Check out some of the papers that were recently published by DMCBH members:
Journal: Acta Neuropathol
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an average lifespan of 2-5 years after diagnosis. Metalloprotein human superoxide dismutase–1 (SOD1) is known to accumulate and form aggregates in patient neural tissue for both sporadic and familial forms of ALS. This study reported the development of a real-time quaking-induced conversion seed amplification assay using a recombinant human SOD1 substrate to measure activity in postmortem spinal cord and motor cortex tissue. Results indicated that SOD1 seeds are present in ALS patient neural tissues independent of SOD1 mutation, suggesting that SOD1 seeding activity may be a promising biomarker, particularly in sporadic ALS cases.
Duncan Leitch: Variations in touch representation in the hummingbird and zebra finch forebrain
Journal: Current Biology
Somatosensation, the ability to perceive the external world through touch, is essential for animals. Studies in rodents have highlighted the organization and processing in mammalian somatosensory pathways, however, variations in somatosensory maps in avian species are not fully understood. It is vital to conduct comparative research across species to understand evolutionary influences and ecological specialization. This study explored somatotopic organization and neural coding in the telencephalon of Anna’s hummingbirds and zebra finches using in vivo extracellular electrophysiology. The researchers used controlled tactile stimuli on various body regions and detected brain activity. They found unique representations of body areas across distinct forebrain somatosensory nuclei, indicating significant differences in the extent of regions dedicated to certain body surfaces.
Teresa Liu-Ambrose, Robin Hsiung: The Effect of Computerized Cognitive Training, with and without Exercise, on Cortical Volume and Thickness and Its Association with Gait Speed in Older Adults: A Secondary Analysis of a Randomized Controlled Trial
Journal: Journal of Alzheimer’s Disease Reports
Walking speed in older adults predicts functional status and general health outcomes. Slowing of walking gait is associated with changes in cortical volume and thickness and is predictive of Alzheimer’s disease. Thus, examining measures that may improve gait speed is important to exploring interventions for older adults. Computerized cognitive training (CCT) and exercise has been shown to improve cortical volume and thickness. A subset of 124 adults aged 65-85 years enrolled in an 8-week randomized controlled trial and completed MRI scans and 4-meter walks at baseline and 8 weeks. The participants were randomized to either an active control group, a CCT group or a CCT and exercise group. It was found that CCT with physical exercise (but not CCT alone) improves cortical volume and thickness in older adults. While there were no significant between-group differences in gait speed, the observed changes in cortical volume and thickness may contribute to the maintenance of gait speed in aging.
Mypinder Sekhon: Improving Outcomes After Post–Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation
Journal: Circulation
This scientific statement presented a conceptual framework for the pathophysiology of post-cardiac arrest brain injury. It also explored reasons for previous failure to translate preclinical data to clinical practice and outlined potential paths forward. Challenges in past research include limitations of lab models, differences in patient groups, overestimating treatment effects, timing issues, and inconsistent care practices. To improve future trials, interventions should be personalized, delivered at the right time and dose, and focus on a combination of treatments rather than single therapies.
Anthony Traboulsee, David Li: Routine MR Imaging Protocol and Standardization in Central Nervous System Demyelinating Diseases
Journal: Neuroimaging Clinics of North America
Standardized MRI protocols are crucial for diagnosing and monitoring multiple sclerosis (MS) and ensuring consistent use in clinical practice. Advances in using MR imaging to establish earlier diagnoses, safety concerns regarding gadolinium-based contrast agents, and the value of spinal cord MR imaging suggest a changing role of MR imaging for clinical management and care. The MRI imaging protocol focuses on using 3-dimensional acquisitions to ensure optimal comparisons over time.
Tim O’Connor: Adult expression of the cell adhesion protein Fasciclin 3 is required for the maintenance of adult olfactory interneurons
Journal: Journal of Cell Science
The proper functioning of the nervous system depends on the establishment and maintenance of intricate networks of neurons that form functional neural circuits. Once neural circuits are assembled during development, their connectivity throughout the organism’s lifespan must be maintained. The researchers demonstrated that Fasciclin 3, an axon guidance cell adhesion protein, is necessary for the maintenance of the olfactory circuit in adult fruit flies. Knocking out Fasciclin 3 resulted in the death of olfactory circuit neurons and reduced survival. Moreover, knockdown also activates caspase-3-mediated cell death, which is reversible with anti-apoptotic protein p35.
Steven Miller: Factors affecting brain maturation trajectories in early childhood
Journal: The Lancet
Neurologists play a key role in promoting, maintaining, and supporting brain health across the lifespan. Promotion of brain development should be emphasized in childhood to ensure that every child has the chance to reach their potential. Miller discussed the findings of a multicohort study published in Nature Neuroscience by Dr. Ann M Alex and colleagues, highlighting the observed developmental trajectories, and the effect of childhood environment, and calls for future research.
Sophia Frangou: Brain-age prediction: Systematic evaluation of site effects, and sample age range and size
Journal: Human Brain Mapping
Data from structural neuroimaging has been used to estimate the biological age of the brain, which is linked to other important measures of brain development and aging. Developing robust, publicly available brain-age models based on healthy individuals is crucial for standardizing brain-age computation. This study expands on a previous developmental brain-age model to cover most of the human lifespan. The researchers analyzed data from 35,683 healthy individuals to find the best-performing model, testing it for longitudinal consistency and cross-dataset generalizability. The study provides empirically validated brain-age models that can be used for studies spanning most of the lifespan.
Martin McKeown: Advances in functional and structural imaging of the brainstem: implications for disease
Journal: Current Opinion in Neurology
Recent years have seen substantial progress in brainstem imaging, allowing us to investigate structure, function, and neuropathology. Particularly, advances in ultrahigh-field MRI technology and improvements in methodology have significantly enhanced the accuracy of brainstem imaging, prompting the creation of brainstem-specific atlases. These technological and methodological breakthroughs have allowed for a deeper analysis of brainstem anatomy. Functional studies have explored activation patterns and functional connectivity, uncovering the brainstem’s involvement in specialized functions and broader neural integration. Importantly, these studies have identified changes in brainstem structure and function linked to various neurological disorders.
Tim Murphy: Decoding state-dependent cortical-cerebellar cellular functional connectivity in the mouse brain
Journal: Cell Reports
The cortex and cerebellum form multi-synaptic reciprocal connections. The researchers investigated the functional connectivity between single spiking cerebellar neurons and the population activity of the mouse dorsal cortex using mesoscale imaging. Cortical-cerebellar connectivity features are observed in mossy fibers and Purkinje cells as well as neurons in different cerebellar lobules. It was observed that complex spikes of Purkinje cells associate with the sensorimotor cortex, while simple spikes displayed more diverse cortical connectivity patterns. The spontaneous functional connectivity patterns correspond with cerebellar neurons’ functional responses to external stimuli depending on the stimulus. Lastly, the tuning properties of cerebellar neurons differ between anesthesia and awake states, demonstrating changes in long-range functional connectivity patterns.
Teresa Liu-Ambrose: The Association of the 24-Hour Activity Cycle Profiles with Cognition in Older Adults with Mild Cognitive Impairment: A Cross-Sectional Study
Journal: The Journals of Gerontology, Series A
Mild cognitive impairment is a transitional stage between healthy cognition and dementia in which cognitive decline is greater than expected. The 24-h activity cycle is composed of measures of physical activity, sedentary behaviour and sleep. This study explored the relationship between the 24-h activity cycle and cognition in older adults with mild cognitive impairment. The researchers conducted a cross-sectional analysis using baseline data from 3 randomized controlled trials with 253 older adults. Using MotionWatch8 actigraphy, the 24-h activity cycle was captured, and cognition was measured with an Alzheimer’s Disease assessment scale. Four distinct activity profiles were identified, and there were no significant differences in cognitive scores between profiles.
Joanne Matsubara: Targeting soluble amyloid-beta oligomers with a novel nanobody
Journal: Scientific Reports
The classic amyloid cascade hypothesis proposes that the aggregation of amyloid plaques and the accumulation of intracellular Tau tangles lead to neuronal death and Alzheimer’s disease. However, emerging research has shown that soluble amyloid-β oligomers (SAβOs) accumulate prior to plaque formation. SAβOs induce memory impairment and disrupt cognitive function even in the absence of plaque formation. This work described the development and characterization of a novel anti-SAβO (E3) nanobody generated from an alpaca immunized with SAβO. The E3 nanobody crosses the blood-brain barrier and binds to amyloid species in the brains of 5XFAD mice. Mouse brain imaging showed that SAβO plaques are different in size, shape, and morphology, and have distinct spatial distributions in the brain. The results demonstrated that the SAβO nanobody can serve as a diagnostic agent with potential therapeutic applications in Alzheimer’s disease.
Jeremy Seamans: Temporal information in the anterior cingulate cortex relates to accumulated experiences
Journal: Current Biology
Activity in the anterior cingulate cortex (ACC) is important for operations that require the ability to integrate multiple experiences over time, such as rule learning, working memory and long-term memory recall. The researchers analyzed neuronal activity while rats repeated the same behaviours over hour–long sessions to investigate how activity in the ACC changed over time. Neuronal state space analysis revealed that each repetition of behaviour was unique, but recent behaviours were more similar than those farther back in time. The activity in the ACC showed a slow, gradual change in representations of neural state space matching the pace of behaviour. Temporal progression was present for every session and driven by the accumulation of experiences, not an internal clock. Notably, the patterns were consistent across subjects, allowing accurate prediction models trained on different animals. About 40% of ACC neurons showed ramping firing rates, and combinations of shorter-duration ramping neurons formed ensembles that tracked longer durations. These results offer insights into how the ACC represents time based on accumulated experiences.
Helen Tremlett: Mediterranean diet and associations with the gut microbiota and pediatric-onset multiple sclerosis using trivariate analysis
Journal: Communications Medicine
The connection between diet, gut microbiome, and multiple sclerosis is not well understood. This study aimed to explore how these factors interact with each other. Researchers conducted a case-control study including 95 participants who had completed a food frequency questionnaire, with 59 providing a stool sample. Results showed that a 1-point increase in Mediterranean diet score is associated with 37% reduced odds of multiple sclerosis. Higher fibre and iron intake are also associated with a decreased likelihood of multiple sclerosis. Diet, not MS, explains the variation of microbiomes between individuals. Several gut microbe abundances were associated with both the Mediterranean diet score and multiple sclerosis and are potential mediators of the protective factors related to healthy diets.
Read the blog written by patient-partner Sharon Roman.
Noah Silverberg and William Panenka: Diagnostic Accuracy of Mental Health Screening Tools After Mild Traumatic Brain Injury
Journal: JAMA Network
Mental health disorders are common after mild traumatic brain injury (mTBI). Early detection could improve clinical outcomes, but the accuracy of screening tools is not well established. This study determined the diagnostic accuracy of the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Primary Care PTSD Screen in 537 adults with mTBI. The self-report mental health screening tools were administered online 12 weeks after mTBI and compared against structured psychodiagnostic interviews over videoconference. Results showed that these brief self-report tools can reliably screen for mental health disorders after mTBI.
