Check out some of the papers that were recently published by DMCBH members:

 

Lara Boyd: Sensitivity of diffusion tensor imaging to regional mixed cerebrovascular pathology 

Journal: Brain Communications 

Diffusion tensor imaging is a promising biomarker for cerebrovascular disease, but little is known about how sensitive it is to mixed forms of cerebrovascular pathology like stroke and white matter hyperintensities. The present study evaluated the sensitivity of diffusion tensor imaging to regional lesion load for these mixed forms. In older adults, tract microstructure is related to white matter hyperintensity lesion load, while in participants with chronic stroke, tract microstructure is related to stroke lesion load. Among both groups, whole-brain normal appearing white matter microstructure did not relate to whole brain lesion volumes. These findings may serve as a preliminary guide for the use and interpretation of diffusion tensor imaging as a biomarker in cerebrovascular disease.  

 

Noah Silverberg, Mypinder Sekhon, William Panenka: Functional outcomes among the survivors of veno-venous extracorporeal membrane oxygenation during the COVID-19 pandemic: a historical cohort study 

Journal: Canadian Journal of anaesthesia  

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a temporary mechanical assistance device which allows for prolonged cardiopulmonary support, used in patients with life-threatening respiratory failure. In the absence of proper lung function, the VV-ECMO maintains oxygenation in the blood for survival. This study investigated psychological and functional outcomes among survivors who used the VV-ECMO during the COVID-19 pandemic, two years later. Of the twenty-four participants, twelve were able to return to full-time work and twenty-two maintained complete independence in daily life. However, thirteen reported moderate pain, while ten and seven screened positive for depression and posttraumatic stress disorder, respectively. Overall, patients experienced significant functional disability, pain, mental health challenges and lower quality of life.  

 

Piotr Kozlowski, Erin MacMillan, Cornelia Laule: The Goldilocks Zone for 3-T MRS Studies Using Semi-LASER: Determining the Optimal Balance Between Repetition Time and Scan Time 

Journal: NMR in Biomedicine 

Magnetic resonance spectroscopy (MRS) can provide information about the biochemical makeup of the brain. Often, 1H-MR spectroscopy studies use a short repetition time, TR, to reduce scan time. However, this can disrupt metabolite estimates due to T1-weighting (T1w). The present study aimed to find the optimal balance between scan time and TR which minimizes the T1w effects in semi-LASER MRS at 3T. Spectra were acquired in the posterior cingulate cortex of five health volunteers, then the Signal-to-noise ratio and metabolite estimates were compared at TR = 2, 5, and 8s. Ultimately, using a semi-LASER MRS with TR = 5 is recommended, as it yielded the highest signal-to-noise ratio and was robust to T1w effects.  

 

Raymond Lam: Strategies for antidepressant medications in the maintenance phase: A systematic review and network Meta-analysis 

Journal: Journal of Affective disorders 

During the maintenance phase of major depression, susceptible patients are protected against relapse of subsequent depressive episodes. This study aimed to compare the effectiveness of different antidepressant medication strategies during this unique time. Overall, results suggest that continuing and reducing antidepressant dose may be effective, tolerable and acceptable, while increased dose was effective but led to a higher chance of patients interrupting treatment. Switching medications had moderate efficacy and acceptability, but with a higher risk of adverse events. Further research is needed to consolidate the best path forward.  

 

William Panenka, Noah Silverberg: Prediction of Mental Health Complications Following Mild Traumatic Brain Injury 

Journal: Journal of Neurotrauma  

Mild traumatic brain injury (mTBI) can sometimes lead to mental health complications, which prognostic models can help prevent. The present study was a secondary analysis of data from a randomized control trial, with the primary outcome set as the presence/absence of new or worsened major depressive disorder, anxiety disorders and post-traumatic stress disorder. Younger age, identifying as a person of colour, prior mTBIs and maladaptive illness perceptions were significant predictors of new/worsened mental health complications 3-6 months down the line. Certain pre-injury and demographic characteristics are associated with increased risk of mental health complications after mTBI. Assessing early postinjury illness beliefs and psychological symptoms can further improve prognostic accuracy. 

  

Robin Hsiung: Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease 

Journal: Acta Neuropathologica 

Monoclonal antibodies attach to amyloid- β in the brain, marking the plaques for clearance by the immune system. Clinical trials of anti-amyloid-β (Aβ) monoclonal antibodies in Alzheimer’s disease (AD) traditionally assess efficacy through positron emission tomography and/or fluid biomarkers. However, these biomarkers, such as cerebrospinal fluid, measure brain Aβ deposits incompletely, so other methods are needed. From the largest clinical trial of its kind of anti-Aβ monoclonal antibodies in dominantly inherited AD, researchers measured immunohistochemistry area fractions (AFs) for Aβ deposits, tauopathy, microgliosis and astrocytosis in participants who received gantenerumab, solanezumab (two monoclonal antibody treatments) and control. Aβ deposit AFs were significantly lower in the gantenerumab group versus controls in almost all areas examined, while other measures showed no AF differences across groups. These results demonstrate with clear evidence that gantenerumab treatment can reduce Aβ deposits in the brain in a dose-dependent manner.  

 

Mark Cembrowski: CSF1R ligands promote microglial proliferation but are not the sole regulators of developmental microglial proliferation 

Journal: Development 

Microglia are the predominant immune cells of the brain and spinal cord, additionally performing essential functions for development and maintenance of the central nervous system. However, it is unclear what exactly regulates microglial proliferation. Using bioinformatics, this study confirmed the timeline of developmental proliferation and identified potential signaling onto microglia in mice from datasets collected at an age of high proliferation. Researchers found that colony stimulating factor 1 receptor (CSF1R) ligands boosted proliferation in vitro and were increasingly expressed in the brain across development. However, in a model of abnormal developmental proliferation, no such alternation to CSF1R levels was found. Although CSF1R ligands can promote microglial proliferation in culture, their developmental expression patterns suggest that they function alongside other unknown factors to regulate development.  

 

Mark Cembrowski, Cheryl Wellington: Widespread and cell-type-specific transcriptomic reorganization following mild traumatic brain injury 

Journal: Cell Reports 

Traumatic brain injury (TBI) is a multiscale problem evoking several disturbances across the brain, often presenting large individual variability. This study employed the murine closed-head impact model of engineered rotational acceleration to produce mild, diffuse TBI reproducibly across mice, then applied spatial transcriptomics to study the multiscale effects of TBI. Researchers found unexpected susceptibility of astrocytes in the molecular layer of the dentate gyrus, as well as dramatic gene expression changes in the neurons of the thalamus. This work clarified the multiscale complexity of TB into interpretable brain regions, cell types and molecular sequelae.  

 

Catharine Winstanley: Divergent effects of win-paired cues on learning from timeout penalties in female and male rats 

Journal: Physiology & Behaviour  

In both males and females, linking rewards with salient audiovisual cues in simulated gambling increases risky choice in both humans and rats. However, there is a reported sex difference in the prevalence and severity of gambling. In the rat gambling task, the optimal strategy is to favor options paired with smaller per-trial gains but shorter time-out penalties. When audiovisual cues are introduced, male rats make riskier decisions by underestimating the relative cost of timeout punishments. This study investigated this phenomenon in female rats. Cues decreased the learning rate from all timeout penalties in females, not just those paired with a risky option. Although they were less sensitive to the shortest timeouts, they still had a lower learning rate, failing to choose this safer often more often. Learning these differences from computational modeling may help us understand the divergent trajectory of gambling in men and women.  

 

Mahmoud Pouladi: A potential role for NADPH oxidase (NOX1/2) in mutant huntingtin-induced anomalous neurite outgrowth 

Journal: Molecular and Cellular Neurosciences 

Neurites are projections from neurons, either axonal or dendritic, and their growth is regulated by NADPH Oxidase (NOX1/2). This study reveals how NADPH Oxidase enzymes NOX1 and NOX2 regulate neurite growth differently: NOX1 limits it, while NOX2 supports it. In Huntington’s disease models, mutant huntingtin (mHtt) speeds early neurite growth but results in fewer and shorter mature neurites. mHtt shifts NOX2 activity into neurites and increases NOX1 secretion via exosomes, while directing NOX2 for degradation. Blocking vesicle formation raises NOX2 levels and neurite growth. These findings suggest altered NOX trafficking contributes to neurite problems in Huntington’s disease. 

 

Judy Illes: A liability framework for high-risk neural devices 

Journal: Science 

High-risk medical devices are integral to modern health care, but unexpected adverse events from performance failures or malfunctions may leave patients irreversibly harmed. Consumers in the US who incur injuries from products can ordinarily seek relief under the product liability laws of their state. However, a 2008 US Supreme Court decision against patient complainants restricted this legal pathway, raising concerns of patient abandonment. With the emergence of implantable brain-computer interfaces (iBCIs) exposing vulnerable patients to a new suite of unknowns and potential physical and neurocognitive impacts, policymakers must revisit the commitment to justice at the forefront of innovation. Focusing on the example of intracranial neurotechnology, we describe a no-fault compensation scheme that may offer relief to injured patients in the US. Its potential advantages may also hold relevance in countries where civil litigation remains the only pathway to patient recourse. 

  

Helen Tremlett: Phenotyping Healthcare Use 2-3 Decades Before the First Multiple Sclerosis Demyelinating Event 

Journal: Annals of clinical and translational neurology  

This study examined hospital, physician and emergency department visits by diagnoses and specialty up to 29 years before multiple sclerosis (MS) onset. Consistently elevated yearly physician visit rate ratios were found 28 years before diagnosis for mental health, ill-defined symptoms, nervous/musculoskeletal injury and respiratory issues. Digestive-system related inquiries were found 22 years before diagnosis. As the diagnosis date approached, healthcare use peaked. Health-related phenotypical differences occur early on in the MS disease process.  

 

Helen Tremlett: Informative patterns of health care utilization preceding the recognition of adult-onset multiple sclerosis: A population-based study 

Journal: Multiple Sclerosis and Related Disorders 

Early recognition of multiple sclerosis (MS) is essential, but little is known about health care use before diagnosis. This study used trajectory models to describe healthcare use as low, moderate, or high.  Individuals in the moderate and high (versus low) trajectories were more likely to be female and older, and have earlier neurologist and ophthalmologist visits, and nervous system diagnoses before their MS diagnosis. The moderate (versus low) trajectory was associated with higher subsequent disability. Earlier detection of MS by general practitioners and prompt MS drug treatment may be possible for patients accessing health care frequently, potentially mitigating disability progression. 

 

Luke Clark, Catharine Winstanley: Effects of Audiovisual Cues on Game Immersion during Simulated Slot Machine Gambling 

Journal: Journal of Gambling studies  

Modern slot machines can be highly immersive, utilizing design features like audiovisual cues to potentially increase the risk of disordered gambling. According to the incentive salience hypothesis of addiction, reward-paired audiovisual cues strongly motivate behaviour. The present study manipulated audiovisual cues during simulated slot machine gambling in undergraduate students to test the effects of varying intensities on self-reported immersion. Contrary to predictions, immersion was highest at the intermediate level of stimulation, not the maximum one. Gender and affective symptoms also impacted immersion, suggesting personal risk factors in susceptibility to disordered gambling.  

 

Liisa Galea: One size does not fit all: how type of menopause and hormone therapy matters for brain health 

Journal: The British Journal of Psychiatry: the journal of mental science  

Menopause is associated with the biological aging of several body systems. This review highlights the importance of considering the effects of menopause on brain health. Using menopausal hormone therapy (MHT) may be key for supporting healthy brain aging, as it has been associated with reduced risk of neurodegenerative diseases, although benefits are variable. This review highlights often overlooked MHT factors that influence its efficacy, including formulation, administration route and dosing schedule in addition to individual characteristics. Menopause factors, including age, abruptness and symptoms, influence brain aging. MHT influences brain health, with transdermal MHT showing more positive effects on brain aging, but its effectiveness may depend on individual factors such as genotype, reproductive and lifestyle factors.  

 

Luke Clark: Gambling website design as a factor in North American betting expansion 

Journal: Addiction  

This commentary explores how website design influences gambling behaviour in the digital world. The design features of gambling websites blur the lines between ‘product’ and ‘environment’ in the traditional triad of risk factors for gambling harm. As North American markets expand, quantifying the risk of website design becomes key for research and regulation.