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Frontiers in Neurology 2024Chorea-acanthocytosis (ChAc) is a rare autosomal recessive inherited syndrome with heterogeneous symptoms, which makes it a challenge for early diagnosis. The mutation...
Case report: Misdiagnosed orolingual dyskinesia as a consequence of seizures in a chorea-acanthocytosis patient with a novel variation from a family with consanguineous marriage.
Chorea-acanthocytosis (ChAc) is a rare autosomal recessive inherited syndrome with heterogeneous symptoms, which makes it a challenge for early diagnosis. The mutation of is considered intimately related to the pathogenesis of ChAc. To date, diverse mutation patterns of , consisting of missense, nonsense, and frameshift mutations, have been reported. In this study, we first report a clinical case that was misdiagnosed as epilepsy due to recurrent seizures accompanied by tongue bite for 9 months, which was not rectified until seizures were controlled and involuntary orolingual movements with awareness became prominent and were confirmed to be orolingual dyskinesia. The patient was eventually diagnosed as ChAc based on whole-exome sequencing revealing novel homozygous c.2061dup (frameshift mutation) and c.6796A > T dual mutations in . The patient from a family with consanguineous marriage manifested epileptic seizures at onset, including both generalized tonic-clonic seizures and absence but normal long-term electroencephalography, and gradually developed orofacial dyskinesia, including involuntary tongue protrusion, tongue biting and ulcers, involuntary open jaws, occasionally frequent eye blinks, and head swings. The first test of the peripheral blood smear was negative, and repeated checks confirmed an elevated percentage of acanthocytes by 15-21.3%. Structural brain MRI indicated a mildly swollen left hippocampus and parahippocampal gyrus and a progressively decreased volume of the bilateral hippocampus 1 year later, along with atrophy of the head of the caudate nucleus but no progression in 1 year. We deeply analyzed the reasons for long-term misdiagnosis in an effort to achieve a more comprehensive understanding of ChAc, thus facilitating early diagnosis and treatment in future clinical practice.
PubMed: 38933328
DOI: 10.3389/fneur.2024.1352467 -
Brain Sciences May 2024Tinnitus is a common phantom auditory percept believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in the absence...
Tinnitus is a common phantom auditory percept believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in the absence of any clinical hearing loss. In this case, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise normal hearing, but the results are not consistent across studies. Here, we aimed to investigate these differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis. Furthermore, there was an interaction between stimulation side and tinnitus in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.
PubMed: 38928544
DOI: 10.3390/brainsci14060544 -
Journal of Osteopathic Medicine Jun 2024Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties...
CONTEXT
Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods.
OBJECTIVES
Our study's primary objective was to examine the relationship between the physical development of the amygdala, hippocampus, and parahippocampus following prenatal alcohol, tobacco, and prescription opioid exposure.
METHODS
We conducted a cross-sectional analysis of the Adolescent Brain and Cognitive Development (ABCD) Study, a longitudinal neuroimaging study that measures brain morphometry from childhood throughout adolescence. Data were collected from approximately 12,000 children (ages 9 and 10) and parents across 22 sites within the United States. Prenatal opioid, tobacco, and alcohol use was determined through parent self-report of use during pregnancy. We extracted variables assessing the volumetric size (mm) of the amygdala, hippocampus, and parahippocampal gyrus as well as brain volume, poverty level, age, sex, and race/ethnicity for controls within our adjusted models. We reported sociodemographic characteristics of the sample overall and by children who had PSE. We calculated and reported the means of each of the specific brain regions by substance exposure. Finally, we constructed multivariable regression models to measure the associations between different PSE and the demographic characteristics, total brain volume, and volume of each brain structure.
RESULTS
Among the total sample, 24.6% had prenatal alcohol exposure, 13.6% had prenatal tobacco exposure, and 1.2% had prenatal opioid exposure. On average, those with prenatal tobacco exposure were found to have a statistically significant smaller parahippocampus.
CONCLUSIONS
We found a significant association between prenatal tobacco exposure and smaller parahippocampal volume, which may have profound impacts on the livelihood of individuals including motor delays, poor cognitive and behavioral outcomes, and long-term health consequences. Given the cumulative neurodevelopmental effects associated with PSE, we recommend that healthcare providers increase screening rates, detection, and referrals for cessation. Additionally, we recommend that medical associations lobby policymakers to address upstream barriers to the effective identification of at-risk pregnant individuals, specifically, eliminating or significantly reducing punitive legal consequences stemming from state laws concerning prenatal substance use.
PubMed: 38915228
DOI: 10.1515/jom-2023-0277 -
Nature Communications Jun 2024Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can...
Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can create novel ideas. Here, we show that cortical offline activity is both necessary and sufficient for building unlearned inferential knowledge from previously acquired information. In a transitive inference paradigm, male C57BL/6J mice gained the inference 1 day after, but not shortly after, complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca imaging suggests that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialog during only REM sleep created inferential knowledge. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.
Topics: Animals; Sleep, REM; Male; Mice, Inbred C57BL; Prefrontal Cortex; Learning; Mice; Gyrus Cinguli; Wakefulness; Sleep, Slow-Wave; Knowledge; Entorhinal Cortex; Neurons
PubMed: 38914541
DOI: 10.1038/s41467-024-48816-x -
Frontiers in Aging Neuroscience 2024To explore the structural and functional changes in cognition-related brain regions in patients with chronic low back pain (CLBP) at earlier ages, and explore the impact...
OBJECTIVE
To explore the structural and functional changes in cognition-related brain regions in patients with chronic low back pain (CLBP) at earlier ages, and explore the impact of the interaction between CLBP and age on the brain.
METHODS
Seventy-six patients with CLBP were recruited and divided into "younger" age group (20-29 years, YA), "middle" age group (30-39 years, MA), and "older" age group (40-49 years, OA). All patients underwent functional magnetic resonance imaging (fMRI) as well as clinical psychological and pain-related symptoms assessments.
RESULTS
Structural analysis showed that patients in OA group had lower gray matter (GM) volumes in the orbitofrontal cortex (OFC) bilaterally and the right superior frontal gyrus (SFG) compared to YA group. The resting-state brain activity analysis showed that amplitude of low-frequency fluctuation (ALFF) values in the bilateral postcentral gyrus and left ventral medial prefrontal cortex (mPFC) were significantly different in the OA group. The functional connectivity (FC) in the right ventral dorsolateral prefrontal cortex (DLPFC) and the right insula was significantly decreased in the OA group compared to the YA and MA groups. Likewise, the FC in the left caudal parahippocampal gyrus (PHG) and left inferior parietal lobule (IPL) were significantly lower in the MA and OA groups compared to the YA group. In addition, both the structural properties and the FC values of these brain regions were significantly correlated with age.
CONCLUSION
This preliminary study concludes that CLBP affects the aging process. The synergistic effects of CLBP and aging accelerate the functional and structural decline of certain areas of the brain, which not only affects pain processing, but are also may be associated with cognitive declines.
PubMed: 38912520
DOI: 10.3389/fnagi.2024.1356507 -
Alzheimer's Research & Therapy Jun 2024Aging and sex are major risk factors for developing late-onset Alzheimer's disease. Compared to men, women experience worse neuropathological burden and cognitive...
Age, sex and Alzheimer's disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer's patients.
BACKGROUND
Aging and sex are major risk factors for developing late-onset Alzheimer's disease. Compared to men, women experience worse neuropathological burden and cognitive decline despite living longer with the disease. Similarly, male 3xTg-AD mice, developed to model Alzheimer's disease, no longer consistently exhibit standard Alzheimer's neuropathology yet experience higher rates of mortality - providing a unique opportunity to further elucidate this dichotomy. We hypothesized that sex differences in the biological aging process yield distinct pathological and molecular Alzheimer's disease signatures in males and females, which could be harnessed for therapeutic and biomarker development.
METHODS
We aged male and female, 3xTg-AD and B6129 control mice across their respective lifespans (n = 3-8 mice per sex, strain, and age group) and longitudinally assessed neuropathological hallmarks of Alzheimer's disease, markers of hepatic inflammation, splenic mass and morphology, as well as plasma cytokine levels. We conducted RNA sequencing analysis on bulk brain tissue and examined differentially expressed genes (DEGs) between 3xTg-AD and B6129 samples and across ages in each sex. We also examined DEGs between clinical Alzheimer's and control parahippocampal gyrus brain tissue samples from the Mount Sinai Brain Bank study in each sex.
RESULTS
3xTg-AD females significantly outlived 3xTg-AD males and exhibited progressive Alzheimer's neuropathology, while 3xTg-AD males demonstrated progressive hepatic inflammation, splenomegaly, circulating inflammatory proteins, and minimal Alzheimer's neuropathological hallmarks. Instead, 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females. Our clinical investigations revealed that individuals with Alzheimer's disease develop similar sex-specific alterations in neuronal and immune function. In diseased males of both species, we observed greater upregulation of complement-related gene expression, and lipopolysaccharide was predicted as the top upstream regulator of DEGs.
CONCLUSIONS
Our data demonstrate that chronic inflammation and complement activation are associated with increased mortality, indicating that age-related changes in immune response contribute to sex differences in Alzheimer's disease trajectories. We provide evidence that aging and transgene-driven disease progression trigger a widespread inflammatory response in 3xTg-AD males, which mimics the impact of lipopolysaccharide stimulation despite the absence of infection.
Topics: Alzheimer Disease; Animals; Female; Male; Mice, Transgenic; Mice; Brain; Humans; Longitudinal Studies; Aging; Disease Models, Animal; Sex Characteristics; Inflammation; Sex Factors; Age Factors; Cytokines
PubMed: 38909241
DOI: 10.1186/s13195-024-01492-x -
BioRxiv : the Preprint Server For... Jun 2024Amblyopia is a developmental disorder associated with reduced performance in visually guided tasks, including binocular navigation within natural environments. To help...
Amblyopia is a developmental disorder associated with reduced performance in visually guided tasks, including binocular navigation within natural environments. To help understand the underlying neurological disorder, we used fMRI to test the impact of amblyopia on the functional organization of scene-selective cortical areas, including the posterior intraparietal gyrus scene-selective (PIGS) area, a recently discovered region that responds selectively to ego-motion within naturalistic environments (Kennedy et al., 2024). Nineteen amblyopic adults (10 female) and thirty age-matched controls (12 female) participated in this study. Amblyopic participants spanned a wide range of amblyopia severity, based on their interocular visual acuity difference and stereoacuity. The visual function questionnaire (VFQ-39) was used to assess the participants' perception of their visual capabilities. Compared to controls, we found weaker scene-selective activity within the PIGS area in amblyopic individuals. By contrast, the level of scene-selective activity across the occipital place area (OPA), parahippocampal place area (PPA), and retrosplenial cortex (RSC)) remained comparable between amblyopic and control participants. The subjects' scores on "general vision" (VFQ-39 subscale) correlated with the level of scene-selective activity in PIGS. These results provide novel and direct evidence for amblyopia-related changes in scene-processing networks, thus enabling future studies to potentially link these changes across the spectrum of documented disabilities in amblyopia.
PubMed: 38895262
DOI: 10.1101/2024.06.05.597579 -
General Psychiatry 2024Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains...
BACKGROUND
Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains limited.
AIMS
This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD.
METHODS
This study enrolled 28 drug-naive adults with OCD aged 18-40 years and 16 healthy controls (HCs). Three-dimensional T1-weighted structural magnetic resonance imaging and F-SynVesT-1 positron emission tomography were conducted. Cognitive function was assessed using the Wisconsin Cart Sorting Test (WCST) in patients with OCD and HCs. Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction.
RESULTS
Compared with HCs, patients with OCD showed reduced synaptic density in regions of the cortico-striato-thalamo-cortical circuit such as the bilateral putamen, left caudate, left parahippocampal gyrus, left insula, left parahippocampal gyrus and left middle occipital lobe (voxel p<0.001, uncorrected, with cluster level above 50 contiguous voxels). The per cent conceptual-level responses of WCST were positively associated with the synaptic density reduction in the left middle occipital gyrus (R=0.1690, p=0.030), left parahippocampal gyrus (R=0.1464, p=0.045) and left putamen (R=0.1967, p=0.018) in patients with OCD.
CONCLUSIONS
Adults with OCD demonstrated lower F-labelled difluoro analogue of F-SynVesT-1 compared with HCs, indicating potentially lower synaptic density. This is the first study to explore the synaptic density in patients with OCD and provides insights into potential biological targets for cognitive dysfunctions in OCD.
PubMed: 38894874
DOI: 10.1136/gpsych-2023-101208 -
International Journal of Molecular... May 2024Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the...
Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity. The primary goal is to investigate if adding such realistic constraints could produce firing patterns similar to those measured in real neurons. Biological characteristics included in the work are excitability, connectivity, and synaptic signaling of neuron types defined primarily by their axonal and dendritic morphologies. We investigate the spiking dynamics in specific neuron types and the synaptic activities between groups of neurons. Modeling the rodent hippocampal formation keeps the simulations to a computationally reasonable scale while also anchoring the parameters and results to experimental measurements. Our model generates grid cell activity that well matches the spacing, size, and firing rates of grid fields recorded in live behaving animals from both published datasets and new experiments performed for this study. Our simulations also recreate different scales of those properties, e.g., small and large, as found along the dorsoventral axis of the medial entorhinal cortex. Computational exploration of neuronal and synaptic model parameters reveals that a broad range of neural properties produce grid fields in the simulation. These results demonstrate that the continuous attractor network model of grid cells is compatible with a spiking neural network implementation sourcing data-driven biophysical and anatomical parameters from Hippocampome.org. The software (version 1.0) is released as open source to enable broad community reuse and encourage novel applications.
Topics: Animals; Models, Neurological; Grid Cells; Synapses; Entorhinal Cortex; Action Potentials; Computer Simulation; Neurons; Hippocampus; Nerve Net; Neural Networks, Computer
PubMed: 38892248
DOI: 10.3390/ijms25116059 -
CNS Neuroscience & Therapeutics Jun 2024Spinal muscular atrophy (SMA) is one of the most common monogenic neuromuscular diseases, and the pathogenesis mechanisms, especially the brain network topological...
BACKGROUND AND OBJECTIVE
Spinal muscular atrophy (SMA) is one of the most common monogenic neuromuscular diseases, and the pathogenesis mechanisms, especially the brain network topological properties, remain unknown. This study aimed to use individual-level morphological brain network analysis to explore the brain neural network mechanisms in SMA.
METHODS
Individual-level gray matter (GM) networks were constructed by estimating the interregional similarity of GM volume distribution using both Kullback-Leibler divergence-based similarity (KLDs) and Jesen-Shannon divergence-based similarity (JSDs) measurements based on Automated Anatomical Labeling 116 and Hammersmith 83 atlases for 38 individuals with SMA types 2 and 3 and 38 age- and sex-matched healthy controls (HCs). The topological properties were analyzed by the graph theory approach and compared between groups by a nonparametric permutation test. Additionally, correlation analysis was used to assess the associations between altered topological metrics and clinical characteristics.
RESULTS
Compared with HCs, although global network topology remained preserved in individuals with SMA, brain regions with altered nodal properties mainly involved the right olfactory gyrus, right insula, bilateral parahippocampal gyrus, right amygdala, right thalamus, left superior temporal gyrus, left cerebellar lobule IV-V, bilateral cerebellar lobule VI, right cerebellar lobule VII, and vermis VII and IX. Further correlation analysis showed that the nodal degree of the right cerebellar lobule VII was positively correlated with the disease duration, and the right amygdala was negatively correlated with the Hammersmith Functional Motor Scale Expanded (HFMSE) scores.
CONCLUSIONS
Our findings demonstrated that topological reorganization may prioritize global properties over nodal properties, and disrupted topological properties in the cortical-limbic-cerebellum circuit in SMA may help to further understand the network pathogenesis underlying SMA.
Topics: Humans; Female; Male; Magnetic Resonance Imaging; Brain; Adult; Spinal Muscular Atrophies of Childhood; Young Adult; Adolescent; Gray Matter; Child; Nerve Net
PubMed: 38887183
DOI: 10.1111/cns.14804