Check out some of the papers that were recently published by DMCBH members:
Christian Schütz, Fidel Vila-Rodriguez: Neuromodulation of the right inferior frontal gyrus in bipolar disorder to target response inhibition: a proof-of-concept study
Journal: CNS Spectrums
Bipolar disorder affects over 1% of the population and is characterized by deficits in response inhibition, the ability to suppress a behaviour which is no longer required or appropriate. Previous research has shown that inhibitory control may be localized at the right inferior frontal gyrus, which could be a potential target for neuromodulation using repetitive transcranial magnetic stimulation (rTMS). After treatment with rTMS, participants with bipolar disorer showed a significant improvement in action withholding, a subcomponent of response inhibition. This is the first study to show that intermittent theta-burst stimulation can neuromodulate a component of response inhibition in bipolar disorder.
Journal: International journal of molecular sciences
Adolescent binge drinking has lasting behavioural consequences by disrupting the endocannabinoid system (ECS), which regulates processes including sleep and mood, and through depletion of brain omega-3. The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining membrane structure, supporting interactions with the ECS and restoring synaptic plasticity and cognition from prenatal ethanol exposure. This study additionally demonstrates that omega-3 supplementation can restore ECS disruptions and performance in a cognitive task (the Barnes maze test). This recovery is likely mediated by modulation of the hippocampal ECS, enhancing endocannabinoid-dependent excitatory synaptic plasticity.
Teresa Liu-Ambrose: Beyond FITT: addressing density in understanding the dose-response relationships of physical activity with health-an example based on brain health
Journal: European journal of applied physiology
When it comes to research on physical activity and health, it’s important to learn more about “dose-response” relationships. Frequency, intensity, time and type (FITT) are the traditional measures of the dosage of physical activity, but it comes with limitations. Researchers propose including density, which is the timing of successive work bouts within a single physical activity as well as the timing between physical activities. Using density may have potential to improve our understanding of these dose-response relationships.
Journal: Pharmacoepidemiology and drug safety
Observational studies of time-dependent treatments often face immortal time bias and residual confounding, which complicate treatment effect estimation. Researchers implemented a high-dimensional propensity score (hdPS) analysis within a nested case-control (NCC) framework to address both biases simultaneously. This was found to reduce both confounds simultaneously, improving the validity of effect estimates in real-world studies.
Journal: GeroScience
Advances in biomarkers and the pathophysiology of vascular contributions to cognitive impairment and dementia are expected to bring greater insights, more targeted treatments and potentially disease-modifying therapies. The 2025 Annual Workshop of the Albert Research Institute for White Matter and Cognition, sponsored by the Leo and Anne Albert Charitable Trust since 2015, focused on novel biomarkers for VCID. The 2025 workshop brought together a diverse range of subspecialty experts to consider the challenges of VCID classification, pathophysiology, and treatment. This article summarizes topics such as the complexity of dementia, novel approaches, new insights, promising tools, potential biomarkers and more.
William Gibson, Douglas Allan: Functional Analysis of Human EED Variants Using Drosophila
Journal: Genetics
The Polycomb Repressive Complex 2 is an epigenetic reader/writer which methylates histone H3K27. Rare germline partial loss of function mutations in members of the complex cause overgrowth and intellectual disability syndromes, while somatic varients are implicated in cancer. However, up to 1 per cent of the general population will have a mutation in one of these genes with uncertain significance. This study reported functional assays in Drosophila to interrogate embryonic ectoderm development (EED) missense variants. Known likely benign variants had wildtype function and known pathogenic variants were loss of function. The researchers further demonstrated the utility of this calibrated assay as a scalable approach to assist clinical interpretation of human EED variants of uncertain significance.
Ujendra Kumar: G-Protein-Coupled Receptor–Microtubule Interactions Regulate Neurite Development and Protect Against β-Amyloid Neurotoxicity
Journal: Molecular Neurobiology
G-protein-coupled receptors (GPCRs) regulate cellular functions such as neurite formation and maturation, processes often disrupted in neurodegenerative diseases. Like GPCRs, microtubule-associated proteins (MAPs) and the synaptic vesicle protein synaptophysin are essential for neurite formation, maturation and organiztion, underpinning brain development. However, the functional crosstalk between GPCRs and MAPs, particularly in conditions such as Alzheimer’s disease, remains poorly understood. Overall, results revealed a novel role of GPCRs in orchestrating interactions with MAPs to regulate neuronal maturation, neurite formation, and synaptic integrity. This study provided a new mechanistic rationale for therapeutic strategies aimed at preserving cognitive function in neurological disorders such as AD.
Blair Leavitt: Cell-specific mechanisms drive connectivity across the time course of Huntington’s disease
Journal: Nature communications
Hyperconnectivity in functional brain networks occurs decades before disease onset in Huntington’s disease, but the biological mechanisms remain unknown. Using Morphometric INverse Divergence (MIND) in three Huntington’s disease cohorts from 2 decades before symptom onset to functional design, authors investigated brain connectivity. They identified stage-specific profiles, with hyperconnectivity 22 years from predicted motor onset, progressing to hypoconnectivity through the late premanifest and manifest stages, showing that hypoconnectivity is correlated with neurofilament light concentrations. Associations with disease epicentres was limited to late premanifest, while cell-autonomous associations were found across the disease lifespan. Researchers additionally identified specific relationships to cholinergic and serotoninergic systems localized to granular and infragranular cortical layers, consistent with serotoninergic layer 5a neuronal vulnerability previously identified in post-mortem brains.
Teresa Liu-Ambrose, Liisa Galea: Investigating biological sex as a moderator of the association of nature exposure with brain health: a cross-sectional UK biobank analysis
Journal: Scientific Reports
This cross-sectional analysis investigated whether biological sex moderates the association of residential nature exposure with brain volume or cognitive function. Residential nature exposure was estimated as the percentage of land classified as a natural environment within 1000m and 300m buffers around each participant’s home. Structural MRI assessed total grey matter volume, total white matter volume and average hippocampal volume, and cognitive tests were done. Researchers found that higher residential nature exposure was associated with greater grey and white matter volume and better accuracy in the symbol digit substitution test. In males, higher nature exposure was associated with a greater increase in grey matter volume alongside faster testing speed. The potential benefits of residential nature exposure may vary by sex.
Brian Christie: Lateral Thinking: Exploring the Lateral Entorhinal Cortex Projections to the Hippocampus in the Rodent Brain
Journal: The Journal of comparative neurology
The lateral entorhinal cortex (LEC) projects to the hippocampus, and these projections play a critical role in cognition and have been associated with cognitive impairments related to aging and neurodegeneration. This review aimed to provide a detailed anatomical description of the LEC to hippocampus pathway, based on tract tracing techniques. Layer II of the LEC projects to the dentate gyrus, while layer III projects to the subiculum and cornu Ammonis. Understanding this pathway is essential for investigating its functions and changes from disease and aging processes.
Sophia Frangou: AI in Scientific Writing and Publishing: A Call for Critical Engagement
Journal: European Psychiatry
Artificial intelligence is transforming nearly every domain of science, including scholarly publishing. From automated language editing to machine-assisted peer review and large-scale content analysis, AI tools are becoming increasingly popular. This viewpoint article summarized the various uses and promises of AI tools in publishing and reviews ethical risks. Finally, it proposed a framework for editors and authors for the responsible and accountable adoption of AI in scientific writing.
Cheryl Wellington: Ambroxol as a Treatment for Parkinson Disease Dementia: A Randomized Clinical Trial
Journal: JAMA Neurology
Carrying a variation in the gene for β-glucocerebrosidase is a major risk factor for Parkinson disease dementia (PDD). Ambroxol is a drug which increases the level of β-glucocerebrosidase, which has been observed to lower α-synuclein in cell and animals. This prevents the accumulation of Lewy bodies, which is a hallmark of Parkinson’s disease. This clinical trial examined the safety and tolerability of ambroxol in PDD and tested its efficacy in improving or slowing the progression of cognitive deficits. Results revealed that ambroxol was safe, well-tolerated, and demonstrated target engagement. However, the effect of ambroxol on cognition was not confirmed.
Journal: Molecular brain
The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) tightly regulate the passage of molecules, including opioid medications, in and out of the central nervous system. This study examined the effects of opioid withdrawal on BBB and BSCB integrity by measuring extravascular levels of peripherally injected dyes in the brain and spinal cord. In morphine-dependent male and female mice, repeated naloxone challenge induced robust withdrawal behaviors as well as region specific dye extravasation. The findings suggested that repeated opioid withdrawal alters permeability of the BBB and BSCB in discrete regions of the brain and spinal cord.
John Kramer: Unpredictable movement-evoked pain alters cortical motor preparatory activity
Journal: Journal of neurophysiology
Although there is evidence that central motor system function is altered both during and after pain removal, the effect of pain on motor preparation is poorly understood. This study used electroencephalography (EEG) to examine whether the predictibility of movement-evoked pain modulates cortical preparatory activity, and whether changes in cortical activity persist after the removal of pain. Findings suggested that unpredictable pain expectancy modulates motor preparation through top-down attentional mechanisms that serve to suppress distractor sensorimotor processing and enhance task-relevant neural activity to support optimal motor programming.
Jon Stoessl: Disease-Modifying Trials in Treated Parkinson’s Disease: “Stable Treated” Does Not Equate with Biological Stability
Journal: Movement disorders
Traditionally, clinical trials of Parkinson’s disease have enrolled untreated patients at the earliest clinical stages of their disease. But, due to the challenges inherent with this approach, there has been a move towards enrolling patients who are already taking “stable” anti-parkinson medication. However, the symptomatic treatment regimen has not been defined uniformly with respect to drugs and dosages used or duration of therapy. More importantly, this approach doesn’t consider major pharmacodynamic changes induced by dopaminergic therapies. This review highlighted what is known about the changes induced by dopaminergic therapy and the challenges these will present in the interpretation of outcomes of studies using this trial design.
Helen Tremlett: High-risk populations should be screened for MS: Yes
Journal: Multiple Sclerosis Journal
Screening tools like mammography are useful for early detection of disease in the absence of symptoms and can improve health outcomes through early treatment. However, multiple sclerosis (MS) lacks a screening procedure, despite promising early treatments and an identified prodromal phase. Individuals with radiologically isolated syndrome (white matter lesions) and those with a monozygotic twin with MS would benefit most from targeted screening. By moving towards targeted screening in well-defined high-risk populations, we can potentially improve long-term outcomes for future MS patients.
Noah Silverberg, William Panenka: New Diagnostic Criteria for Mild Traumatic Brain Injury: Medical-Legal Considerations
Journal: Archives of physical medicine and rehabilitation
The new American Congress of Rehabilitation Medicine (ACRM) diagnostic criteria for mild traumatic brain injury (mTBI) were published in 2023. This article discussed some medical-legal issues and implications relating to the use of the new ACRM diagnostic criteria. First, the new criteria differ from previously published definitions, and the criteria can be applied weeks, months or years following an injury through clinical interviews and review of records. Next, when there is diagnostic uncertainty, and the “suspected” mTBI classification is used, this is not meant to convey a level of diagnostic certainty. In addition, the diagnostic process could be influenced by subjectivity or biases on the part of the person or the examiner. Lastly, the review highlighted that the criteria are diagnostic, not prognostic – while they determine whether a person sustained a mTBI, they do not determine if health problems later on are related to the mTBI.
Catharine Winstanley: Most rats prefer gambling opportunities featuring win-paired cues that drive risky choice: Synergistic interactions between choice of and choice during the cued rat gambling task
Journal: Brain and neuroscience advances
Win-paired cues drive maladaptive decision-making in laboratory-based gambling tasks. However, humans prefer these cued games that facilitate gambling addiction – but what about rats? If rats share the same preference, researchers can use rodent models to investigate problem gambling. Collectively, results supported the use of high-risk preference at baseline as a proxy for vulnerability to problem gambling. Furthermore, diverse computational mechanisms could be responsible for the negative impact of win-paired cues on gambling-like behaviour in at-risk versus resilient individuals.
Cheryl Wellington: Effects of interval exercise and diurnal variation on blood biomarkers for sport-related concussion: A crossover cohort study
Journal: Journal of science and medicine in sport
This study aimed to investigate exercise and diurnal effects on neurofilament light, glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and total tau. After moderate and high intensity exercise, participants showed transient decreases in neurofilament light and glial fibrillary acidic protein. Total tau declined throughout the day across all conditions on average. Preliminary findings highlighted potential considerations for future sport-related concussion biomarker investigations collecting acute post-injury data in a sports context, as exercise may have immediate transient effects, and diurnal variations may affect plasma concentrations. Future research is needed to examine blood biomarkers affected by exercise and sport-related concussion in populations with consideration for concussion history, age, and sex.
Robin Hsiung: Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial
Journal: Alzheimer’s and Dementia: the journal of the Alzheimer’s Association
Monoclonal anti-amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. Researchers investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer’s disease (DIAD). Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB-PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design. There was no regional effect on FDG-PET metabolism or MRI volumetrics after 4 years.
Brian Christie: Synaptic signatures of perinatal cannabinoids: A systematic review of rodent hippocampal synaptic plasticity, learning, and memory
Journal: Drugs and alcohol dependence reports
The expanding legalization of cannabis raises significant public health concerns about its use during pregnancy, particularly due to the limited understanding of its impact on neurodevelopment. Research suggests that cannabis exposure may impair learning and memory, but variations in study design hinder the ability to draw generalizable conclusions. The objective of this systematic review was to consolidate findings from existing preclinical research that investigates the effects of perinatal cannabinoid exposure on learning and memory and the putative mechanism of learning and memory, hippocampal synaptic plasticity, in rodents. Perinatal cannabinoid-induced impairments were reported in the two synaptic plasticity studies, and in 24 out of 30 studies that examined learning and memory, with spatial memory tasks showing the most consistent deficits. While the existing evidence converges on the notion that perinatal cannabinoid exposure negatively impacts hippocampal physiology and associated memory functions, further research is needed to disentangle the influnce of various methodological factors, including offspring sex and age, cannabinoid type, time of gestational exposure, and method of administration.
Michael Gordon, Tao Huan: Insulin/insulin-like growth factor signaling pathway promotes higher fat storage in Drosophila females
Journal: Cell Reports
In Drosophila, adult females store more fat than males. While the mechanisms that restrict body fat in males are becoming clearer, less is known about how females achieve higher fat storage. Here, researchers performed a detailed investigation of the mechanisms that promote higher fat storage in females. They found that a greater intake of dietary sugar supports higher fat storage due to female-biased remodeling of the fat body lipidome. Dietary sugar stimulates a female-specific increase in Drosophila insulin-like peptide 3 (Dilp3), which acts together with greater peripheral insulin sensitivity to augment insulin/insulin-like growth factor signaling pathway (IIS) activity in adult females. Indeed, Dilp3 overexpression prevented the female-biased decrease in body fat after removal of dietary sugar. Given that adult-specific IIS inhibition caused a female-biased decrease in body fat, our data reveal IIS as a key determinant of female fat storage.
Mypinder Sekhon: Clinical heterogeneity and phenotyping of post cardiac arrest brain injury: one size may not fit all
Journal: Intensive Care Medicine
Post-cardiac arrest brain injury (PCABI) occurs after injurious events that take place during and after resuscitation from cardiac arrest. Regrettably, identification of efficacious management strategies to mitigate PCABI has been disappointing with numerous well-conducted randomized control trials yielding neutral results. In this review, researchers described the clinical heterogeneity and phenotypes of PCABI as related to the underlying pathophysiology, selective anatomical vulnerability and electrographic patterns. The overarching aim of the review was to propose a shift to expeditious phenotyping of PCABI severity that focuses on assessing in vivo severity and patterns of injury that could be used for future targeted therapies. Authors also discussed potential causes of heterogeneous clinical responses to interventions and highlight future research areas for PCABI that focus on phenotyping and incorporating these considerations into clinical trials.
Journal: Multiple Sclerosis and related disorders
Higher healthcare use before recognition of adult-onset multiple sclerosis (MS) raises the possibility of earlier disease detection. Before the first demyelinating event, 9 pathways emerged: pathways for low, moderate and high healthcare use; pathways representing steadily increasing and decreasing healthcare use over the 5 years; specialist-specific pathways for visits to neurologists/neurosurgeons, ophthalmologists and psychiatrists, and a musculoskeletal diagnoses-related pathway. Adults with a pattern of recurrent visits to a neurologist/neurosurgeon or ophthalmologist could be targeted for earlier MS detection.
