Check out some of the papers that were recently published by DMCBH members:
Yu Tian Wang: Activation of the supramammillary-dentate gyrus circuit enhances alertness and cognitive function in a rat model of ADHD
Journal: Translational Psychiatry
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity, with growing evidence suggesting hypoalertness as a contributing factor to its associated cognitive impairments. Researchers identified the supramammillary nucleus (SuM) as a critical neural substrate involved in modulating alertness and cognitive deficits associated with ADHD. They showed that hypoactivity of SuM neurons correlates with reduced alertness and impaired recognition using a rat ADHD model. Moreover, SuM neurons influence recognition through projections to the dentate gyrus), primarily by facilitating long-term depression within this pathway. Importantly, chemogenetic and optogenetic activation of the SuM-DG circuit resulted in significant enhancement of alertness and restoration of cognitive performance in ADHD rats, aligning their cognitive function with that of control animals.
Journal: Neurology
Menopause and menopausal hormone therapy (MHT) affect cognition, although existing studies are inconclusive. Researchers conducted a cross-sectional observational cohort study using baseline data from the Canadian Longitudinal Study of Aging. Earlier age at menopause was significantly associated with lower scores across all cognitive domains tested. However, for executive functions, an earlier age at menopause only had a negative effect in those with 4 or more children. Transdermal E2 treatment was associated with higher episodic memory scores, while oral E2 was associated with higher prospective memory scores, compared with individuals who had never taken MHT. E2-based MHT efficacy depends on the route of administration and cognitive domain, underscoring the importance of considering MHT type.
Khaled Abdelrahman: Positive Allosteric Modulation of M1 mAChRs with VU0486846 Reverses Cognitive Deficits in Male APPswe/PSEN1ΔE9 Alzheimer’s Mice
Journal: Neuropharmacology
Alzheimer’s disease (AD) is an age-associated neurodegenerative disease marked by progressive cognitive deterioration and beta-amyloid (Aβ) protein buildup. The M1 muscarinic acetylcholine receptor (mAChR) is integral to synaptic plasticity and memory processes and has emerged as a critical target for improving AD-associated cognitive deficits. Although M1 mAChR agonists have pro-cognitive potential, their clinical application is limited by significant cholinergic side effects. Researchers found that VU0486846, an M1 mAChR positive allosteric modulator devoid of cholinergic toxicity, exhibits therapeutic benefits in a female Alzheimer’s disease mouse model. This compound reversed memory deficits, alleviated anxiety-like behaviours, reduced Aβ pathology, and attenuated neuroinflammation in female mice. It also restored cognitive function in male mice but doesn’t alter Aβ pathology. Collectively, this study highlighted the therapeutic potential of VU0486846 in modulating AD pathophysiology, albeit via sex-specific signaling pathways.
Journal: Brain, Behaviour and Immunity
Middle age is a pivotal period for brain and body health, especially as obesity and diabetes rise. Researchers tested a therapy combining glucagon-like peptide-1 (GLP-1) with estradiol (GE2) in middle-aged male and female rats on standard or Western diets. GE2 reduced body weight, boosted memory, lowered brain inflammation, and enhanced neurogenesis, but its effects differed by sex: in females, it improved blood glucose and reduced visceral fat, while in males, it restored hippocampal neurogenesis after a Western diet. These findings highlight the need for sex-specific strategies in developing metabolic and neuroprotective treatments.
Noah Silverberg: Progress in Concussion/Traumatic Brain Injury Science and Clinical Care Over the Last 40 Years
Journal: Journal of head trauma rehabilitation
This Special Communication summarizes how knowledge and clinical practice have evolved over the 40 years since the Journal of Head Trauma Rehabilitation’s topical issue (volume 1, issue 2) on “Minor Head Injury.” The authors review important insights from this 1986 issue and highlight how research since has refined our understanding of concussion/traumatic brain injury pathophysiology, recovery, and long-term effects. They also discuss shifts in terminology and outline how assessment and rehabilitation approaches have developed over time. Finally, the authors call attention to areas of ongoing uncertainty and innovations that could help resolve them.
Silke Appel-Cresswell: Validation of the English version of the Parkinson Anxiety Scale in two Canadian Parkinson’s disease samples
Journal: Clinical parkinsonism & related disorders
The 12-item Parkinson Anxiety Scale (PAS) is used to assess anxiety symptoms in people with Parkinson’s disease, but evidence supporting the English self-rated version has been limited. This study evaluated the PAS in two Canadian samples, examining its acceptability, reliability, validity, and factor structure. Results showed good internal consistency, strong convergent and divergent validity, and support for the three-factor model. Optimal cut-off scores were identified for detecting anxiety disorders, confirming the PAS as a valid and reliable tool for screening and assessing anxiety in Parkinson’s disease.
Rebecca Todd, Trisha Chakrabarty, Stan Floresco, Luke Clark: Depression levels are associated with reduced capacity to learn to actively avoid aversive events in young adults
Journal: eNeuro
Depression and anxiety are often linked to changes in reward-seeking and avoidance behaviors, but how depressive symptoms relate to avoidance is less understood. In two studies of young adults, participants completed go/no-go avoidance tasks modeled after rodent paradigms. Higher depressive symptoms were associated with poorer learning of active avoidance, while all participants were more accurate on inhibitory avoidance, suggesting a prepotent tendency to withhold action to escape aversive outcomes. These findings connect preclinical and clinical research, highlighting how depressive symptoms may hinder active avoidance and informing future targeted interventions.
Manu Madhav: Advancements in neural closed-loop manipulations in awake, behaving animals
Journal: Current opinion in behavioural sciences
Experimental neuroscience is increasingly embracing “closed-loop” approaches that measure or stimulate brain activity in real time based on behavior or neural signals. Advances in tracking, miniaturized sensors, and machine learning now enable stimulation tied to complex behavioral and physiological variables, and even allow animals to generate neural patterns for reward. New tools spanning electrical, optical, acoustic, and chemical channels permit simultaneous recording and stimulation, reshaping our ability to dissect neural computation. This review surveyed and presented closed-loop methods by feedback mode, discussing their scientific impact and remaining challenges.
Manu Madhav: Allothetic and idiothetic spatial cues control the multiplexed theta phase coding of place cells
Journal: Nature Neuroscience
Theta oscillations provide a temporal scaffold for hippocampal place cells, with late-theta phases supporting prospective spatial coding via phase ‘precession.’ Early-theta phases may support retrospective coding and new learning via phase ‘procession.’ Using virtual reality, electrophysiology, and computational modeling, researchers showed that during learning of landmark–self-motion associations, phase precession persisted while phase procession was reduced. This multiplexed phase code may allow the hippocampus to alternate different computations on a sub-second timescale.
Teresa Liu-Ambrose: Association of point-of-care ultrasound-derived subcutaneous fat thickness with DXA-measured body fat percentage in older adults
Journal: Diabetes, obesity and metabolism
This study investigated the relationship between subcutaneous fat thickness (SFT) measured by point-of-care ultrasound and body fat percentage (BF%) measured by DXA in adults over 65. Quadriceps and biceps SFT were significantly correlated with DXA-measured total and regional BF%, with stronger correlations in females. Quadriceps SFT showed the highest predictive value for total BF%. These findings suggest that B-mode ultrasound provides a practical, non-invasive method for estimating body composition in older adults, though standardization and validation are needed.
Noah Silverberg, William Panenka, Donna Lang, Cheryl Wellington, Jon Stoessl, Mypinder Sekhon, Vesna Sossi: Memory and metamemory performance in individuals with and without post-COVID-19 subjective cognitive symptoms
Journal: Journal of clinical and experimental neuropsychology
Metamemory—the awareness of one’s own cognitive abilities—may help explain persistent cognitive symptoms after COVID-19. In this study, individuals with prior COVID-19 completed memory and metamemory tests, comparing those with and without self-reported ongoing cognitive symptoms. Results showed no differences in memory accuracy or metamemory performance between groups, indicating intact cognitive and metacognitive function. However, participants with persistent cognitive symptoms reported higher levels of depression, anxiety, and somatic symptoms. These findings suggest that psychological distress, rather than memory impairment, may contribute to ongoing cognitive complaints after COVID-19, highlighting a target for future research and intervention.
Naznin Virji-Babul: Linking a Deep Learning Model for Concussion Classification with Reorganization of Large-Scale Brain Networks in Female Youth
Journal: Bioengineering
Concussion is a major public health concern, particularly in young females who often experience prolonged symptoms. Researchers collected five minutes of resting-state EEG from concussed and non-concussed females aged 15–24 and applied deep learning to classify concussion directly from the raw data. A long short-term memory network achieved 84.2% accuracy. Complementary analyses of effective connectivity revealed altered, posterior and left-lateralized network patterns in concussed participants, suggesting large-scale brain reorganization. These findings highlight the potential of deep learning for objective concussion detection and connectivity analyses for mechanistic insights.
Helen Tremlett: The multiple sclerosis prodrome: insights into how and when disease starts
Journal: Nature Reviews Neurology
Multiple sclerosis (MS) is increasingly viewed as a disease continuum, encompassing both a prodromal phase and radiologically isolated syndrome (RIS). The 2024 revisions to the McDonald criteria now allow some individuals with RIS to be diagnosed with MS, highlighting the importance of recognizing early disease features. Recent research on the MS prodrome sheds light on the initial pathological processes, offering opportunities to identify risk factors, optimize preventive strategies, and enable earlier recognition and management of this common neurological condition.
Helen Tremlett: Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria
Journal: The Lancet Neurology
The 2024 revisions of the McDonald criteria update the approach to diagnosing multiple sclerosis (MS) across all ages and disease courses. The optic nerve is now recognized as a fifth CNS location for diagnosis, and biomarkers such as the central vein sign, paramagnetic rim lesions, and CSF kappa free-light chains can provide additional specificity. The criteria also allow diagnosis in select cases of radiologically isolated syndrome or atypical neurological symptoms, and provide guidance for older adults and those with comorbidities. These updates aim to accelerate MS diagnosis while preserving accuracy.
Helen Tremlett: Use of the Emergency Department Before Pediatric-Onset Multiple Sclerosis
Journal: Neurology
Higher health care use before multiple sclerosis (MS) onset may indicate a prodromal phase. In this study, pediatric-onset MS (POMS) patients in Ontario were compared to matched non-MS peers for emergency department (ED) visits up to 18 years before the first demyelinating event. POMS patients had elevated ED utilization starting 12 years before onset, peaking the year prior, with increased visits for respiratory, nervous system, mental health, musculoskeletal, and other conditions. These findings suggest that earlier patterns of health care use could help identify POMS sooner and enable timely intervention.
Noah Silverberg: Action Collaborative on Traumatic Brain Injury Care: Adapted Clinical Practice Guideline
Journal: Journal of Neurotrauma
Outpatient follow-up for traumatic brain injury (TBI) is often inconsistent. The Action Collaborative on TBI Care, under the National Academies of Sciences, developed a clinical practice guideline for community-dwelling adults with TBI. Using existing evidence-based guidelines and input from patients and clinicians, the guideline provides recommendations across 11 priority areas, including diagnosis confirmation, emergency evaluation, neuroimaging, symptom management, mental health screening, patient education, and referral to specialty care. These guidelines aim to standardize care and improve outcomes for adults recovering from TBI.
Teresa Liu-Ambrose: Synergistic effects of exercise, cognitive training and vitamin D on gait performance and falls in mild cognitive impairment-secondary outcomes from the SYNERGIC trial
Journal: Age and Ageing
Older adults with mild cognitive impairment (MCI) are at higher risk of gait problems and falls, but the effects of combined interventions are unclear. In the SYNERGIC trial, 161 participants underwent 20 weeks of aerobic-resistance exercise, cognitive training, and/or vitamin D supplementation. Exercise combined with cognitive training improved gait speed at 6 months and significantly reduced falls and injurious falls at 12 months. Vitamin D provided no additional benefit. These findings highlight the value of multimodal exercise and cognitive training in improving mobility and safety in older adults with MCI.
Brian MacVicar: White matter interactome in vascular dementia
Journal: Cell Research
This research highlight summarizes work by Tian et al., who combined an immune-competent mouse model of focal white matter ischemia with human single-nucleus transcriptomic data to map conserved ligand–receptor interactions in vascular dementia (VaD). Functional validation identified two therapeutic targets: Serpine2-LRP1, which promotes oligodendrocyte differentiation and remyelination, and CD39-A3AR, which enhances microglial repair and myelination. This cross-species, cell type–specific approach provides mechanistic insights and translational strategies for addressing white matter injury in VaD.
