Check out some of the papers that were recently published by DMCBH members:
Cornelia Laule, Anthony Traboulsee: 2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis
Journal: The Lancet, Neurology
MRI has played an increasingly important role in the diagnosis of multiple sclerosis (MS). Researchers presented recommendations for image interpretation and avoidance of misdiagnosis and extend the recommendations to the use of MRI in the diagnosis of multiple sclerosis in older people, children, people with vascular comorbidities or migraine, and people living outside Europe and North America. Additionally, researchers provided recommendations for standardization of MRI acquisition and communication of results to enable an earlier diagnosis while maintaining high diagnostic specificity.
Paul Pavlidis, Terrance Snutch: Cataloging the potential functional diversity of Cacna1e splice variants using long-read sequencing
Journal: BMC Genomics
The degree to which alternative RNA splicing influences the function and structure of voltage gated calcium channel splice variants is poorly understood. Researchers used long-read RNA-sequencing to catalog rat Cacna1e (Cav2.3) splice variants and computationally prioritize which are likely to impact channel function. This work provides the first long-read sequencing of Cacna1e and the first computational evaluation of Cacna1e splice variants for future follow-up. Using this strategy, we can improve our understanding of Cacna1e function and its role in neurological disorders such as epilepsy, migraine, and schizophrenia.
Deanna Gibson, Kiran Soma: Prenatal exposure to dietary levels of glyphosate disrupts metabolic, immune, and behavioral markers across generations in mice
Journal: The science of the total environment
Glyphosate is a widely used herbicide in North America, becoming prevalent in the food supply and raising concerns about potential health impacts. In this exploratory study, male and female mice were exposed to glyphosate through drinking water during mating and gestation. Researchers investigated whether prenatal exposure at human-relevant levels altered gut, metabolic and behavioural outcomes across two generations in mice with or without genetic susceptibility to colitis, inflammation of the colon. Healthy offspring showed changes in chemical signaling profiles and developed metabolic dysfunction, including impaired glucose tolerance and insulin resistance. Behavioural deficits were also observed, including reduced locomotion and working memory. Researchers also found significant shifts in gut microbiome composition and associations between specific molecules. Findings suggested that prenatal glyphosate exposure may disrupt multiple physiological systems across generations, highlighting the need for further research and potential regulatory consideration.
Ryan Hoiland, Mypinder Sekhon: Effect of Phenylephrine on Cerebrovascular Regulation: A Translational Perspective
Journal: Journal of the American Heart Association
Phenylephrine is an alpha 1-adrenergic receptor (α1R) agonist drug. Past studies have shown that activation of α1Rs can initiate both vasoconstrictor and dilator signaling. However, it’s unclear how that affects cerebrovascular regulation. A retrospective analysis of data examining cerebral perfusion and blood pressure during drug infusion in humans and swine was completed. Follow-up experiments examining cerebral hemodynamics during intracarotid arterial infusion of phenylephrine in anesthetized swine were performed. Systemic phenylephrine infusion increased indices of cerebrovascular resistance in both humans and swine but did not decrease perfusion. Neither systemic nor intracarotid phenylephrine infusion compromised cerebral perfusion, possibly related to increased endothelial NO signaling and reduced α1R density in downstream pial arteries.
Noah Silverberg: Associations between illness perceptions, distress, self-reported cognitive difficulties and cognitive performance after mild traumatic brain injury
Journal: Brain Impairment
Researchers aimed to examine associations between subjective and objective cognitive problems and factors that might modify those relationships after mild traumatic brain injury (mTBI). Treatment seeking adults were assessed 6 weeks and 6 months after mTBI. Questionnaires were used to assess cognitive, emotional and somatic mTBI symptoms, distress, catastrophizing, and beliefs about symptoms and recovery. Researchers found medium to large correlations between subjective cognitive symptoms, post-concussion symptom burden and psychological factors. Having many post-concussion symptoms and fears of nonrecovery may increase the risk of experiencing persisting cognitive symptoms. These findings may guide targeted treatment efforts focusing on factors with potential to influence cognitive symptom reporting after concussion.
Thalia Field: Brain Frailty and Functional Outcomes After Thrombolysis for Acute Ischemic Stroke
Journal: JAMA Network Open
Acute ischemic stroke can lead to chronic vascular and neurodegenerative changes, leading to brain frailty and hindering recovery. This study aimed to evaluate associations between brain frailty assessed on non-contrast-enhanced computed tomography (NCCT) and magnetic resonance imaging (MRI) and functional outcome in patients with AIS treated with intravenous thrombolysis. Among the participants in this post-hoc analysis, brain frailty markers such as white matter changes, cortical atrophy and total brain frailty were associated with worse outcomes. Consideration of these neuroimaging markers may better inform clinicians and patients about treatment expectations from thrombolytic therapy.
Shernaz Bamji: Micro-scale control of oligodendrocyte morphology and myelination by the intellectual disability-linked protein acyltransferase ZDHHC9
Journal: ELife
Mutations in the X-linked ZDHHC9 gene, known to cause intellectual disability and sometimes epilepsy, have now been linked to defects in oligodendrocytes, the brain cells that make myelin. This study shows that ZDHHC9 is highly expressed in these cells and helps modify Myelin Basic Protein (MBP) through palmitoylation, a lipid-based process essential for proper myelin structure. Mice lacking Zdhhc9 showed abnormal myelin despite normal cell development, suggesting that disrupted myelin formation may be involved in ZDHHC9-related cognitive deficits.
Wolfram Tetzlaff, Cheryl Wellington: Age and Sex Affect the Chronic Trajectory of Plasma Neurofilament Light and Glial Fibrillary Acidic Protein Levels in a Murine Thoracic Contusion Spinal Cord Injury Model
Journal: Topics in spinal cord injury rehabilitation
Mouse models of traumatic spinal cord injury (SCI) are used to understand pathophysiology and test potential interventions. Blood biomarkers may be a promising additional metric to assess severity and detect efficacy of interventions, but they have not been examined previously in mouse spinal cord injury (SCI). In a mouse SCI model, plasma NfL and GFAP are elevated chronically after injury. Sex and age at injury may affect biomarker trajectories, which may indicate underlying pathology relevant to treatment and recovery. Establishing the trajectory of NfL and GFAP after experimental injury may help to standardize injury paradigms, assess recovery, and detect efficacy of interventions.
Tim Murphy: Synthetic patient and interview transcript creator: an essential tool for LLMs in mental health
Journal: Frontiers in digital health
Developing large language models (LLMs) for mental health applications requires high-quality, privacy-safe training data. To address this, researchers built a synthetic patient–interview framework using two locally run Llama 3.3:70B models—one acting as the interviewer and the other as the patient. The system generates realistic, demographically tailored interview transcripts with human-like lexical diversity, measured by Distinct-1 scores comparable to real conversations. Synthetic patient profiles also matched real-world demographic patterns and showed strong linguistic diversity. This approach offers a privacy-preserving way to create rich, realistic mental health datasets for LLM development.
Kamyar Keramatian, Lakshmi Yatham, Erin Michalak: Participant and facilitator perspectives on a psychoeducational intervention for individuals at risk of bipolar disorder
Journal: BJPsych Open
Bipolar disorder is often unrecognized for years, delaying treatment and worsening outcomes. The PREP-BD programme is a novel telehealth-based group intervention designed to improve help-seeking and resilience among adolescents and young adults at high risk. Feedback from participants, families, and facilitators was largely positive, highlighting the sessions’ engaging and informative nature. Suggestions included adding more practical resources, nuanced content, and greater family involvement. While the online format was convenient, some felt it limited deeper connections. These findings suggested that PREP-BD is a promising early intervention tool, with future refinements needed to maximize its impact.
Joanne Matsubara, Robin Hsiung, Ian Mackenzie: Decoding amyloid beta clearance systems at inner blood–retina barrier using three-dimensional ex vivo retinal imaging in Alzheimer’s disease
Journal: Alzheimer’s & Dementia
This study investigated retinal Aβ clearance involving neuronal, glial, and vascular interactions at the inner blood–retina barrier (iBRB), a functional analog of the blood–brain barrier (BBB). Neuroretinas from donors with Alzheimer’s disease displayed increased larger Aβ42 deposits, microglial elongation, and substantial reductions in macroglial support and water channel expression. The uptake of soluble Aβ oligomers was also diminished. In a mouse model, elevated glia levels and increased APP/Aβ expression suggested gliosis and failures in clearance processes with disease progression. Ex vivo three-dimensional retinal imaging at the iBRB provided novel insights into Aβ clearance in AD, which is difficult to replicate in ex vivo brain studies at the BBB.
Scott Ramsay: The Social Determinants of Health in Pediatric Concussion: A Scoping Review
Journal: The journal of head trauma rehabilitation
In North America, concussions are a common injury in the pediatric population. Consideration of psychological, social and ecological factors, specifically the social determinants of health (SDH), relevant to concussion, is important for improving treatments for pediatric concussion. This scoping review found that lower socioeconomic status (SES), limited English proficiency, and housing instability were linked to a higher incidence of concussions. Non-White pediatric patients, those with public insurance, and rural residents were more likely to use emergency departments instead of specialized concussion services. Non-White participants often had shorter recovery times, while the connections between socioeconomic status, public school attendance, and recovery duration were inconsistent.
Michael Hayden, Cheryl Wellington, Mahmoud Pouladi: Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease
Journal: Molecular therapy, nucleic acids
Therapies that reduce mutant huntingtin (mHTT) offer potential disease-modifying treatment for Huntington disease (HD) but require reliable biomarkers. In YAC128 HD mice, researchers administered HTT-lowering antisense oligonucleotides (HTT ASO) and monitored plasma and imaging biomarkers from 6 to 12 months. Treatment sustained mHTT reduction, slowed plasma neurofilament light chain increases, and moderately reduced GFAP elevation. While mHTT levels were correlated with brain volume, regional atrophy was not significantly prevented. HTT ASO also partially reversed striatal transcriptome dysregulation and restored oligodendrocyte-specific gene expression. Overall, plasma neurofilament light chain, but not brain imaging, emerged as a sensitive biomarker of treatment response.
Mark Cembrowski: Quantification and analysis of multiplexed fluorescence insitu hybridization data using open-source tools
Journal: STAR protocols
Researchers presented a protocol to quantify and analyze multiplexed fluorescence in situ hybridization (mFISH) data using two open-source tools, FijiFISH and RUHi. FijiFISH, an ImageJ-based plugin, enables image registration, cell segmentation, and gene expression quantification. RUHi, an R-based package, supports dimensionality reduction, clustering, and visualization through both code and a Shiny app. The protocol also accommodates experimentally induced exogenous fluorophores, providing multimodal, single-cell resolution insights into spatial gene expression.
Mypinder Sekhon, Cheryl Wellington, Ryan Hoiland: Characterizing the physiology of circulatory arrest in humans
Journal: Nature Medicine
The dying process from circulatory arrest remains underexplored in humans. Researchers conducted a prospective observational study of 39 adults, using multimodal monitoring of cerebrovascular and cardiovascular physiology. They found that cerebral blood velocities and brain tissue oxygen levels ceased before systemic hemodynamics, with diffusion-limited oxygen extraction in the brain compared with extracranial tissues. Anterior and posterior brain circulation differed in the timing of cessation and physiological responses. Blood-based neurological biomarkers did not change during brain ischemia, while heart pathology was linked to the duration of the dying process. This study provides proof-of-concept for an in vivo human model to investigate severe cerebral ischemia and the dying process.
Martin McKeown: Automated Shoulder Girdle Rigidity Assessment in Parkinson’s Disease via an Integrated Model- and Data-Driven Approach
Journal: Sensors
Parkinson’s disease (PD) motor symptoms, like rigidity, are traditionally assessed with subjective clinical scales. Researchers developed a hybrid framework combining biomechanical features (damping ratio, decay rate) and statistical features from wearable sensor data during a modified pendulum test. Using weak supervision, the approach improved PD/healthy control classification accuracy by 10% compared with purely data-driven methods and revealed velocity-dependent aspects of rigidity, challenging traditional views. The outputs correlated strongly with clinical UPDRS rigidity scores (r = 0.78), providing robust, objective biomarkers for remote and telehealth assessment of PD.
Journal: The journal of neuroscience
The orbitofrontal cortex mediates risk/reward decisions across species. This region can be partitioned into medial and lateral compartments that have distinct connectivity, yet there have been few studies directly comparing their involvement in these types of decisions. In this study, researchers showed that these two orbitofrontal regions play opposing roles in biasing risky choices guided by external stimuli informing about the likelihood of receiving larger, uncertain rewards, while playing complementary roles in using cues to guide action towards larger deterministic rewards. These findings broaden our understanding of how different frontal lobe regions influence these types of decisions and further highlight differences in how these systems are recruited in shaping decision biases guided by external cues vs internal representations of risk/reward contingencies.
Mark Cembrowski: Distinct Layer 6b transcriptomic subtypes parcellate the cortical mantle
Journal: Progress in neurobiology
Layer 6b (L6b) neurons, a sparse population in the deep cortex, play key roles in healthy and disordered brain states, but their precise properties and spatial organization remained unclear. Researchers combined single-cell RNA sequencing, multiplexed fluorescent in situ hybridization, and single-cell spatial transcriptomics to characterize L6b cell types and molecular heterogeneity. They identified multiple distinct L6b subtypes and mapped their spatial distribution across 450,496 cells—the most extensive spatial dataset for L6b to date. Findings revealed a patchwork-like organization that sometimes extended beyond the traditionally defined deep cortical layer and showed intermingling with Layer 6a neurons, demonstrating that depth alone does not define L6b identity. This work provides a comprehensive cellular and spatial framework for understanding L6b function in brain health and disease.
Helen Tremlett: Disease modifying treatment of radiologically isolated syndrome: A systematic review of the use, efficacy, effectiveness, and safety
Journal: Revue Neurologique
Radiologically isolated syndrome (RIS) involves incidental demyelinating brain lesions without multiple sclerosis (MS) symptoms. Researchers systematically reviewed 20 studies including 1,401 individuals with RIS, 291 of whom received disease-modifying therapies (DMTs). Treatment with DMTs, including teriflunomide and dimethyl fumarate, reduced the risk of clinical demyelinating events (adjusted hazard ratio = 0.37) but increased adverse events compared with placebo (risk ratio = 1.44). There was also a higher rate of adverse events in DMT treated patients with RIS versus placebo. No studies assessed long-term benefits or harms, highlighting the need for further research on prolonged DMT use in RIS.
Read the blog post here.
Helen Tremlett: Risk of cardiovascular and autoimmune disease in people with multiple sclerosis on long-term interferon-β therapy
Journal: Brain communications
Chronically elevated type I interferons can promote atherosclerosis, but the long-term effects of interferon-β in multiple sclerosis (MS) patients were unclear. Researchers followed 19,360 people with MS in a Canadian population-based cohort for a median of 11.2 years, including 3,138 interferon-β users. Longer interferon-β therapy was associated with higher cardiovascular risk (hazard ratio = 1.18 per 5 years) but not with increased autoimmunity. These findings highlight a new safety signal, emphasizing the need for cardiovascular risk management in MS patients on interferon-β and careful consideration when prescribing to high-risk individuals.
Read the blog post here.
Helen Tremlett: Psychiatric morbidity during the multiple sclerosis prodrome is associated with future disability
Journal: Multiple Sclerosis journal
Evidence suggests that a prodromal phase in multiple sclerosis (MS) exists and can be detected through healthcare use, including for psychiatric symptoms. The association between psychiatric morbidity, which is defined as the presence of mental health disorders, and subsequent disability is not well understood. Researchers examined psychiatric morbidity 5 years before the onset of MS and subsequent disability scores from MS patients in British Columbia. Males, younger individuals, and those with relapsing-onset MS were more predisposed to increased future disability in the presence of psychiatric morbidity in the 5 years before onset of MS. These associations were stronger in individuals with a high burden of psychiatric-related visits and psychiatric hospitalizations.
Read the blog post here.
