Exposure to Radiofrequency Induces Synaptic Dysfunction in Cortical Neurons Causing Learning and Memory Alteration in Early Postnatal Mice.

The widespread use of wireless communication devices has necessitated unavoidable exposure to radiofrequency electromagnetic fields (RF-EMF). In particular, increasing RF-EMF exposure among children is primarily driven by mobile phone use. Therefore, this study investigated the effects of 1850 MHz RF-EMF exposure at a specific absorption rate of 4.0 W/kg on cortical neurons in mice at postnatal day 28. The results indicated a significant reduction in the number of mushroom-shaped dendritic spines in the prefrontal cortex after daily exposure for 4 weeks. Additionally, prolonged RF-EMF exposure over 9 days led to a gradual decrease in postsynaptic density 95 puncta and inhibited neurite outgrowth in developing cortical neurons. Moreover, the expression levels of genes associated with synapse formation, such as synaptic cell adhesion molecules and cyclin-dependent kinase 5, were reduced in the cerebral cortexes of RF-EMF-exposed mice. Behavioral assessments using the Morris water maze revealed altered spatial learning and memory after the 4-week exposure period. These findings underscore the potential of RF-EMF exposure during childhood to disrupt synaptic function in the cerebral cortex, thereby affecting the developmental stages of the nervous system and potentially influencing later cognitive function.

Development and Maturation of the Human Brain, from Infancy to Adolescence.

This chapter describes basic principles and key findings regarding the development and maturation of the human brain, the former referring to the pre-natal and early post-natal periods and the latter concerning childhood and adolescence. In both cases, we focus on brain structure as revealed in vivo with multi-modal magnetic resonance imaging (MRI). We begin with a few numbers about the human brain and its cellular composition and a brief overview of a number of MRI-based metrics used to characterize age-related variations in grey and white matter. We then proceed with synthesizing current knowledge about developmental and maturational changes in the cerebral cortex (its thickness, surface area, and intra-cortical myelination) and the underlying white matter (volume and structural properties). To facilitate biological interpretations of MRI-derived metrics, we introduce the concept of virtual histology. We conclude the chapter with a few notes about future directions in the study of factors shaping the human brain from conception onwards.

Analyses of Neurite and Spine Formation by In Utero Electroporation in Mice.

Dendrite morphology and dendritic spines are key features of the neuronal networks in the brain. Abnormalities in these features have been observed in patients with psychiatric disorders and mouse models of these diseases. In utero electroporation is an easy and efficient gene transfer system for developing mouse embryos in the uterus. By combining with the Cre-loxP system, the morphology of individual neurons can be clearly and sparsely visualized. Here, we describe how this labeling system can be applied to visualize and evaluate the dendrites and dendritic spines of cortical neurons.

Spatial-temporal representation of the astroglial markers in the developing human cortex.

Specific spatiotemporal patterns of the normal glial differentiation during human brain development have not been thoroughly studied. Immunomorphological studies on postmortem material have remained a basic method for human neurodevelopmental studies so far. The main problem for the immunohistochemical research of astrogliogenesis is that now there are no universal astrocyte markers, that characterize the whole mature astrocyte population or precursors at each stage of development. To define the general course of astrogliogenesis in the developing human cortex, 25 fetal autopsy samples at the stages from eight postconceptional weeks to birth were collected for the immunomorphological analysis. Spatiotemporal immunoreactivity patterns with the panel of markers (ALDH1L1, GFAP, S100, SOX9, and Olig-2), related to glial differentiation were described and compared. The early S100 + cell population of ventral origin was described as well. This S100 + cell distribution deviated from the SOX9-immunoreactivity pattern and was similar to the Olig-2 one. In the given material the dorsal gliogenic wave was characterized by ALDH1L1-, GFAP-, and S100-immunoreactivity manifestation in the dorsal proliferative niche at the end of the early fetal period. The time point of dorsal astrogliogenesis was agreed upon not later than the 17 GW stage. ALDH1L1 + , GFAP + , S100 + , and SOX9 + cell expansion patterns from the ventricular and subventricular zones to the intermediate zone, subplate, and cortical plate were described at the end of early fetal, middle, and late fetal periods. The ALDH1L1-, GFAP-, and S100-immunoreactivity patterns were shown to be not completely identical.

Quantitative Electroencephalography and Balance Test Correlations in Patients with Chronic Patellofemoral Pain.

Background: Quantitative Electroencephalography (QEEG) is a tool helping better understand the electrical activity of the brain and a non-invasive method to assess cortical activity. To date, the brain activity of patients with chronic patellofemoral pain (PFP) has not been investigated. Objective: The current study aimed to investigate the effect of PFP on higher levels of the central nervous system by assessing the correlation between QEEG and modified excursion balance test (mSEBT) in patients with PFP. Material and Methods: Twenty-two patients with chronic PFP participated in this observational study. Their cortical electrical activity was recorded in a resting state with their eyes open, via a 32-channel QEEG. C3, C4, and Cz were considered as regions of interest. In addition to QEEG, the balance performance of the participants was evaluated via mSEBT. Results: The obtained findings revealed a negative and moderate to high correlation between theta absolute power and posteromedial direction of mSEBT in C4 (P 0.000, r -0.68), Cz (P 0.001, r -0.66), and C3 (P 0.000, r -0.70). Additionally, a significantly close correlation is between alpha absolute power in C3 (P 0.001, r -0.70), C4 (P 0.000, r -0.71), and Cz (P 0.000, r -0.74) and the posteromedial direction of mSEBT. No significant correlations were between the other two directions of mSEBT, alpha, and theta. Conclusion: According to our results, balance impairment in patients with chronic PFP correlated with their QEEG neurodynamics. Moreover, our findings demonstrated the efficiency of QEEG as a neuromodulation method for patients with PFP.

Developmental trajectory and sex differences in auditory processing in a PTEN-deletion model of autism spectrum disorders.

Autism Spectrum Disorders (ASD) encompass a wide array of debilitating symptoms, including severe sensory deficits and abnormal language development. Sensory deficits early in development may lead to broader symptomatology in adolescents and adults. The mechanistic links between ASD risk genes, sensory processing and language impairment are unclear. There is also a sex bias in ASD diagnosis and symptomatology. The current study aims to identify the developmental trajectory and genotype- and sex-dependent differences in auditory sensitivity and temporal processing in a Pten-deletion (phosphatase and tensin homolog missing on chromosome 10) mouse model of ASD. Auditory temporal processing is crucial for speech recognition and language development and deficits will cause language impairments. However, very little is known about the development of temporal processing in ASD animal models, and if there are sex differences. To address this major gap, we recorded epidural electroencephalography (EEG) signals from the frontal (FC) and auditory (AC) cortex in developing and adult Nse-cre PTEN mice, in which Pten is deleted in specific cortical layers (layers III-V) (PTEN conditional knock-out (cKO). We quantified resting EEG spectral power distribution, auditory event related potentials (ERP) and temporal processing from awake and freely moving male and female mice. Temporal processing is measured using a gap-in-noise-ASSR (auditory steady state response) stimulus paradigm. The experimental manipulation of gap duration and modulation depth allows us to measure cortical entrainment to rapid gaps in sounds. Temporal processing was quantified using inter-trial phase clustering (ITPC) values that account for phase consistency across trials. The results show genotype differences in resting power distribution in PTEN cKO mice throughout development. Male and female cKO mice have significantly increased beta power but decreased high frequency oscillations in the AC and FC. Both male and female PTEN cKO mice show diminished ITPC in their gap-ASSR responses in the AC and FC compared to control mice. Overall, deficits become more prominent in adult (p60) mice, with cKO mice having significantly increased sound evoked power and decreased ITPC compared to controls. While both male and female cKO mice demonstrated severe temporal processing deficits across development, female cKO mice showed increased hypersensitivity compared to males, reflected as increased N1 and P2 amplitudes. These data identify a number of novel sensory processing deficits in a PTEN-ASD mouse model that are present from an early age. Abnormal temporal processing and hypersensitive responses may contribute to abnormal development of language function in ASD.

The impact of metabolic syndrome on the cerebral cortex: a Mendelian randomization study.

Metabolic syndrome exhibits associations with diverse neurological disorders, and its potential influence on the cerebral cortex may be one of the many potential factors contributing to these adverse outcomes. In this study, we aimed to investigate the causal relationship between metabolic syndrome and changes in cerebral cortex structure using Mendelian randomization analysis. Genome-wide association study data for the 5 components of metabolic syndrome were obtained from individuals of European descent in the UK Biobank. Genome-wide association study data for 34 known cortical functional regions were sourced from the ENIGMA Consortium. Data on Alzheimer's disease, major depression, and anxiety disorder were obtained from the IEU Open genome-wide association study database. The causal links between metabolic syndrome elements and cerebral cortex architecture were evaluated using inverse variance weighting, Mendelian randomization-Egger, and weighted median techniques, with inverse variance weighting as the primary method. Inverse variance weighting, Mendelian randomization Egger, weighted median, simple mode, and weighted mode methods were employed to assess the relationships between metabolic syndrome and neurological diseases (Alzheimer's disease, major depression, and anxiety disorder). Outliers, heterogeneity, and pleiotropy were assessed using Cochran's Q test, MR-PRESSO, leave-one-out analysis, and funnel plots. Globally, no causal link was found between metabolic syndrome and overall cortical thickness or surface area. However, regionally, metabolic syndrome may influence the surface area of specific regions, including the caudal anterior cingulate, postcentral, posterior cingulate, rostral anterior cingulate, isthmus cingulate, superior parietal, rostral middle frontal, middle temporal, insula, pars opercularis, cuneus, and inferior temporal. It may also affect the thickness of the medial orbitofrontal, caudal middle frontal, paracentral, superior frontal, superior parietal, and supramarginal regions. These findings were nominally significant and withstood sensitivity analyses, showing no substantial heterogeneity or pleiotropy. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. This study suggests a potential association between metabolic syndrome and changes in cerebral cortex structure, which may underlie certain neurological disorders. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. Early diagnosis of metabolic syndrome holds significance in preventing these neurological disorders.

A brief history of somatostatin interneuron taxonomy or: how many somatostatin subtypes are there, really?

We provide a brief (and unabashedly biased) overview of the pre-transcriptomic history of somatostatin interneuron taxonomy, followed by a chronological summary of the large-scale, NIH-supported effort over the last ten years to generate a comprehensive, single-cell RNA-seq-based taxonomy of cortical neurons. Focusing on somatostatin interneurons, we present the perspective of experimental neuroscientists trying to incorporate the new classification schemes into their own research while struggling to keep up with the ever-increasing number of proposed cell types, which seems to double every two years. We suggest that for experimental analysis, the most useful taxonomic level is the subdivision of somatostatin interneurons into ten or so "supertypes," which closely agrees with their more traditional classification by morphological, electrophysiological and neurochemical features. We argue that finer subdivisions ("t-types" or "clusters"), based on slight variations in gene expression profiles but lacking clear phenotypic differences, are less useful to researchers and may actually defeat the purpose of classifying neurons to begin with. We end by stressing the need for generating novel tools (mouse lines, viral vectors) for genetically targeting distinct supertypes for expression of fluorescent reporters, calcium sensors and excitatory or inhibitory opsins, allowing neuroscientists to chart the input and output synaptic connections of each proposed subtype, reveal the position they occupy in the cortical network and examine experimentally their roles in sensorimotor behaviors and cognitive brain functions.

Maternal exposure to low-dose bisphenol A and its potential neurotoxic impact on male pups: A histological, immunohistochemical, and ultrastructural study.

BACKGROUND: Bisphenol A (BPA) is a widely used chemical with a harmful effect on animal and human. The neonatal and juvenile period is a highly risky neurodevelopmental period. AIM: This study aimed to determine how male albino rat pups' cerebral cortex was altered by low doses of BPA given to mothers and the role of the oxidative stress. METHODS: Thirty pregnant rats were randomly split into three equal groups, negative control, and positive control: received 1 cc of corn oil once a day through gastric tube and BPA treated: a dose of 200 µg/kg/day (dissolved in 1 cc corn oil). The male rat pups of each group were sacrificed at 1 week, 3 weeks and 6 weeks. The cerebra were then separated from the brain for histological and biochemical studies. RESULTS: Rats administered BPA had raised levels of lipid peroxidation marker (MDA), lower levels of enzymatic antioxidants (SOD and CAT) with decreased body, cerebral weights, and decreased levels of non-enzymatic antioxidant defense (GSH). Histo-pathologically, shrunken pyramidal cells with congested blood vessels appeared. GFAP displayed increased number of positive immune-reactive astrocytes with high statistically significant increase in the area % in BPA treated group when compared to the control groups, on contrary to MBP. Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus and broken nuclear membranes. Lysosomes, dilated endoplasmic reticulum cisternae with noticeable increase in unmyelinated nerve fibers were also observed. CONCLUSION: The structure of the developing cerebral cortex is negatively impacted by BPA due to oxidative stress.

Lamivudine modulates the expression of neurological impairment-related genes and LINE-1 retrotransposons in brain tissues of a Down syndrome mouse model.

Elevated activity of retrotransposons is increasingly recognized to be implicated in a wide range of neurodegenerative and neurodevelopmental diseases, including Down syndrome (DS), which is the most common chromosomal condition causing intellectual disability globally. Previous research by our group has revealed that treatment with lamivudine, a reverse transcriptase inhibitor, improved neurobehavioral phenotypes and completely rescued hippocampal-dependent recognition memory in a DS mouse model, Ts65Dn. We hypothesized that retrotransposition rates would increase in the Ts65Dn mouse model, and lamivudine could block retrotransposons. We analyzed the differentially expressed long interspersed element-1 (LINE-1 or L1) mapping on MMU16 and 17, and showed for the first time that retrotransposition could be associated with Ts65Dn's pathology, as misregulation of L1 was found in brain tissues associated with trisomy. In the cerebral cortex, 6 out of 26 upregulated L1s in trisomic treated mice were located in the telomeric region of MMU16 near Ttc3, Kcnj6, and Dscam genes. In the hippocampus, one upregulated L1 element in trisomic treated mice was located near the Fgd4 gene on MMU16. Moreover, two downregulated L1s rescued after treatment with lamivudine were located in the intronic region of Nrxn1 (MMU17) and Snhg14 (MMU7), implicated in a variety of neurodegenerative disorders. To gain further insight into the mechanism of this improvement, we here analyzed the gene expression profile in the hippocampus and cerebral cortex of trisomic mice treated and no-treated with lamivudine compared to their wild-type littermates. We found that treatment with lamivudine rescued the expression of 24% of trisomic genes in the cortex (located on mouse chromosome (MMU) 16 and 17) and 15% in the hippocampus (located in the human chromosome 21 orthologous regions), with important DS candidate genes such as App and Ets2, rescued in both regions.

SYNGAP1 deficiency disrupts synaptic neoteny in xenotransplanted human cortical neurons in vivo.

Human brain ontogeny is characterized by a considerably prolonged neotenic development of cortical neurons and circuits. Neoteny is thought to be essential for the acquisition of advanced cognitive functions, which are typically altered in intellectual disability (ID) and autism spectrum disorders (ASDs). Human neuronal neoteny could be disrupted in some forms of ID and/or ASDs, but this has never been tested. Here, we use xenotransplantation of human cortical neurons into the mouse brain to model SYNGAP1 haploinsufficiency, one of the most prevalent genetic causes of ID/ASDs. We find that SYNGAP1-deficient human neurons display strong acceleration of morphological and functional synaptic formation and maturation alongside disrupted synaptic plasticity. At the circuit level, SYNGAP1-haploinsufficient neurons display precocious acquisition of responsiveness to visual stimulation months ahead of time. Our findings indicate that SYNGAP1 is required cell autonomously for human neuronal neoteny, providing novel links between human-specific developmental mechanisms and ID/ASDs.

Identifying the genetic association between the cerebral cortex and fibromyalgia.

Fibromyalgia (FM) is a central sensitization syndrome that is strongly associated with the cerebral cortex. This study used bidirectional two-sample Mendelian randomization (MR) analysis to investigate the bidirectional causality between FM and the cortical surface area and cortical thickness of 34 brain regions. Inverse variance weighted (IVW) was used as the primary method for this study, and sensitivity analyses further supported the results. The forward MR analysis revealed that genetically determined thinner cortical thickness in the parstriangularis (OR = 0.0567 mm, PIVW = 0.0463), caudal middle frontal (OR = 0.0346 mm, PIVW = 0.0433), and rostral middle frontal (OR = 0.0285 mm, PIVW = 0.0463) was associated with FM. Additionally, a reduced genetically determined cortical surface area in the pericalcarine (OR = 0.9988 mm2, PIVW = 0.0085) was associated with an increased risk of FM. Conversely, reverse MR indicated that FM was associated with cortical thickness in the caudal middle frontal region (ß = -0.0035 mm, PIVW = 0.0265), fusiform region (ß = 0.0024 mm, SE = 0.0012, PIVW = 0.0440), the cortical surface area in the supramarginal (ß = -9.3938 mm2, PIVW = 0.0132), and postcentral regions (ß = -6.3137 mm2, PIVW = 0.0360). Reduced cortical thickness in the caudal middle frontal gyrus is shown to have a significant relationship with FM prevalence in a bidirectional causal analysis.

Dysembryoplastic Neuroepithelial Tumor: A Case Report of A Benign Intracranial Lesion Masquerading as Seizure Disorder.

The uncommon, benign dysembryoplastic neuroepithelial tumor (DNET, WHO grade 1) is frequently linked to epilepsy. It is a glioneuronal neoplasm in the cerebral cortex of children or young adults defined by the presence of a pathognomonic glioneuronal element that may be linked to glial nodules and activating mutations of fibroblast growth factor receptor 1 (FGFR1) (CNS WHO grade 1 according to WHO classification of CNS and pituitary tumors, 2021 ). The cerebral cortex is primarily affected. The most frequent areas are the temporal lobe, particularly the medial lobe, frontal lobe, and other cortex. This study reports the instance of a 31-year-old male who had a history of seizures for the past 20 years and complained of a sudden headache and vomiting at the hospital. MRI revealed a cortical-based lesion in the left posterior temporo-occipital region. A biopsy sample was sent for histopathological examination. DNETs are usually benign, non-recurring lesions and rarely can be a malignant transformation. Although they are frequently stable tumors, surgical excision seldom results in recurrence.

Early neuronal inhibition sculpts adult cortical interhemispheric connectivity.

The maturation of cerebral cortical networks during early life involves a major reorganization of long-range axonal connections. In a recent study, Bragg-Gonzalo, Aguilera, et al. discovered that in mice, the interhemispheric connections sent by S1L4 callosal projection neurons are pruned via the tight control of their ipsilateral synaptic integration, which relies on the early activity of specific interneurons.

Neuroactive steroids fluctuate with regional specificity in the central and peripheral nervous system across the rat estrous cycle.

Neuroactive steroids (i.e., sex steroid hormones and neurosteroids) are important physiological regulators of nervous function and potential neuroprotective agents for neurodegenerative and psychiatric disorders. Sex is an important component of such effects. However, even if fluctuations in sex steroid hormone level during the menstrual cycle are associated with neuropathological events in some women, the neuroactive steroid pattern in the brain across the ovarian cycle has been poorly explored. Therefore, we assessed the levels of pregnenolone, progesterone, and its metabolites (i.e., dihydroprogesterone, allopregnanolone and isoallopregnanolone), dehydroepiandrosterone, testosterone and its metabolites (i.e., dihydrotestosterone, 3α-diol and 17ß-estradiol) across the rat ovarian cycle to determine whether their plasma fluctuations are similar to those occurring in the central (i.e., hippocampus and cerebral cortex) and peripheral (i.e., sciatic nerve) nervous system. Data obtained indicate that the plasma pattern of these molecules generally does not fully reflect the events occurring in the nervous system. In addition, for some neuroactive steroid levels, the pattern is not identical between the two brain regions and between the brain and peripheral nerves. Indeed, with the exception of progesterone, all other neuroactive steroids assessed here showed peculiar regional differences in their pattern of fluctuation in the nervous system during the estrous cycle. These observations may have important diagnostic and therapeutic consequences for neuropathological events influenced by the menstrual cycle.

Prosopis africana exerts neuroprotective activity against quaternary metal mixture-induced memory impairment mediated by oxido-inflammatory response via Nrf2 pathway.

The beneficial effects of Prosopis africana (PA) on human health have been demonstrated; however, its protective effects against heavy metals (HM) are not yet understood. This study evaluated the potential neuroprotective effects of PA in the cerebral cortex and cerebellum. To accomplish this, we divided 35 albino Sprague Dawley rats into five groups. Group I did not receive either heavy metal mixture (HMM) or PA. Group II received a HMM of PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg) orally for a period of two months. Groups III, IV, and V received HMM along with PA at doses of 500, 1000, and 1500 mg/kg, respectively. PA caused decreased levels of HM accumulation in the cerebral cortex and cerebellum and improved performance in the Barnes maze and rotarod tests. PA significantly reduced levels of IL-6 and TNF-α. PA increased concentrations of SOD, CAT, GSH, and Hmox-1 and decreased the activities of AChE and Nrf2. In addition, levels of MDA and NO decreased in groups III, IV, and V, along with an increase in the number of live neurons. In conclusion, PA demonstrates a complex neuroprotective effect with the potential to alleviate various aspects of HM-induced neurotoxicity.

Netrin-1 Is an Important Mediator in Microglia Migration.

Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3ß activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin α6/ß1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin α6 subunit and ß1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin α6/ß1 and Netrin-1. Importantly, activation of Integrin α6/ß1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases.

Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.

Purinergic receptors regulate the processing of neural information in the hippocampus and cerebral cortex, structures related to cognitive functions. These receptors are activated when astrocytic and neuronal populations release adenosine triphosphate (ATP) in an autocrine and paracrine manner, following sustained patterns of neuronal activity. The modulation by these receptors of GABAergic transmission has only recently been studied. Through their ramifications, astrocytes and GABAergic interneurons reach large groups of excitatory pyramidal neurons. Their inhibitory effect establishes different synchronization patterns that determine gamma frequency rhythms, which characterize neural activities related to cognitive processes. During early life, GABAergic-mediated synchronization of excitatory signals directs the experience-driven maturation of cognitive development, and dysfunctions concerning this process have been associated with neurological and neuropsychiatric diseases. Purinergic receptors timely modulate GABAergic control over ongoing neural activity and deeply affect neural processing in the hippocampal and neocortical circuitry. Stimulation of A2 receptors increases GABA release from presynaptic terminals, leading to a considerable reduction in neuronal firing of pyramidal neurons. A1 receptors inhibit GABAergic activity but only act in the early postnatal period when GABA produces excitatory signals. P2X and P2Y receptors expressed in pyramidal neurons reduce the inhibitory tone by blocking GABAA receptors. Finally, P2Y receptor activation elicits depolarization of GABAergic neurons and increases GABA release, thus favoring the emergence of gamma oscillations. The present review provides an overall picture of purinergic influence on GABAergic transmission and its consequences on neural processing, extending the discussion to receptor subtypes and their involvement in the onset of brain disorders, including epilepsy and Alzheimer's disease.

Intrinsic structural covariation links cerebellum subregions to the cerebral cortex.

The human cerebellum is increasingly recognized to be involved in non-motor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole-brain exploration with a unified analytical framework. Here, we characterized dissociable cortical-cerebellar structural covariation patterns based on regional gray matter volume (GMV) across the brain in n=38,527 UK Biobank participants. Our results invigorate previous observations in that important shares of cortical-cerebellar structural covariation are described as i) a dissociation between the higher-level cognitive system and lower-level sensorimotor system, as well as ii) an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel pattern of ipsilateral, rather than contralateral, cerebral-cerebellar associations. Furthermore, phenome-wide association assays revealed key phenotypes, including cognitive phenotypes, lifestyle, physical properties, and blood assays, associated with each decomposed covariation pattern, helping to understand their real-world implications. This systems neuroscience view paves the way for future studies to explore the implications of these structural covariations, potentially illuminating new pathways in our understanding of neurological and cognitive disorders.

Primary Motor Area Activity in Phantom Limb Imagery of Traumatic Unilateral Lower Limb Amputees With Phantom Limb Pain.

Introduction: Estimates of the worldwide increase in amputees raises the awareness to solve long-standing problems. Understanding the functional brain modifications after a lower limb amputation (LLA) is one of the first steps towards proposing new rehabilitation approaches. Functional modifications in the central nervous system due the amputation could be involved in prosthesis use failures and Phantom Limb Pain (PLP), increasing costs and overwhelming the health services. Objective: This study analyses orphan primary motor area (M1-Orphan) hemodynamic and metabolic behaviour, which previously controlled the limb that was amputated, in comparison with the M1-Preserved, responsible for the intact limb (IL) during phantom limb imagery moving during Mirror Therapy (MT), compared to Isolated Intact Limb Movement Task (I-ILMT). Methodology: A case-control study with unilateral traumatic LLA with moderate PLP who measured [oxy-Hb] and [deoxy-Hb] in the M1 area by Functional Near InfraredSpectroscopy (fNIRS) during the real (I-ILMT) and MT task. Results: Sixty-five patients, with 67.69% of men, young (40.32 ± 12.91), 65.63% amputated due motorcycle accidents, 4.71 ± 7.38 years ago, predominantly above the knee (57.14%). The M1 activation in the orphan cortex did not differ from the activation in the intact cortex during MT (P > .05). Conclusion: The perception of the Phantom limb moving or intact limb moving is metabolically equivalent in M1, even in the absence of a limb. In other words, the amputation does not alter the brain metabolism in control of phantom movement.