Activity In Supplementary Motor Area Research Articles

Effects of motor and cognitive complex training on obstacle walking and brain activity in people with Parkinson's disease: a randomized controlled trial.

The difficulties in obstacle walking are significant in people with Parkinson's disease (PD) leading to an increased fall risk. Effective interventions to improve obstacle walking with possible training-related neuroplasticity changes are needed. We developed two different exercise programs, complex walking training and motor-cognitive training, both challenging motor and cognitive function for people with PD to improve obstacle walking. To investigate the effects of these two novel training programs on obstacle walking and brain activities in PD. A single-center randomized, single-blind controlled study. University laboratory; outpatient. Individuals with idiopathic PD. Thirty-two participants were randomly assigned to the complex walking training group (N.=11), motor-cognitive training group (N.=11) or control group (N.=10). Participants in training groups received exercises for 40 minutes/session, with a total of 12-session over 6 weeks. Control group did not receive additional training. Primary outcomes included obstacle walking, and brain activities (prefrontal cortex (PFC), premotor cortex (PMC), and supplementary motor area (SMA)) during obstacle walking by using functional near-infrared spectroscopy. Secondary outcomes included obstacle crossing, timed up and go test (TUG), cognitive function in different domains, and fall efficacy scale (FES-I). The motor-cognitive training group demonstrated greater improvements in obstacle walking speed and stride length, SMA activity, obstacle crossing velocity and stride length, digit span test, and TUG than the control group. The complex walking training did not show significant improvement in obstacle walking or change in brain activation compared with control group. However, the complex walking training resulted in greater improvements in Rey-Osterrieth Complex Figure test, TUG and FES-I compared with the control group. Our 12-session of the cognitive-motor training improved obstacle walking performance with increased SMA activities in people with PD. However, the complex walking training did not lead such beneficial effects as the cognitive-motor training. The cognitive-motor training is suggested as an effective rehabilitation program to improve obstacle walking ability in individuals with PD.

Changes in Clinical and Network Functional Connectivity Parameters in Motor Networks and Cerebellum Based on Resting-State Functional Magnetic Resonance Imaging Data in Patients with Post-Stroke Hemiparesis Receiving Interactive Brain Stimulation Neurotherapy

Introduction. Interactive brain stimulation (IBS) neurotherapy is an advanced neurofeedback technology (NFB) that involves the organization of a feedback “target” based on signals recorded by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The NFB allows patients to volitionally self-regulate their current brain activity and may therefore be a useful treatment option for diseases with altered activation and functional connectivity (FC) patterns.
 Our objective was to assess the effects of IBS on the FC changes in motor networks and correlations between clinical and network parameters in patients with post-stroke hand paresis.
 Materials and methods. Patients with a history of stroke 2 months were randomized into a main group (n = 7) and a control group (n = 7). All the patients followed the stroke physical rehabilitation for 3 weeks. The main group received IBS training, where the patients learned to imagine movements of the paretic hand trying to amplify the fMRI signal from the primary motor cortex (M1) and the supplementary motor area (SMA) on the lesion side with simultaneous desynchronizing the μ- and β-2 EEG rhythms in the central leads. Clinical tests and MRI were performed prior to and immediately after the treatment. FC matrices were constructed using CONN software based on resting-state fMRI data.
 Results. By the end of the training, M1–M1 functional connectivity in the control group weakened, while no changes were observed in the main group. The FC strength was positively correlated with the grip strength (ρ = 0.69; p 0.01) and with the results of the Box and Blocks test (BBT score, ρ = 0.72; p 0.01) and the Fugl-Meyer assessment for upper extremity (FM-UE score, ρ = 0.87; p 0.005). Ipsilesional SMA connectivity with contralesional cerebellum weakened (p 0.05 in the main group). Its strength was negatively correlated with the BBT and FM-UE scores (both tests ρ = –0.44; p 0.05).
 Conclusions. Volitional control of M1 and SMA activity in the lesion hemisphere during the post-stroke IBS training alters the architecture of the entire motor network affecting clinically significant FC types. We studied a possible mechanism of this technology and its potential use in treatment programs.

Cortico-cortical connectivity is influenced by levodopa in tremor-dominant Parkinson's disease

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor.

(227) Use of the CNS Agent Bremelanotide in Men with Sexual Dysfunction: Results from a Sexual Medicine Clinic

Abstract Introduction Bremelanotide is a centrally acting, cyclic heptapeptide analog of the neuropeptide α-melanocyte-stimulating hormone with elevated affinity for the melanocortin-4 receptor. Bremelanotide modulates dopaminergic pathways involved in sexual desire and arousal. In an fMRI study, compared to placebo, bremelanotide was shown to improve connectivity between the amygdala and the insula during visual sexual stimulation, improve sexual brain processing, enhance cerebellar and supplementary motor area activity, and deactivate the secondary somatosensory cortex. Bremelanotide 1.75 mg/0.3 ml (Vyleesi®) is subcutaneously delivered by a single-use auto injector which has been shown to result in increased genital blood flow within hours of administration in both men and women. While phase 2 studies were performed in men with erectile dysfunction (ED), bremelanotide is currently FDA approved as an on-demand treatment for premenopausal women with generalized, acquired hypoactive sexual desire disorder (HSDD). Since its availability in September 2019, providers in our facility have been prescribing bremelanotide to premenopausal women, but off label to postmenopausal women, and to men diagnosed with ED and other types of sexual dysfunction after undergoing a biopsychosocial evaluation. Objective To better understand the use at our sexual medicine clinic of bremelanotide in men, we analyzed on and off label prescribing patterns and refill rates over a 46-month period in both our male and female patients with various sexual dysfunctions. Methods Bremelanotide prescription dispensing data specific to our sexual medicine facility during the period of September 2019 (inception) through June 30, 2023, was compiled. The analysis included the breakdown of prescription dispenses for men, premenopausal women (categorized by age 18-50) and postmenopausal women (categorized by age >50), with further analysis regarding refills and refill rates. Results Over the 46-month period, bremelanotide has been dispensed for various sexual dysfunctions: 76 times to premenopausal women, 104 times to postmenopausal women, and 444 times to men in our clinic. For premenopausal women, 29% of these dispenses were refills, for postmenopausal women, 52% of these dispenses were refills, and for men, 65% of these dispenses were refills. Over the last 18 months (January 1, 2022, through June 30, 2023), refill rates have been 47% for premenopausal women (n = 30), 52% for postmenopausal women (n = 29), and 73% for men (n = 219). Conclusions The refill rate and prescribing practices of any medication reflects, in part, the safety and efficacy of the treatment in a real-world setting. We observed increasing refill rates of bremelanotide in all patients. Of note, our male patients have particularly high refill rates, implying that bremelanotide, a centrally acting agent, can be used on demand to successfully treat a variety of sexual dysfunctions. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Palatin Technologies, Sprout Pharmaceuticals.

Hooked on a thought: Associations between rumination and neural responses to social rejection in adolescent girls

Rumination is a significant risk factor for psychopathology in adolescent girls and is associated with heightened and prolonged physiological arousal following social rejection. However, no study has examined how rumination relates to neural responses to social rejection in adolescent girls; thus, the current study aimed to address this gap. Adolescent girls (N = 116; ages 16.95–19.09) self-reported on their rumination tendency and completed a social evaluation fMRI task where they received fictitious feedback (acceptance, rejection) from peers they liked or disliked. Rejection-related neural activity and subgenual anterior cingulate cortex (sgACC) connectivity were regressed on rumination, controlling for rejection sensitivity and depressive symptoms. Rumination was associated with distinctive neural responses following rejection from liked peers including increased neural activity in the precuneus, inferior parietal gyrus, dorsolateral prefrontal cortex, and supplementary motor area (SMA) and reduced sgACC connectivity with multiple regions including medial prefrontal cortex, precuneus and ventrolateral prefrontal cortex. Greater precuneus and SMA activity mediated the effect of rumination on slower response time to report emotional state after receiving rejection from liked peers. These findings provide clues for distinctive cognitive processes (e.g., mentalizing, conflict processing, memory encoding) following the receipt of rejection in girls with high levels of rumination.

Regional activity and effective connectivity within the frontoparietal network during precision walking with visual cueing: an fNIRS study.

Precision walking (PW) incorporates precise step adjustments into regular walking patterns to navigate challenging surroundings. However, the brain processes involved in PW control, which encompass cortical regions and interregional interactions, are not fully understood. This study aimed to investigate the changes in regional activity and effective connectivity within the frontoparietal network associated with PW. Functional near-infrared spectroscopy data were recorded from adult subjects during treadmill walking tasks, including normal walking (NOR) and PW with visual cues, wherein the intercue distance was either fixed (FIX) or randomly varied (VAR) across steps. The superior parietal lobule (SPL), dorsal premotor area (PMd), supplementary motor area (SMA), and dorsolateral prefrontal cortex (dlPFC) were specifically targeted. The results revealed higher activities in SMA and left PMd, as well as left-to-right SPL connectivity, in VAR than in FIX. Activities in SMA and right dlPFC, along with dlPFC-to-SPL connectivity, were higher in VAR than in NOR. Overall, these findings provide insights into the roles of different brain regions and connectivity patterns within the frontoparietal network in facilitating gait control during PW, providing a useful baseline for further investigations into brain networks involved in locomotion.

Supplementary Motor Area Activity Differs in Parkinson's Disease with and without Freezing of Gait.

The study aimed to investigate the neural changes that differentiate Parkinson's disease patients with freezing of gait and age-matched controls, using ambulatory electroencephalography event-related features. Compared to controls, definite freezers exhibited significantly less alpha desynchronization at the motor cortex about 300 ms before and after the start of overground walking and decreased low-beta desynchronization about 300 ms before and about 300 and 700 ms after walking onset. The late slope of motor potentials also differed in the sensory and motor areas between groups of controls, definite, and probable freezers. This difference was found both in preparation and during the execution of normal walking. The average frontal peak of motor potential was also found to be largely reduced in the definite freezers compared with the probable freezers and controls. These findings provide valuable insights into the underlying structures that are affected in patients with freezing of gait, which could be used to tailor drug development and personalize drug care for disease subtypes. In addition, the study's findings can help in the evaluation and validation of nonpharmacological therapies for patients with Parkinson's disease.

Increased interhemispheric functional connectivity during non-dominant hand movement in right-handed subjects

Hand preference is one of the behavioral expressions of lateralization in the brain. Previous fMRI studies showed the activation in several regions including the motor cortex and the cerebellum during single-hand movement. However, functional connectivity related to hand preference has not been investigated. Here, we used the generalized psychophysiological interaction (gPPI) approach to investigate the alteration of functional connectivity during single-hand movement from the resting state in right-hand subjects. The functional connectivity in interhemispheric motor-related regions including the supplementary motor area, the precentral gyrus, and the cerebellum was significantly increased during non-dominant hand movement, while functional connectivity was not increased during dominant hand movement. The general linear model (GLM) showed activation in contralateral supplementary motor area, contralateral precentral gyrus, and ipsilateral cerebellum during right- or left-hand movement. These results indicate that a combination of GLM and gPPI analysis can detect the lateralization of hand preference more clearly.

Association of Cortico-Striatal Engagement During Cue Reactivity, Reappraisal, and Savoring of Drug and Non-Drug Stimuli With Craving in Heroin Addiction.

The authors investigated cortico-striatal reactivity to drug cues (as compared with neutral and food cues), drug cue reappraisal, food cue savoring, and their correlations with heroin craving in individuals with heroin use disorder compared with healthy control subjects. Cross-sectional changes in functional MRI blood-oxygen-level-dependent signal during a novel cue reactivity task were assessed in 32 individuals with heroin use disorder (mean age, 40.3 years; seven women) and 21 age- and sex-matched healthy control subjects (mean age, 40.6 years; eight women). Drug cue reactivity (vs. neutral cues) was significantly higher in the nucleus accumbens in the heroin use disorder group compared with the control group and nominally significantly higher in the orbitofrontal cortex (OFC); ventromedial prefrontal cortex (vmPFC) activity positively correlated with drug craving. Drug cue reactivity (vs. salient food cues) was also higher in the inferior frontal gyrus (IFG) in the heroin use disorder group compared with the control group. Drug reappraisal and food savoring (vs. passive viewing) showed increased IFG and supplementary motor area activity in all participants; in the heroin use disorder group, higher IFG/dorsolateral PFC (dlPFC) activity during drug reappraisal and rostral anterior cingulate cortex (ACC) activity during food savoring were associated with lower drug cue-induced craving and longer treatment, respectively. A direct comparison of regulation of reactivity to both salient cues revealed widespread group differences such that drug reappraisal activity was higher in the heroin use disorder group and food savoring activity was higher in the control group in both cortical (e.g., OFC, IFG, ACC, vmPFC, and insula) and subcortical (e.g., dorsal striatum and hippocampus) regions. Higher drug reappraisal versus food savoring in the dlPFC was associated with higher self-reported methadone dosage in the heroin use disorder group. The results demonstrate cortico-striatal upregulation during drug cue exposure and impaired reactivity during processing of alternative non-drug rewards in the heroin use disorder group. Normalizing cortico-striatal function by reducing drug cue reactivity and enhancing natural reward valuation may inform therapeutic mechanisms for reducing drug craving and seeking in heroin addiction.

Brain Activation Evoked by Motor Imagery in Pediatric Patients with Complete Spinal Cord Injury.

Currently, there is no effective treatment for pediatric patients with complete spinal cord injury. Motor imagery has been proposed as an alternative to physical training for patients who are unable to move voluntarily. Our aim was to reveal the potential mechanism of motor imagery in the rehabilitation of pediatric complete spinal cord injury. Twenty-six pediatric patients with complete spinal cord injury and 26 age- and sex-matched healthy children as healthy controls were recruited. All participants underwent the motor imagery task-related fMRI scans, and additional motor execution scans were performed only on healthy controls. First, we compared the brain-activation patterns between motor imagery and motor execution in healthy controls. Then, we compared the brain activation of motor imagery between the 2 groups and compared the brain activation of motor imagery in pediatric patients with complete spinal cord injury and that of motor execution in healthy controls. In healthy controls, compared with motor execution, motor imagery showed increased activation in the left inferior parietal lobule and decreased activation in the left supplementary motor area, paracentral lobule, middle cingulate cortex, and right insula. In addition, our results revealed that the 2 groups both activated the bilateral supplementary motor area, middle cingulate cortex and left inferior parietal lobule, and supramarginal gyrus during motor imagery. Compared with healthy controls, higher activation in the bilateral paracentral lobule, supplementary motor area, putamen, and cerebellar lobules III-V was detected in pediatric complete spinal cord injury during motor imagery, and the activation of these regions was even higher than that of healthy controls during motor execution. Our study demonstrated that part of the motor imagery network was functionally preserved in pediatric complete spinal cord injury and could be activated through motor imagery. In addition, higher-level activation in sensorimotor-related regions was also found in pediatric complete spinal cord injury during motor imagery. Our findings may provide a theoretic basis for the application of motor imagery training in pediatric complete spinal cord injury.

Emotion processing in youths with conduct problems: an fMRI meta-analysis

Functional magnetic resonance imaging (fMRI) studies consistently indicate differences in emotion processing in youth with conduct problems. However, no prior meta-analysis has investigated emotion-specific responses associated with conduct problems. This meta-analysis aimed to generate an up-to-date assessment of socio-affective neural responding among youths with conduct problems. A systematic literature search was conducted in youths (ages 10–21) with conduct problems. Task-specific seed-based d mapping analyses examined responses to threatening images, fearful and angry facial expressions, and empathic pain stimuli from 23 fMRI studies, which included 606 youths with conduct problems and 459 comparison youths. Whole-brain analyses revealed youths with conduct problems relative to typically developing youths, when viewing angry facial expressions, had reduced activity in left supplementary motor area and superior frontal gyrus. Additional region of interest analyses of responses to negative images and fearful facial expressions showed reduced activation in right amygdala across youths with conduct problems. Youths with callous-unemotional traits also exhibited reduced activation in left fusiform gyrus, superior parietal gyrus, and middle temporal gyrus when viewing fearful facial expressions. Consistent with the behavioral profile of conduct problems, these findings suggest the most consistent dysfunction is found in regions associated with empathic responding and social learning, including the amygdala and temporal cortex. Youth with callous-unemotional traits also show reduced activation in the fusiform gyrus, consistent with reduced attention or facial processing. These findings highlight the potential role of empathic responding, social learning, and facial processing along with the associated brain regions as potential targets for interventions.

Attachment Security and Cortical Activity Measured by Functional Near-Infrared Spectroscopy During a Working Memory Task in Healthy Young Adults.

Attachment style has been associated with socio-emotional outcomes, however little evidence suggests a possible association with executive functioning. Few studies have demonstrated that attachment style mediates working memory and learning relationships. We hypothesized that attachment style affects performance and cortical activity patterns of working memory. We compared working memory performance and cortical activity in securely and insecurely attached first-year college students (N=49) using three n-back task conditions. Cortical activity was recorded by functional near-infrared spectroscopy during these three conditions of the n-back task. Attachment style was assessed using the Relationship Scale Questionnaire, categorized into four groups. Both study groups showed similar working memory performance. The cortical representation of working memory was different between the two groups. The securely attached group demonstrated higher activity in the right superior frontal and superior-medial frontal areas across all n-back conditions as well as in the right superior frontal cortex during the two-back and three-back conditions. The insecurely attached group displayed higher activity in the bilateral supplementary motor area and the left premotor area only during the three-back condition. These findings emphasize the potential influence of attachment style on the cortical representation of working memory. Different activity maps between the two groups may reflect varying cognitive strategies employed to achieve a comparable working memory performance. Moreover, these results suggest that each style may have a distinct strategy to achieve attachment-relevant and irrelevant neurocognitive tasks.

Shared and distinct neural activity during anticipation and outcome of win and loss: A meta-analysis of the monetary incentive delay task

Reward and punishment motivate decision making and behavioral changes. Numerous studies have examined regional activities during anticipation and outcome of win and loss in the monetary incentive delay task (MIDT). However, the great majority of studies reported findings of anticipation or outcome and of win or loss alone. It remains unclear how the neural correlates share and differentiate amongst these processes. We conducted an Activation Likelihood Estimation meta-analysis of 81 studies of the MIDT (5,864 subjects), including 24 published since the most recent meta-analysis, to identify and, with conjunction and subtraction, contrast regional responses to win anticipation, loss anticipation, win outcome, and loss outcome. Win and loss anticipation engaged a shared network of bilateral anterior insula (AI), striatum, thalamus, supplementary motor area (SMA), and precentral gyrus. Win and loss outcomes did not share regional activities. Win and loss outcome each engaged higher activity in medial orbitofrontal cortex (mOFC) and dorsal anterior cingulate cortex. Bilateral striatum and right occipital cortex responded to both anticipation and outcome of win, and right AI to both phases of loss. Win anticipation vs. outcome engaged higher activity in bilateral AI, striatum, SMA and precentral gyrus and right thalamus, and lower activity in bilateral mOFC and posterior cingulate cortex as well as right inferior frontal and angular gyri. Loss anticipation relative to outcome involved higher activity in bilateral striatum and left AI. These findings collectively suggest shared and distinct regional responses during monetary wins and losses. Delineating the neural correlates of these component processes may facilitate empirical research of motivated behaviors and dysfunctional approach and avoidance in psychopathology.

RF01 | PMON43 Melanocortin-4 Receptor Agonism Enhances Sexual Brain Processing in Women with Hypoactive Sexual Desire Disorder

Abstract Introduction Hypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress or interpersonal difficulty. It is the most prevalent female sexual health problem worldwide, affecting approximately 1 in 10 women, but has limited treatment options despite its substantial health, social, and economic burden. Melanocortin-4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, although, to date, their mechanism of action is unknown. This study aims to use functional MRI to delineate the reproductive neuroendocrine pathways involved and elucidate how MC4R agonists treat HSDD in women. Methods We conducted a randomized, double-blinded, placebo-controlled, crossover clinical study, using psychometric, functional neuroimaging and hormonal analyses, to assess the effects of MC4R agonism on sexual brain processing in 31 premenopausal women with HSDD. Participants attended on two occasions, receiving either a subcutaneous injection of an MC4R agonist (Bremelanotide 1.75 mg), or placebo, at each study visit, thereby acting as their own controls. Results 31 randomized women were included (mean age 32 years, mean duration of HSDD 41 months). MC4R agonism significantly increased self-reported sexual desire for up to 24-hours post administration, compared to placebo (P=0.007). During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity, as well as deactivating the secondary somatosensory cortex, specifically in response to visual erotic videos, compared to placebo (Z=2.3, P<0.05). In addition, MC4R agonism enhanced functional connectivity between the amygdala-insula and amygdala-thalamus during prolonged visual erotic stimuli, compared to placebo (P=0.025). MC4R agonism resulted in a mean increase in LH of 1.1 iU/L (F [1,58] = 13.38, P=0.0005), and FSH of 0.35 iU/L (F [1,60] = 10.97, P=0.0016) across the 300-minute duration of the study, with no effect observed on circulating estradiol or progesterone levels. Interpretation of results and conclusions:We demonstrate that MC4R agonism deactivates the secondary somatosensory cortex which can reduce the detrimental self-monitoring process often observed in HSDD, thereby increasing sexual desire. Furthermore, cerebellar and supplementary motor area activation by MC4R agonism are associated with increased sexual arousal and sexual motor imagery respectively. Finally, MC4R agonism enhanced functional connectivity between key limbic structures which can be disrupted in HSDD. In summary, these data identify the previously undescribed neural substrates and connections through which MC4R agonism modulates sexual brain processing to increase sexual desire. These findings provide mechanistic insight for the action of MC4R agonism in sexual behaviour and are relevant to ongoing therapeutic development for HSDD and for MC4R agonist development more widely. Trial registration: ClinicalTrials.gov identifier NCT04179734.Funding: Investigator-sponsored study funded by AMAG Pharmaceuticals Inc, MRC and NIHR. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder.

BACKGROUNDHypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODSUsing psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTSMC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSIONThese data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATIONClinicalTrials.gov NCT04179734.FUNDINGThis is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (CS-2018-18-ST2-002 and RP-2014-05-001).

Age differences in brain activity in dorsolateral prefrontal cortex and supplementary motor areas during three different walking speed tasks.

Functional Near-Infrared Spectrometry (fNIRS) is a novel neuroimaging method that can detect brain activity during functional activities. The prefrontal cortex and supplemental motor area (SMA) are active during normal and fast speed walking. However, it is unclear how age difference affects brain activity in the dorsolateral prefrontal cortex (DLPFC) and SMA when walking at different speeds. The purpose of this study was to investigate the age differences in DLPFC and SMA activation during different walking speeds. 10 younger (5F; 25±8 y.o.) and 10 older adults (5F; 73±6 y.o.) completed three visits in this study. Functional Near-Infrared Spectroscopy was used to detect hemodynamic changes on right and left hemispheres over the DLPFC and SMA during self-selected slow, preferred, and fast walking speeds. The results showed significantly increased DLPFC and SMA activity in older adults compared to younger adults when walking at preferred normal, fast, and slow speeds. Older adults also had a higher left DLPFC activation during preferred fast walking speed than younger adults. The results suggest that there are age differences in the DLPFC and SMA activation, with older adults demonstrating increased DLPFC and SMA activity across all walk conditions compared to younger adults. This may indicate older adults require higher cognitive demand and need to recruit indirect motor pathways when changing gait speed by increasing SMA activation.

Emotion regulation strategies differentially modulate neural activity across affective prediction stages: An HD-EEG investigation.

Emotion regulation (ER) strategies can influence how affective predictions are constructed by the brain (generation stage) to prearrange action (implementation stage) and update internal models according to incoming stimuli (updating stage). However, neurocomputational mechanisms by which this is achieved are unclear. We investigated through high-density EEG if different ER strategies (expressive suppression vs. cognitive reappraisal) predicted event-related potentials (ERPs) and brain source activity across affective prediction stages, as a function of contextual uncertainty. An S1-S2 paradigm with emotional faces and pictures as S1s and S2s was presented to 36 undergraduates. Contextual uncertainty was manipulated across three blocks with 100, 75, or 50% S1-S2 affective congruency. The effects of ER strategies, as assessed through the Emotion Regulation Questionnaire, on ERP and brain source activity were tested for each prediction stage through linear mixed-effects models. No ER strategy affected prediction generation. During implementation, in the 75% block, a higher tendency to suppress emotions predicted higher activity in the left supplementary motor area at 1,500–2,000 ms post-stimulus, and smaller amplitude of the Contingent Negative Variation at 2,000–2,500 ms. During updating, in the 75% block, a higher tendency to cognitively reappraise emotions predicted larger P2, Late Positive Potential, and right orbitofrontal cortex activity. These results suggest that both ER strategies interact with the levels of contextual uncertainty by differently modulating ERPs and source activity, and that different strategies are deployed in a moderately predictive context, supporting the efficient updating of affective predictive models only in the context in which model updating occurs.

The Effect of Non-immersive Virtual Reality Exergames Versus Band Stretching on Cardiovascular and Cerebral Hemodynamic Response: A Functional Near-Infrared Spectroscopy Study

BackgroundExercise is one of the effective ways to improve cognition. Different forms of exercises, such as aerobic exercise, resistance exercise, and coordination exercise, have different effects on the improvement of cognitive impairment. In recent years, exergames based on Non-Immersive Virtual Reality (NIVR-Exergames) have been widely used in entertainment and have gradually been applied to clinical rehabilitation. However, the mechanism of NIVR-Exergames on improving motor cognition has not been clarified. Therefore, the aim of this study is to find whether NIVR-Exergames result in a better neural response mechanism to improve the area of the cerebral cortex related to motor cognition under functional near-infrared spectroscopy (fNIRS) dynamic monitoring in comparison with resistance exercise (resistance band stretching).MethodsA cross-over study design was adopted in this study, and 15 healthy young subjects (18–24 years old) were randomly divided into group A (n = 8) and group B (n = 7) according to a computerized digital table method. Task 1 was an NIVR-Exergame task, and Task 2 was resistance band stretching. Group A first performed Task 1, rested for 30 min (i.e., a washout period), and then performed Task 2. Group B had the reverse order. The fNIRS test was synchronized in real time during exercise tasks, and heart rate measurements, blood pressure measurements, and 2-back task synchronization fNIRS tests were performed at baseline, Post-task 1, and Post-task 2. The primary outcomes were beta values from the general linear model (GLM) in different regions of interest (ROIs), and the secondary outcomes were heart rate, blood pressure, reaction time of 2-back, and accuracy rate of 2-back.ResultsThe activation differences of Task 1 and Task 2 in the right premotor cortex (PMC) (P = 0.025) and the left PMC (P = 0.011) were statistically significant. There were statistically significant differences in the activation of the right supplementary motor area (SMA) (P = 0.007), left dorsolateral prefrontal cortex (DLPFC) (P = 0.031), left and right PMC (P = 0.005; P = 0.002) between baseline and Post-task 1. The differences in systolic pressure (SBP) between the two groups at three time points among women were statistically significant (P1 = 0.009, P2 < 0.001, P3 = 0.044).ConclusionIn this study, we found that NIVR-Exergames combined with motor and challenging cognitive tasks can promote the activation of SMA, PMC and DLPFC in healthy young people compared with resistance exercise alone, providing compelling preliminary evidence of the power for the rehabilitation of motor and cognitive function in patients with central nervous system diseases.

ID:16195 Cortical Neuromodulation of Pelvic Floor Muscle Tone: A Proof-of-Concept Study

In the human brain, supplementary motor area (SMA) is involved in the control of pelvic floor muscles (PFMs). SMA dysfunction has been implicated in several disorders involving PFMs, including urinary incontinence and urologic pelvic pain. Here, we aimed to provide a proof-of-concept study to demonstrate the feasibility of modulating resting PFM activity (tone) as well as SMA activity with noninvasive stimulation of SMA.

0247 Sleep Disturbance is Associated with Dysregulation of Positive and Negative Affect Systems

Abstract Introduction Sleep disturbance is a risk factor for the development of mood disorders and up to 90% of mood disorder patients report sleep problems. However, the neural mechanisms by which poor sleep contributes to mood disorders are not well understood. We investigated whether sleep disturbance was associated with dysregulation of positive and negative affect systems, including passive reactivity and active emotion regulation. Methods Participants (n=55, Mage=24.4 years, 53% female) selected for high, medium, and low scores on the PROMIS Sleep Disturbance scale completed a cognitive reappraisal task in an fMRI scanner. Participants were presented with International Affective Picture Stimuli (30 positive, 30 negative, 15 neutral) and were instructed to either passively view or actively up- or down-regulate their emotional experience. We tested five conditions: view-positive, upregulate-positive, view-negative, downregulate-negative, view-neutral. Participants also completed objective (i.e., 7-day actigraphy) and self-report (i.e., Insomnia Severity Index [ISI]) measures of sleep prior to the scan. Analyses in AFNI were constrained within an emotion regulation network, identified using a Neurosynth mask, and treated as a single region of interest. Voxelwise (puncorr&amp;lt;.005) and clusterwise thresholds (p&amp;lt;.05) were used to correct for multiple comparisons. Results Actigraphy-assessed sleep duration was associated with supplementary motor area (SMA) activity when upregulating positive affect relative to passively viewing positive images (k=44 voxels, clusterwise p=.04); participants who slept less showed greater SMA activity. ISI score was marginally associated with dorsolateral prefrontal cortex (dlPFC) activity when downregulating negative affect relative to an implicit baseline (k=30 voxels, clusterwise p=.10); individuals with greater insomnia severity showed more dlPFC activity. PROMIS Sleep Disturbance showed no significant associations. Conclusion Markers of poor sleep (i.e., lower sleep duration, greater insomnia severity) were associated with heightened SMA and dlPFC activity during cognitive reappraisal. This may suggest inefficiency in modulating positive affect via verbal and motor processes (i.e., SMA) and negative affect via cognitive control (i.e., dlPFC). Alternatively, individuals with poor sleep may have greater emotional reactivity to modulate. Mood disorders are commonly associated with increased negative affect and blunted positive affect. Our findings suggest a plausible neural substrate for how sleep disturbance contributes to dysregulation of these systems. Support (If Any) NIMH R21 MH102412.