Volume 5, Issue 1, 2023

Our editor introduces an early career researcher prize for the first author of a paper published in Brain Communications in 2022.

Our Associate Editor, Graciela Muniz Terrera, discusses the importance of reproducibility in neuroscience and our special collection of papers on the topic.

Paul et al. show that motor impairment post-stroke is best characterized by combining compartment-specific anisotropy of descending ipsilesional corticospinal tract fibres capturing Wallerian degeneration and extrapyramidal brainstem structures serving as compensational structural reserve.

Rahman Siddiquee et al. report a deep learning-based classification method that automatically discovered imaging biomarkers specifically associated with migraine (for example, caudate, caudal anterior cingulate and superior frontal), acute post-traumatic headache (for example, lateral occipital, cuneus and lingual) and persistent post-traumatic headache (for example, cerebellum, middle temporal and inferior temporal).

Using a novel method to describe hippocampal intra-network based on structural imaging of MRI imaging, Watanabe et al. report a disturbed network that works bilateral hippocampal tail in major depressive disorders. Further, the intra-hippocampal network might be used as a diagnostic aid for major depressive disorders.

Zevgolatakou et al. report that measures of narrative speech in post-stroke aphasia correspond to (i) general impairment severity and sentence/utterance complexity, which are associated with damage in a large temporo-parietal region and (ii) lexical syntax, which is associated with damage in a relatively small set of fronto-parietal regions.

Thomas et al. use dynamic causal modelling applied to functional MRI to show that both decreased bottom-up connectivity and increased top-down connectivity within the visual network contribute to visual hallucinations in Parkinson’s disease and that this pattern of directional connectivity is associated with the clinical severity of hallucinations.

Jung et al. demonstrated that involving simulated connectomes generated by whole-brain dynamical models can improve the prediction performance of machine learning methods at classification of Parkinsonian patients against healthy subjects for appropriate data processing and invented here behavioural model fitting.

Dickson et al. report that the nuclear pore complex component nucleoporin 98 is mislocalized in primary tauopathies and that the degree of nucleoporin 98 mislocalization is correlated with the burden of pathological tau aggregates. These results indicate nucleoporin 98 mislocalization is a feature of primary tauopathies.

Baldini et al. report in patients with multiple sclerosis an altered functioning of large-scale networks in resting by microstates analysis, supporting brain reorganization. Information processing speed function correlates with auditory microstates, providing a marker of cognitive dysfunctions and progression of disease.

In a longitudinal observational study, Kwan, Arfaie et al. used [¹⁸F]-MK-6420, a high-affinity tau-PET tracer, to provide evidence that the presence of tau in the medial temporal lobe predicts longitudinal memory decline in cognitively normal elderly individuals during the preclinical phase of Alzheimer’s disease.

Mesbah et al. proposed an image-based approach for neuroanatomical mapping of the lumbosacral spinal cord in individuals with spinal cord injury and showed a considerable amount of variability of neuroanatomical substrates of the spinal cord in humans highlighting the importance of personalized spinal cord modelling for neuromodulation applications in this population.

Stam et al. report on the placebo-controlled, double-blind, cross-over trial in 35 patients with spinal muscular atrophy types 2–4 to investigate the safety and efficacy of fatigability and motor function of the acetylcholinesterase inhibitor pyridostigmine. Pyridostigmine was well-tolerated, with suggestive evidence of reduced self-reported fatigability and improved performance on endurance tests.

Lee et al. report that MRI-based white-matter abnormalities are more pronounced in presymptomatic GRN and C9orf72 mutation carriers, compared with family controls who do not carry the mutations. They suggest that white-matter changes may represent early markers of familial frontotemporal dementia associated with a genetic cause.

Scarrott et al. report a recently generated clustered regularly interspaced short palindromic repeat-mediated mouse model of hereditary spastic paraplegia 47 displays neuroanatomical and behavioural deficits consistent with those observed in human patients and concordant with previous studies in other mouse models of adaptor protein Complex 4 deficiency.

Ascending cholinergic and noradrenergic inputs regulate cognitive abilities and their dysfunction is a major hallmark in pathologies with memory loss. Here, de Leo et al. report that these inputs converge to hippocampus to regulate different cognitive domains but they functionally interact and can efficiently compensate for each other when disrupted.

Phan et al. report a longitudinal lipidomics analysis of amyotrophic lateral sclerosis serum and have provided new insights into multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis.

Catron et al. report that increased slow-wave oscillations cause epileptic activity in one Dravet syndrome mouse model with Gabrg2^+/Q390X mutation. Meanwhile, the suppression of slow-wave oscillation-related synaptic plasticity in vivo dramatically inhibits epileptic activity in the het Gabrg2^+/Q390X mice, suggesting that slow-wave oscillations can trigger seizures during non-rapid eye movement sleep.

Kernbach et al. present a novel data-led framework capitalizing on non-negative matrix factorization to deconvolute generalizable topological patterns in brain tumours (meta-topologies). The meta-topologies identified in primary brain tumours map to distinct histopathologic, molecular and clinical findings.

Murray et al. assessed brain volume changes in naturally occurring sheep models of neuronal ceroid lipofuscinosis using MRI. Diseased sheep showed progressive decline in overall brain volume driven by loss of grey matter and more severe atrophy in cortical regions compared to subcortical structures.

Using structural magnetic resonance imaging, Schmitz-Koep et al. observed aberrant allometric scaling of cortical surface and cortical thickness in preterm-born adults. Results suggest altered cortical folding in human prematurity.

Gardner et al. report that blood-based glial fibrillary acidic protein level has good-excellent discrimination across key traumatic brain injury diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients.

In this study, Ksendzovsky et al. examine lactate dehydrogenase A protein upregulation as a long-term cellular adaptation to elevated metabolic demand from chronic neuronal activation in epilepsy. Their data reveal a novel long-term bioenergetic adaptation that occurs in chronically activated neurones during epilepsy.

Willumsen et al., generate patient-derived induced pluripotent stem cells containing the Presenilin 1 E280G mutation. The E280G lines displayed a high relative production of Abeta43, a finding matched in post-mortem tissue with the same mutation. This mutation also disrupts presenilin 1 protein maturity. Together these findings indicate mutation-specific pathogenic mechanisms.

Siponkoski et al. report that group-based multicomponent singing training can enhance communication and spoken language production in chronic aphasia as well as improve psychosocial wellbeing in patients and caregivers. The findings demonstrate that singing provides a versatile, motivating, scalable, and potentially cost-effective approach to aphasia rehabilitation.

Behavioural variant frontotemporal dementia and semantic dementia display co-occurring changes across multiple domains of behaviour, cognitive and affective functions that reflect graded, inter-individual variations along a multidimensional space of cognitive–behavioural functions and are underpinned by degeneration of overlapping regions within distributed neural networks.

To explore the connection between Parkinson’s disease and inflammatory bowel disease, Kang et al. harnessed the largest genome-wide association studies and identified 23 novel loci that have never been associated with both diseases. The discovered genetic overlap implies the presence of both synergistic and antagonistic mechanisms underlying the two diseases.

Heilig et al. used cerebral microdialysis to quantify brain extracellular tau protein as a prognostic biomarker in poor-grade subarachnoid haemorrhage patients. As a marker for axonal injury, higher tau protein levels were associated with an unfavourable long-term functional and neuropsychological outcome after a non-traumatic subarachnoid haemorrhage.

This paper reports significant alterations of cerebrospinal fluid synaptic proteins throughout the biological continuum of Alzheimer`s disease. The high translatability of this synaptic profile from Alzheimer animal models to patients is essential to envisage the outcome of a treatment more accurately in patients according to Medina-Vera et al.

Winchester et al. used a Parkinson’s disease protein study with combined multiple cohorts and different measures (blood, brain and cerebrospinal fluid) to find a multi-protein panel representative of Parkinson’s and understand more about disease mechanisms from protein expression profiles.

Munch et al. report 121 hydrocephalus candidate genes were screened in a whole-exome-sequenced cohort comprising 72 hydrocephalus patients and 4181 background population controls. The results 11 point to the significance of hydrocephalus as a ciliary disease in many cases, which may explain the frequent co-occurrence of other brain disease.

Huckemann et al. report that the mean and right cross-sectional area of the vagus nerve in patients with Parkinson's syndrome was reduced compared to the control group and patients with inflammatory demyelinating neuropathy as a sign of degeneration. Furthermore, it correlated with markers of parasympathetic dysfunction in head-up tilt test.

Using a moderate spinal cord injury paradigm combined with histological analyses and multiplexed behavioural analyses of gait, Griffin et al. show that pharmacological microtubule stabilization and rehabilitation act on complementary aspects of locomotion to enhance functional recovery.

Aksman et al. investigated which socioeconomic, health and lifestyle factors affect the white matter hyperintensity (WMH) load in older Indians, finding that high blood pressure, high body mass index and low levels of physical activity contribute to WMH load in this population.

Dionisi, Chazalon et al., report the identification of defects in axonal extension and synaptic transmission in sensory neurons in Friedreich ataxia. Pathological features are not fully reverted after removal of the GAA expansion mutation. Further investigations are needed to clarify the effects of FXN silencing in proprioceptive neurons.

Smith et al. have analysed the temporal and spatial appearance of aggregated HTT in the brains of the zQ175 Huntington’s disease mouse model. They find that the mutant exon 1 HTT protein initiates aggregation and that this can be detected throughout the CNS by one to 2 months of age.

Burman et al. measured CSF concentrations of 92 cytokines in patients with multiple sclerosis. CCL3, IL-12B, CXCL10 and IL-8 discriminated best between patients and healthy controls. The CSF concentrations of CCL3, IL-12B and CXCL10 decreased after treatment intervention with autologous haematopoietic stem cell transplantation for relapsing-remitting multiple sclerosis.

Park et al. report on eight patients homozygous for the SOD1 mutation p.C112Wfs*11. By characterizing the clinical and biochemical phenotypes associated with a loss of Superoxide dismutase-1 enzymatic function, they highlight the specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and complete loss of the enzyme.

Lahti et al. report diminished dynamics in brain functional connectivity studied with the functional MRI in resting state as a possible sign of long-lasting consequences of very premature birth on brain connectivity in 13-year-old adolescents compared to the term-born peers.

In this study, Piarulli et al. conduct a thorough classification procedure for EEG data acquired from tinnitus patients and healthy controls. The authors develop two classifiers that can accurately distinguish tinnitus patients from healthy controls as well as tinnitus patients with low and high distress levels.

Kant et al. report that patients with postoperative delirium have an increased progression of grey matter loss compared to patients without postoperative delirium. These changes may contribute to impaired long-term cognitive outcomes of postoperative delirium.

To evaluate the spatial accuracy of electrical source imaging (ESI) for known sources, Unnwongse et al. systematically performed ESI of averaged stimulation potentials recorded on simultaneous stereo-EEG and 37-electrode scalp EEG using individual finite element method models to determine the localization error.

den Braber et al. report that plasma levels of amyloid-β_1-42/1-40, p-tau181 and GFAP can be used to predict amyloid-β pathology in older cognitively unimpaired individuals, as long as 10 years before the presence of amyloid-β pathology, indicating the potential of these markers as early diagnostic tools in the normal aging population.

Mortari et al. report a new wasp venom-derived peptide capable of protecting against seizures induced in both acute and chronic models. This peptide provides a unique platform for the development of innovative treatments for epilepsy.

Diaz-Galvan et al. report a pattern of hypo- and hyper-cerebral glucose metabolism in patients with isolated rapid eye movement sleep behaviour disorder. Hypermetabolism in certain regions was associated with nigrostriatal degeneration. This pattern also differed between patients with isolated rapid eye movement sleep behaviour disorder who clinically progressed and those who remain stable over time.

Chen et al. report that alterations in the neural network underlying emotional conflict monitoring might already be present before clinically measurable cognitive and affective decrements in Type 2 diabetes were apparent, thereby bridging the gap between dementia and anxiety/depression in diabetes sufferers.

This 52-week, open-label, multicentre study reported by Okuda et al. assessed safety and efficacy of up to 80 mg/day arbaclofen extended-release in adults with multiple sclerosis–related spasticity. Treatment-emergent adverse events were reported by 86.1% of patients. Most were of mild–moderate severity and commonly included muscle weakness and urinary tract infection.

Priestley et al. report that the ever-expanding brain injury literature and scarcity of testable hypotheses hinder progress toward reliable science. When coupled with more rigorous approaches (pre-registration; strong, falsifiable hypotheses), meta-science and computational methods will improve our ability to track meaningful replication of the fittest hypotheses and transform the neurosciences.

Zetterberg et al. report that neurofilament light is a useful inclusion criterion supporting participant stratification in genetic frontotemporal lobar degeneration trials. Annualized rate of change in blood neurofilament light may distinguish frontotemporal dementia-GRN and -C9orf72 mutation subtypes and provide prognostic value, especially in combination with other pathophysiological and topographic biomarkers.