Altered Activation Patterns Research Articles

Real-Time fMRI Neurofeedback Training as a Neurorehabilitation Approach on Depressive Disorders: A Systematic Review of Randomized Control Trials.

Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-nf) training is an emerging intervention for neurorehabilitation. However, its translation into clinical use on participants with clinical depression is unclear, the effect estimates from randomized control trials and the certainty of the supporting evidence on the effect estimates are unknown. As the number of studies on neurofeedback increases every year, and better quality evidence becomes available, we evaluate the evidence of all randomized control trials available on the clinical application of rt-fMRI-nf training on participants with clinical depression. We performed electronic searches in Pubmed, Embase, CENTRAL, rtFIN database, Epistemonikos, trial registers, reference lists, other systematic reviews, conference abstracts, and cross-citation in Google Scholar. Reviewers independently selected studies, extracted data and evaluated the risk of bias. The certainty of the evidence was judged using the GRADE framework. This review complies with PRISMA guidelines and was submitted to PROSPERO registration. We found 435 results. After the selection process, we included 11 reports corresponding to four RCTs. The effect of rt-fMRI-nf on improving the severity of clinical depression scores demonstrated a tendency to favor the intervention; however, the general effect was not significant. At end of treatment, SMD (standardized mean difference): -0.32 (95% CI -0.73 to 0.10). At follow-up, SMD: -0.33 (95% CI -0.91, 1.25). All the studies showed changes in BOLD fMRI activation after training; however, only one study confirmed regulation success during a transfer run. Whole-brain analyses suggests that rt-fMRI nf may alter activity patterns in brain networks. More studies are needed to evaluate quality of life, acceptability, adverse effects, cognitive tasks, and physiology measures. We conclude that the current evidence on the effect of rt-fMRI-nf training for decision-making outcomes in patients with clinical depression is still based on low certainty of the evidence.

Skeletal Muscle Dysfunction in People With Multiple Sclerosis: A Physiological Target for Improving Physical Function and Mobility

Impaired mobility is amongst the most debilitating symptoms reported by people with multiple sclerosis (MS). Historically, it has been viewed that walking impairments in people with MS are directly caused by the physical damage to the neurons in the central nervous system (CNS) which results from the immunopathology of MS. However, research from over the past 4 decades has revealed that physical function in people with MS is also affected by skeletal muscle dysfunction characterized by a reduced capacity to produce, regulate, and sustain the force-generating muscle contractions that propel human movement. While the immediate CNS damage caused by MS can alter the neural activation of muscle by disrupting neuromotor transmission, chronic reductions in mobility and extreme fatigue can lead to physically inactive lifestyles that negatively affect skeletal muscle through mechanisms of deconditioning. Consequently, people with MS can experience alterations in activation patterns, muscle mass and tissue composition, contractility, metabolism, and perfusion that contribute to reductions in muscle function that ultimately impair key physical functions such as walking. This article provides an overview of the cellular mechanisms that contribute to skeletal muscle dysfunction in people with MS and a discussion of the current evidence suggesting that skeletal muscle may be a key physiological target for interventions aiming to improve mobility in this population. We specifically highlight recent evidence demonstrating the potential for rehabilitation and exercise interventions to induce muscle plasticity in people with MS who have moderate to severe levels of disability. In conclusion, we discuss future directions in basic science and clinical research that may advance our understanding of muscle dysfunction in MS and lead to the development of more precise and effective treatment strategies.

Isolated BAP1 Genomic Alteration in Malignant Pleural Mesothelioma Predicts Distinct Immunogenicity with Implications for Immunotherapeutic Response.

Malignant pleural mesothelioma (MPM), an aggressive cancer of the mesothelial cells lining the pleural cavity, lacks effective treatments. Multiple somatic mutations and copy number losses in tumor suppressor genes (TSGs) BAP1, CDKN2A/B, and NF2 are frequently associated with MPM. The impact of single versus multiple genomic alterations of TSG on MPM biology, the immune tumor microenvironment, clinical outcomes, and treatment responses are unknown. Tumors with genomic alterations in BAP1 alone were associated with a longer overall patient survival rate compared to tumors with CDKN2A/B and/or NF2 alterations with or without BAP1 and formed a distinct immunogenic subtype with altered transcription factor and pathway activity patterns. CDKN2A/B genomic alterations consistently contributed to an adverse clinical outcome. Since the genomic alterations of only BAP1 was associated with the PD-1 therapy response signature and higher LAG3 and VISTA gene expression, it might be a candidate marker for immune checkpoint blockade therapy. Our results on the impact of TSG genotypes on MPM and the correlations between TSG alterations and molecular pathways provide a foundation for developing individualized MPM therapies.

Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists. MethodsThis prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software. ResultsOf 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN– (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN– had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN– compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN– patients was detected. ConclusionsBefore administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.

Decreased functional connectivity in salience network is associated with symptom severity in betel quid-dependent chewers.

Betel quid (BQ) is the fourth most popular psychoactive agent worldwide. Neuroimaging studies have showed that substance-addicted individuals including alcohol, heroin, nicotine and other addictive substance exhibit altered activity patterns of the salience network (SN). However, no study has yet investigated the neural correlates of the resting-state SN and BQ dependence (BQD)-related physiopathological characteristics. Thirty-two BQ-dependent (BQD) chewers and 32 healthy controls were recruited to participate in this study. Resting-state functional magnetic resonance imaging (fMRI) data were analysed by independent component analysis (ICA). BQD chewers exhibited decreased functional connectivity in bilateral insula, anterior cingulate cortex (ACC), medial superior frontal gyrus (MSFG) and inferior orbital frontal gyrus (IOFG) [false discovery rate (FDR) correction, p < 0.05]. In the BQD group, the decreased functional connectivity in left ACC correlated negatively with BQDS (BQD Scale) and the duration of BQ. We reported decreased functional connectivity in resting-state SN of BQD individuals. The decreased functional connectivity in left ACC correlated negatively with BQDS and the duration of BQ. Our findings provided evidence for the importance of the SN in the pathophysiology of BQD and indicated that the SN dysfunction might provide a potential mechanism in BQD development.

RF24 | PSUN110 A Cross-Sectional Study Evaluating the Impact of Combined Hormonal Contraceptives on Components of Energy Balance in Pre-Menopausal Women with Overweight or Obesity

Abstract Background Combined estrogen and progestin hormonal contraceptives (CHCs, including combined oral contraceptives, hormonal patches, or vaginal rings) expose women to supraphysiologic levels of reproductive hormones, which in turn suppress endogenous estrogen and progesterone. Sustained elevations of synthetic estrogen/progestin or suppression of endogenous hormones in CHC users may lead to altered dietary intake and/or patterns of physical activity (PA). Previously, we reported that CHC use was associated with higher energy intake (EI) and weight regain over 1 year after weight loss in women with overweight and obesity enrolled in a behavioral weight loss program, suggesting a potential impact of CHCs on energy balance in the weight reduced state. The aim of this secondary data analysis was to compare dietary intake and PA in weight-stable women with overweight or obesity using CHCs to non-CHC users. Methods Pre-menopausal women with overweight or obesity (n=269, age 18-55 years, BMI 27-45kg/m2) enrolled in 3 different interventional weight loss trials were categorized as CHC users (CHC, n=48) or non-CHC controls (CON, n=221). Fat mass (FM) and lean mass (LM) were measured with DXA. Self-reported dietary energy and macronutrient intake was obtained from either 3-day (n=178) or 7-day (n=91) written diet diaries and analyzed using Nutrition Data System for Research (NDSR) software. Healthy eating index (HEI) scores for diet quality were calculated in a subset (CHC=17, CON=84) of participants using variables available in NDSR output files. Additionally, average daily step counts were measured over 1 week in a subset (CHC=27, CON=143) of participants using the activPAL device. Results Age was lower in CHC users (mean±SD; CHC 35.3±9.0 vs. CON 39.4±7.6 years, p&amp;lt;0.01), but race and ethnicity did not differ between the two groups. After controlling for age, there were no significant differences between groups in baseline BMI (mean±SEM; CHC 34.3±0.7 vs. CON 34.8±0.3 kg/m2), weight (93.6±2.4 vs. 94.2±1.1 kg), %FM (43.3±0.6 vs. 42.7±0.3%), or %LM (54.3±0.6 vs. 54.7±0.3%). There were no significant differences between groups in EI (mean±SEM; CHC 1763.7±78.1 vs. CON 1768.8±36.7 kcal); proportions of fat (36.7±0.9 vs. 36.9±0.4%), carbohydrate (43.9±1.1 vs. 44.3±0.5%), and protein intake (17.7±0.6 vs. 17.3±0.3%); or HEI scores (58.3±2.9 vs. 56.8±1.3). There was a trend for lower daily step count in CHC users (mean±SEM; CHC 5978±460 vs. CON 6913±197 steps/day, p=0.07). Conclusion Daily steps tended to be lower in CHC users compared to controls, while differences in self-reported dietary intake were not observed. Future studies that are done in larger samples over a greater range of BMI and with more detailed measures of PA timed to the menstrual cycle are needed to explore the extent to which CHC use may impact energy balance in women. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:06 p.m. - 1:11 p.m.

Altered regional homogeneity and functional connectivity of brain activity in young HIV-infected patients with asymptomatic neurocognitive impairment.

ObjectiveAsymptomatic neurocognitive impairment (ANI) is a predominant form of cognitive impairment in young HIV-infected patients. However, the neurophysiological mechanisms underlying this disorder have not been clarified. We aimed to evaluate the altered patterns of functional brain activity in young HIV-infected patients with ANI by quantifying regional homogeneity (ReHo) and region of interest (ROI)-based functional connectivity (FC).MethodsThe experiment involved 44 young HIV-infected patients with ANI and 47 well-matched healthy controls (HCs) undergoing resting-state functional magnetic resonance imaging (rs-fMRI) and neurocognitive tests. Reho alterations were first explored between the ANI group and HC groups. Subsequently, regions showing differences in ReHo were defined as ROIs for FC analysis. Finally, the correlation of ReHo and FC with cognitive function and clinical variables was assessed.ResultsCompared with HCs, ANI patients had a significant ReHo decrease in the right lingual gyrus (LING. R), right superior occipital gyrus (SOG. R), left superior occipital gyrus (SOG. L), left middle occipital gyrus (MOG. L), right middle frontal gyrus (MFG. R), cerebellar vermis, ReHo enhancement in the left middle frontal gyrus (MFG. L), and left insula (INS L). The ANI patients showed increased FC between the LING. R and MOG. L compared to HC. For ANI patients, verbal and language scores were negatively correlated with increased mean ReHo values in the MFG.L. Increased mean ReHo values in the INS. L was positively correlated with disease duration—the mean ReHo values in the LING. R was positively correlated with the abstraction and executive function scores. Increased FC between the LING. R and MOG. L was positively correlated with verbal and language performance.ConclusionThe results suggest that the visual network might be the most vulnerable area of brain function in young HIV-infected patients with ANI. The middle frontal gyrus, cerebellar vermis, and insula also play an important role in asymptomatic neurocognitive impairment. The regional homogeneity and functional connectivity of these regions have compound alterations, which may be related to the course of the disease and neurocognitive function. These neuroimaging findings will help us understand the characteristics of brain network modifications in young HIV-infected patients with ANI.

Evaluation of Muscle Synergy During Exoskeleton-Assisted Walking in Persons With Multiple Sclerosis.

Gait deficit after multiple sclerosis (MS) can be characterized by altered muscle activation patterns. There is preliminary evidence of improved walking with a lower limb exoskeleton in persons with MS. However, the effects of exoskeleton-assisted walking on neuromuscular modifications are relatively unclear. The objective of this study was to investigate the muscle synergies, their activation patterns and the differences in neural strategies during walking with (EXO) and without (No-EXO) an exoskeleton. Ten subjects with MS performed walking during EXO and No-EXO conditions. Electromyography signals from seven leg muscles were recorded. Muscle synergies and the activation profiles were extracted using non-negative matrix factorization. The stance phase duration was significantly shorter during EXO compared to the No-EXO condition (p<0.05). Moreover, typically 3-5 modules were extracted in each condition. The module-1 (comprising Vastus Medialis and Rectus Femoris muscles), module-2 (comprising Soleus and Medial Gastrocnemius muscles), module-3 (Tibialis Anterior muscle) and module-4 (comprising Biceps Femoris and Semitendinosus muscles) were comparable between conditions. During EXO condition, Semitendinosus and Vastus Medialis emerged in module-5 in 7/10 subjects. Compared to No-EXO, average activation amplitude was significantly reduced corresponding to module-2 during the stance phase and module-3 during the swing phase during EXO. Exoskeleton-assistance does not alter the existing synergy modules, but could induce a new module to emerge, and alters the control of these modules, i.e., modifies the neural commands indicated by the reduced amplitude of the activation profiles. The work provides insights on the potential underlying mechanism of improving gait functions after exoskeleton-assisted locomotor training.

Altered Muscle Activation Patterns During Unexpected Single-leg Landing In Chronic Ankle Instability Patients

Chronic ankle instability (CAI) patients display altered motor controls during inversion perturbation. Although these alterations may be vulnerable motor controls compared to controls, inversion perturbation under anticipatory conditions makes a less realistic simulation of lateral ankle sprains. PURPOSE: To examine differences in muscle activation during an unexpected inversion perturbation among CAI, coper, and control groups. METHODS: Twenty-two CAI patients (M = 11, F = 11; 22 ± 3 yr, 174 ± 8 cm, 71 ± 10 kg), 22 controls (M = 11, F = 11; 21 ± 2 yr, 173 ± 7 cm, 71 ± 10 kg), and 22 copers (M = 11, F = 11; 21 ± 2 yr, 174 ± 8 cm, 70 ± 13 kg) participated. Participants completed 5 trials of unexpected ankle inversion perturbation during single-leg landing onto a tilted force platform (25º) from a height of 30 cm. EMG data of tibialis anterior (TA), peroneus longus (PL), medial gastrocnemius (MG), and gluteus maximus (GX) were collected from 200 ms before and after initial contact (IC). Functional linear models were used to detect between-group differences. If 95% CIs did not cross zero, differences were significant. RESULTS: Figure 1 shows that CAI patients displayed greater TA and MG activation before IC relative to copers and/or controls. In addition, CAI patients showed greater TA and PL activation after IC relative to copers and/or controls. Copers and controls had similar muscle activation patterns. CONCLUSION: While copers and controls showed similar muscle activation during unexpected ankle perturbation, increased TA and MG activation prior to IC in CAI patients may indicate a neuromuscular effort to stabilize the ankle to prevent further sprains. Increased TA and PL activation after IC in CAI patients may also represent a protective motor control to prevent excessive displacement of the rear foot from the inversion perturbation. However, similar patterns in copers and controls seem to elicit coping mechanisms in an attempt to prevent further injuries after their initial injuries.

The interaction between depression diagnosis and BMI is related to altered activation pattern in the right inferior frontal gyrus and anterior cingulate cortex during food anticipation.

BackgroundDepression and overweight/obesity often cooccur but the underlying neural mechanisms for this bidirectional link are not well understood.MethodsIn this functional magnetic resonance imaging study, we scanned 54 individuals diagnosed with depressive disorders (DD) and 48 healthy controls (HC) to examine how diagnostic status moderates the relationship between body mass index (BMI) and brain activation during anticipation and pleasantness rating of food versus nonfood stimuli.ResultsWe found a significant BMI‐by‐diagnosis interaction effect on activation in the right inferior frontal gyrus (RIFG) and anterior cingulate cortex (ACC) during food versus nonfood anticipation (p < .0125). Brain activation in these regions was greater in HC with higher BMI than in HC with lower BMI. Individuals with DD showed an opposite pattern of activation. Structural equation modeling revealed that the relationship between BMI, activation in the RIFG and ACC, and participants’ desire to eat food items shown in the experiment depended on the diagnostic status.ConclusionsConsidering that food anticipation is an important component of appetitive behavior and that the RIFG and ACC are involved in emotion regulation, response inhibition and conflict monitoring necessary to control this behavior, we propose that future clinical trials targeting weight loss in DD should investigate whether adequate mental preparation positively affects subsequent food consumption behaviors in these individuals.

Effects of a Core Strengthening Program on Muscle Activity Patterns, Strength, and Endurance in People with and without a History of Low Back Pain: A Randomized Controlled Trial

Background of Study: Altered patterns of abdominal and low back muscle activity have been reported in people in the sub-acute phase of low back injury. Specifically, higher overall muscle activity and less ability to match activity to task demands have been found. Objective: This study determined if an 8-week group exercise intervention would alter muscle activity, strength, and endurance in people with/without a history of low back pain (LBP). Method: In this randomized controlled trial 46 participants (age 19-55) with a history of LBP were randomized to exercise (LBPEx, n=24) and no-exercise (LBPCon, n=22) groups. 27 participants without a history of LBP (NoLBP) also exercised. 17 LBPEx and 19 NoLBP participants completed the intervention. 19 LBPCon were tested at 8-week follow-up. The exercise intervention was an 8-week, choreographed, 30-minute group exercise intervention (Les Mills CoreTM) focused on building core strength, stability, and endurance. Pre and post-intervention surface electromyograms from abdominal and low back muscles were recorded during a trunk stability task (TST), and analyzed using Principal Component Analysis to extract patterns corresponding to overall amplitude and relative activation during the TST loading phase. Abdominal and back extensor strength and endurance were also measured. Results: It was found that overall abdominal activity decreased for left anterior external oblique (p=0.019 for TST level 3), left lateral external oblique (p=0.012 for TST level 3), and right posterior external oblique (p=0.035 for TST level 3) in LBPEx and for right lateral external oblique (p=0.009 for TST level 2 and p=0.004 for TST level 3) and left posterior external oblique (p=0.014 for TST level 2 and p=0.011 for TST level 3) in NoLBP during the TST. Abdominal strength and endurance, and back extensor endurance increased for LBPEx and NoLBP (p0.05). Back extensor strength increased for NoLBP (p0.05). Relative abdominal activation during the TST level 2 loading phase increased for right upper rectus abdominus (p=0.05), right lateral external oblique (p=0.002), and left posterior external oblique (p=0.006) for NoLBP, and for left anterior external oblique (p=0.042) for LBPEx. Conclusion: Les Mills CoreTM is readily available and may be recommended as a safe, accessible, and effective intervention to increase abdominal strength and endurance, and back extensor endurance, even for people with a history of LBP.

Poster 165: Psychosocial Factors Play a Greater Role in Preoperative Symptoms for Patients with Atraumatic Shoulder Instability: Data from the Moon-Shoulder Instability Group

Objectives:Previous studies have demonstrated altered brain activation patterns on functional MRI for those with shoulder instability suggesting a potential link between recurrent instability, depression, and emotional wellbeing. It is unknown whether this potential link would differ between those with traumatic vs. atraumatic instability. The purpose of this study was to determine whether psychosocial factors and/or comorbid depression play a greater role in preoperative symptoms for patients with atraumatic or traumatic mechanisms of shoulder instability. We hypothesized that when controlling age, sex, and direction of instability, psychosocial factors and comorbid depression would be more predictive of shoulder-related pain and symptoms for patients with atraumatic instability than patients with traumatic instability.Methods:As part of the IRB-approved Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, 1553 patients provided informed consent and completed pre- and intraoperative data collection. Patients were categorized based on self-reports of whether the mechanism of shoulder instability was traumatic (n=1267) or atraumatic (n=286). Multivariable linear regressions were performed to determine whether psychological factors (VR12, Mental Component Score (MCS), Depression Diagnosis, PAS-22) were predictive of preop ASES and WOSI score in the atraumatic group, controlling for age, sex, and the direction of instability. The same model was repeated for the traumatic instability group, and the model fit was compared between groups using the methods described by Cohen, Cohen, and West with p < 0.05 considered statistically significant.Results:Sex and Mental Component Scores (MCS) were significantly predictive of preop ASES and WOSI scores for the group with atraumatic instability (ASES r2=0.15, p<0.001; WOSI r2=0.17 p<0.001). The same model performed significantly worse for both ASES and WOSI scores in the group with traumatic instability (ASES r2=0.06, WOSI r2=0.07, p<0.05 for both ASES and WOSI).Conclusions:Preoperative psychosocial factors were found to be more predictive of shoulder-related pain and symptoms for patients with atraumatic instability. Across multiple orthopedic conditions, depression and emotional wellbeing have been associated with worse preoperative symptoms and inferior postoperative patient-reported outcomes. As opposed to medically optimizing patients prior to surgery, the current findings identify a subset of shoulder instability patients that may need to be psychologically optimized either prior to surgery or early in the postoperative period to potentially improve postoperative outcomes.

Classification of Functional Movement Disorders with Resting-State Functional Magnetic Resonance Imaging.

Introduction: Functional movement disorder (FMD) is a type of functional neurological disorder characterized by abnormal movements that patients do not perceive as self-generated. Prior imaging studies show a complex pattern of altered activity, linking regions of the brain involved in emotional responses, motor control, and agency. This study aimed to better characterize these relationships by building a classifier using a support vector machine to accurately distinguish between 61 FMD patients and 59 healthy controls using features derived from resting-state functional magnetic resonance imaging. Materials and Methods: First, we selected 66 seed regions based on prior related studies, then we calculated the full correlation matrix between them before performing recursive feature elimination to winnow the feature set to the most predictive features and building the classifier. Results: We identified 29 features of interest that were highly predictive of the FMD condition, classifying patients and controls with 80% accuracy. Several key features included regions in the right sensorimotor cortex, left dorsolateral prefrontal cortex, left cerebellum, and left posterior insula. Conclusions: The features selected by the model highlight the importance of the interconnected relationship between areas associated with emotion, reward, and sensorimotor integration, potentially mediating communication between regions associated with motor function, attention, and executive function. Exploratory machine learning was able to identify this distinctive abnormal pattern, suggesting that alterations in functional linkages between these regions may be a consistent feature of the condition in many FMD patients. Clinical-Trials.gov ID: NCT00500994 Impact statement Our research presents novel results that further elucidate the pathophysiology of functional movement disorder (FMD) with a machine learning model that classifies FMD and healthy controls correctly 80% of the time. Herein, we demonstrate how known differences in resting-state functional magnetic resonance imaging connectivity in FMD patients can be leveraged to better understand the complex pattern of neural changes in these patients. Knowing that there are measurable predictable differences in brain activity in patients with FMD may help both clinicians and patients conceptualize and better understand the illness at the point of diagnosis and during treatment. Our methods demonstrate how an effective combination of machine learning and qualitative approaches to analyzing functional brain connectivity can enhance our understanding of abnormal patterns of brain activity in FMD patients.

Neural mechanisms of intergroup exclusion and retaliatory aggression

ABSTRACT Aggression occurs frequently and severely between rival groups. Although there has been much study into the psychological and socio-ecological determinants of intergroup aggression, the neuroscience of this phenomenon remains incomplete. To examine the neural correlates of aggression directed at outgroup (versus ingroup) targets, we recruited 35 healthy young male participants who were current or former students of the same university. While undergoing functional MRI, participants completed an aggression task against both an ingroup and an outgroup opponent in which their opponents repeatedly provoked them at varying levels and then participants could retaliate. Participants were then socially included and then excluded by two outgroup members and then completed the same aggression task against the same two opponents. Both before and after outgroup exclusion, aggression toward outgroup members was positively associated with activity in the ventral striatum during decisions about how aggressive to be toward their outgroup opponent. Aggression toward outgroup members was also linked to greater post-exclusion activity in the rostral and dorsal medial prefrontal cortex during provocation from their outgroup opponent. These altered patterns of brain activity suggest that frontostriatal mechanisms may play a significant role in motivating aggression toward outgroup members.

Association between carotid atherosclerosis and brain activation patterns during the Stroop task in older adults: An fNIRS investigation

There is an increasing body of evidence suggesting that vascular disease could contribute to cognitive decline and overt dementia. Of particular interest is atherosclerosis, as it is not only associated with dementia, but could be a potential mechanism through which cardiovascular disease directly impacts brain health. In this work, we evaluated the differences in functional near infrared spectroscopy (fNIRS)-based measures of brain activation, task performance, and the change in central hemodynamics (mean arterial pressure (MAP) and heart rate (HR)) during a Stroop color-word task in individuals with atherosclerosis, defined as bilateral carotid plaques (n = 33) and healthy age-matched controls (n = 33). In the healthy control group, the left prefrontal cortex (LPFC) was the only region showing evidence of activation when comparing the incongruous with the nominal Stroop test. A smaller extent of brain activation was observed in the Plaque group compared with the healthy controls (1) globally, as measured by oxygenated hemoglobin (p = 0.036) and (2) in the LPFC (p = 0.02) and left sensorimotor cortices (LMC)(p = 0.008) as measured by deoxygenated hemoglobin. There were no significant differences in HR, MAP, or task performance (both in terms of the time required to complete the task and number of errors made) between Plaque and control groups. These results suggest that carotid atherosclerosis is associated with altered functional brain activation patterns despite no evidence of impaired performance of the Stroop task or central hemodynamic changes.

Altered Spontaneous Brain Activity Patterns of Meibomian Gland Dysfunction in Severely Obese Population Measured Using the Fractional Amplitude of Low-Frequency Fluctuations.

ObjectiveUtilizing the fractional amplitude of low-frequency fluctuations (fALFF) technique, this study sought to correlate spontaneous cerebral abnormalities with the clinical manifestations of meibomian gland dysfunction (MGD) in severely obese (SO) population.Subjects and MethodsTwelve MGD patients in SO population (PATs) (4 males and 8 females) and twelve healthy controls (HCs) (6 males and 6 females) matched by gender and age were enrolled. Every participant underwent resting-state functional magnetic resonance imaging (rs-MRI) scanning. Spontaneous cerebral activity alterations were examined using the fALFF method. Receiver operating characteristic (ROC) curves were utilized to classify the medial fALFF values of the PATs and HCs. PATs were also asked to complete anxiety and depression score forms, permitting a correlation analysis.ResultsIn contrast with HCs, PATs had prominently increased fALFF values in the left lingual gyrus, the right globus pallidus, the right anterior cingulate and paracingulate gyri and the left middle occipital lobe (P < 0.05), and decreased fALFF values in the right cerebellum, the left fusiform gyrus, the right medial orbitofrontal gyrus, the left triangle inferior frontal gyrus and the left inferior parietal gyrus (P < 0.05). The results of the ROC curve indicated that changes in regional fALFF values might help diagnose MGD in SO population. Moreover, fALFF values in the right cerebellum of PATs were positively correlated with hospital anxiety and depression scores (HADS) (r = 0.723, P = 0.008). The fALFF values in the left triangle inferior frontal gyrus of PAT were negatively correlated with HADS (r = −0.651, P = 0.022).ConclusionsAberrant spontaneous activity was observed in multiple regions of the cerebrum, offering helpful information about the pathology of MGD in SO population. Aberrant fALFF values in these regions likely relates to the latent pathologic mechanisms of anomalous cerebral activities in PATs.

Exposure to DDT and DDE and functional neuroimaging in adolescents from the CHAMACOS cohort

BackgroundEpidemiological studies suggest that exposure to p,p’-dichloro-diphenyl-trichloroethane (p,p’-DDT) is associated with poorer cognitive function in children and adolescents, but the neural mechanisms underlying this association remain unclear. ObjectiveWe investigated associations of prenatal and childhood exposure to p,p’-DDT and its metabolite p,p’-dichloro-diphenyl-dichloroethylene (p,p’-DDE) with cortical activation in adolescents using functional near-infrared spectroscopy (fNIRS). MethodsWe administered fNIRS to 95 adolescents from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) aged 15–17 years. We assessed cortical activity in the frontal, temporal, and parietal brain regions while participants completed tasks of executive function, language comprehension, and social cognition. We measured serum p,p’-DDT and -DDE concentrations at age 9 years and then estimated exposure-outcome associations using linear regression models adjusted for sociodemographic characteristics. In secondary analyses, we back-extrapolated prenatal concentrations using prediction models and examined their association with cortical activation. ResultsMedian (P25–P75) p,p’-DDT and -DDE concentrations in childhood were 1.4 (1–2.3) and 141.5 (75.0–281.3) ng/g lipid, respectively. We found that childhood exposure to p,p’-DDT and -DDE was associated with altered patterns of brain activation during tasks of cognition and executive functions. For example, we observed increased activity in the left frontal lobe during a language comprehension task (β per 10 ng/g lipid increase of serum p,p’-DDE at age 9 years = 3.4; 95% CI: 0.0, 6.9 in the left inferior frontal lobe; and β = 4.2; 95% CI: 0.9, 7.5 in the left superior frontal lobe). We found no sex differences in the associations of childhood p,p’-DDT and -DDE concentrations with neural activity. Associations between prenatal p,p’-DDT and p,p’-DDE concentrations and brain activity were similar to those observed for child p,p’-DDT and -DDE concentrations. ConclusionsChildhood p,p’-DDT and -DDE exposure may impact cortical brain activation, which could be an underlying mechanism for its previously reported associations with poorer cognitive function.

P 36 Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with Multiple Sclerosis

Introduction: Multiple Sclerosis (MS) is a chronic neurological disease leading to gait impairment in 40-60% of people with MS (PwMS). The following loss of mobility and increased risk of falls is a key concern due to the interference with activities of daily living and independence. Further, a heightened fear of falling constitutes a vicious cycle leading to deconditioning and social isolation. The management of motor symptoms in MS remains a therapeutic challenge. Therefore, it is of utmost importance to develop effective and alternative approaches to motor symptom management. Split-belt treadmill (SBT) paradigms are a promising tool for improving gait and balance in PwMS due to its ability to improve walking symmetry. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory method that is emerging as a promising rehabilitative tool. Objective: We aimed to evaluate the therapeutic potential of a non-pharmacological intervention combining multiple sessions of SBT with cerebellar anodal tDCS (ca-tDCS) on gait and balance in PwMS. We hypothesized that the combination of motor training and stimulation would be complementary, further translating to a reduction in risk of falls and increased mobility in PwMS. Patients and Methods: 22 PwMS received six sessions of anodal (PwMSreal, n = 12) or sham (PwMSsham, n = 10) tDCS to the cerebellum ipsilateral to the faster leg prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention on gait and balance, functional gait assessment (FGA) scores and distance walked in 2 minutes (2MWT) were measured at baseline (T0), day 6 (T5) and at 4-week follow up (T6). Results: PwMSreal and PwMSsham showed the same level of performance and changes on the motor outcomes independent from tDCS stimulation mode applied to the cerebellum (anodal vs. sham, p > 0.05 on FGA and 2MWT). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, an improvement in FGA scores relative to baseline by 3.3 and 5.1 points at T5 and T6 respectively was found (p < 0.001). The change in FGA at T6 was significantly higher than at T5 ( p = 0.010) underlining a long-lasting improvement. An improvement in distance walked during the 2MWT was also observed by 12.31 m on T5 and 11.56 m T6 relative to T0 (p < 0.050) . Conclusion: While no effect of ca-tDCS was found on improving gait and balance in PwMS, multiple sessions of SBT walking resulted in a significant and lasting improvement in gait stability and endurance as measured by FGA and 2MWT respectively. Before we can rule out any potential beneficial effect of combining tDCS with training, more thorough investigations into altered brain activation and functional connectivity patterns in PwMS are needed which could aid the selection of more effective tDCS parameters that will be able to boost therapeutic outcomes.

Altered Spontaneous Brain Activity Patterns in Children With Strabismic Amblyopia After Low-Frequency Repetitive Transcranial Magnetic Stimulation: A Resting-State Functional Magnetic Resonance Imaging Study

ObjectivePrevious studies have demonstrated altered brain activity in strabismic amblyopia (SA). In this study, low-frequency repetitive transcranial magnetic stimulation (rTMS) was applied in children with strabismic amblyopia after they had undergone strabismus surgery. The effect of rTMS was investigated by measuring the changes of brain features using the amplitude of low-frequency fluctuation (ALFF).Materials and MethodsIn this study, 21 SA patients (12 males and 9 females) were recruited based on their age (7–13 years old), weight, and sex. They all had SA in their left eyes and they received rTMS treatment one month after strabismus surgery. Their vision before and after surgery were categorized as pre-rTMS (PRT) and post-rTMS (POT). All participants received rTMS treatment, underwent magnetic resonance imaging (MRI), and their data were analyzed using the repeated measures t-test. The team used correlation analysis to explore the relationship between logMAR visual acuity and ALFF.ResultsPre- versus post-rTMS values of ALFF were significantly different within individuals. In the POT group, ALFF values were significantly decreased in the Angular_R (AR), Parietal_Inf_L (PIL), and Cingulum_Mid_R (CMR) while ALFF values were significantly increased in the Fusiform_R (FR) and Frontal_Inf_Orb_L(FIL) compared to the PRT stage.ConclusionOur data showed that ALFF recorded from some brain regions was changed significantly after rTMS in strabismic amblyopes. The results may infer the pathological basis of SA and demonstrate that visual function may be improved using rTMS in strabismic amblyopic patients.

Proactive inhibition is marked by differences in the pattern of motor cortex activity during movement preparation and execution.

Successful human behavior relies on the ability to flexibly alter movements depending on the context in which they are made. One such context-dependent modulation is proactive inhibition, a type of behavioral inhibition used when anticipating the need to stop or change movements. We investigated how the motor cortex might prepare and execute movements made under different contexts. We used transcranial magnetic stimulation (TMS) in different coil orientations [postero-anterior (PA) and antero-posterior (AP) flowing currents] and pulse widths (120 and 30 µs) to probe the excitability of different inputs to corticospinal neurons while participants performed two reaction time tasks: a simple reaction time task and a stop-signal task requiring proactive inhibition. We took inspiration from state space models to assess whether the pattern of motor cortex activity changed due to proactive inhibition (PA and AP neuronal circuits represent the x and y axes of a state space upon which motor cortex activity unfolds during motor preparation and execution). We found that the rise in motor cortex excitability was delayed when proactive inhibition was required. State space visualizations showed altered patterns of motor cortex activity (combined PA120 and AP30 activity) during proactive inhibition, despite adjusting for reaction time. Overall, we show that the pattern of neural activity generated by the motor cortex during movement preparation and execution is dependent upon the context under which the movement is to be made.NEW & NOTEWORTHY Using directional TMS, we find that the human motor cortex flexibly changes its pattern of neural activity depending on the context in which a movement is due to be made. Interestingly, this occurs despite adjusting for reaction time. We also show that state space and dynamical systems models of movement can be noninvasively visualized in humans using TMS, thereby offering a novel method to study these powerful models in humans.