Journal of neurophysiology最新文献

Functional magnetic resonance imaging (fMRI) is a noninvasive method for measuring human brain activity based on blood oxygenation level-dependent (BOLD) responses. Although many studies have reported positive BOLD responses evoked by sensory stimuli, others have reported negative BOLD responses (NBRs) in the sensory cortex when stimuli from different sensory modalities are presented (i.e., cross-modal NBRs). We conducted an fMRI experiment to better understand the characteristics of cross-modal NBRs in subcortical and cortical regions. Auditory and visual stimuli were presented unilaterally to one ear and to either the left or right visual field, respectively. The lateral geniculate nucleus and medial geniculate nucleus did not show a significant cross-modal NBR. In contrast, the primary auditory cortex showed a significant cross-modal NBR when visual stimuli were presented in either the contralateral or ipsilateral visual fields. Finally, we found that the cross-modal NBR in the early visual cortex was highly variable across subjects and did not exhibit consistent trends. However, each subject's data exhibited considerable split-half reliability. Our results suggest that cross-modal NBR in the auditory cortex likely reflects mechanisms such as interhemispheric suppression, rather than those coordinated within the same hemisphere.NEW & NOTEWORTHY This study demonstrated that the human primary auditory cortex showed a significant cross-modal negative BOLD response bilaterally, regardless of the visual field in which the visual stimuli were presented. This result suggests that the cross-modal negative BOLD response is not an epiphenomenon of visual cortex activation predominantly observed in the contralateral hemisphere, but is more likely to reflect interhemispheric suppression mechanisms.

Up to 70% of astronauts develop spaceflight-associated neuro-ocular syndrome (SANS), a constellation of ocular structural changes, in microgravity; the mechanisms are unknown but have hypothesized to stem from elevated CO₂, glymphatic dysfunction, and other processes. In this preliminary study, we examined whether brain and ocular tissue signal enhancement on MRI at delay following intravenous gadolinium differs when participants breathe elevated CO₂ versus ambient air across two counterbalanced sessions. We scanned 12 participants at baseline using structural MRI and at 90 and 360 min following intravenous gadolinium administration. We observed that parietal and occipital lobe white matter showed a significant main effect of gas versus ambient day, with greater T₁ tissue enhancement when participants were breathing elevated CO₂. The vitreous chamber of the eye showed larger enhancements on the T₁ sequence for 1.0% and 2.0% CO₂ conditions. The findings suggest that some brain and ocular regions show delayed glymphatic clearance with elevated CO₂.NEW & NOTEWORTHY In this study, we investigated the effects of elevated CO₂ on delayed signal enhancement in brain MRI following gadolinium contrast injection. We found CO₂ effects on brain white matter and vitreous chamber of the eye, with higher tissue enhancement at 90 min relative to when participants breathed ambient air. These findings suggest delayed glymphatic clearance with elevated CO₂.

Transcutaneous vagus nerve stimulation (tVNS) has emerged as a method for interrogating the role of the locus coeruleus (LC) norepinephrine system in human behavior. Tuning of excitability in the corticospinal tract is central to many cognitive and motor processes, but little is known about how the LC contributes to this tuning. In particular, no existing studies have examined the effect of tVNS on corticospinal excitability "online" during active stimulation, where the largest effects on pupil size are observed. To address this question, we delivered repeated 4-s trains of tVNS and sham stimulation and elicited motor-evoked potentials (MEPs) during stimulation trains (online) and shortly after train offset (offline). Pupil size was concurrently recorded throughout each train. We discovered that tVNS significantly increases corticospinal excitability compared with sham stimulation, but only when measured online and not offline. The excitatory effects on corticospinal excitability were greater in the latter half of tVNS trains. Pupil size was also significantly increased by tVNS compared with sham; however, the effect on pupil size peaked earlier during the tVNS trains compared with corticospinal excitability. In line with these distinct temporal profiles, changes in corticospinal excitability and pupil size were not significantly correlated, likely reflecting differences in the anatomical circuits underpinning each effect. This work demonstrates for the first time that tVNS increases corticospinal excitability at rest, but the effect only emerges when corticospinal excitability is measured online during active tVNS. Implications for basic and clinical neuroscientific research are discussed.NEW & NOTEWORTHY Four-second trains of transcutaneous vagus nerve stimulation (tVNS) increase corticospinal excitability and pupil size compared with sham stimulation, but only "online" during active stimulation. Corticospinal excitability and pupil size show distinct temporal profiles of change in response to 4-s trains of tVNS. tVNS-induced changes in corticospinal excitability and pupil size are not correlated, which is likely reflective of the distinct anatomical circuits underpinning each effect.

The ability to move is a vital and essential feature of human existence. We are experts at producing a variety of movements and have refined their control through evolution. As gravity is a major feature of our every-day environment, we have learned to take advantage of it by optimising its effects to minimise the cost of our actions. This can be illustrated by systematic differences in the temporal organisation of our movements according to their direction. Studying motor control in the face of various gravitational level modifications (hypergravity, hypogravity or weightlessness), the scientific literature has shown that movement kinematics are rapidly adapted to new gravitational conditions. Hitherto, most researchers varied gravitational intensity to probe its neural integration into sensorimotor control. Here, we investigated the effects of a reversal of gravitational direction in the egocentric reference frame. Our results reveal a major effect of body-orientation reversal on motor control. This effect then progressively disappears, such that arm kinematics reached values that were close to the known baseline optimal ones. These results reveal that the effects of a simple reversal of body-orientation cannot be fully anticipated to produce arm movements. Furthermore, comparing the evolution of varied parameters that were collected at different time points during each movement, our results reveal that adaptation first occured during the late movement phases (i.e., around the time to peak velocity and time to peak deceleration), where online feedback contributions are typically larger, while not ruling out trial-to-trial updates of predictive control.

Our motor system can accurately control movement within both very low and very high force ranges, despite working through noisy cortical neurons, each with individually limited dynamic range. The visual system has peripheral gain mechanisms whereby neurons in the CNS see only a small fraction of the enormous range of luminance in the visual scene encountered throughout the day. The motor system might use an analogous system. One such mechanism could be mediated through monoaminergic input to the spinal cord and its modulation of the gain of motoneurons through its effect on persistent inward currents (PICs). To test this possibility, we measured cortical activity of three monkeys during a power grasp task before and after giving them systemic serotonin agonist or antagonist drugs. We hypothesized that the drugs would alter the effect of serotonin on the PICs in motoneurons, thereby changing the relation between cortical activity and motor output. In two monkeys, this was largely the case, although in two conditions the results were not statistically significant. However, in a third monkey, the results were opposite our hypothesis. These conflicting results raise further questions as to the roles monoamines may play in regulating motor excitability to maintain accurate force control across the wide range needed for grasping movements.

Neurons in the primary visual cortex (V1) are best known for their selectivity to orientation. Is orientation the most sensitive dimension among the stimulus parameters that influence their responses? To address this question, we aimed to analyze the responses of neurons in the cat primary visual cortex using a modified reverse correlation technique to obtain spectral receptive fields in the three-dimensional (3D) spatiotemporal frequency domain. Comparison of tuning bandwidths revealed that neurons in the primary visual cortex were more sharply tuned to orientation than to spatial or temporal frequency, indicating that orientation was the most sensitive dimension in this stimulus space. Analysis of natural scenes showed that fine salient features were more elongated along the orientation axis than coarse ones. The same scale-dependent asymmetry between the orientation and orthogonal directions was observed in the tuning properties of these neurons in the 2D spatial frequency domain, suggesting that they became specialized for orientation through adaptation to natural image statistics. Most cat striate neurons had spectral receptive fields separable between the 2D spatial frequency plane and temporal frequency domain, allowing them to represent local motion energy in the 3D frequency domain. When the responses were compared across contrasts, complex cells signaled optimal orientation robustly (i.e. with minimal fluctuation) in the spectral receptive fields. Extensive spatial pooling of feature detectors along the orientation axis appeared to explain this property at least partially. Such spatial pooling may underlie the reliable signaling of visual inputs in noisy contexts as well as position-tolerant representation.

(R,S)-Ketamine, a dissociative anesthetic, has shown rapid and sustained antidepressant effects at lower doses than those required for anesthetic effects in patients with treatment-resistant depression. However, its use is limited because it causes side effects, including psychotomimetic symptoms and dependence. The enantiomer (R)-ketamine was reported to promote antidepressant-like effects in rodents with a potentially lower risk for adverse effects compared with (S)-ketamine. This study compared the effects of (R)-ketamine, (S)-ketamine, their metabolites, and another N-methyl-D-aspartate antagonist, MK-801, on the electroencephalograms (EEGs) of rhesus macaques across a wide range of doses. The results showed that the dose level of (R,S)-ketamine, corresponding to the clinically effective antidepressant concentration in humans, produced increase in gamma power as reported in clinical trials. Compared with (S)-ketamine, (R)-ketamine produced a comparable increase in gamma power but had weaker effects on EEG features thought to be associated with adverse effects. The EEG changes induced by the ketamine metabolites were relatively mild, indicating a minimal contribution to the EEG effects of ketamine. This comprehensive EEG evaluation in a non-human primate, together with measurements of plasma drug concentrations, when interpreted in comparison with existing clinical data, provide increased translational insight into the dose-dependent neurophysiological characteristics of (R,S)-ketamine, its enantiomers and metabolites. EEG-based comparisons of (R)-ketamine with (R,S)-ketamine and (S)-ketamine suggest that (R)-ketamine exhibits neurophysiological features consistent with a potentially broader therapeutic range for antidepressant effects.

Neurometabolism is increasingly recognized as a pathogenic contributor to neurodegenerative disease. However, commonly reported mitochondrial functional outcomes (e.g., respiration) often lack specificity with respect to energetic demand, carbon substrate utilization, and key bioenergetic parameters such as mitochondrial membrane potential. To address this limitation, the present study sought to determine whether oxidative phosphorylation conductance differs across brain regions and as a function of carbon substrate. Oxidative phosphorylation conductance was investigated in permeabilized frontal cortex and hippocampus of female and male C57BL/6J mice using pyruvate/malate substrate (PM, supporting complex I) or succinate with rotenone complex-I inhibition (SR, supporting complex II). Both mitochondrial volume (multiphoton microscopy) and abundance (flow cytometry) assessments showed no regional differences (p > 0.05 in both sexes). Mitochondria's ability to titer respiration to clamped energetic demands was lower with SR compared to PM in both sexes, regardless of brain region (p < 0.001). The production of ATP-to-respiration ratio (P/O ratio) was less at low energetic demands with SR compared to PM in males (p < 0.001) and less regardless of energetic demand with SR compared to PM in females (p < 0.05). This study, utilizing otherwise healthy, young brain tissue, demonstrates the necessity for greater precision in mitochondrial bioenergetic approaches to rigorously advance understanding of neurometabolism.

Proper timing is essential for effective neural processing. Yet, how early postnatal vision shapes the temporal stability of human visual cortical processing remains unknown. Here, using electroencephalography, we examined cortical timing properties in individuals who were born pattern-vision blind due to congenital cataracts, but surgically recovered sight. While sight-recovery individuals exhibited an attenuated cortical oscillatory phase coherence (i.e., higher temporal variability) during visual processing, their cortical oscillatory strength was unimpaired. Moreover, phase coherence information, but not activation strength, allowed classification of sight-recovery individuals from control individuals. Finally, exchanging phase information between sight-recovery and control individuals indicated oscillatory timing impairments as the source of group differences in higher-order visual cortical processing. Neural timing impairments were specific to reversed congenital blindness, that is, were not observed in individuals with reversed developmental (late-onset) cataracts. These results suggest that the development of intricately temporally orchestrated visual cortical processing in humans requires early visual experience.

The neural and biomechanical mechanisms that control a change in direction during locomotion remain poorly understood, particularly sensorimotor processing. In this study, we investigated cycle and phase durations, muscle activity, and cutaneous reflexes during forward (FW) and backward (BW) hindlimb-only walking in seven adult cats stepping on a treadmill at 0.2 m/s, with their forelimbs placed on a stationary platform. We recorded electromyography (EMG) bilaterally from six hindlimb muscles, and cutaneous reflexes were evoked with electrical stimulation of the superficial peroneal (SP) nerve to probe sensorimotor processing. Results show that BW is associated with changes in the timing of EMG activity in all muscles selected and increased EMG amplitudes in specific hindlimb muscles, particularly those that extend the hip Overall, reflex responses evoked by SP nerve stimulation were modulated with phase in both FW and BW. While most response patterns were similar in both directions, some direction-specific patterns emerged, particularly inhibitory responses in ipsilateral and contralateral extensor during BW. Overall, our results are consistent with shared neural circuits for sensorimotor processing when walking forward and backward, with some direction-specific specialized circuits.