Neurophysiological adaptations to spaceflight and simulated microgravity

Changes in physiological functions after spaceflight and simulated spaceflight involve several mechanisms. Microgravity is one of them and it can be partially reproduced with models, such as head down bed rest (HDBR). Yet, only a few studies have investigated in detail the complexity of neurophysiological systems and their integration to maintain homeostasis. Central nervous system changes have been studied both in their structural and functional component with advanced techniques, such as functional magnetic resonance (fMRI), showing the main involvement of the cerebellum, cortical sensorimotor, and somatosensory areas, as well as vestibular-related pathways. Analysis of electroencephalography (EEG) led to contrasting results, mainly due to the different factors affecting brain activity. The study of corticospinal excitability may enable a deeper understanding of countermeasures' effect, since greater excitability has been shown being correlated with better preservation of functions. Less is known about somatosensory evoked potentials and peripheral nerve function, yet they may be involved in a homeostatic mechanism fundamental to thermoregulation. Extending the knowledge of such alterations during simulated microgravity may be useful not only for space exploration, but for its application in clinical conditions and for life on Earth, as well.     

Suckling in litters with different sizes,and early and late swimming exercise differentially modulates anxiety-like behavior,memory and electrocorticogram potentiation after spreading depression in rats

Objective: Analyze the hypothesis that swimming exercise, in rats suckled under distinct litter sizes, alters behavioral parameters suggestive of anxiety and recognition memory, and the electrocorticogram potentiation that occurs after the excitability-related phenomenon that is known as cortical spreading depression (CSD).

Methods: Male Wistar rats were suckled in litters with six or 12 pups (L₆ and L₁₂ groups). Animals swam at postnatal days (P) 8–23, or P60–P75 (early-exercised or late-exercised groups, respectively), or remained no-exercised. Behavioral tests (open field – OF and object recognition – OR) were conducted between P77 and P80. Between P90 and P120, ECoG was recorded for 2 hours. After this ‘baseline’ recording, CSD was elicited every 30 minutes over the course of 2 hours.

Results: Early swimming enhanced the number of entries and the percentage of time in the OF-center (P?<?0.05). In animals that swam later, this effect occurred in the L6 group only. Compared to the corresponding sedentary groups, OR-test showed a better memory in the L6 early exercised rats, and a worse memory in all other groups (P?<?0.05). In comparison to baseline values, ECoG amplitudes after CSD increased 14–43% for all groups (P?<?0.05). In the L₆ condition, early swimming and late swimming, respectively, reduced and enhanced the magnitude of the post-CSD ECoG potentiation in comparison with the corresponding L₆ no-exercised groups (P?<?0.05).

Discussion: Our data suggest a differential effect of early- and late-exercise on the behavioral and electrophysiological parameters, suggesting an interaction between the age of exercise and the nutritional status during lactation.     

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.     

Light aerobic exercise modulates executive function and cortical excitability

Single bouts of aerobic exercise can modulate cortical excitability and executive cognitive function, but less is known about the effect of light‐intensity exercise, an intensity of exercise more achievable for certain clinical populations. Fourteen healthy adults (aged 22 to 30) completed the following study procedures twice (≥7 days apart) before and after 30 min of either light aerobic exercise (cycling) or seated rest: neurocognitive battery (multitasking performance, inhibitory control and spatial working memory), paired‐pulse TMS measures of cortical excitability. Significant improvements in response times during multitasking performance and increases in intracortical facilitation (ICF) were seen following light aerobic exercise. Light aerobic exercise can modulate cortical excitability and some executive function tasks. Populations with deficits in multitasking ability may benefit from this intervention.     

Changes in long term peripheral nerve biophysical properties in childhood cancer survivors following neurotoxic chemotherapy

ObjectiveIn the context of increasing numbers of childhood cancer survivors (CCS), this study aimed to enhance understanding of the biophysical basis for long term chemotherapy induced peripheral neuropathy from different chemotherapy agents in CCS.MethodsDetailed cross-sectional neurophysiological examination, using median nerve axonal excitability studies, alongside clinical assessments, in 103 long term CCS (10.5 ± 0.6 years post-treatment).ResultsCisplatin treated CCS (n = 16) demonstrated multiple sensory axonal excitability changes including increased threshold (P < 0.05), alterations in depolarising and hyperpolarising threshold electrotonus (P < 0.05) and reduction in resting and minimum IV slope (P < 0.01). Vincristine treated CCS (n = 73) were comparable to controls, except for prolonged distal motor latency (P = 0.001). No differences were seen in the non-neurotoxic chemotherapy group (n = 14). Abnormalities were more evident in the cisplatin subgroup with greater clinical neuropathy manifestations.ConclusionPersistent long term changes in axonal biophysical properties vary with different chemotherapy agents, most evident after cisplatin exposure. Longitudinal studies of nerve function during chemotherapy treatment are required to further evaluate these differences and their mechanistic basis.SignificanceThis study provides a unique biophysical perspective for persistent cisplatin related neurotoxicity in children, previously under recognised.     

The estrous cycle modulates rat caudate–putamen medium spiny neuron physiology

The neuroendocrine environment in which the brain operates is both dynamic and differs by sex. How differences in neuroendocrine state affect neuron properties has been significantly neglected in neuroscience research. Behavioral data across humans and rodents indicate that natural cyclical changes in steroid sex hormone production affect sensorimotor and cognitive behaviors in both normal and pathological contexts. These behaviors are critically mediated by the caudate–putamen. In the caudate–putamen, medium spiny neurons (MSNs) are the predominant and primary output neurons. MSNs express membrane‐associated estrogen receptors and demonstrate estrogen sensitivity. However, how the cyclical hormone changes across the estrous cycle may modulate caudate–putamen MSN electrophysiological properties remains unknown. Here, we performed whole‐cell patch‐clamp recordings on male, diestrus female, proestrus female, and estrus female caudate–putamen MSNs. Action potential, passive membrane, and miniature excitatory post‐synaptic current properties were assessed. Numerous MSN electrical properties robustly differed by cycle state, including resting membrane potential, rheobase, action potential threshold, maximum evoked action potential firing rate, and inward rectification. Strikingly, when considered independent of estrous cycle phase, all but one of these properties do not significantly differ from male MSNs. These data indicate that female caudate–putamen MSNs are sensitive to the estrous cycle, and more broadly, the importance of considering neuroendocrine state in studies of neuron physiology.     

Pinging the brain with transcranial magnetic stimulation reveals cortical reactivity in time and space

BackgroundSingle-pulse transcranial magnetic stimulation (TMS) elicits an evoked electroencephalography (EEG) potential (TMS-evoked potential, TEP), which is interpreted as direct evidence of cortical reactivity to TMS. Thus, combining TMS with EEG can be used to investigate the mechanism underlying brain network engagement in TMS treatment paradigms. However, controversy remains regarding whether TEP is a genuine marker of TMS-induced cortical reactivity or if it is confounded by responses to peripheral somatosensory and auditory inputs. Resolving this controversy is of great significance for the field and will validate TMS as a tool to probe networks of interest in cognitive and clinical neuroscience.ObjectiveHere, we delineated the cortical origin of TEP by spatially and temporally localizing successive TEP components, and modulating them with transcranial direct current stimulation (tDCS) to investigate cortical reactivity elicited by single-pulse TMS and its causal relationship with cortical excitability.MethodsWe recruited 18 healthy participants in a double-blind, cross-over, sham-controlled design. We collected motor-evoked potentials (MEPs) and TEPs elicited by suprathreshold single-pulse TMS targeting the left primary motor cortex (M1). To causally test cortical and corticospinal excitability, we applied tDCS to the left M1.ResultsWe found that the earliest TEP component (P25) was localized to the left M1. The following TEP components (N45 and P60) were largely localized to the primary somatosensory cortex, which may reflect afferent input by hand-muscle twitches. The later TEP components (N100, P180, and N280) were largely localized to the auditory cortex. As hypothesized, tDCS selectively modulated cortical and corticospinal excitability by modulating the pre-stimulus mu-rhythm oscillatory power.ConclusionTogether, our findings provide causal evidence that the early TEP components reflect cortical reactivity to TMS.