned pattern of rapid ejaculation maintained by anxiety about sexual failure, whereas neuropsychological accounts hypothesizes that PE is the result of dysfunction of central nervous system regulating ejaculatory. However, the central neural mechanism underlying PE patients with anxiety remains unclear. Resting-state functional magnetic resonance imaging (fMRI) data were collected in 20 PE (diagnoses based on PE Guidelines drafted by the International Society for Sexual Medicine [ISSM]) patients with anxiety and 25 matched healthy controls (HCs) from January 2019 to December 2020. The values of fractional amplitude of low-frequency fluctuation (fALFF) were compared between groups. Moreover, the correlations between fALFF and the severity of PE and anxiety of patients were examined. PE patients with anxiety had increased fALFF values in the right inferior frontal gyrus (opercular part) and middle frontal gyrus. In addition, significant positive correlations were found between the scores of PE diagnostic tool (PEDT) and fALFF values of the right inferior frontal gyrus (opercular part), as well as the right middle frontal gyrus. Moreover, fALFF values of the right inferior frontal gyrus (opercular part) and middle frontal gyrus were positively correlated with the scores of self-rating anxiety scale (SAS). Our results suggested that increased attentional network activity might play a critical role in the neural basis of PE patients with anxiety.

Proprioception: Blurring the boundaries of central and peripheral control

New research has shown that mechanosensitive neurons in the lateral spinal cord of the adult zebrafish sense lateral bending and inhibit both their rostrally-located counterparts and the central-rhythm-generating networks across the midline. The interplay of central and peripheral neural mechanisms has never been seen to be so tight.

Sarcopenia and Neuroscience: Learning to Communicate.

In the 1990s and early 2000s, the common definition for sarcopenia was age-related loss of skeletal muscle, and low levels of muscle mass were central to sarcopenia diagnosis. In more recent consensus definitions, however, low muscle strength displaces low muscle mass as a defining feature of sarcopenia. The change stems from growing evidence that muscle weakness is a better predictor of adverse health outcomes (eg, mobility limitations) than muscle mass. This evidence accompanies an emerging recognition that central neural mechanisms are critical determinants of age-related changes in strength and mobility that can occur independently of variations in muscle mass. However, strikingly little practical attention is typically given to the potential role of the central nervous system in the etiology or remediation of sarcopenia (ie, low muscle function). In this article, we provide an overview of some mechanisms that mediate neural regulation of muscle contraction and control, and highlight the specific contributions of neural hypoexcitability, dopaminergic dysfunction, and degradation of functional and structural brain connectivity in relation to sarcopenia. We aim to enhance the lines of communication between the domains of sarcopenia and neuroscience. We believe that appreciation of the neural regulation of muscle contraction and control is fundamental to understanding sarcopenia and to developing targeted therapeutic strategies for its treatment.

Mechanisms underlying the sensation of dyspnea.

Dyspnea is defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity. It is a common symptom among patients with respiratory diseases that reduces daily activities, induces deconditioning, and is self-perpetuating. Although clinical interventions are needed to reduce dyspnea, its underlying mechanism is poorly understood depending on the intertwined peripheral and central neural mechanisms as well as emotional factors. Nonetheless, experimental and clinical observations suggest that dyspnea results from dissociation or a mismatch between the intended respiratory motor output set caused by the respiratory neuronal network in the lower brainstem and the ventilatory output accomplished. The brain regions responsible for detecting the mismatch between the two are not established. The mechanism underlying the transmission of neural signals for dyspnea to higher sensory brain centers is not known. Further, information from central and peripheral chemoreceptors that control the milieu of body fluids is summated at higher brain centers, which modify dyspneic sensations. The mental status also affects the sensitivity to and the threshold of dyspnea perception. The currently used methods for relieving dyspnea are not necessarily fully effective. The search for more effective therapy requires further insights into the pathophysiology of dyspnea.

A GABAergic neural circuit in the ventromedial hypothalamus mediates chronic stress-induced bone loss.

Homeostasis of bone metabolism is regulated by the central nervous system, and mood disorders such as anxiety are associated with bone metabolism abnormalities, yet our understanding of the central neural circuits regulating bone metabolism is limited. Here, we demonstrate that chronic stress in crewmembers resulted in decreased bone density and elevated anxiety in an isolated habitat mimicking a space station. We then used a mouse model to demonstrate that GABAergic neural circuitry in the ventromedial hypothalamus (VMH) mediates chronic stress-induced bone loss. We show that GABAergic inputs in the dorsomedial VMH arise from a specific group of somatostatin neurons in the posterior region of the bed nucleus of the stria terminalis, which is indispensable for stress-induced bone loss and is able to trigger bone loss in the absence of stressors. In addition, the sympathetic system and glutamatergic neurons in the nucleus tractus solitarius were employed to regulate stress-induced bone loss. Our study has therefore identified the central neural mechanism by which chronic stress-induced mood disorders, such as anxiety, influence bone metabolism.

Peripheral and central mechanisms of cough hypersensitivity.

Chronic cough is a difficult to treat symptom of many respiratory and some non-respiratory diseases, indicating that varied pathologies can underpin the development of chronic cough. However, clinically and experimentally it has been useful to collate these different pathological processes into the single unifying concept of cough hypersensitivity. Cough hypersensitivity syndrome is reflected by troublesome cough often precipitated by levels of stimuli that ordinarily don’t cause cough in healthy people, and this appears to be a hallmark feature in many patients with chronic cough. Accordingly, a strong argument has emerged that changes in the excitability and/or normal regulation of the peripheral and central neural circuits responsible for cough are instrumental in establishing cough hypersensitivity and for causing excessive cough in disease. In this review, we explore the current peripheral and central neural mechanisms that are believed to be involved in altered cough sensitivity and present possible links to the mechanism of action of novel therapies that are currently undergoing clinical trials for chronic cough.

Cardiorespiratory Alterations in a Newborn Ovine Model of Systemic Inflammation Induced by Lipopolysaccharide Injection.

Although it is well known that neonatal sepsis can induce important alterations in cardiorespiratory control, their detailed early features and the mechanisms involved remain poorly understood. As a first step in resolving this issue, the main goal of this study was to characterize these alterations more extensively by setting up a full-term newborn lamb model of systemic inflammation using lipopolysaccharide (LPS) injection. Two 6-h polysomnographic recordings were performed on two consecutive days on eight full-term lambs: the first after an IV saline injection (control condition, CTRL); the second, after an IV injection of 2.5 μg/kg Escherichia coli LPS 0127:B8 (LPS condition). Rectal temperature, locomotor activity, state of alertness, arterial blood gases, respiratory frequency and heart rate, mean arterial blood pressure, apneas and cardiac decelerations, and heart-rate and respiratory-rate variability (HRV and RRV) were assessed. LPS injection decreased locomotor activity (p = 0.03) and active wakefulness (p = 0.01) compared to the CTRL. In addition, LPS injection led to a biphasic increase in rectal temperature (p = 0.01 at ∼30 and 180 min) and in respiratory frequency and heart rate (p = 0.0005 and 0.005, respectively), and to an increase in cardiac decelerations (p = 0.05). An overall decrease in HRV and RRV was also observed. Interestingly, the novel analysis of the representations of the horizontal and vertical visibility network yielded the most statistically significant alterations in HRV structure, suggesting its potential clinical importance for providing an earlier diagnosis of neonatal bacterial sepsis. A second goal was to assess whether the reflexivity of the autonomic nervous system was altered after LPS injection by studying the cardiorespiratory components of the laryngeal and pulmonary chemoreflexes. No difference was found. Lastly, preliminary results provide proof of principle that brainstem inflammation (increased IL-8 and TNF-α mRNA expression) can be shown 6 h after LPS injection. In conclusion, this full-term lamb model of systemic inflammation reproduces several important aspects of neonatal bacterial sepsis and paves the way for studies in preterm lambs aiming to assess both the effect of prematurity and the central neural mechanisms of cardiorespiratory control alterations observed during neonatal sepsis.

Role of inferior colliculus in vestibular vertigo induced by water caloric irrigation

Background: Vestibular vertigo is a common clinical symptom; however, the central neural mechanism of it is still poorly understood.Objective: To demonstrate the changes of neural excitability and ascorbate in inferior colliculus (IC) in a rat vertigo model induced by water caloric irrigation.Methods: In vertigo model induced by water caloric irrigation, we recorded the changes of spontaneous firing rate (SFR) of IC. Then a technique that combining in vivo microanalysis with an online electrochemical system (OECS) was employed to monitor the changes of extracellular ascorbate in IC.Results: Electrophysiological studies showed that after vestibular ice water stimulation, the level of SFR in IC significantly increased, reaching (989 ± 9) % and (941 ± 62) % respectively at 2.0 h after contralateral ice water vestibular stimulation and ipsilateral ice water vestibular stimulation. However, the level of ascorbate in IC dramatically decreased after ice stimulation, decreased to (30 ± 12) % and (57 ± 24) % of the basal level respectively in the contralateral group and ipsilateral group.Conclusions and significance: These findings suggest that inferior colliculus plays a role in peripheral vertigo, which would appear useful for uncovering neural mechanisms of vertigo and help finding novel therapeutic targets for vertigo.

Subcortical Brain Abnormalities and Clinical Relevance in Patients With Hemifacial Spasm.

Purpose: Hemifacial spasm (HFS), a rare neuromuscular movement disorder, is characterized by unilateral, irregular, and paroxysmal facial muscle contractions. To explore the central neural mechanisms of HFS, we conducted vertex-wise shape analyses to investigate volume and shape alterations of subcortical structures, which could help to better understand the abnormality in distinct subcortical regions and determine alternative biomarkers of HFS.Methods: Thirty patients with HFS and 30 age- and sex-matched healthy controls provided written informed consent. T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants. Vertex-wise shape analyses were performed to assess the volume and shape alterations of subcortical structures following HFS. Post hoc correlations with spasm severity and measures of mood dysfunction were applied to characterize subcortical brain alterations.Results: Compared with healthy controls, patients with HFS showed increased volume in the right caudate specifically. Furthermore, patients exhibited significant shape atrophy in the anterior medial aspect of left pallidum, together with shape expansion in the anterior ventrolateral aspect of right caudate head. In addition, shape alteration in right caudate was positively correlated with both anxiety and depression severity in patients with HFS.Conclusions: This is the first study to employ vertex-wise shape analysis to investigate subcortical brain abnormalities in patients with HFS. Our findings provide compelling evidence for subcortical brain alterations specific to HFS, and further may shed light on the pathophysiology of HFS and apply to the translational medicine.

Comparison of Neural Activity in Chronic Pain Patients During Tonic and Burst Spinal Cord Stimulation Using Fluorodeoxyglucose Positron Emission Tomography

Burst spinal cord stimulation (SCS) is a novel stimulation paradigm that seems to provide better pain relief compared to the classic tonic SCS with minimal paresthesia sensation. Based on source localized electroencephalography and clinical data, it has been proposed that burst stimulation as defined by Dirk De Ridder exerts this greater effect by not only modulating the lateral and the descending pain-inhibitory pathways (similar to tonic SCS) but also modulating the medial pain pathway, which encodes the affective, motivational aspects of pain. The current study evaluates the supraspinal differences between burst and tonic stimulation with another functional imaging technique, namely fluorodeoxyglucose positron emission tomography (FGD-PET) scanning, in seven patients, who underwent both burst and tonic SCS, to confirm this notion of medial pain pathway modulation. The results of the current FGD-PET study show that burst stimulation, in contrast to tonic stimulation, indeed modulates the dorsal anterior cingulate cortex (i.e., medial pain pathway) more than tonic stimulation. Our data suggest an inherent difference in the central neural mechanisms during burst and tonic stimulation, which could potentially alter the patient's perception of pain. Dr. Yearwood, Dr. De Ridder, Dr. Falowski, and Dr. Vanneste are the consultants of Abbott. Dr. Venkatesan is an employee of Abbott. Hye Bin Yoo and Dr. Wing Ting To have no conflicts of interest to report.