Check out some of the papers that were recently published by DMCBH members:
Sarah Kraeutner, Lara Boyd: Continuous Theta Burst Stimulation Inhibits Contralesional Parietal and Occipital Activity During Imagined Movements After Stroke
Journal: The European Journal of Neuroscience
After a stroke, motor skills are impacted. In this study, researchers used a type of transcranial magnetic stimulation called continuous theta burst stimulation (cTBS) to reduce activity in the cortex opposite to the side of the stroke, the “healthy” cortex, which increases activity in the homologous motor area of the “damaged” cortex. The study consisted of 30 participants with middle cerebral artery stroke who went through active and placebo cTBS. Before and after cTBS, participants completed a task pertaining to the mental rehearsal of a movement, involving opening a door with their stroke-affected arm/hand. Researchers found that brain activity in the parietal and occipital regions were greater pre-cTBS than post-cTBS, and there were no changes in brain activity after the placebo stimulation. These results imply that cTBS can decrease brain activity in regions involved in higher-order processing, and these findings are critical in studying cTBS as a potential therapy for individuals with stroke.
Khaled Abdelrahman: Membrane Proteome Remodeling in Female APP/PS1 Mice Following M1 Muscarinic Receptor Modulation Revealed by Peptidisc-Enabled DIA-MS
Journal: Journal of Proteome Research
Most Alzheimer’s disease (AD) research investigates proteins within the cell, rather than within the cell membrane, which contain proteins controlling amyloid processing, synaptic signaling, and neuronal communication. In this study, researchers applied a drug to normal mice and mice modeling AD, which examined changes in the cortical membrane proteome. Certain AD-associated membrane proteins became more enriched, along with shifts in pathways involved in calcium signaling, synaptic organization, and membrane trafficking. The drug had little effect in normal mice, but enhanced proteins in AD-modeled mice. Findings indicate that many AD-related changes occur on the cell membrane level, and membrane-focused approaches are a powerful tool in investigating disease mechanisms and therapeutic engagement.
Rebecca Todd, Trisha Chakrabarty, Stan Floresco, Luke Clark: Beyond passivity: Depressive symptoms predict persistent active avoidance under ambiguity
Journal: Behaviour Research and Therapy
Avoidance behaviours involve initiating or suppressing actions to avoid harm. Its involvement in depression remains poorly understood, especially when initiating and suppressing strategies compete in unclear situations. In this study, researchers developed an instrumental avoidance generalization task. Undergraduates with a wide range of depressive symptoms were presented with a signal, to either rapidly press a button or withhold from pressing to prevent aversive sounds. Once the signal was learned, researchers presented participants with an ambiguous signal similar to the trained signal without letting them know if their response was correct or incorrect. Researchers found that depressive symptoms were not associated with worsened learning of avoidance strategies. Instead, individuals with higher depressive symptoms were more likely to stick with the same avoidance strategy, even under ambiguity. These findings do not support the common account of depression that individuals have reduced motivation but instead suggest that individuals with depressive symptoms are likely to persist with actions that once worked for them.
Silke Appel-Cresswell, Fidel Vila-Rodriguez: Probiotic supplementation for anxiety symptoms in people with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial
Journal: Nature Partner Journals (NPJ) Parkinson’s Disease
Anxiety is a common, non-motor symptom of Parkinson’s disease (PD), but it is not often discussed in PD conversation, and the treatment options are limited. Researchers conducted a study with 61 participants with PD and clinically significant anxiety symptoms, analyzing the potential anxiety-reducing effects of a 12-week multi-strain probiotic supplement. The study was randomized and the participants and researchers did not know who received the prebiotic supplement or the placebo. Researchers found that both the probiotic and placebo groups showed significant improvements on the Parkinson Anxiety Scale, with no significant differences between the two groups. However, the probiotic group showed statistically significant improvement on the Montreal Cognitive Assessment, compared with the placebo group. These findings do not indicate that the probiotic reduces anxiety more than the placebo, but it is cause for further investigation in terms of potential cognitive improvements for those with PD.
Fidel Vila-Rodriguez: Clinical and Cognitive Outcomes Comparing Right Unilateral Ultrabrief Electroconvulsive Therapy Versus Magnetic Seizure Therapy for Bipolar Depression: The CORRECT-BD Trial
Journal: American Journal of Psychiatry
Electroconvulsive therapy (ECT) is an established clinical effective treatment for those with bipolar depression, but there are concerns due to cognitive adverse effects. Magnetic seizure therapy (MST) has potential in treating patients with depression, with less cognitive adverse results. Researchers assessed the efficacy and the cognitive adverse effects of MST compared to ECT in the treatment of bipolar depression. The pilot clinical trial was randomized and both the participants and researchers were not aware of who would receive MST or ECT. Researchers assessed for clinical remission utilizing the 24-item Hamilton Rating Scale for Depression, and cognitive adverse effects assessed with the Autobiographical Memory Test (AMT). Out of the 45 participants, 30% in the ECT group and 20% in the MST group achieved clinical remission. 22.2% in the ECT group and 7.1% in the MST group experienced worsening in autobiographical memory. The trial’s preliminary findings indicated that those who went through MST appeared to have less worsening of autobiographical memory and was overall better tolerated, and researchers suggest it may be a safer clinical application for bipolar depression treatment.
Teresa Liu-Ambrose: Feasibility and exploratory cognitive outcomes of three exercise modalities in oldest-old adults in assisted living facilities: A 24-week pilot randomized controlled trial
Journal: Journal of Affective Disorders
This pilot study explores the effects, feasibility, and safety of aerobic, resistance and mind-body exercise on cognition in assisted living facilities (ALF) residents over 80 years old. 76 participants were randomly assigned to aerobic, resistance, mind-body (simplified Tai Chi), or non-exercise control groups. Over 24 weeks, participants exercised for thirty minutes three times a week. Researchers used six different cognitive assessments: the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Immediate Story Recall (ISR), Boston Naming Test (BNT), Trail Making Test-A (TMT-A), and Trail Making Test-B (TMTB) to assess cognition at baseline, week 12, and week 24. Researchers concluded that the exercises were feasible and safe, and there were no serious adverse events. Aerobic and mind-body exercise improved cognition, but larger trials are required to confirm the findings.
Journal: Hormones and Behaviour
Researchers inquired if caregiving corresponds to a distinct hormone profile, or if it occurs within a hormonal system that supports shifts in behaviour. This study investigated red-winged blackbirds, a species in which males either provide none or high rates of chick care, and females always provide care. Researchers used continuous (24-48 hour) nest recordings and a panel of hormones to examine how these hormones related to the bird’s breeding stage, sex and paternal care. Mating-stage males and post-hatching stage males displayed clear difference in their hormone profiles, which confirms the breeding stage as a big factor of hormone variation. During the nestling-stage, caregiving females and males differed in hormone profiles. Though both male and female birds were caregiving, their hormone profiles were different. Parental caregiving and non-caregiving male blackbirds overlapped in hormone profiles, and no single hormone could indicate whether the bird would provide caregiving. Researchers concluded that male blackbird parental caregiving efforts came from a combination of multiple hormones.
Journal: Biology of Sex Differences
Researchers understand that aging, the female sex and the APOEɛ4 allele are top risk factors for Alzheimer’s disease (AD). In this study, researchers investigated female-specific experiences, such as parity and hormone therapy (HT), and their effects on AD risk. An estrogen hormone in HT, Estradiol (E2), can affect cognition and brain health. Researchers fed middle-aged female wildtype (WT) or “normal” rats, and rats modified with the APOEɛ4 allele either a Western (WD) or a standard diet (SD), then they gave them E2 or placebo oil injections. Results indicated that APOEɛ4 allele female rats that were previously pregnant and fed a WD showed poor results in terms of increased inflammation, decreased memory, and less weight-loss from E2. These findings highlight the importance of considering parity and genotype when evaluating midlife metabolic and cognitive risk.
Helen Tremlett: The gut microbiome in pediatric-onset acquired demyelinating syndromes by myelin oligodendrocyte glycoprotein antibody status
Journal: Multiple Sclerosis and Related Disorders
While it has been studied in pediatric multiple sclerosis (MS), the role of the gut microbiome in other pediatric onset acquired demyelinating syndromes (ADS) remains unknown. Researchers compared the composition of the gut microbiome between pediatric-onset ADS participants under 21 who are myelin oligodendrocyte glycoprotein antibody-positive (MOG+) and antibody-negative (MOG-). Stool sample-derived DNA and antibodies were tested. Diversity in a single area and diversity compared between different areas were similar between groups, but researchers identified a lower level of specific bacteria in MOG+ than MOG- participants. Results indicate youth with demyelinating disease and MOG antibodies may have a different microbiome composition than those without MOG antibodies, but larger, longitudinal work is warranted.
Ilker Hacihaliloglu: MonoUNet: A Robust Tiny Neural Network for Automated Knee Cartilage Segmentation on Point-of-care Ultrasound Devices
Journal: Ultrasound in Medicine and Biology
Researchers proposed a model called MonoUNet to locate knee cartilage in ultrasound images, specifically on point-of-care ultrasound (POCUS) devices. The model consists of three main components: a reduced U-Net backbone, a trainable monogenic block that extracts local phase features, such as edges and lines, from ultrasound images, and a gating mechanism, which injects these features into an encoder and improves the appearance of ultrasound images. This model was tested on a dataset from multiple places and multiple devices. The findings showed MonoUNet outperforming existing segmentation models.
Sophia Frangou: Empirical validation of race-neutral normative brain morphometry models across ethnoracially diverse populations
Journal: Proceedings of the National Academy of Science of the United States of America
Models of brain structure analysis (morphometry) can provide information about individual differences from typical brain patterns to improve clinical decision-making. However, the utility of these normative models depends on the ability to function consistently across diverse ethnoracial populations. Researchers developed a model for brain morphometry using a diverse sample of healthy individuals. This model was tested on individuals from Africa, Asia, Europe and the Americas, either self-defined or ancestry-defined ethnoracial classification and compared its function against models developed from a single-population of Chinese participants. The results indicated that the newly developed model remained highly accurate and consistent and provides support for the diverse application of a race-neutral normative model.
Irene Vavasour, Cornelia Laule, Anthony Traboulsee, Vesna Sossi, Shannon Kolind: Increased PET 11C-PBR28 binding in multiple sclerosis normal-appearing white matter correlates with MRI measures of myelin loss
Journal: Multiple Sclerosis and Related Disorders
Researchers used the Positron Emission Tomography (PET) tracer 11C-PBR28 to bind to the Translocator Protein (TSPO), which increases when microglia are activated. The objective of this study was to compare 11C-PBR28 binding between different MS subtypes, and to assess the correlation between 11C-PBR28 binding and advanced Magnetic Resonance (MR) measures in normal-appearing white matter (NAWM) and lesions. Researchers found that increased inflammation and gliosis shown by increased 11C-PBR28 binding in NAWM are associated with demyelination.
Journal: NeuroMarkers
Researchers studied how different Quanterix assays (laboratory procedures) analyzing two biomarkers common in many neurological conditions, neurofilament light chain (NfL) and glial fibrillary protein (GFAP), may impact performance and comparability. These two biomarkers are available in many different assays due to their utility and performance, and the aim of this study was to compare how one assay formulation translated to other assay formulations to assess generalizability. Researchers conducted seven comparisons using Spearman correlation and Bland-Altman analysis. NfL and GFAP concentrations were correlated between assay formulations, but biases were found between formulations, indicating the need for data correction to ensure data comparability.
Noah Silverberg: Smartphone App-Delivered Mindfulness-Based Intervention for Concussion in Adolescents (MBI-4-mTBI): Feasibility Randomized Controlled Trial
Journal: JMIR Rehabilitation and Assistive Technologies
Around one-third of youth face persisting symptoms after a concussion. Researchers conducted a study to assess the feasibility and effectiveness of a digital therapeutic (DTx) trial vs a sham intervention, inquiring that early psychological intervention conducted via smartphones, such as mindfulness-based intervention (MBI), may improve youths’ ability to regulate emotions and reduce post-concussion symptoms. Adolescents aged 12 to under 18 with a diagnosed concussion were randomized to participate in the experimental group, which consisted of an app (AmDTx) with 8 modules of guided mindfulness exercises, goal setting, journaling and psychoeducation, or the control group, which consisted of the same app with the game “2048.” Participants engaged with the app for at least 10 minutes a day, 4 days a week. Overall, the study supported a progression to a larger randomized controlled trial (RCT) to further evaluate the efficacy of the DTx-MBI on youth with persisting post-concussion symptoms. Researchers concluded that DTX-MBI could be a low-burden, cost-effective addition to youth concussion recovery.
Leigh Anne Swayne: Early Surge in Brain GFAP Distribution in Female Hamsters With Mild Peripheral COVID-19
Journal: Journal of Neurochemistry
COVID-19 is commonly a respiratory disease; however, it has been associated with multiple neurological symptoms. Researchers proposed two mechanisms that link COVID-19 to the brain: peripheral circulating cytokines entering a compromised blood-brain barrier, and/or brain infection. As a result, inflammation in the brain could cause cognitive issues, and a key aspect of neuroinflammation is increased astrocyte reactivity, called astrogliosis. Researchers assessed astrogliosis in various brain areas within hamsters with mild to moderate COVID-19 by extracting brains at different days post-inoculation and capturing imaging of brain sections. The results indicated an increase in astrocyte (GFAP) distribution in the brain regions of female hamsters, and no changes in male hamsters, providing insight into sex differences in astrogliosis as part of COVID-19.
Helen Tremlett: Phenotyping healthcare use before pediatric-onset multiple sclerosis, including by sex and age: A matched cohort study
Journal: Multiple Sclerosis Journal
Researchers assessed early signs and symptoms (prodrome) in pediatric-onset multiple sclerosis (POMS), especially in age and sex differences. Using Ontario administrative data, researchers compared annual hospitalization and physician visit rates in youth pre-first demyelinating event. Results indicated that youth who were diagnosed with POMS experienced hospitalization and physician visits prior to diagnosis more frequently than youth without multiple sclerosis (MS), such as 14 years prior for respiratory-related physician visits, and 11 years prior for nervous system and mental-related visits. The main sex difference was nervous system related visits 12 years prior in males and 6 years prior in females. The main age difference was a spike in physician visits among 12- to 15-year-olds. These findings suggest prolonged healthcare prior to POMS diagnoses, with some sex and age-related differences.
Sophia Frangou: Brain morphology in Anorexia Nervosa and its subtypes: A multi-cohort study of individual participant data
Journal: Public Library of Science (PLoS) Medicine
In a previous study, researchers reported gray matter differences in patients with anorexia nervosa (AN). In this study, researchers looked at individual differences in brain structure in patients with AN, between AN and healthy control (HC) individuals, and between AN subgroups. Data from sites in the ENIGMA Eating Disorders Working Group were analyzed between AN and HC participants and compared AN restricting and binge-eating/purging subgroups. Results reinforced the previous finding of pronounced GM deficits in AN vs HC and found abnormalities in brain structure in patients with AN.
Lawrence Ward: Phenomenology of the stream of thought: dissociable dynamic dimensions revealed through experience sampling
Journal: Neuroscience of Consciousness
This consciousness-related study looks at dynamic dimensions of thought and its role in forming conscious experiences. Two dynamic dimensions derived from the Dynamic Framework of Thought (DFT), freely moving and deliberately directed, were investigated through four experiments to assess the consistency of the relationship between the two thought dynamics. Participants sat quietly viewing a blank screen and reported on the dynamic of their thoughts. Researchers found that participants were able to access their thought dynamics and distinguish freely moving and deliberately directed thoughts. The two dynamic dimensions were negatively correlated but not anticorrelated, and results indicated that stream of thought can be described by at least two dynamic dimensions.
Terrance Snutch: Bridging Simplicity and Depth in Single-Cell Proteomics: A Cost-Effective Workflow and an Expanded Framework for Data Evaluation
Journal: Journal of Proteome Research
Researchers developed an accessible single-cell proteomics (SCP) workflow that allows for broader adoption of proteome studies, as SCP allows for functional protein analyses. This workflow optimizes many variables, such as trypsin concentration, incubation time, reduction/alkylation, digestion conditions, and plate types. Optimizing these sample preparation variables maximizes the quality and replicability of data. Researchers also developed a data quality framework that covers individual proteins to emphasize consistency. The efforts of these researchers improve accessibility to SCPs and improve SCP analysis for various research contexts.
Journal: Journal of Neuroengineering and Rehabilitation
Individuals with spinal cord injury (SCI) may go through a treatment for motor recovery called transcutaneous spinal cord stimulation (tSCS), but some individuals respond less effectively than others. Researchers wanted to identify markers that separate those who respond to the treatment and those who do not. This study assessed 10 people with SCI and they received lower back tSCS, and their voluntary leg movements were measured along with various other biomarker assessments. 5 individuals out of 10 with SCI demonstrated voluntary motor activity against gravity (not only muscle twitches), however, researchers could not identify specific factors that differentiated those who responded to tSCS and those who did not, though there are possible trends within responders. Overall, the study shows promise for tSCS but highlights the need for better tests to predict who is most likely to benefit from the treatment.
Teresa Liu-Ambrose, Roger Tam: Explainable machine learning for predicting longitudinal dementia status: Establishing a leakage-free benchmark
Journal: Public Library of Science (PLoS) Digital Health
Researchers wanted to address label and subject information leakages that are common in dementia research. This study identifies and addresses three gaps in dementia research: (i) including Clinical Dementia Rating (CDR) in predictor sets, which can unintentionally leak the outcome and artificially boost performance, (ii) using improper splitting strategies for longitudinal data, risking information leakage, and (iii) inadequate incorporation of temporal dynamics in classification models. Researchers addressed these gaps by removing CDR from input features, implementing a group-aware data-splitting method, and introduced temporal features. Several AI models were tested and the best-performing models were SVC and LightGBM. The results also showed that key factors like memory test scores, age, education, and brain volume were most important for predictions, and that models worked slightly better for females than males, suggesting possible bias. Overall, the study shows when data leakage is properly controlled, dementia prediction is more realistic and also provides a reference point for improving dementia models.
