Journal of neurophysiology最新文献

Explicit and implicit components of motor learning have been widely studied, but the extent to which movement information encoded and maintained in working memory (Motor Working Memory; MWM) contributes to motor learning remains unclear. Building on recent work pointing to separate effector-independent (abstract) and effector-specific (limb-bound) information formats in MWM, we conducted a correlational study in which human participants completed both a MWM task and a visuomotor rotation task. We observed that: 1) the fidelity of effector-independent MWM was selectively correlated with the degree of explicit visuomotor learning, and 2) the fidelity of inferred effector-specific MWM was selectively correlated with the degree of implicit visuomotor learning. Together, these results point to a possible relationship in which different formats of motor information stored in WM may contribute to distinct components of long-term motor learning, shedding light on a novel cognitive-motor interaction.NEW & NOTEWORTHY Working memory is important for motor learning, yet its role beyond visuospatial domains remains unclear. Here, we examine whether and how non-visual Motor Working Memory (MWM) is related to long-term motor learning. Specifically, we identified selective correlations between effector-independent MWM and explicit motor learning processes, and between effector-specific MWM and implicit motor learning processes. These findings extend prior research relating visuospatial working memory to motor learning and highlight distinct MWM mechanisms supporting different learning processes.

Previous studies have shown an association between interindividual variations in the frequency of α-band EEG oscillations such as estimates of peak alpha frequency (PAF) and pain sensitivity. Whether differences in PAF also influence the susceptibility to develop central sensitization (CS) is unknown. This study aimed to determine whether the PAF of vision- and sensorimotor-related alpha-band activity is associated with the magnitude and extent of secondary mechanical hyperalgesia induced by high-frequency stimulation (HFS) of the skin, a surrogate marker of CS. The EEG was recorded in 32 healthy participants at rest during eyes open and eyes closed conditions, and during bilateral finger movements. Then, HFS was applied to the right forearm. Pinprick sensitivity was assessed at both forearms, before and 40 min after HFS, to assess the magnitude and extent of HFS-induced secondary hyperalgesia. Two methods were used to isolate vision- and sensorimotor-related alpha-band activity based on sensitivity to eye closure and movement: one based on an independent component analysis, the other on spectral subtraction. PAF was characterized using a center-of-gravity approach and also using Gaussian fitting after removal of the aperiodic EEG component. Neither sensorimotor- nor vision-related PAF were significantly correlated with the magnitude or extent of HFS-induced secondary hyperalgesia. However, exploratory analyses revealed that participants with higher vision-related PAF showed greater pinprick habituation at the nonsensitized forearm, indicating a possible link between PAF and perceptual habituation. Interindividual variations of PAF at baseline were not significantly associated with the susceptibility to develop HFS-induced secondary hyperalgesia.NEW & NOTEWORTHY Using several methods to estimate vision- and sensorimotor-related peak alpha frequency (PAF) in the EEG frequency spectrum, we found no significant association between interindividual variations in PAF at baseline and the susceptibility to develop secondary hyperalgesia following high-frequency stimulation (HFS) of the skin in healthy participants.

Studying naturalistic hand behaviors is challenging due to the limitations of conventional marker-based motion capture, which can be costly, time-consuming, and encumber participants. Although markerless pose estimation exists-an accurate, off-the-shelf solution validated for hand-object manipulation is needed. We present Automatically Tracking Hands Expertly with No Annotations (ATHENA), an open-source, Python-based toolbox for three-dimensional (3-D) markerless hand tracking. To validate ATHENA, we concurrently recorded hand kinematics using ATHENA and an industry-standard optoelectronic marker-based system (OptiTrack). Participants performed unimanual, bimanual, and naturalistic object manipulation and we compared common kinematic variables like grip aperture, wrist velocity, index metacarpophalangeal flexion, and bimanual span. Our results demonstrated high spatiotemporal agreement between ATHENA and OptiTrack. This was evidenced by extremely high matches (R² > 0.90 across the majority of tasks) and low root mean square differences (<1 cm for grip aperture, <4 cm/s for wrist velocity, and <5°-10° for index metacarpophalangeal flexion). ATHENA reliably preserved trial-to-trial variability in kinematics, offering identical scientific conclusions to marker-based approaches, but with significantly reduced financial and time costs and no participant encumbrance. In conclusion, ATHENA is an accurate, automated, and easy-to-use platform for 3-D markerless hand tracking that enables more ecologically valid motor control and learning studies of naturalistic hand behaviors, enhancing our understanding of human dexterity.NEW & NOTEWORTHY An accurate, easy-to-use Python-based toolbox is shared to perform automated three-dimensional (3-D) tracking of the hands. When validated against an industry standard marker-based system, the toolbox demonstrated high spatiotemporal agreement and preserved trial-to-trial variability for tasks ranging from simple reaching to complex object manipulation behaviors. The toolbox offers reduced financial and time costs and does not require the use of markers that may encumber participant movements, thereby facilitating ecologically valid motor control studies of the hand.

Gluten is a protein that is present in a variety of grains and is added to many food products, such as pasta and bread. There are three disorders related to gluten consumption: celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity (NCGS). CD and wheat allergies can be tested for and involve intestinal and extraintestinal symptoms, including a variety of neurological conditions. Individuals with NCGS are diagnosed if they have an adverse reaction to gluten, including intestinal and neurological effects such as "brain fog." To study the impact of gluten on brain function and test our hypothesis that diets with gluten would impair cognitive function in the presence of a high-fat diet, wild-type mice were fed 35% fat (kcal) in the absence or presence of gluten (3.4 g/100g diet). Body fat, food consumption, oral glucose tolerance tests, and various behavioral tests were evaluated after 2-3 mo of dietary intervention. Mice had similar body weights, body fat percentages, and oral glucose tolerance tests regardless of dietary gluten. Food consumption was also similar in both groups of mice. In behavioral studies, mice fed gluten stayed longer and traveled further in the open arm of an elevated platform maze, an indication of reduced anxiety, and had increased locomotor activity compared to mice not fed gluten, whereas mice fed diets with or without gluten had similar results from the Morris water maze and a restraint test, indications of similar memory and stress. Thus, dietary gluten impacts behavior in mice fed high-fat diets.NEW & NOTEWORTHY Recently, a growing number of individuals have associated dietary gluten with adverse neurological symptoms. In the current study, we examined the impact of gluten on the behaviors of mice, using behaviors to represent a culmination of various neurological processes. We discovered that behaviors did indeed differ in mice fed gluten versus not fed gluten in the presence of a high-fat diet.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite advances in acute care and neurological intensive care units, predicting long-term outcomes for patients with TBI remains challenging. Aquaporin-4 (AQP4) has emerged as a potential biomarker for assessing TBI severity and prognosis. Our goal is to evaluate AQP4 as a novel agent in the accurate diagnosis and prognosis of patients with TBI. This study included patients with TBI classified into mild (n = 80), moderate (n = 139), and severe (n = 96) groups based on Glasgow Coma Scale (GCS) scores. Cerebrospinal fluid (CSF) samples were collected at 1-, 7-, 14-, and 28-days postadmission, and AQP4 concentrations were measured using ELISA. The prognosis was evaluated using the Glasgow Outcome Scale (GOS) at 3 mo postinjury. The relationship between AQP4 levels and TBI severity, and their predictive value for patient outcomes, was analyzed. AQP4 levels in CSF peaked at 14 days postadmission and significantly decreased by 28 days in patients with both moderate and severe TBI. Higher AQP4 levels were consistently associated with worse prognosis at all measured time points. receiver operating characteristic (ROC) analysis revealed that AQP4 levels had predictive values at 1-, 7-, 14-, and 28-days postadmission, and the highest was shown at 14 days postadmission, with an area under the curve (AUC) of 0.79, sensitivity of 67.82%, and specificity of 83.78%. AQP4 in CSF is a promising biomarker for assessing TBI severity and predicting prognosis. Monitoring AQP4 levels could be an effective way to enhance prognostic accuracy, guide therapeutic interventions, and improve clinical decision-making in TBI management.NEW & NOTEWORTHY Our study is the first to comprehensively track dynamic changes in cerebrospinal fluid (CSF) aquaporin-4 (AQP4) levels in patients with moderate to severe traumatic brain injury. We show that AQP4 peaks at 14 days, correlates with injury severity, and consistently predicts 3-mo outcomes, with the strongest prognostic accuracy at day 14. These findings identify CSF AQP4 as a promising biomarker for assessing severity and prognosis, offering potential to improve early prediction and guide clinical decision-making in TBI management.

Exposure to acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF). We have shown that nucleus tractus solitarii (nTS) activity is necessary for both the development and maintenance of pLTF. Activation of glutamatergic N-methyl-d-aspartate receptors (NMDARs) and CaMKII contribute to in vitro long-term potentiation, to nTS hypoxic responses, and possibly to pLTF. This study investigated the role of nTS NMDARs and CaMKII in the development and maintenance of AIH-induced pLTF. Phrenic nerve and splanchnic sympathetic nerve activity (PhrNA and sSNA) were recorded in male Sprague-Dawley rats in response to AIH [10 bouts of 10% O₂ (45 s, interspersed by 5 min)]. Time control (TC) rats underwent a single hypoxia bout and were monitored for 2 h afterward. After AIH, PhrNA amplitude increased compared to initial baseline (BL) and TC, indicating induction of pLTF. pLTF development was associated with increased nTS neuronal Ca²⁺ and action potential discharge recorded via GCaMP8 fiber photometry and an array probe, respectively. Inhibition of nTS CaMKII activity before AIH exposure attenuated the development of pLTF and elevation of nTS neuronal discharge. In contrast, after pLTF had developed, inhibiting nTS CaMKII activity had no effect on the maintenance of pLTF. Nevertheless, after AIH, blocking NMDARs specifically in the nTS by bilateral nanoinjection of AP5 reduced the magnitude of pLTF. Altogether, these results indicate that increased nTS neuronal activity likely due to activation of NMDARs and their downstream CaMKII signaling complex are critical components for AIH-induced neuroplasticity in central cardiorespiratory output.NEW & NOTEWORTHY Exposure to acute intermittent hypoxia (AIH) induced sustained increases in phrenic nerve activity (phrenic long-term facilitation, pLTF) that were associated with increased nucleus tractus solitarii (nTS) neuronal Ca²⁺ and action potential discharge. nTS CaMKII activity was critical for pLTF development and AIH-induced increases in neuronal discharge. In contrast, nTS NMDA receptor (NMDAR) activation, but not CaMKII activity, was required for maintaining AIH-induced pLTF. Increased nTS neuronal activity, NMDAR activation, and CaMKII are critical for AIH-induced neuroplasticity in central cardiorespiratory output.

Humans can adapt their motor commands in response to errors when they perform reaching movements in new dynamic conditions, a process called motor adaptation. They acquire knowledge about the new dynamics, which they can use when they are reexposed and, limitedly, generalize to untrained reaching directions. Although force field adaptation, retention, and generalization have been thoroughly investigated at a kinematic and kinetic task level, the underlying coordination at a muscular level remains unclear. Many studies propose that the central nervous system uses low-dimensional control, that is, coordinates muscles in functional groups: so-called muscle synergies. Accordingly, we hypothesized that changes in muscle synergy structure and activation patterns represent the acquired knowledge underlying force field adaptation, retention, and generalization. To test this, 36 male humans practiced reaching to a single target in a viscous force field and were tested for retention and generalization to new directions, while we simultaneously measured muscle activity from 13 upper-body muscles. We found that muscle synergies used for unperturbed reaching cannot explain the muscle patterns when adapted. Instead, muscle synergies specific to this adapted state were necessary, alongside a novel four-phasic pattern of muscle synergy activation. Furthermore, these structural changes and patterns were also evident during retention and generalization. Our results suggest that reaching in an environment with altered dynamics requires structural changes to muscle synergies compared with unperturbed reaching, and that these changes facilitate retention and generalization. These findings provide new insights into how the central nervous system coordinates the muscles underlying motor adaptation, retention, and generalization.NEW & NOTEWORTHY Humans can adapt reaching movements to new dynamics, use the acquired knowledge when reexposed, and partly generalize it to new conditions. Although force field adaptation, retention, and spatial generalization have been thoroughly investigated at a kinematic and kinetic task level, the coordination of the underlying muscles remains elusive. We observed structural changes in muscle synergies-functionally coactivated muscles-with adaptation. These changes facilitated retention and spatial generalization. These findings provide new insights into motor adaptation.

The reported memory-related effects of stimulating different nodes within the classical Circuit of Papez have been inconsistent, though the possibility of immediate or chronic memory benefit remains. We undertook memory experiments during deep brain stimulation (DBS) in human subjects with mild, early Alzheimer's disease (2 males, 3 females; n = 5) to rigorously investigate the effects of fornix stimulation on acute memory function. We sought to assess whether some of the reported variability may be attributed to the stimulation protocol and to determine whether stimulation alters memory formation per se, rather than influencing a process required for but not directly related to memory encoding. We tested fornix stimulation during both awake DBS surgery and postoperatively, in subjects participating in a broader clinical trial (ADvance II). In both settings, using a parametric episodic memory task with distinct encoding, attention, and delayed recall phases, we found that fornix stimulation generally impaired memory, with higher frequencies producing the greatest detriments on memory performance. Furthermore, stimulation specifically interacted with trial-by-trial memory encoding, rather than with other functions such as visual-spatial processing, attention, or short-term working memory. Therefore, in both contexts and across a wide range of stimulation frequencies, open-loop fornix stimulation directly impaired acute, item-specific memory encoding, though the effects of more chronic stimulation on memory and cognitive function are yet to be determined.NEW & NOTEWORTHY Electrical stimulation of different nodes within the Circuit of Papez has been assessed in a variety of human studies with conflicting or indeterminate results. Our goal was to combine a precise psychophysical paradigm with varying stimulation protocols across two experimental settings (intra-op, post-op) to more robustly identify and characterize the interaction between fornix stimulation and memory and to isolate whether those effects are specific to memory encoding, rather than related to distinct, supporting cognitive functions.

Metabotropic glutamate receptor 5 (mGluR5) plays a pivotal role in neurodevelopment. Here, we investigated the consequences of mGluR5 loss-of-function on the development of glutamatergic transmission onto the medial nucleus of the trapezoid body (MNTB). Using the Cre-loxP system, we generated a conditional knockout (KO) mouse line in which mGluR5 expression was selectively eliminated in vesicular glutamate transporter 2 (VGluT2)-expressing glutamatergic pathways, including the calyx of Held synapse innervating MNTB neurons. Whole cell patch-clamp recordings from mice of either sex at postnatal days 30-38 were used to compare the excitatory synaptic properties of MNTB neurons between KO mice and wild-type controls. Upon afferent stimulation of the trapezoid body, MNTB neurons exhibited two distinct types of evoked EPSCs (eEPSCs): large calyceal all-or-none and smaller non-calyceal responses. In mGluR5 KO mice, there was a significant increase in the proportion of neurons exhibiting non-calyceal eEPSCs. The calyceal all-or-none eEPSCs showed significantly prolonged latency, along with slower kinetics in both eEPSCs and asynchronous EPSCs. Analysis of short-term synaptic plasticity of the non-calyceal eEPSCs revealed an increased paired-pulse ratio in mGluR5 KO mice. In addition, membrane capacitance was significantly reduced, consistent with a smaller somatic area in mGluR5 KO mice. These results suggest that mGluR5 plays a critical role in shaping the excitatory synaptic properties necessary for fast temporal processing in the MNTB.NEW & NOTEWORTHY Metabotropic glutamate receptor 5 (mGluR5) is known to play critical roles in neurodevelopment, but its specific contribution to auditory circuit formation has remained unknown. Using a conditional mGluR5 knockout mouse model, we show that a major glutamatergic pathway in the auditory brainstem is impaired, particularly in synaptic timing, and is accompanied by a reduced somatic area of the postsynaptic neurons. These findings highlight a pivotal role for mGluR5 in shaping auditory brainstem circuitry.