Neuroscience Insights最新文献

Background: Obstetric brachial plexus palsy (OBPP) is a condition impairing limb function caused by birth injury. In 20 to 30% of cases, severe OBPP can cause life constraints in feeding, grooming, and clothing tasks.

Objective: The present study, using voxel- and surface-based morphometry (VBM and SBM), examined the brain structure of pediatric OBPP patients to better understand the effects of this peripheral motor deficit on early brain development.

Methods: Thirty-six T1-weighted images of 18 patients (2-17 years old, mean age = 11.3, 8 females) and 18 healthy controls (2-17 years old, mean age = 10.1, 8 females) were collected for this study. MRI data were processed and analyzed using the Statistical Parametric Mapping 12 (SPM12) toolbox. The custom pediatric tissue probability map was created with the CerebroMatic (COM) toolbox. The results were considered significant if they survived whole-brain family-wise error correction (P < .05).

Results: We have found differences in grey matter volumes in the bilateral anterior hippocampus (left P < .001 and right P = .01) and left cerebellum exterior (Crus I) (P < .001). We have also found differences in cortical thickness in the bilateral parahippocampal gyri (left P = .001 and right P = .005) and right orbitofrontal cortex (OFC) (P < .001).

Conclusions: These structural differences might be linked to the altered environmental adaptation that children with OBPP face due to their primary motor deficit. Our findings hint at a complex interplay between motor capabilities, brain structure development, and cognitive functions. However, more research combining neuroimaging, behavioral, cognitive, and clinical data is needed to support stronger conclusions on this subject.

The insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular efferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix. These striatal compartments have distinct embryologic origins, afferent and efferent connectivity, dopamine pharmacology, and susceptibility to injury. Striosome and matrix appear to occupy separate sets of cortico-striato-thalamo-cortical loops, so a bias in insulo-striate projections toward one compartment may also embed an insular subregion in distinct regulatory and functional networks. Compartment-specific mapping of insulo-striate structural connectivity is sparse; the insular subregions are largely unmapped for compartment-specific projections. In 100 healthy adults, diffusion tractography was utilized to map and quantify structural connectivity between 19 structurally-defined insular subregions and each striatal compartment. Insulo-striate streamlines that reached striosome-like and matrix-like voxels were concentrated in distinct insular zones (striosome: rostro- and caudoventral; matrix: caudodorsal) and followed different paths to reach the striatum. Though tractography was generated independently in each hemisphere, the spatial distribution and relative bias of striosome-like and matrix-like streamlines were highly similar in the left and right insula. 16 insular subregions were significantly biased toward 1 compartment: 7 toward striosome-like voxels and 9 toward matrix-like voxels. Striosome-favoring bundles had significantly higher streamline density, especially from rostroventral insular subregions. The biases in insulo-striate structural connectivity that were identified mirrored the compartment-specific biases identified in prior studies that utilized injected tract tracers, cytoarchitecture, or functional MRI. Segregating insulo-striate structural connectivity through either striosome or matrix may be an anatomic substrate for functional specialization among the insular subregions.

Even before the advent of fMRI, the amygdala occupied a central space in the affective neurosciences. Yet this amygdala-centred view on emotion processing gained even wider acceptance after the inception of fMRI in the early 1990s, a landmark that triggered a goldrush of fMRI studies targeting the amygdala in vivo. Initially, this amygdala fMRI research was mostly confined to task-activation studies measuring the magnitude of the amygdala's response to emotional stimuli. Later, interest began to shift more towards the study of the amygdala's resting-state functional connectivity and task-based psychophysiological interactions. Later still, the test-retest reliability of amygdala fMRI came under closer scrutiny, while at the same time, amygdala-based real-time fMRI neurofeedback gained widespread popularity. Each of these major subdomains of amygdala fMRI research has left its marks on the field of affective neuroscience at large. The purpose of this review is to provide a critical assessment of this literature. By integrating the insights garnered by these research branches, we aim to answer the question: What part (if any) can amygdala fMRI still play within the current landscape of affective neuroscience? Our findings show that serious questions can be raised with regard to both the reliability and validity of amygdala fMRI. These conclusions force us to cast doubt on the continued viability of amygdala fMRI as a core pilar of the affective neurosciences.

Identification of early influences on cognitive decline is of paramount importance in order to stem the impacts of decrements in cognitive functioning and to potentially intervene. Thus, here we focused on 132 healthy adult women (age range 26-98 years) to (a) determine whether factors circulating in serum may exert neurotoxic effects in vitro, (b) evaluate associations between serum neurotoxicity and cognitive performance, and (c) assess the influence of human herpes virus (HHV) seroprevalence and other factors on apoptosis and cognitive performance. The results documented that the addition of serum from healthy adult women to neural cell cultures resulted in apoptosis, indicating the presence of circulating neurotoxic factors in the serum. Furthermore, apoptosis increased with age, and was associated with decreased cognitive performance. Stepwise regression evaluating the influence of 6 HHVs on apoptosis and cognitive function revealed that only HHV5 (cytomegalovirus; CMV) seropositivity was significantly associated with apoptosis and cognitive decline, controlling for age. These findings document neurotoxic effects of serum from healthy women across the adult lifespan and suggest a unique detrimental influence associated with CMV seropositivity.

Our minds impact motor outputs. Such mind-motor interactions are critical for understanding motor control mechanisms and optimizing motor performance. In particular, incentive motivation strongly enhances motor performance. Dopaminergic neurons located in the ventral midbrain (VM) are believed to be the center of incentive motivation. Direct projections from the VM to the primary motor cortex constitute a mesocortical pathway. However, the functional role of this pathway in humans remains unclear. Recently, we demonstrated the functional role of the mesocortical pathway in human motor control in the context of incentive motivation by using functional magnetic resonance imaging (fMRI). Incentive motivation remarkably improved not only reaction times but also the peak grip force in subsequent grip responses. Although the reaction time has been used as a proxy for incentive motivation mediated by dopaminergic midbrain activity, the premovement activity of the mesocortical pathway is involved in controlling the force strength rather than the initiation of subsequent force generation. In this commentary, we review our recent findings and discuss remaining questions regarding the functional role of the mesocortical pathway in mind-motor interactions.

Parkinson's Disease (PD) occurs as a result of the progressive loss of dopaminergic neurons within the substantia nigra causing motor and non-motor symptoms and has become more prevalent within the last several decades. With mitochondria being essential to cellular survival, mitochondrial dysfunction contributes to the disease progression by increasing neuron loss through (1) insufficient ATP production and (2) reactive oxygen species generation. MicroRNAs (miRNAs) are small molecules located throughout cells that regulate gene expression, particularly mitochondrial function. Through their own dysregulation, miRNAs offset the delicate balance of mitochondrial function by altering or dysregulating the expression of proteins, increasing neuroinflammation, increasing retention of toxic substances, limiting the removal of reactive oxygen species, and preventing mitophagy. Improper mitochondrial function places cells at increased risk of apoptosis, a major concern in individuals with PD due to their reduced number of dopaminergic neurons. This article has identified the 17 most promising mitochondrial associated miRNAs within PD: hsa-miR-4639-5p, miR-376a, miR-205, miR-421, miR-34b/c, miR-150, miR-7, miR-132, miR-17-5p, miR-20a, miR-93, miR-106, miR-181, miR-193b, miR-128, miR-181a, and miR-124-3p. These miRNAs alter mitochondrial function and synaptic energy by impeding normal gene expression when up or downregulated. However, there is limited research regarding mitochondria-localized miRNAs that are typically seen in other diseases. Mitochondria-localized miRNA may have a greater impact on mitochondrial dysfunction due to their proximity. Further research is needed to determine the location of these miRNAs and to better understand their regulatory capabilities on mitochondrial and synaptic function within PD.

Historically known as neuronal support cells, astrocytes are now widely studied for their close structural and functional interactions with multiple neural cell types and cerebral vessels where they maintain an ideal environment for optimized brain function. Under pathological conditions, astrocytes become reactive and lose key protective functions. In this commentary, we discuss our recent work in The Journal of Neuroscience (Sompol et al., 2023) that showed Ca2+ dysregulation in reactive astrocytes, as well as hyperactivation of the Ca2+-dependent protein phosphatase calcineurin (CN) and the Nuclear Factor of Activated T Cells (NFATs), in a diet-induced hyperhomocystienemia (HHcy) mouse model of Vascular Contributions to Cognitive Impairment and Dementia (VCID). Intravital multiphoton imaging coupled with whisker stimulation was used to explore astrocyte Ca2+ signaling and neurovascular function under active phase, fully awake conditions. Interestingly, evoked Ca2+ transients in individual astrocytes were greater, even though intercorrelated Ca2+ signaling across networks of astrocytes was impaired in HHcy mice. Blockade of astrocytic CN/NFAT reduced signs of astrocyte reactivity, normalized cerebrovascular function, and improved hippocampal synaptic strength and hippocampal dependent cognition in HHcy mice, revealing a previously unrecognized deficit regarding neuron-astrocyte-vascular interactions. These findings strongly support the use of astrocyte targeting strategies to mitigate pathophysiological changes associated with VCID and other Alzheimer's-related dementias.

Cholesterol and calcium play crucial roles as integral structural components and functional signaling entities within the central nervous system. Disruption in cholesterol homeostasis has been linked to Alzheimer's, Parkinson's, and Huntington's Disease while alterations in calcium signaling is hypothesized to be a key substrate for neurodegeneration across many disorders. Despite the importance of regulated cholesterol and calcium homeostasis for brain health there has been an absence of research investigating the interdependence of these signaling molecules and how they can tune each other's abundance at membranes to influence membrane identity. Here, we discuss the role of cholesterol in shaping calcium dynamics in a neurodegenerative disorder that arises due to mutations in the lysosomal cholesterol transporter, Niemann Pick Type C1 (NPC1). We discuss the molecular mechanisms through which altered lysosomal cholesterol transport influences calcium signaling pathways through remodeling of ion channel distribution at organelle-organelle membrane contacts leading to neurodegeneration. This scientific inquiry not only sheds light on NPC disease but also holds implications for comprehending other cholesterol-associated neurodegenerative disorders.

Inflammation is a prominent hypothesis in the neurobiology of depression. In our transcriptomic profiling study of microglia in chronic major depressive disorder (MDD), we revealed a distinct disease-associated microglia (DAM) transcriptomic profile exclusively found in cortical gray matter, that we have designated DepDAM. These DepDAM revealed an immune-suppressed state, with a possible upstream mechanism for microglial suppression, by upregulation of CD200 and CD47 ("don't eat me signals") located on synapses. We extensively report on disease characteristics, such as cause of death, reason for euthanasia, and psychiatric state when deceased. When excluding MDD donors in a euthymic state, the trend of lower CD45 membrane expression on white matter microglia became significant, and the difference in gray matter microglia became larger. For Western blot analysis of CD47 and CD200, both means of the definitely depressed donor groups (MDD-D) increased. This underscores the utmost importance of reporting on patient and episode characteristics, such as severity, episode traits, (type of) suicidality, mode of decease, and state of illness at death in post-mortem- and biological psychiatric research. For psychiatric post-mortem research, we suggest using well-characterized donors (eg, after "psychological autopsy") selected by an experienced clinician.

Objective: This study aims to determine sex differences in poststroke hypertriglyceridemia (serum triglyceride levels ⩾ 200 mg/dl) and high stroke severity in ischemic stroke patients.

Method: Our study analyzed data from 392 males and 373 females with hypertriglyceridemia. Stroke severity on admission was measured using the National Institute of Health Stroke Scale (NIHSS) with a value ⩽7 indicating a more favorable post-stroke prognosis while a score of >7 indicates poorer post-stroke outcomes. Logistic regression models adjusted for demographic and risk factors. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each clinical risk factor were used to predict the increasing odds of an association of a specific clinical baseline risk factor with the male or female AIS with hypertriglyceridemia.

Results: In the adjusted analysis, male patients with hypertriglyceridemia, diastolic blood pressure (OR = 1.100, 95% CI, 1.034-1.171, P = .002), and Ischemic stroke mortality (OR = 6.474, 95% CI, 3.262-12.847, P < .001) were significantly associated with increased stroke severity. In female patients with hypertriglyceridemia, age (OR = 0.920, 95% CI, 0.866-0.978, P = .008) was associated with reduced stroke severity, while ischemic stroke mortality score (OR = 37.477, 95% CI, 9.636-145.756, P < .001) was associated with increased stroke severity.

Conclusion: Increased ischemic stroke mortality risk score was associated with increased severity in both male and female AIS patients with hypertriglyceridemia. Our findings provide information about sex differences in specific risk factors that can be managed to improve the care of male and female ischemic stroke patients with hypertriglyceridemia.