Check out some of the papers that were recently published by DMCBH members:
Helen Tremlett: Comorbidities and their association with outcomes in the multiple sclerosis population: a rapid review
Journal: Multiple Sclerosis and Related Disorders
Multiple Sclerosis (MS) has a high comorbidity rate, meaning that it co-occurs with many other medical conditions. This study was a comprehensive evaluation of the specific associations between comorbidities and disability, treatment initiation and mortality. A review spanning January 2002 to October 2023 was conducted to examine these associations including 100 primary studies. It was found that people with psychiatric, metabolic and neurological conditions may be at a higher risk for MS progression. Depression, epilepsy, restless leg syndrome, peripheral vascular disease, and psychotic disorders were most consistently associated with worse disability. Also, depression, diabetes, epilepsy, and cancer were consistently linked to an increased mortality risk in the MS population. By addressing these comorbidities, prevention and management can be improved for MS patients.
Sarah Kraeutner: Transformation but not generation of motor images is disrupted following stimulation over the left inferior parietal lobe
Journal: Neuropsychologia
Motor imagery is the internal generation, maintenance and transformation of motor images. The neural underpinnings of each stage are not well understood, so the researchers investigated the role of the left inferior parietal lobe (IPL) during motor imagery tasks using transcranial magnetic stimulation (TMS). During the task, which involved making judgements about hand orientation, participants either received TMS or sham treatment. When TMS was delivered 750ms after trial onset, reaction times were longer, and accuracy decreased. The findings suggested that the left IPL is involved in image transformation.
Journal: Journal of the Neurological Sciences
A novel statistical approach was used to analyze the effectiveness of Radicava IV in a phase 3 clinical trial. Participants in the trial treated with Radicava showed significantly slower physical functional decline compared to placebo-treated participants. Disease trajectories of the participants were further investigated using latent class analysis (LCA) statistical models which looked for nonlinear patterns. 4 unique nonlinear trajectory latent classes were found, with latent classes 2-4 showing statistically significant slowing of ALS progression. This post-hoc analysis supported the notion that Radicava slows functional decline in most predicted nonlinear trajectories and illustrates the utility of LCA.
Erik Pioro: Graph theory network analysis reveals widespread white matter damage in brains of patients with classic ALS
Journal: Amyotrophic lateral sclerosis and frontotemporal degeneration
Classic amyotrophic lateral sclerosis (ALS-Cl) is the most common phenotype and presents with roughly equal upper motor neuron and lower motor neuron deficits. This study uses exploratory whole brain gray matter and white matter network analysis to examine ALS-Cl. No significant gray matter differences were observed between ALS-Cl and neurologic controls, while white matter network analysis revealed a significant (p < 0.05) reduction and increase in degree measure in several extramotor brain regions in the ALS-Cl group. Both global and local graph metrics showed significant abnormal values in ALS-Cl patients. Overall, significant changes in white matter but not gray matter suggested that neurodegeneration may begin as “axonopathy” in this ALS subtype, where lesions affect neuronal axons.
Blair Leavitt: New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates
Journal: Scientific Reports
Compact cell type-specific promoters are short DNA sequences that drive gene expression in particular cell types. The present study designed novel MiniPromoters to target D1 and D2 dopaminoceptive medium spiny neurons in the striatum. The designs were tested for specificity and robustness through intravenous injection in mice, intracerebroventricular injection in mice and intracerebroventricular injection in non-human primates. Twelve MiniPromoters from eight genes were created, with three showing strong, selective expression in the striatum when injected intravenously in mice. The Ple389 (ADORA2A) MiniPromoter showed high co-localization with dopamine D2-receptor cells. These three MiniPromoters also showed enriched expression and DARPP32 co-localization when delivered via ICV injection in mice. In non-human primates, Ple389 (ADORA2A) displayed similar striatal expression patterns. Overall, Ple389 (ADORA2A) consistently targeted medium spiny neurons and demonstrated strong D2-MSN and DARPP32 co-labeling, making it a promising candidate for gene therapy for Parkinson’s and Huntington’s diseases.
Lara Boyd: Oculomotor functional connectivity associated with motor sequence learning
Journal: Cerebral cortex
Learning motor sequences requires visual information, involving directed eye movements known as saccades. The role of brain regions controlling these during motor sequence learning is still unclear, thus this study aimed to determine whether resting-state functional connectivity of oculomotor regions is linked to behavioural changes following motor sequence learning. Twenty adults underwent brain scans before three days of motor task practice and again after a 24-hour retention test to evaluate sequence-specific learning. During testing, both saccades and reaching movements were recorded. Findings revealed that stronger pre-training connectivity in oculomotor regions predicted greater sequence-specific learning for both saccades and reaches. Additionally, greater negative changes in oculomotor connectivity from pre- to post-training were associated with improved learning outcomes. Overall, oculomotor functional connectivity was associated with the magnitude of behavioral change resulting from motor sequence learning. These results provided insights into the function of the oculomotor system during motor sequence learning.
Craig Brown: A pathogenic role for IL-10 signalling in capillary stalling and cognitive impairment in type 1 diabetes
Journal: Nature Metabolism
Vascular pathology is associated with cognitive impairment in diseases such as Type 1 diabetes, but the underlying mechanisms are unknown. The present study shows that capillaries in diabetic mice brains are prone to stalling irrespective of sex, with blockages composed primarily of erythrocytes in branches off ascending venules. Additionally, screening for inflammatory cytokines revealed consistently higher levels of interleukin-10 (IL-10) in diabetic mice. Stimulating IL-10 signalling surprisingly increased capillary obstruction, while inhibiting its receptors with neutralizing antibodies reversed these impairments, as did endothelial specific knockdown in diabetic mice. Chronic treatment with IL-10 neutralizing antibodies improved cerebral blood flow, increased capillary flux and diameter, down-regulated hemostasis and cell adhesion-related gene expression in addition to reversed cognitive deficits. IL-10 may have an unexpected pathogenic role in cerebral microcirculatory defects and cognitive impairment associated with type 1 diabetes.
Brian Kwon: Spinal Cord Injuries Secondary to Mountain Biking Accidents — A Cause for National Alarm
Journal: Neurotrauma Reports
In North America, much focus has been on hockey and other high-impact sports as leading causes of spinal cord injury (SCI). However, over the past two decades, the Level 1 trauma center has observed a higher number of SCI cases linked to off-road mountain biking (MTB). The researchers conducted a retrospective review of patients with SCI from mountain biking who were treated at their Level 1 trauma centre from 2008-2022. Over the 14-year period, 58 patients suffered SCI while mountain biking. 27 suffered complete SCI while 31 had motor incomplete SCI. With an average of 4 SCI cases from MTB annually, these findings highlighted the urgent need for awareness and preventative strategies to mitigate the risk of these severe injuries, particularly in regions where mountain biking is popular.
Alexander Weber, Steven Miller, Tamara Vanderwal: Temporal complexity of the BOLD-signal in preterm versus term infants
Journal: Cerebral Cortex
Preterm birth results in changes in structural and functional cerebral development that are not fully understood. The present study investigated whether basic characteristics of the blood-oxygen-level-dependent (BOLD) signal in fMRI might differ across preterm, term equivalent and term infants. Anatomical, fMRI and diffusion weighted imaging data from 716 infants were obtained from the Developing Human Connectome project. The Hurst exponent, a measure of temporal complexity in time-series data, was calculated for 13 resting-state networks. Linear mixed effects models found that H increased with age, earlier birth age contributed to lower H values and H increased the most in sensory and motor networks. There were also moderate but significant correlations between temporal complexity and structural development, using H and DTI-based estimates of myelin at ion. The findings suggested that temporal complexity of the BOLD signal relates to age and known developmental trajectories in the brain. Understanding how these signal-based differences might relate to maturation could reveal new information about neurophysiological vulnerabilities during this developmental period.
Journal: Trials
Mild traumatic brain injury (mTBI), synonymous with concussion affects more than 30-50 million annually worldwide. Although complete resolution normally occurs within a few weeks, up to a third develop post-concussion symptoms (PPCS) lasting more than 3 months. An open-label, parallel-group, two-arm randomized controlled superiority trial is proposed to evaluate the efficacy of the novel intervention GAIN Lite in addition to enhanced usual care. GAIN Lite is a complex intervention involving an initial remote interview, self-administered e-learning videos and voluntary remote counseling. The primary outcomes are mean changes in PPCS and limitations in daily life from baseline to 24 weeks later.
Helen Tremlett: The multiple sclerosis gut microbiome and disease activity: A systematic review
Journal: Multiple Sclerosis and Related Disorders
This systematic review investigated the relationship between the gut microbiome and MS disease activity, course, and disability progression. The majority of studies examining gut diversity did not find an association with disease. However, several gut taxa showed significant associations with study directions – 3 taxa were associated with better MS outcomes, while another 4 were linked to worse outcomes.
