NeuroSci

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, and numerous functional and structural differences have been identified in the brains of individuals with ADHD compared to controls. This study uses data from the baseline sample of the large, epidemiologically informed Adolescent Brain Cognitive Development Study of children aged 9–10 years old (N = 7979). Cross-validated Poisson elastic net regression models were used to predict a dimensional measure of ADHD symptomatology from within- and between-network resting-state correlations and several known risk factors, such as biological sex, socioeconomic status, and parental history of problematic alcohol and drug use. We found parental history of drug use and biological sex to be the most important predictors of attention problems. The connection between the default mode network and the dorsal attention network was the only brain network identified as important for predicting attention problems. Specifically, we found that reduced magnitudes of the anticorrelation between the default mode and dorsal attention networks relate to increased attention problems in children. Our findings complement and extend recent studies that have connected individual differences in structural and task-based fMRI to ADHD symptomatology and individual differences in resting-state fMRI to ADHD diagnoses. Full article

Trehalose is a naturally occurring disaccharide that has recently gained significant attention for its neuroprotective properties in various models of neurodegeneration. This review provides an overview of available experimental data on the beneficial properties of trehalose for central nervous system pathological conditions. Trehalose’s impact on neuronal cell survival and function was also examined. As a result, we identified that trehalose’s neuroprotection includes autophagy modulation as well as its capability to stabilize proteins and inhibit the formation of misfolded ones. Moreover, trehalose mitigates oxidative stress-induced neuronal damage by stabilizing cellular membranes and modulating mitochondrial function. Furthermore, trehalose attenuates excitotoxicity-induced neuroinflammation by suppressing pro-inflammatory cytokine release and inhibiting inflammasome activation. A possible connection of trehalose with the gut–brain axis was also examined. These findings highlight the potential therapeutic effects of trehalose in neurodegenerative diseases. According to the conclusions drawn from this study, trehalose is a promising neuroprotective agent as a result of its distinct mechanism of action, which makes this compound a candidate for further research and the development of therapeutic strategies to combat neuronal damage and promote neuroprotection in various neurological diseases. Full article

Detecting stress is important for improving human health and potential, because moderate levels of stress may motivate people towards better performance at cognitive tasks, while chronic stress exposure causes impaired performance and health risks. We propose a Brain–Computer Interface (BCI) system to detect stress in the context of high-pressure work environments. The BCI system includes an electroencephalogram (EEG) headband with dry electrodes and an electrocardiogram (ECG) chest belt. We collected EEG and ECG data from 40 participants during two stressful cognitive tasks: the Cognitive Vigilance Task (CVT), and the Multi-Modal Integration Task (MMIT) we designed. We also recorded self-reported stress levels using the Dundee Stress State Questionnaire (DSSQ). The DSSQ results indicated that performing the MMIT led to significant increases in stress, while performing the CVT did not. Subsequently, we trained two different models to classify stress from non-stress states, one using EEG features, and the other using heart rate variability (HRV) features extracted from the ECG. Our EEG-based model achieved an overall accuracy of 81.0% for MMIT and 77.2% for CVT. However, our HRV-based model only achieved 62.1% accuracy for CVT and 56.0% for MMIT. We conclude that EEG is an effective predictor of stress in the context of stressful cognitive tasks. Our proposed BCI system shows promise in evaluating mental stress in high-pressure work environments, particularly when utilizing an EEG-based BCI. Full article

Background: The optimal management of CSF drainage in acute hydrocephalus, in particular when to initiate drain weaning, remains uncertain. This study aimed to evaluate the impact of timing and method of drain weaning on patient outcomes. Methods: This prospective observational study in a large-volume tertiary neuroscience centre included all adult patients who required temporary CSF drainage for acute hydrocephalus of any cause between January 2020 and March 2021. Contemporaneous data collection was conducted, including patient demographics, time to clamp, weaning methods, and clinical outcomes of hospital length of stay (LOS), rate of shunt insertion, drain-related infections, and mechanical complications. Univariate and multivariate statistical analyses were performed to identify the independent associations of timing-related factors. Results: A total of 69 patients were included (mean age = 59.4 years). A total of 59% had CSF diversion for aneurysmal subarachnoid haemorrhage, and 88% had EVD drainage. The length of drainage prior to the first clamp was significantly associated with the overall length of drainage (p < 0.0001), LOS (p = 0.004), and time to shunt (p = 0.02) following multivariate adjustment. For each day delayed in initiating the drain challenge, the overall LOS increased by an additional 1.25 days. There was no association between the weaning method and LOS, the rate of shunting, or CNS infection; however, those in the gradually weaned group had more mechanical complications, such as drain blockage or CSF leakage, than those rapidly weaned (p = 0.03) after adjustment. Discussion: This study recommends challenging the drain early via a rapid wean to reduce LOS, mechanical complications, and possibly infections. The consequences of temporary CSF diversion have significant implications at financial and patient levels, but the quality of evidence regarding weaning remains poor. Further randomised multicentre studies and national databases of practice are required to allow definitive conclusions to be drawn. Full article

Background: This study was designed to adapt the Delis–Kaplan Executive System (D-KEFS) version of the Color-Word Interference (CWIT) and Trail Making Tests (TMTs) for the Greek adult population from 20 to 49 years old, since it is of research as well as clinical importance to detect executive functions’ impairment in young adults with neurological or/and psychiatric conditions. Aims: Norms for the Greek adult population have been calculated to be available for neuropsychologists and health professionals who work in relevant settings. Methods: The study sample consisted of 101 healthy adults (41% male and 60% female) aged 20 to 49 years (M = 32.16, SD = 11.57) with education from 12 to 19 years of schooling (M = 14.51, SD = 0.89). A Pearson correlation test as well as a chi square test were conducted to examine potential associations between gender, age, education, and participants’ performance. Afterwards, we calculated normative data using raw scores and transformed them into percentile scores. Finally, Greek norms were compared to the original raw scores, which were transformed into scaled scores by Delis et al. (2001). Results: The findings showed that age was the only variable which affected CWIT, whereas level of education as well as age were predictive factors for most TMT conditions, except for the visual scanning test (Condition 1). Gender did not affect both tests. Finally, D-KEFS norms for CWIT and TMT are available for the Greek adult population to help clinicians detect executive functions’ deficits and therefore adjust tailored therapeutic strategies. Additionally, it is of great importance to use these tests for research purposes. Conclusion: Given that executive functions are assumed as high-level skills, which are highly related to everyday functionality, adapted tests contribute not only to assess the progression of any existing neurological as well as psychiatric disorders, but they can also be used to evaluate patients’ ability to live independently, as well as their access to work. Full article

Over the last decade there has been increasing interest in the links between the consumption of ultra-processed foods and various neuropsychiatric disorders, aggression, and antisocial behavior. Neurolaw is an interdisciplinary field that seeks to translate the rapid and voluminous advances in brain science into legal decisions and policy. An enhanced understanding of biophysiological mechanisms by which ultra-processed foods influence brain and behavior allows for a historical reexamination of one of forensic neuropsychiatry’s most famous cases—The People v. White and its associated ‘Twinkie Defense’. Here in this Viewpoint article, we pair original court transcripts with emergent research in neurolaw, including nutritional neuroscience, microbiome sciences (legalome), pre-clinical mechanistic research, and clinical intervention trials. Advances in neuroscience, and related fields such as the microbiome, are challenging basic assumptions in the criminal justice system, including notions of universal free will. Recent dismissals of criminal charges related to auto-brewery syndrome demonstrate that courts are open to advances at the intersection of neuromicrobiology and nutritional neuroscience, including those that relate to criminal intent and diminished capacity. As such, it is our contention that experts in the neurosciences will play an increasing role in shaping research that underpins 21st-century courtroom discourse, policy, and decision-making. Full article

Sensory processing challenges are crucial yet often neglected aspects in the care of children with neurodevelopmental disorders and genetic conditions. They represent a key area of interest in neuroscience, as they significantly impact children’s daily functioning and quality of life. This observational study examines these challenges in a group of 614 children, aged 3 to 14 years and 11 months, divided into three groups: 183 with neurodevelopmental disorders (autism spectrum disorder, attention deficit hyperactivity disorder, developmental delays, and learning disorders), 89 with genetic conditions (22q11.2 deletion syndrome, Williams syndrome, and pseudohypoparathyroidism), and 342 controls. Sensory processing was assessed using Sensory Profile 2 (SP2). Results indicated that children with neurodevelopmental disorders and genetic conditions exhibited significant sensory processing difficulties compared to controls. SP2 identified distinct sensory challenges across different sensory systems, varying by diagnosis. Notably, genetic conditions appeared to have a more generalised impact across multiple sensory systems, while neurodevelopmental disorders tended to affect specific systems more narrowly. These findings highlight the importance of early identification and tailored evidence-based interventions to address these specific sensory processing issues. Further research should explore the long-term impact of these interventions in these different populations and their integration into broader therapeutic programmes. Full article

Evidence supporting a link between gait and cognition is accumulating. However, the relation between executive functioning and spatiotemporal gait parameters has received little attention. This is surprising since these gait variables are related to falls. The goal of this preliminary study was to determine whether performance on measures of inhibition, reasoning, and fluency is related to variability in stride length and step width during dual-task treadmill walking in a sample of healthy adults. Nineteen healthy adults averaging 40 years of age were evaluated. Results indicated that processing speed was reduced, t(18) = 6.31, p = 0.0001, step width increased, t(18) = −8.00, p = 0.0001, and stride length decreased, t(18) = 3.06, p = 0.007, while dual tasking, but variability in gait parameters did not significantly change, consistent with a gait/posture-first approach. As hypothesized, better performance on a visual design fluency task which assesses cognitive flexibility was associated with less dual-task stride length variability, r_s(17) = −0.43, p = 0.034, and step width variability, r = −0.56, p = 0.006. The results extend previous findings with older adults walking over ground and additionally suggest that cognitive flexibility may be important for gait maintenance while dual tasking. Full article

Relatively little attention has been given to mixed anxiety and depression in autistic youth, particularly how this differs between males and females. This study investigated sex-based differences in the prevalence and correlates of mixed anxiety and depression in a sample of 51 autistic males (M age = 10.16 yr, SD = 2.81 yr, and range = 6 yr to 17 yr) and 51 autistic females (M age = − 10.07 yr, SD = 2.76 yr, and range = 6 yr to 17 yr), matched for age, IQ, and autism severity. Self-reports on generalised anxiety disorder and major depressive disorder, morning salivary cortisol, ADOS-2 scores, and WASI-II full-scale scores were collected from these autistic youth, and data on the ASD-related symptoms of these youth were collected from their parents. The data were analysed for total anxiety–depression score levels, for the underlying components of this scale, and for the individual items used in the scale. The results indicate no significant sex differences for the prevalence of mixed anxiety and depression total scores or the underlying components of anxiety and depression or for the individual items of the mixed anxiety–depression scale. There were sex differences in the significant correlates of mixed anxiety and depression: morning cortisol and ASD-related difficulties in social interaction for females, and ASD-related behaviour for males. Males’ feelings of being restless or edgy were correlated with their social interaction and repetitive and restricted behaviour. Females’ difficulties in social interaction were correlated with their concerns about their abilities and their sleeping problems. Females’ sleeping problems, their tendency to talk about dying, and feeling worthless, were correlated with their morning cortisol. These findings suggest that, while mixed anxiety and depression is experienced similarly by autistic males and females at the global, component, and individual item levels, specific aspects of the symptomatology of mixed anxiety and depression are differently associated with aspects of their ASD-related symptomatology and their levels of chronic physiological stress for males and females. Full article

Leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are involved in the pathogenesis of Parkinson’s disease. The activity of LRRK2 in microglial cells is associated with neuroinflammation, and LRRK2 inhibitors are crucial for alleviating this neuroinflammatory response. α-synuclein contributes to oxidative stress in the dopaminergic neuron and neuroinflammation through Toll-like receptors in microglia. In this study, we investigated the effect of the marine alga Padina arborescens on neuroinflammation by examining LRRK2 activation and the aggregation of α-synuclein. P. arborescens extract inhibits LRRK2 activity in vitro and decreases lipopolysaccharide (LPS)-induced LRRK2 upregulation in BV2, a mouse microglial cell line. Treatment with P. arborescens extract decreased tumor necrosis factor-α (TNF-α) gene expression by LPS through LRRK2 inhibition in BV2. It also attenuated TNF-α gene expression, inducible nitric oxide synthase, and the release of TNF-α and cellular nitric oxide in rat primary microglia. Furthermore, P. arborescens extract prevented rotenone (RTN)-induced oxidative stress in primary rat astrocytes and inhibited α-synuclein fibrilization in an in vitro assay using recombinant α-synuclein and in the differentiated human dopaminergic neuronal cell line SH-SY5Y (dSH). The extract increased lysosomal activity in dSH cells. In addition, P. arborescens extract slightly prolonged the lifespan of Caenorhabditis elegans, which was reduced by RTN treatment. Full article

The burden of simultaneous acute code stroke activation (ACSA) is not known. We aim to assess the effect of simultaneous ACSA on workflow metrics and home time at 90 days in patients undergoing reperfusion therapies in the emergency department. Simultaneous ACSA was defined as code activation within 60 min of the arrival of any patient receiving intravenous thrombolysis, within 150 min of the arrival of any patient receiving endovascular thrombectomy, within 45 min of the arrival of any patient receiving no reperfusion therapies (based on mean local door-to-needle and door-to-puncture times). Simultaneous ACSA was further graded as 1, 2 and 3. We assessed workflow metrics as door-to-CT (DTC) time, in minutes, and functional outcome as home time at 90 days. A total of 2605 patients were assessed as ACSA at a mean ± SD activations of 130.8 ± 17.1/month and 859 (33%) were simultaneous. Among all ACSA, 545 (20.9%) underwent acute reperfusion therapy with a mean age of 70.6 ± 14.2 years, 45.9% (n = 254) were female with a median (IQR) NIHSS of 13 (8–18). A total of 220 (40.4%) patients underwent simultaneous treatments. The median DTC time, in minutes, was prolonged in grade 3 simultaneous ACSA (18 (13, 28)) compared to non-simultaneous ACSA (15 (11, 21) β = 0.23, p < 0.0001). There was no difference in the median home time at 90 days between the simultaneous (58, 0–84.5 days) and non-simultaneous (54, 0–85 days) patients. Simultaneous ACSA is frequent in patients receiving acute reperfusion therapies. An optimal workflow in high-volume centers may help mitigate the clinical and system burden associated with simultaneity. Full article

Autism rates have been reported to be increasing rapidly in industrialized societies. The pathology most often combines neurological symptoms associated with language and social impairments with gastrointestinal symptoms. This study aimed to measure differences in oral metatranscriptome and mitochondrial health between ASD children and neurotypical USA and Colombia (“Blue Zone”) children. In addition, this study aimed to determine whether using prebiotics and probiotics would change the oral microbiome and mitochondrial health of ASD children. Buccal swabs and saliva samples were obtained from 30 autistic individuals (USA) at three intervals: prior to intervention, post-prebiotic, and post-probiotic. In addition, a subject component who were neurotypical, which included individuals from the USA (30) and Colombia (30), had buccal swabbing and salivary sampling performed for metatranscriptomic and mitochondrial comparison. Significant differences were observed in the temporal data, demonstrating shifts that interventions with probiotics and polyols may have precipitated. Particular bacterial strains were significantly more prevalent in the autism group, including a strain that reduced neurotransmitter levels via enzymatic degradation. This supports the hypothesis that the microbiome may influence the occurrence and degree of autism. Verbal skills increased in six of the 30 ASD subjects following xylitol and three more after probiotic supplementation, according to both parental reports and the subjects’ healthcare providers. Full article

The purpose of the article is to provide a practical guide for manual and semi-automated image segmentation of common neurosurgical cranial lesions, namely meningioma, glioblastoma multiforme (GBM) and subarachnoid haemorrhage (SAH), for neurosurgical trainees and researchers. Materials and Methods: The medical images used were sourced from the Medical Image Computing and Computer Assisted Interventions Society (MICCAI) Multimodal Brain Tumour Segmentation Challenge (BRATS) image database and from the local Picture Archival and Communication System (PACS) record with consent. Image pre-processing was carried out using MRIcron software (v1.0.20190902). ITK-SNAP (v3.8.0) was used in this guideline due to its availability and powerful built-in segmentation tools, although others (Seg3D, Freesurfer and 3D Slicer) are available. Quality control was achieved by employing expert segmenters to review. Results: A pipeline was developed to demonstrate the pre-processing and manual and semi-automated segmentation of patient images for each cranial lesion, accompanied by image guidance and video recordings. Three sample segmentations were generated to illustrate potential challenges. Advice and solutions were provided within both text and video. Conclusions: Semi-automated segmentation methods enhance efficiency, increase reproducibility, and are suitable to be incorporated into future clinical practise. However, manual segmentation remains a highly effective technique in specific circumstances and provides initial training sets for the development of more advanced semi- and fully automated segmentation algorithms. Full article

Nowadays, artificial intelligence is used in many fields to diagnose and treat different diseases. Robots are also useful tools that substitute for human work. Despite robots being used also for touch therapy, can they substitute for the human touch? Human touch has a strong social component, and it is necessary for the correct development of newborns and the treatment of pathological situations. To substitute human touch, it is necessary to integrate robots with artificial intelligence as well as with sensors that mimic human skin. Today, the question remains without answer: Can human touch be substituted with AI in its social and affiliative components? Full article

Prechtl’s General Movement Assessment (GMA) is a qualitative video assessment that is an early predictor of cerebral palsy (CP) in infants. GMA raters undergo two levels of training: basic and advanced. Using a retrospective study design, we evaluated the impact of the GMA training level on three key measures: inter-rater reliability (IRR), predictability for a later CP diagnosis, and generalizability for both medically trained and non-medically trained raters. As part of a larger study on former level-IV neonatal intensive care unit (NICU) infants, participants had a GMA video at 3–4 months of corrected age with parental consent. Four GMA raters with basic training interpreted the videos. Subsequently, two raters underwent advanced training and reinterpreted the videos. We evaluated IRR with Gwet’s AC1 coefficient, CP prediction with logistic regression, and generalizability with Gwet’s Linearization method and McNemar’s test. Following basic GMA training, all four raters had moderate to almost perfect agreement. The CP predictability of the raters’ individual GMA scores ranged from 73% to 81%. Advanced GMA training significantly improved IRR and enhanced CP predictability. GMA rater proficiency was similar regardless of medical training. Advanced GMA training improved readers’ capabilities to correctly identify abnormal movement patterns and aid in early CP diagnosis. Full article

Background: Chronic pain is highly burdening and multifactorial in etiology. The endogenous-pain-healing system restores body tissue to a non-painful state after an injury leading to pain, and its disruption could represent a relevant mechanism, especially for nursing interventions. Aim: To review the literature and summarize the results that support this hypothesis. Methods: We hypothesized that the mechanism behind this system mainly depends on the endogenous pain modulatory system (EPMS), which is responsible for inhibiting pain after tissue healing is complete and facilitating it when tissue damage is still present. Different biomarkers can quantify EPMS functioning. We reviewed the literature and included relevant information regarding this hypothesis. Results: First, conditioned pain modulation (CPM) measures pain inhibition and is a possible predictor for pain chronification. Second, motor cortex excitability measures the cortical control of the EPMS, which can be assessed through transcranial magnetic stimulation (using intracortical inhibition) or electroencephalography. Modifiable factors disrupt its functioning, such as sleep deprivation, medication overuse, and mental health status, but could be protective, such as exercise, certain medications, mind–body techniques, and non-invasive neuromodulation therapies. The acquisition of neurophysiological knowledge of how the chronicity of pain occurs and the EPMS involvement in this process may allow for better management of these patients. Conclusions: We raised the hypothesis that the impairment of the EPMS (altered cortical excitability and descendent pain modulation pathways) seems to be related to the disruption of the pain healing process and its chronicity. Further longitudinal studies evaluating the relationship between these biomarkers and chronic pain development are necessary. Full article

Background: We have previously shown that static and dynamic resting-state functional connectivity differ between migraineurs with and without photophobia, phonophobia, or osmophobia. Furthermore, some patients with photophobia also experience phonophobia or osmophobia. To investigate the functional connectivity specific to migraineurs with photophobia, we examined the differences in static and dynamic resting-state functional connectivity between patients with and without photophobia, with no phonophobia or osmophobia. Methods: Fifteen migraineurs with photophobia but without phonophobia or osmophobia, as well as 15 sex- and age-matched migraineurs without photophobia, phonophobia, or osmophobia, underwent 3-T functional magnetic resonance imaging during the interictal phase. Static and dynamic resting-state functional connectivity were compared using region-of-interest analyses of 91 cortical, 15 subcortical, and 26 cerebellar areas. Results: Static resting-state functional connectivity analysis revealed ten significant connectivity pairs in patients with photophobia, while dynamic resting-state functional connectivity analysis revealed six significant connectivity pairs in patients with photophobia. Migraineurs with photophobia had significantly lower connectivity between the cerebellar hemisphere and the temporal region than those without photophobia in both static and dynamic studies. Conclusions: Our results show that lower resting-state functional connectivity between the cerebellar hemisphere and the temporal region is specific to migraineurs with photophobia. Full article

The maintenance of energetic homeostasis relies on a tight balance between glycolysis and mitochondrial oxidative phosphorylation. The case of the brain is a peculiar one, as although entailing a constant demand for energy, it is believed to rely mostly on glucose, particularly at the level of neurons. Nonetheless, this has been challenged by studies that show that alternatives such as lactate, ketone bodies, and glutamate can be used as fuels to sustain neuronal activity. The importance of fatty acid (FA) metabolism to this extent is still unclear, albeit sustaining a significant energetic output when compared to glucose. While several authors postulate a possible role of FA for the energetic homeostasis of the brain, several others point out the intrinsic features of this pathway that make its contribution difficult to explain in the context of neuronal bioenergetics. Moreover, fueling preference at the synapse level is yet to be uncovered. In this review, we discuss in detail the arguments for and against the brain usage of FA. Furthermore, we postulate that the importance of this fuel may be greater at the synapse, where local mitochondria possess a set of features that enable a more effective usage of this fuel source. Full article

Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0–42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0–4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease. Full article