Use-dependent corticospinal excitability is associated with resilience and physical performance during simulated military operational stress.

Simulated military operational stress (SMOS) provides a useful model to better understand resilience in humans as the stress associated with caloric restriction, sleep deficits, and fatiguing exertion degrades physical and cognitive performance. Habitual physical activity may confer resilience against these stressors by promoting favorable use-dependent neuroplasticity, but it is unclear how physical activity, resilience, and corticospinal excitability (CSE) relate during SMOS. To examine associations between corticospinal excitability, physical activity, and physical performance during SMOS. Fifty-three service members (age: 26 ± 5 yr, 13 women) completed a 5-day and -night intervention composed of familiarization, baseline, SMOS (2 nights/days), and recovery days. During SMOS, participants performed rigorous physical and cognitive activities while receiving half of normal sleep (two 2-h blocks) and caloric requirements. Lower and upper limb CSE were determined with transcranial magnetic stimulation (TMS) stimulus-response curves. Self-reported resilience, physical activity, military-specific physical performance (TMT), and endocrine factors were compared in individuals with high (HIGH) and low CSE based on a median split of lower limb CSE at baseline. HIGH had greater physical activity and better TMT performance throughout SMOS. Both groups maintained physical performance despite substantial psychophysiological stress. Physical activity, resilience, and TMT performance were directly associated with lower limb CSE. Individual differences in physical activity coincide with lower (but not upper) limb CSE. Such use-dependent corticospinal excitability directly relates to resilience and physical performance during SMOS. Future studies may use noninvasive neuromodulation to clarify the interplay among CSE, physical activity, and resilience and improve physical and cognitive performance.NEW & NOTEWORTHY We demonstrate that individual differences in physical activity levels coincide with lower limb corticospinal excitability. Such use-dependent corticospinal excitability directly relates to resilience and physical performance during a 5-day simulation of military operational stress with caloric restriction, sleep restriction and disruption, and heavy physical and cognitive exertion.

Reliability of corticospinal excitability estimates for the vastus lateralis: Practical considerations for lower limb TMS task selection.

Transcranial magnetic stimulation (TMS) is increasingly used to examine lower extremity corticospinal excitability (CSE) in clinical and sports research. Because CSE is task-specific, there is growing emphasis on the use of ecological tasks. Nevertheless, the comparative reliability of CSE measurements during established (e.g. knee extensions; KE) and more recent ecological (e.g. squats; SQT) lower extremity tasks has received less attention. The aim of this study was to compare the test-retest reliability of CSE, force, and muscle activity (EMG) during isometric SQT and KE. 19 right-footed men (age: 25 ± 5 yrs) with similar fitness and body composition performed SQT (N = 7) or KE (N = 12) on two consecutive days. Force and EMG were recorded during maximum voluntary isometric contractions (MVC). Corticospinal excitability was determined in the dominant leg during light (15% MVC) contractions based on motor evoked potential (MEP) stimulus-response-curves (SRC). Test-retest reliability, absolute agreement, and consistency were determined for force, EMG, and SRC MEP maximum (MEPMAX) and rising phase midpoint (V50). As a secondary analysis, all outcomes were compared between groups with mixed-methods ANCOVAs (Task × Time, covariate: body-fat-percentage). Compared with SQT, KE displayed better test-retest reliability and agreement for MEPMAX whereas V50, force, and EMG were similarly reliable. Force (p = 0.01) and MEPMAX (p = 0.02) were also greater during KE despite a similar V50 (p = 0.11). Differences in test-retest reliability, absolute agreement, and between-group comparisons highlight the need to carefully select lower limb TMS assessment tasks and encourage future efforts to balance ecological validity with statistical sensitivity.

Characterizing off-target corticospinal responses to double-cone transcranial magnetic stimulation.

INTRODUCTION: The double-cone coil (D-CONE) is frequently used in transcranial magnetic stimulation (TMS) experiments that target the motor cortex (M1) lower-limb representation. Anecdotal evidence and modeling studies have shed light on the off-target effects of D-CONE TMS but the physiological extent remains undetermined. PURPOSE: To characterize the off-target effects of D-CONE TMS based on bilateral corticospinal responses in the legs and hands. METHODS: Thirty (N = 30) participants (9 women, age: 26 ± 5yrs) completed a stimulus-response curve procedure with D-CONE TMS applied to the dominant vastus lateralis (cVL) and motor-evoked potentials (MEPs) recorded in each active VL and resting first dorsal interosseous (FDI). As a positive control (CON), the dominant FDI was directly targeted with a figure-of-eight coil and MEPs were similarly recorded in each active FDI and resting VL. MEPMAX, V50 and MEP latencies were compared with repeated-measures ANOVAs or mixed-effects analysis and Bonferroni-corrected pairwise comparisons. RESULTS: Off-target responses were evident in all muscles, with similar MEPMAX in the target (cVL) and off-target (iVL) leg (p = 0.99) and cFDI compared with CON (p = 0.99). cFDI and CON MEPMAX were greater than iFDI (p < 0.01). A main effect of target (p < 0.001) indicated that latencies were shorter with CON but similar in all muscles with D-CONE. DISCUSSION: Concurrent MEP recordings in bilateral upper- and lower-extremity muscles confirm that lower-limb D-CONE TMS produces substantial distance-dependent off-target effects. In addition to monitoring corticospinal responses in off-target muscles to improve targeting accuracy in real-time, future studies may incorporate off-target information into statistical models post-hoc.

Topographic and sex-related differences in sleep spindles in major depressive disorder: a high-density EEG investigation.

BACKGROUND: Sleep spindles are believed to mediate several sleep-related functions including maintaining disconnection from the external environment during sleep, cortical development, and sleep-dependent memory consolidation. Prior studies that have examined sleep spindles in major depressive disorder (MDD) have not demonstrated consistent differences relative to control subjects, which may be due to sex-related variation and limited spatial resolution of spindle detection. Thus, this study sought to characterize sleep spindles in MDD using high-density electroencephalography (hdEEG) to examine the topography of sleep spindles across the cortex in MDD, as well as sex-related variation in spindle topography in the disorder. METHODS: All-night hdEEG recordings were collected in 30 unipolar MDD participants (19 women) and 30 age and sex-matched controls. Topography of sleep spindle density, amplitude, duration, and integrated spindle activity (ISA) were assessed to determine group differences. Spindle parameters were compared between MDD and controls, including analysis stratified by sex. RESULTS: As a group, MDD subjects demonstrated significant increases in frontal and parietal spindle density and ISA compared to controls. When stratified by sex, MDD women demonstrated increases in frontal and parietal spindle density, amplitude, duration, and ISA; whereas MDD men demonstrated either no differences or decreases in spindle parameters. LIMITATIONS: Given the number of male subjects, this study may be underpowered to detect differences in spindle parameters in male MDD participants. CONCLUSIONS: This study demonstrates topographic and sex-related differences in sleep spindles in MDD. Further research is warranted to investigate the role of sleep spindles and sex in the pathophysiology of MDD.

Cortical mechanisms of loss of consciousness: insight from TMS/EEG studies.

In a recent series of experiments we recorded the electroencephalogram (EEG) response to a direct cortical stimulation in humans during wakefulness, NREM sleep, REM sleep and anesthesia by means of a combination of transcranial magnetic stimulation (TMS) and high-density EEG (hd-EEG). TMS/hd-EEG measurements showed that, while during wakefulness and REM sleep the brain is able to sustain long-range specific patterns of activation, during NREM sleep and Midazolam-induced anesthesia, when consciousness fades, this ability is lot: the thalamocortical system, despite being active and reactive, either breaks down in causally independent modules (producing a local slow wave), or it bursts into an explosive and non-specific response (producing a global EEG slow wave). We hypothesize that, like spontaneous sleep slow waves, the slow waves triggered by TMS during sleep and anaesthesia are due to bistability between upand down-states in thalamocortical circuits. In this condition, the inescapable occurrence of a silent, down state after an initial activation impairs the ability of thalamocortical circuits to sustain long-range, differentiated patterns of activation, a theoretical requisite for consciousness. According to animal experiments and computer simulations, thalamocortical bistability may result from increased K-currents, from alterations of the balance between excitation and inhibition and from partial cortical de-afferentation. We hypothesize that these factor may play an important role in determining loss, and recovery, of consciousness also in brain-injured subjects. If this is the case, some types of brain lesions may impair information transmission, above and beyond the associated anatomical disconnection, by inducing bistability in portions of the thalamocortical system that are otherwise healthy.

Electrophysiological traces of visuomotor learning and their renormalization after sleep.

OBJECTIVE: Adapting movements to a visual rotation involves the activation of right posterior parietal areas. Further performance improvement requires an increase of slow wave activity in subsequent sleep in the same areas. Here we ascertained whether a post-learning trace is present in wake EEG and whether such a trace is influenced by sleep slow waves. METHODS: In two separate sessions, we recorded high-density EEG in 17 healthy subjects before and after a visuomotor rotation task, which was performed both before and after sleep. High-density EEG was recorded also during sleep. One session aimed to suppress sleep slow waves, while the other session served as a control. RESULTS: After learning, we found a trace in the eyes-open wake EEG as a local, parietal decrease in alpha power. After the control night, this trace returned to baseline levels, but it failed to do so after slow wave deprivation. The overnight change of the trace correlated with the dissipation of low frequency (<8 Hz) NREM sleep activity only in the control session. CONCLUSIONS: Visuomotor learning leaves a trace in the wake EEG alpha power that appears to be renormalized by sleep slow waves. SIGNIFICANCE: These findings link visuomotor learning to regional changes in wake EEG and sleep homeostasis.

Non-fluent aphasia and neural reorganization after speech therapy: insights from human sleep electrophysiology and functional magnetic resonance imaging.

Stroke is associated with long-term functional deficits. Behavioral interventions are often effective in promoting functional recovery and plastic changes. Recent studies in normal subjects have shown that sleep, and particularly slow wave activity (SWA), is tied to local brain plasticity and may be used as a sensitive marker of local cortical reorganization after stroke. In a pilot study, we assessed the local changes induced by a single exposure to a therapeutic session of IMITATE (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects), a behavioral therapy used for recovery in patients with post-stroke aphasia. In addition, we measured brain activity changes with functional magnetic resonance imaging (fMRI) in a language observation task before, during and after the full IMITATE rehabilitative program. Speech production improved both after a single exposure and the full therapy program as measured by the Western Aphasia Battery (WAB) Repetition subscale. We found that IMITATE induced reorganization in functionally-connected, speech-relevant areas in the left hemisphere. These preliminary results suggest that sleep hd-EEGs, and the topographical analysis of SWA parameters, are well suited to investigate brain plastic changes underpinning functional recovery in neurological disorders.

Cortical reactivity and effective connectivity during REM sleep in humans.

We recorded the electroencephalographic (EEG) responses evoked by transcranial magnetic stimulation (TMS) during the first rapid eye movement (REM) sleep episode of the night and we compared them with the responses obtained during previous wakefulness and NREM sleep. Confirming previous findings, upon falling into NREM sleep, cortical activations became more local and stereotypical, indicating a significant impairment of the intracortical dialogue. During REM sleep, a state in which subjects regain consciousness but are almost paralyzed, TMS triggered more widespread and differentiated patterns of cortical activation, that were similar to the ones observed in wakefulness. Similarly, TMS/hd-EEG may be used to probe the internal dialogue of the thalamocortical system in brain injured patients that are unable to move and communicate.

A direct demonstration of cortical LTP in humans: a combined TMS/EEG study.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly being used to promote cortical reorganization, under the assumption that it can induce long-term potentiation (LTP) of neural responses. This assumption is supported by several lines of indirect evidence. For example, rTMS of motor cortex can induce a potentiation of muscle motor evoked potentials that outlasts the stimulation by several minutes. In animal models, a direct demonstration of LTP is typically obtained by high-frequency electrical stimulation coupled with local field recordings of population responses. In this study, we exploited a new approach based on combined rTMS/high-density electroencephalography (hd-EEG) to obtain direct, noninvasive evidence for LTP in humans. Cortical responses to single TMS pulses were measured with hd-EEG before and after applying rTMS to motor cortex (5Hz, 1500 pulses). The results demonstrate that, after rTMS, EEG responses at latencies of 15-55ms were significantly potentiated. A topographic analysis revealed that this potentiation was significant at EEG electrodes located bilaterally over premotor cortex. Thus, these findings provide a direct demonstration in humans of LTP induced by rTMS.