Neuroscience Insights最新文献

Recently we demonstrated a critical role for temporal coding of corticospinal activity in a prehension movement requiring precise forelimb control. Learning of precision isometric pull drives large-scale remodeling of corticospinal motor networks. Optogenetic modulation of corticospinal activity and full transection of the corticospinal tract disrupted critical functions of the network in expert animals resulting in impaired modulation of precise movements. In contrast, we observed more widespread corticospinal co-activation and limited temporal coding on a similar, yet more simplistic prehension task, adaptive isometric pull. Disrupting corticospinal neuron activity had much more limited effects on adaptive isometric pull, which was found to be corticospinal independent by transection of the corticospinal tract. Here we discuss these results in context of known roles for corticospinal and corticostriatal neurons in motor control, as well as some of the questions our study raised.

Non-fatal opioid overdoses are associated with significant morbidity. Hypoxic brain injury caused by opioid-induced respiratory depression is a key mechanism of such morbidity. For example, reports describe an amnestic syndrome in opioid users associated with acute injury to the hippocampus, a brain region that is highly susceptible to hypoxic injury. In our recent study we investigated the effects of non-fatal opioid overdose on the hippocampal volume in a well-characterized sample of opioid use disorder (OUD) patients with a history of overdose (OD) compared to those with no prior overdose (NOD). Using structural magnetic resonance imaging (MRI) and voxel-based morphometry, we observed lower hippocampal volume in patients with a history OD than in the NOD group. These findings support an association between non-fatal opioid overdose and hippocampal injury, which we hypothesize contributes to recently reported cases of OUD related amnestic syndrome. Here we review our study findings and the potential pathophysiological mechanisms underlying the acute and delayed hippocampal injury in nonfatal opioid overdose. We also discuss the implications for the risk of overdose and brain injury with the increased prevalence of fentanyl and xylazine contamination of the illicit opioid supply. Lastly, we highlight considerations for clinical management of the underappreciated neurological injury and cognitive dysfunction in OUD patients.

Brain development and function are highly reliant on adequate establishment and maintenance of vascular networks. Early impairments in vascular health can impact brain maturation and energy metabolism, which may lead to neurodevelopmental anomalies. Our recent work not only provides novel insights into the development of cerebrovascular networks but also emphasizes the importance of their well-being for proper brain maturation. In particular, we have demonstrated that endothelial dysfunction in autism spectrum disorders (ASD) mouse models is causally related to altered behavior and brain metabolism. In the prenatal human brain, vascular cells change metabolic states in the second trimester. Such findings highlight the need to identify new cellular and molecular players in neurodevelopmental disorders, raising awareness about the importance of a healthy vasculature for brain development. It is thus essential to shift the mostly neuronal point of view in research on ASD and other neurodevelopmental disorders to also include vascular and metabolic features.

Over the past 30 years, behavioral, computational, and neuroscientific investigations have yielded fresh insights into how pigeons adapt to the diverse complexities of their visual world. A prime area of interest has been how pigeons categorize the innumerable individual stimuli they encounter. Most studies involve either photorealistic representations of actual objects thus affording the virtue of being naturalistic, or highly artificial stimuli thus affording the virtue of being experimentally manipulable. Together those studies have revealed the pigeon to be a prodigious classifier of both naturalistic and artificial visual stimuli. In each case, new computational models suggest that elementary associative learning lies at the root of the pigeon's category learning and generalization. In addition, ongoing computational and neuroscientific investigations suggest how naturalistic and artificial stimuli may be processed along the pigeon's visual pathway. Given the pigeon's availability and affordability, there are compelling reasons for this animal model to gain increasing prominence in contemporary neuroscientific research.

Spinal muscular atrophy (SMA) is treated by increasing the level of Survival Motor Neuron (SMN) protein through correction of SMN2 exon 7 skipping or exogenous expression of SMN through gene therapy. Currently available therapies have multiple shortcomings, including poor body-wide distribution, invasive delivery, and potential negative consequences due to high doses needed for clinical efficacy. Here we test the effects of a combination treatment of a splice-correcting antisense oligonucleotide (ASO) Anti-N1 with the small compounds risdiplam and branaplam. We show that a low-dose treatment of Anti-N1 with either compound produces a synergistic effect on the inclusion of SMN2 exon 7 in SMA patient fibroblasts. Using RNA-Seq, we characterize the transcriptomes of cells treated with each compound as well as in combination. Although high doses of each individual treatment trigger widespread perturbations of the transcriptome, combination treatment of Anti-N1 with risdiplam and branaplam results in minimal disruption of gene expression. For individual genes targeted by the 3 compounds, we observe little to no additive effects of combination treatment. Overall, we conclude that the combination treatment of a splice-correcting ASO with small compounds represents a promising strategy for achieving a high level of SMN expression while minimizing the risk of off-target effects.

Objectives-background: Postoperative cognitive dysfunction (POCD) involves decline in several cognitive domains after surgery and is particularly common after cardiac surgery, while also common among other types of surgery. Given the potential effects of such cognitive dysfunction on the quality of life, it is important to study it in multiple populations in order to limit its occurrence.

Study design: We present the long-term neuropsychological outcome of 200 patients, 100 of whom had orthopedic surgery and 100 oncological surgery.

Methods: We administered a series of neuropsychological tests assessing attention, complex scanning, verbal working memory, executive functioning, short-term and long-term memory, and visuospatial perception before surgery, prior to discharge, at 3-month follow-up and 6 years after surgery. We compared the performance of these patients to normative datasets.

Results: Despite equivalent levels of pre-surgery performance between patients, oncology patients exceeded their preoperative neurocognitive levels, suggesting less postoperative cognitive dysfunction in orthopedic patients overall, in all neuropsychological domains at a 6-year follow-up, except short-term retention. In contrast, orthopedic patients showed no improvement, and, instead, showed some cognitive decline, which remained consistent over time.

Conclusions: Our findings highlight the critical role of the type of surgery utilized in the development of POCD and have implications for clinical management and patients' quality of life in the very long term. Health policy professionals should be aware that patients' low POCD may persist in the long term, and this is useful from a clinician's point of view.

Recent experiments in rats and humans have indicated that the effects of non-invasive electrical stimulation are primarily due to transcutaneous stimulation of peripheral nerves, specifically the greater occipital nerve. This stimulation pathway activates communication gateways from the periphery to the brain, impacting memory consolidation. In this invited commentary, I delve into and offer additional insights concerning the enhancement of episodic memory through transcutaneous electrical stimulation of the greater occipital nerve, building upon the findings published by my laboratory in both Science Advances and Elife. Our research on non-invasive transcutaneous electrical stimulation of the greater occipital nerve (NITESGON) has shown to enhance episodic memory consolidation and promote communication between the locus coeruleus (LC) pathway and the hippocampus based on resting connectivity functional MRI. The LC, primarily responsible for releasing noradrenaline and dopamine, plays a crucial role in post-encoding memory stabilization. This suggests that NITESGON can improve memory but does not affect immediate learning. The concept of behavioural tagging, where weak memories can be stabilized through strong or novel events, and how NITESGON activates a memory consolidation through this mechanism are discussed. The role of NITESGON in enhancing memory stabilization is highlighted, providing a non-pharmaceutical solution with minimal side effects. The potential application of NITESGON in neurological conditions, including Alzheimer's disease, attention deficit hyperactivity disorder and post-traumatic stress disorder, is also discussed, emphasizing its promising therapeutic prospects.

Alzheimer's disease (AD) is the most common type of dementia, and AD individuals often present significant cerebrovascular disease (CVD) symptomology. AD with significant levels of CVD is frequently labeled mixed dementia (or sometimes AD-CVD), and the differentiation of these two neuropathologies (AD, AD-CVD) from each other is challenging, especially at early stages. In this study, we compared the gray matter (GM) and white matter (WM) volumes in AD (n = 83) and AD-CVD (n = 37) individuals compared with those of cognitively healthy controls (n = 85) using voxel-based morphometry (VBM) of their MRI scans. The control individuals, matched for age and sex with our two dementia groups, were taken from the ADNI. The VBM analysis showed widespread patterns of significantly lower GM and WM volume in both dementia groups compared to the control group (P < .05, family-wise error corrected). While comparing with AD-CVD, the AD group mainly demonstrated a trend of lower volumes in the GM of the left putamen and right hippocampus and WM of the right thalamus (uncorrected P < .005 with cluster threshold, K = 10). The AD-CVD group relative to AD tended to present lower GM and WM volumes, mainly in the cerebellar lobules and right brainstem regions, respectively (uncorrected P < .005 with cluster threshold, K = 10). Although finding a discriminatory feature in structural MRI data between AD and AD-CVD neuropathologies is challenging, these results provide preliminary evidence that demands further investigation in a larger sample size.

The auditory brainstem response (ABR) is important for both clinical and basic auditory research. It is a non-invasive measure of hearing function with millisecond-level precision. The ABR can not only measure the synchrony, speed, and efficacy of auditory physiology but also detect different modalities of hearing pathology and hearing loss. ABRs are easily acquired in vertebrate animal models like reptiles, birds, and mammals, and complement existing molecular, developmental, and systems-level research. One such model system is the chicken; an excellent animal for studying auditory development, structure, and function. However, the ABR for chickens was last reported nearly 4 decades ago. The current study examines how decades of ABR characterization in other animal species support findings from the chicken ABR. We replicated and expanded on previous research using 43 chicken hatchlings 1- and 2-day post-hatch. We report that click-evoked chicken ABRs presented with a peak waveform morphology, amplitude, and latency like previous avian studies. Tone-evoked ABRs were found for frequencies from 250 to 4000 Hertz (Hz) and exhibited a range of best sensitivity between 750 and 2000 Hz. Objective click-evoked and tone-evoked ABR thresholds were comparable to subjective thresholds. With these revisited measurements, the chicken ABR still proves to be an excellent example of precocious avian development that complements decades of molecular, neuronal, and systems-level research in the same model organism.