eNeuro最新文献

The subjective visual vertical (VV), the visually estimated direction of gravity, is essential for assessing vestibular function and visuospatial cognition. In this study, we aimed to investigate the mechanisms underlying altered VV perception in stroke participants with unilateral spatial neglect (USN), specifically by examining their eye movement patterns during VV judgment tasks. Participants with USN demonstrated limited eye movement scanning along a rotating bar, often fixating on prominent ends, such as the top or bottom. This suggests a reflexive response to visually salient areas, potentially interfering with accurate VV perception. In contrast, participants without USN showed broader scanning around the center of the bar. Notably, participants with USN without frontal lobe lesions occasionally exhibited extended scanning that included the bar's center, which was associated with accurate VV judgments. These findings suggest that (1) a tendency to fixate on peripheral, prominent areas and (2) frontal lobe involvement in disengaging and redirecting spatial attention may influence VV perception in USN. Based on these results, targeted rehabilitation strategies that encourage individuals with USN to extend their visual scanning beyond prominent endpoints and include central areas could improve VV accuracy. This study highlights the specific eye movement behaviors contributing to VV misperception, emphasizing the importance of training that broadens scanning to improve VV perception effectively.

Psychiatric disorders, including anxiety and depression, are highly comorbid in people with epilepsy. However, the mechanisms mediating the shared pathophysiology are currently unknown. There is considerable evidence implicating the basolateral amygdala (BLA) in the network communication of anxiety and fear, a process demonstrated to involve parvalbumin-positive (PV) interneurons. The loss of PV interneurons has been well described in the hippocampus of chronically epileptic mice and in postmortem human tissue of patients with temporal lobe epilepsy (TLE). We hypothesize that a loss of PV interneurons in the BLA may contribute to comorbid mood disorders in epilepsy. To test this hypothesis, we employed a ventral intrahippocampal kainic acid model of TLE in mice, which exhibits profound behavioral deficits associated with chronic epilepsy. We demonstrate a loss of PV interneurons and dysfunction of the remaining PV interneurons in the BLA of chronically epileptic mice. Furthermore, we demonstrate altered principal neuron function and impaired coordination of BLA network and behavioral states in chronically epileptic mice. To determine whether the loss of PV interneurons contributes to these altered network and behavioral states, we partially ablated PV interneurons in the BLA by stereotaxically injecting AAV-Flex-DTA into the BLA of PV-Cre mice. Loss of PV interneurons in the BLA is sufficient to alter behavioral states, such as increasing avoidance behaviors and impairing fear learning. These data suggest that compromised inhibition in the BLA in chronically epileptic mice may contribute to behavioral deficits, suggesting a novel mechanism contributing to comorbid anxiety and epilepsy.

Short-term motor adaptation to novel movement dynamics has been shown to involve at least two concurrent learning processes: a slow process that responds weakly to error but retains information well and a fast process that responds strongly to error but has poor retention. This modeling framework can explain several properties of motion-dependent motor adaptation (e.g., 24 h retention). An important assumption of this computational framework is that learning is only based on the experienced movement error, and the effect of noise (either internally generated or externally applied) is not considered. We examined the respective error sensitivity by quantifying adaptation in three subject groups distinguished by the noise added to the motion-dependent perturbation. We assessed the feedforward adaptive changes in motor output and examined the adaptation rate, retention, and decay of learning. Applying a two-state modeling framework showed that the applied noise during training mainly affected the fast learning process, with the slow process largely unaffected; participants in the higher noise groups demonstrated a reduced force profile following training, but the decay rate across groups was similar, suggesting that the slow process was unimpaired across conditions. Collectively, our results provide evidence that noise significantly decreases motor adaptation, but this reduction may be due to its influence over specific learning mechanisms. Importantly, this may have implications for how the motor system compensates for random fluctuations, especially when affected by brain disorders that result in movement tremor (e.g., essential tremor).

Epilepsy, a neurological disorder characterized by recurrent unprovoked seizures, significantly impacts patient quality of life. Current classification methods focus primarily on clinical observations and electroencephalography (EEG) analysis, often overlooking the underlying dynamics driving seizures. This study uses surface EEG data to identify seizure transitions using a dynamical systems-based framework-the taxonomy of seizure dynamotypes-previously examined only in invasive data. We applied principal component and independent component (IC) analysis to surface EEG recordings from 1,177 seizures in 158 patients with focal epilepsy, decomposing the signals into ICs. The ICs were visually labeled for clear seizure transitions and bifurcation morphologies (BifMs), which were then examined using Bayesian multilevel modeling in the context of clinical factors. Our analysis reveals that certain onset bifurcations (saddle node on invariant circle and supercritical Hopf) are more prevalent during wakefulness compared with their reduced rate during nonrapid eye movement (NREM) sleep, particularly NREM3. We discuss the possible implications of our results in the context of modeling approaches and suggest additional avenues to continue this exploration. Furthermore, we demonstrate the feasibility of automating this classification process using machine learning, achieving high performance in identifying seizure-related ICs and classifying interspike interval changes. Our findings suggest that the noise in surface EEG may obscure certain BifMs, and we suggest technical improvements that could enhance detection accuracy. Expanding the dataset and incorporating long-term biological rhythms, such as circadian and multiday cycles, may provide a more comprehensive understanding of seizure dynamics and improve clinical decision-making.

The human medial parietal cortex (MPC) is recruited during multiple cognitive processes. Previously, we demonstrated regions specific to recall of people or places and proposed that the functional organization of MPC mirrors the category selectivity defining the medial-lateral axis of the ventral-temporal cortex (VTC). However, prior work considered recall of people and places only, and VTC also shows object selectivity sandwiched between face- and scene-selective regions. Here, we tested a strong prediction of our proposal: like VTC, MPC should show a region specifically recruited during object recall, and its relative cortical position should mirror the one of VTC. While responses during people and place recall showed a striking replication of prior findings, we did not observe any evidence for object-recall effects within MPC, which differentiates it from the spatial organization in VTC. Importantly, beyond MPC, robust recall effects were observed for people, places, and objects on the lateral surface of the brain. Place-recall effects were present in the angular gyrus, frontal eye fields, and peripheral portions of the early visual cortex, whereas people recall selectively drove response in the right posterior superior temporal sulcus. Object-recall effects were largely restricted to a region posterior to the left somatosensory cortex, in the vicinity of the supramarginal gyrus. Taken together, these data demonstrate that while there are distributed regions active during recall of people, places, and objects, the functional organization of MPC does not mirror the medial-lateral axis of VTC but reflects only the most salient features of that axis-namely, representations of people and places.

A unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons and likely supports local neuronal maturation and emerging synaptogenesis. Microglia may alter neuronal growth following environmental perturbations such as stress. Using multiple measures in rhesus macaques, we found that microglia in the infant primate PL had relatively large somas and a small arbor size. In contrast, microglia in the adolescent PL had a smaller soma and a larger dendritic arbor. We then examined microglial morphology in the PL after a novel maternal separation protocol, to examine the effects of early life stress. After maternal separation, the microglia had increased soma size, arbor size, and complexity. Surprisingly, strong effects were seen not only in the infant PL, but also in the adolescent PL from subjects who had experienced the separation many years earlier. We conclude that under normal maternal-rearing conditions, PL microglia morphology tracks PL neuronal growth, progressing to a more "mature" phenotype by adolescence. Maternal separation has long-lasting effects on microglia, altering their normal developmental trajectory, and resulting in a "hyper-ramified" phenotype that persists for years. We speculate that these changes have consequences for neuronal development in young primates.

Fragile X autosomal homolog 1 (FXR1), a member of the fragile X messenger riboprotein 1 family, has been linked to psychiatric disorders including autism and schizophrenia. Parvalbumin (PV) interneurons play critical roles in cortical processing and have been implicated in FXR1-linked mental illnesses. Targeted deletion of FXR1 from PV interneurons in mice has been shown to alter cortical excitability and elicit schizophrenia-like behavior. This indicates that FXR1 regulates behaviorally relevant electrophysiological functions in PV interneurons. We therefore expressed a genetically encoded hybrid voltage sensor in PV interneurons and used voltage imaging in slices of mouse somatosensory cortex to assess the impact of targeted FXR1 deletion. These experiments showed that PV interneurons lacking FXR1 had excitatory synaptic potentials with larger amplitudes and shorter latencies compared with wild type. Synaptic potential rise-times, decay-times, and half-widths were also impacted to degrees that varied between cortical layer and synaptic input. Thus, FXR1 modulates the responsiveness of PV interneurons to excitatory synaptic inputs. This will enable FXR1 to control cortical processing in subtle ways, with the potential to influence behavior and contribute to psychiatric dysfunction.

Mammalian parenting is an unusually demanding commitment. How has the reward system been co-opted to ensure parental care? Previous work has implicated the lateral habenula (LHb), an epithalamic nucleus, as a potential intersection of parenting behavior and reward. Here, we examine the role of the LHb in the maternal behavior of naturally parturient primiparous mouse dams. We show that kainic acid lesions of the LHb induced a severe maternal neglect phenotype in dams toward their biological pups. Next, we demonstrate that chronic chemogenetic inactivation of the LHb using inhibitory DREADDs impaired acquisition and performance of various maternal behaviors, such as pup retrieval and nesting. We present a random intercept model suggesting LHb inactivation prevents the acquisition of pup retrieval, a novel maternal behavior in primiparous mouse dams, and decreases nest building performance, an already-established behavior, in primiparous mouse dams. Lastly, we examine the spatial histology of kainic acid-treated dams with a random intercept model, which suggests the role of LHb in maternal behavior may be preferentially localized at the posterior aspect of this structure. Together, these findings serve to establish the LHb as required for maternal behavior in the mouse dam, thereby complementing previous findings implicating the LHb in parental behavior using pup-sensitized virgin female mice.

It is widely believed that axons in the central nervous system of adult mammals do not regrow following injury. This failure is thought, at least in part, to underlie the limited recovery of function following injury to the brain or spinal cord. Some studies of fixed tissue have suggested that, counter to dogma, norepinephrine (NE) axons regrow following brain injury. Here, we have used in vivo two-photon microscopy in layer 1 of the primary somatosensory cortex in transgenic mice harboring a fluorophore selectively expressed in NE neurons. This protocol allowed us to explore the dynamic nature of NE axons following injury with the selective NE axon toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Following DSP4, NE axons were massively depleted and then slowly and partially recovered their density over a period of weeks. This regrowth was dominated by new axons entering the imaged volume. There was almost no contribution from local sprouting from spared NE axons. Regrown axons did not appear to use either the paths of previously lesioned NE axons or NE axons that were spared and survived DSP4 as a guide. To measure NE release, GCaMP8s was selectively expressed in neocortical astrocytes and startle-evoked, NE receptor-mediated Ca²⁺ transients were measured. These Ca²⁺ transients were abolished soon after DSP4 lesion but returned to pre-lesion values after 3-5 weeks, roughly coincident with NE axon regrowth, suggesting that the regrown NE axons are competent to release NE in response to a physiological stimulus in the awake mouse.

The relationships between facial expression and color affect human cognition functions such as perception and memory. However, whether these relationships influence selective attention and brain activity contributed to selective attention remains unclear. For example, reddish angry faces increase emotion intensity, but it is unclear whether brain activity and selective attention are similarly enhanced. To investigate these questions, we examined whether event-related potentials for faces vary depending on facial expression and color by recording electroencephalography (EEG) data. We conducted an oddball task using stimuli that combined facial expressions (angry, neutral) and facial colors (original, red, green). The participants counted the number of times a rarely appearing target face stimulus appeared among the standard face stimuli. The results indicated that the difference in P3 amplitudes for the target and standard faces depended on the combinations of facial expressions and facial colors; the P3 for red angry faces were greater than those for red neutral faces. Additionally, facial expression or facial color had no significant main effect or interaction effect on P1 amplitudes for the target, and facial expression had significant main effects only on the N170 amplitude. These findings suggest that the interaction between facial expression and color modulates the P3 associated with selective attention. Moreover, the response enhancement resulting from this interaction appears to occur at a cognitive processing stage that follows the processing stage associated with facial color or expression alone. Our results support the idea that red color increases the human response to anger from an EEG perspective.