Parkinson’s Disease (PD) and vitamin D share a unique link as Vitamin D deficiency (VDD) prevails in PD. Thus, an in-depth understanding of Vitamin D biology in PD might be crucial for therapeutic strategies emphasizing Vitamin D. Specifically, explicating the effect of VDD and genetic polymorphisms of vitamin D-associated genes in PD, like VDR (Vitamin D Receptor) or GC (Vitamin D Binding Protein), may aid the process along with polymorphisms of Vitamin D metabolizing genes (e.g., CYP2R1, CYP27A1) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to Vitamin D levels [GC (GC1-rs7041, GC2-rs4588), CYP2R1, CYP24A1, CYP27B1] and Vitamin D function [VDR (FokI - rs2228570, ApaI - rs7976091, BsmI-rs1544410, TaqI-rs731236)] was conducted to explore their relationship with PD severity globally. Furthermore, the DisGeNET database was utilized to explore the gene-disease associations in PD, and STRING alongside Cytoscape was utilized to identify critical genes associated with PD. VDR-FokI polymorphism was reported to be significantly associated with PD in Hungarian, Chinese, and Japanese populations, whereas VDR-ApaI polymorphism was found to affect PD in the Iranian population. However, VDR-TaqI and BsmI polymorphisms had no significant association with PD severity. Conversely, GC1 polymorphisms reportedly affected Vitamin D levels without influencing the disease severity. CYP2R1 (excluding rs1993116) was also reportedly linked to clinical manifestations of PD. Genetic polymorphisms might cause VDD despite enough sunlight exposure and vitamin D-rich food intake, enhancing inflammation, and thereby influencing PD pathophysiology. Knowledge of the polymorphisms associated with vitamin D appears promising for developing new therapeutic strategies against PD.

It is well known that the nervous system adjusts itself to its environment during development. Although a great deal of effort has been directed toward understanding the developmental processes of the individual sensory systems (e.g., vision, hearing, etc.), only one major study has examined the maturation of multisensory processing of cortical neurons. Therefore, the present investigation sought to evaluate multisensory development in a different cortical region and species. Using multiple single-unit recordings in anesthetized ferrets (n=18) of different ages (from postnatal day 80 through 300), we studied the responses of neurons from the rostral posterior parietal area (PPr) to presentations of visual, tactile and combined visual-tactile stimulation. The results showed that multisensory neurons were infrequent at the youngest ages (pre-pubertal) and progressively increased through the later ages. Significant response changes that result from multisensory stimulation (defined as multisensory integration, MSI) were observed in post-pubertal adolescent animals and the magnitude of these integrated responses also increased across this age group. Furthermore, non-significant multisensory response changes were progressively increased in adolescent animals. Collectively, at the population level, MSI was observed to shift from primarily suppressive levels in infants to increasingly higher levels in later stages. These data indicate that, like the unisensory systems from which it is derived, multisensory processing shows developmental changes the specific time course of which may be regionally and species dependent.

Post-stroke depression (PSD), a common complication after stroke, severely affects the recovery and quality of life of patients with stroke. Owing to its complex mechanisms, PSD treatment remains highly challenging. Hippocampal synaptic plasticity is one of the key factors leading to PSD; however, the precise molecular mechanisms remain unclear. Numerous studies have found that neurotrophic factors, protein kinases, and neurotransmitters influence depressive behavior by modulating hippocampal synaptic plasticity. This review further elaborates on the role of hippocampal synaptic plasticity in PSD by summarizing recent research and analyzing possible molecular mechanisms. Evidence for the correlation between hippocampal mechanisms and PSD helps to better understand the pathological process of PSD and improve its treatment.

Environmental factors interact with biological and genetic factors influencing the development and well-being of an organism. The interest to better understand the role of environment on behavior and physiology led to the development of animal models of environmental manipulations. Environmental Enrichment (EE), an environmental condition that allows cognitive and sensory stimulation as well as social interaction, improves cognitive function, reduces anxiety and depressive-like behavior, and promotes neuroplasticity. In addition, it exerts protection against neurodegenerative disorders, cognitive aging and deficits aggravated by stressful experiences. Given the beneficial effects of EE on brain and behavior, preclinical studies focus on its protective role as an alternative, non-invasive manipulation, to help an organism to cope better with stress. A valid, reliable and effective animal model of chronic stress that enhances anxiety and depression-like behavior is the Chronic Unpredictable Mild Stress (CUMS). The variety of stressors and the unpredictability in the time and sequence of exposure to prevent habituation, render CUMS an ethologically relevant model. CUMS has been associated with dysregulation of the Hypothalamic-Pituitary-Adrenal axis, elevation in the basal levels of stress hormones, reduction in brain volume, dendritic atrophy and alterations in markers of synaptic plasticity. Although numerous studies have underlined the compensatory role of EE against the negative effects of various chronic stress regimens (e.g., restraint, social isolation), research concerning the interaction between EE and CUMS is sparse. The purpose of the current systematic review is to present up-to-date research findings regarding the protective role of EE against the negative effects of CUMS.

Background: Cross-education, a phenomenon where unilateral strength (or skill) training enhances strength (or skill) in the contralateral untrained limb, has been well studied in able-bodied individuals. However, whether non-paretic leg movements can modulate corticomotor excitability (CME) and improve motor control of the paretic leg in stroke remains unclear. Objective: To determine the effects of non-paretic leg movements on corticomotor responses and motor control of the paretic leg in persons with severe stroke. Methods: Seventeen post stroke individuals with severe leg motor impairment performed three 20-min motor trainings using their non-paretic ankle: skill (targeted dynamic movements), strength (isometric resistance), and sham (sub-threshold electrical nerve stimulation). Transcranial magnetic stimulation measured CME of the contralateral pathways from the non-lesioned motor cortex (M1) to the non-paretic tibialis anterior (TA) muscle, ipsilateral pathways to the paretic TA, and transcallosal inhibition (TCI) from the non-lesioned to lesioned M1. Paretic ankle motor control was measured using a reaction time paradigm. Results: CME of the non-paretic TA increased after skill (23%) and strength (19%) training (p<0.01). Ipsilateral CME of the paretic TA (23%) and TCI (36%) increased after skill (p<0.05) but not strength training. Reaction time of the paretic ankle improved after skill and strength training (~12%; p<0.05) and was sustained at 60 minutes. No changes were observed during the sham condition. Conclusion: Our findings may inform future studies for using non-paretic leg movements as a priming modality, especially for those who are contraindicated to other priming paradigms (e.g., brain stimulation) or unable to perform paretic leg movements.

Obesity is rising globally and is associated with neurodevelopmental and psychiatric disorders among children, adolescents, and young adults. Whether obesity is the cause or the consequence of these disorders remains unclear. To examine the behavioural effects of obesity systematically, locomotion, anxiety, and social behaviour were assessed in male and female C57Bl/6J mice using the open field (OF), elevated plus maze (EPM) and social preference (SP) task. First, the effects of age, sex and prior exposure to the tasks were examined in control mice, before investigating post-weaning consumption of a high fat, high sugar (HFHS) diet commonly consumed in human populations with high rates of obesity. In the OF and EPM, locomotor activity and anxiety-related behaviours were reduced by age in both sexes, but with different sex-specific profiles. Prior exposure to the tasks reduced locomotion in the OF in a sex-specific manner but had little effect on behaviour in the EPM in either sex. The HFHS diet reduced food and calorie intake and increased body mass and fat deposition in both sexes. In the OF, both male and female HFHS mice showed reduced locomotion, whereas, in the EPM, only HFHS female mice displayed reduced anxiety-related behaviours. Both male and female HFHS mice had a significantly higher SP index than controls. Collectively, the findings demonstrate that the behavioural effects of age, prior exposure and of diet-induced obesity all depend on the sex of the mouse. This emphasises the importance of including both sexes when assessing behavioural phenotypes arising from dietary manipulations.

Sensorimotor atypicalities are common in Autism Spectrum Disorder (ASD) and are often evident prior to classical ASD symptoms. Despite evidence of differences in neural processing during imitation in ASD, research on integrity of basic sensorimotor processing is surprisingly sparce. To address this gap in the literature, here we examined basic sensorimotor processing in autism by analyzing EEG data recorded from a large sample of children and adolescents while they performed an audio-visual speeded reaction time task. Using response-locked signal averaging, we investigated the neural processes associated with execution of a cued movement in a large sample of children and adolescents with ASD (n=84) and without ASD (n=84). Analyses focused on motor related brain responses that are well-characterized in adults: the late berichtsheft potential, the motor potential, and the reafferent potential. Group differences were examined in data parsed by age (6-9 years, 9-12 years, 12-15 years), sensory cue preceding the response (auditory, visual, bi-sensory audio-visual), and reaction time quartile. Overall, the data revealed robust sensorimotor neural responses in ASD. Nevertheless, subtle sensorimotor atypicalities were present in autistic children across all parcellations, and these differences were most prominent in the youngest group of children (age 6-9). Future studies focused on younger children are needed to understand if differences in basic sensorimotor processing are more prominent earlier in development in autism.

The rise of deepfakes and AI-generated images has raised concerns regarding their potential misuse in society. However, this commentary highlights the valuable opportunities these technologies offer for neuroscience research. Deepfakes provide accessible, realistic, and customisable dynamic face stimuli, while generative adversarial networks (GANs) can generate and modify diverse and high-quality static content. These advancements enhance the variability and ecological validity of research methods, and enable the creation of previously unattainable stimuli. When AI-generated images are informed by brain responses, they provide unique insights into the structure and function of visual systems. The authors encourage experimental psychologists and cognitive neuroscientists to stay informed about these emerging tools and embrace their potential to advance visual neuroscience.

I comment on the article JN-2022-11-29991.R1 by quickly summarizing the findings and going further by putting it in the context of current knowledge and elaborate on open questions that this article raises

Alzheimer’s disease (AD) is a neurological ailment that primarily affects the elderly and necessitates an efficient treatment regimen backed up by extensive care. At the moment, treatment for AD is still in its early stages and is often regarded as insufficient by the medical community, with synthetic medications commonly used that have several side-effects. Consequently, research groups are constantly attempting to improve its early detection, particularly through biomarkers, as well as to find effective complementary and alternative therapies for its management. Medicinal plants have long been used as a source of biomolecules as well as complementary medicines. Africa ranks second among biodiversity hotspots in the world due to geographical variances in distribution and vegetation zones. In comparison to nations like India and China, it is believed that much of its biodiversity remains unexplored, and that it may be home to many previously unknown medicinal plants. This calls for more research on African medicinal herbs and finding a key remedy to treat and manage AD. The major scientific biomedical literature databases viz. PubMed, Scifinder, The Lens, Google Scholar, etc. were accessed and the information available till September 2022 was reviewed, with a focus on documenting such herbs along with their active biomolecules that could lead to noble drugs against AD. Also, the review has looked up on the risk factors prevalent among African communities to have a perspective on how race may affect AD risk and expression.

When performing bimanual tasks, hands are typically not controlled individually but rather as a coupled system to achieve high spatiotemporal coordination. On a brain level, intra- and interhemispheric connections networks that control the left and right hand are necessary to exchange information between hemispheres and to couple movements. Behaviorally, coupling is, however, highly task-specific requiring, for example, to maintain a specific relative phase in cyclic tasks (e.g., in- or antiphase) or to perform a role differentiated task where one hand is modulating and the other hands is stabilizing and needs to be kept as still as possible (e.g., holding a notepad and writing on it). In this study, we used electroencephalography to investigate functional brain network characteristics (task-related activation and connectivity) in bimanual force-control tasks with different coordination modes: inphase, antiphase and role-differentiated with the left- or right-hand stabilizing and the other hand manipulating. We aimed to examine i) how network characteristics differ with respect to the coordination mode and ii) how they are related to the performance. Results showed, task-related differences in the overall activation and connectivity, but no task-specific patterns (i.e., different regions being more active or integrated during some tasks than others). We did show, however, that the strength of bimanual coupling is modulated in a task-specific way through networks including C3, FC3 and F3 electrodes. Results suggest that interhemispheric crosstalk for bimanual coordination is modulated in a task-specific way through left frontocentral networks.

Temporal processing of auditory data plays a crucial role in our proposed model of tinnitus development through stochastic resonance (SR). The model assumes a physiological mechanism optimizing auditory information transmission (as quantified by autocorrelation (AC) analysis) into the brain by adding the optimal amount of neuronal noise to otherwise subthreshold signals. We hypothesize that this takes place at the second synapse of the auditory pathway in the dorsal cochlear nucleus (DCN). We propose that after hearing loss, this neuronal noise is increased in the affected frequency-band to improve hearing thresholds at the cost of upward propagation of this added noise, which finally may be perceived as tinnitus. We already showed the improvement of hearing thresholds in a large population of patients. Until now, we did not investigate the differences in hearing thresholds based on the biological constraints of early auditory temporal processing (phase locking) that is only possible up to frequencies of 5 kHz. In this report, we grouped our patient database (N=47986) according to tinnitus pitch (TP) of below (TP<5kHz) or above (TP>5kHz) the 5 kHz limit or having no tinnitus (NT) and compared their mean audiograms. We found that TP<5kHz patients showed significantly better hearing thresholds than all other patient groups independent of age. No improvement was seen for TP>5kHz patients who even showed worse thresholds than NT patients for high frequencies. These results are further evidence for our SR model of tinnitus development and the existence of AC analysis at the level of the DCN.

Ageing is accompanied by numerous changes within the sensory and motor component of the muscle spindle pathway. To further document these age-related changes, this study compared the characteristics of the Hoffmann (H) reflex and M wave, evoked with several pulse durations, between young and old adults. The H-reflex and M-wave recruitment curves were analysed from recordings performed at rest in the flexor carpi radialis of 12 young (21-36 yrs) and 12 old adults (62-80 yrs). For each pulse duration (0.05-ms, 0.2-ms, and 1-ms), the maximal H-reflex amplitude (HMAX), the associated M wave (MHmax), and the H-reflex amplitude for a stimulus intensity evoking an M-wave of 5% MMAX (HM5%) were measured. The strength-duration time constant and response threshold were estimated from the charge/stimulus-duration relation for H reflex and M wave. The main results indicate that varying pulse duration mainly induces similar effect on H-reflex and M-wave recruitment curves between young and old adults. However, regardless of pulse duration, old adults had lesser HMAX (p = 0.029) but greater HM5% (p<0.001) and MHmax (p<0.001). The strength-duration time constant was lesser in old than young adults for the H reflex (p=0.048) but not the M wave (p=0.21). The H-reflex and M-wave response thresholds were greater in old than young adults (p=0.003). These results suggest greater age-related changes in the sensory than motor component of the H-reflex pathway, which may be indicative of a greater loss of sensory than motor axons or alterations of synapses between Ia afferents and motor neurones.

The pro-inflammatory cytokines IL-1α, IL-6 and TNF-α are associated with major depressive disorder, psychological distress, cardiovascular health, and obesity. However, there is limited research that has examined multiple associations between these variables, among individuals with major depressive disorder in comparison to a control cohort, including sex differences. In this study, data was analysed from 60 individuals with major depressive disorder and 60 controls, including plasma IL-1α, IL-6 and TNF-α, adiposity measures (body mass index; waist circumference), cardiovascular health indices (blood pressure; heart rate) and psychological symptoms (depressive severity; anxiety; hostility; stress). The cytokines were compared by group and sex, and correlated with measures of adiposity, cardiovascular health indices and psychological health. Plasma IL-1α and IL-6 were higher in major depressive disorder group versus control, but with a sex interaction for IL-6, with this group difference only among females. TNF-α did not differ between groups. IL-1α and IL-6 correlated with depressive severity, anxiety, hostility, and stress, while TNF-α correlated only with anxiety and hostility. Psychopathology was associated with IL-1α in males only, and with IL-6 and TNF-α in females only. None of the cytokines correlated with body mass index, waist circumference, blood pressure or heart rate. The result of group by sex interaction for IL-6, and sex specific associations between pro-inflammatory cytokines and psychometrics could be aetiologically important in depression interventions and treatments for females versus males, warranting further investigation.

The innate immune response plays an important role in the pathological process of ischemic stroke. Increasing evidence suggests that the inflammatory response triggered by the innate immune system hinders neurological and behavioral recovery after stroke. The perception of abnormal DNA and its downstream effects are an important part of the innate immune system. The abnormal DNA is the major inducing factor for innate immune response and is sensed by a series of DNA sensors. In this review, we discussed the multiple roles of DNA sensing in the pathological process of ischemic stroke, with a special focus on DNA sensors Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2) and cyclic GMP-AMP synthase (cGAS).

Visual attention is mainly goal-directed and allocated based on the upcoming action to be performed. However, it is unclear how far this feature of gaze behavior generalizes in more naturalistic settings. The present study investigates active inference processes revealed by eye movements during interaction with familiar and novel tools with two levels of realism of the action affordance. In a between-subject design, a cohort of participants interacted with a VR controller in a low realism environment; another performed the task with an interaction setup that allowed differentiated hand and finger movements in a high-realism environment. We investigated the differences in odds of fixations and their eccentricity towards the tool parts before action initiation. The results show that participants fixate more on the tool’s effector part before action initiation when asked to use the tool and during interaction with unfamiliar tools. The spatial viewing bias on the tool reveals early fixations are influenced by the task and the familiarity of the tools. Our findings suggest that fixations are made in a task-oriented way to plan the intended action well before action initiation. With more realistic action affordances, more fixations were allocated toward the tool handle. We hypothesize that these fixations are made towards the proximal goal of planning the grasp even though the perceived action on the tools is identical for both experimental setups. Taken together, proximal and distal goal-oriented planning is contextualized to the realism of action/interaction afforded by an environment.

The search for robust, reliable biomarkers of schizophrenia remains a high priority in psychiatry. Biomarkers are valuable because they can reveal the underlying mechanisms of symptoms and monitor treatment progress, and may predict future risk of developing schizophrenia. Despite the existence of various promising biomarkers that relate to symptoms across the schizophrenia-spectrum, and despite published recommendations encouraging multivariate metrics, they are rarely investigated simultaneously within the same individuals. In those with schizophrenia, the magnitude of purported biomarkers is complicated by comorbid diagnoses, medications, and other treatments. Here, we argue three points. First, we reiterate the importance of assessing multiple biomarkers simultaneously. Second, we argue that investigating biomarkers in those with schizophrenia-related traits (schizotypy) in the general population can accelerate progress in understanding the mechanisms of schizophrenia. We focus on biomarkers of sensory and working memory in schizophrenia and their smaller effects in individuals with nonclinical schizotypy. Third, we note irregularities across research domains leading to the current situation in which there is a preponderance of data on auditory sensory memory and visual working memory, but markedly less in visual (iconic) memory and auditory working memory, particularly when focusing on schizotypy where data are either scarce or inconsistent. Together, this review highlights opportunities for researchers without access to clinical populations to address gaps in knowledge. We conclude by highlighting the theory that early sensory memory deficits contribute negatively to working memory and vice versa. This presents a mechanistic perspective where biomarkers may interact with one another and impact schizophrenia-related symptoms.

Marco Capogna PhD, Professor of Neuroscience at Aarhus University Faculty of Health, Department of Biomedicine, Aarhus, Denmark, died from cancer aged 64 on 2nd December 2022.