The interplay of perceptual processing demands and practice in modulating voluntary and involuntary motor responses.

Understanding how sensory processing demands affect the ability to ignore task-irrelevant, loud auditory stimuli (LAS) during a task is key to performance in dynamic environments. For example, tennis players must ignore crowd noise to perform optimally. We investigated how practice affects this ability by examining the effects of delivering LASs during preparatory phase of an anticipatory timing (AT) task on the voluntary and reflexive responses in two conditions: lower and higher visual processing loads. Twenty-four participants (mean age = 23.1, 11 females) completed the experiment. The AT task involved synchronizing a finger abduction response with the last visual stimulus item in a sequence of four Gabor grating patches briefly flashed on screen. The lower demand condition involved only this task, and the higher demand condition required processing the orientations of the patches to report changes in the final stimulus item. Our results showed that higher visual processing demands affected the release of voluntary actions, particularly in the first block of trials. When the perceptual load was lower, responses were released earlier by the LAS compared to the high-load condition. Practice reduced these effects largely, but high perceptual load still led to earlier action release in the second block. In contrast, practice led to more apparent facilitation of eyeblink latency in the second block. These findings indicate that a simple perceptual load manipulation can impact the execution of voluntary motor actions, particularly for inexperienced participants. They also suggest distinct movement preparation influences on voluntary and involuntary actions triggered by acoustic stimuli.

Transcutaneous auricular vagus nerve stimulation modifies cortical excitability in middle-aged and older adults.

There is a growing interest in the clinical application of transcutaneous auricular vagus nerve stimulation (taVNS). However, its effect on cortical excitability, and whether this is modulated by stimulation duration, remains unclear. We evaluated whether taVNS can modify excitability in the primary motor cortex (M1) in middle-aged and older adults and whether the stimulation duration moderates this effect. In addition, we evaluated the blinding efficacy of a commonly reported sham method. In a double-blinded randomized cross-over sham-controlled study, 23 healthy adults (mean age 59.91 ± 6.87 years) received three conditions: active taVNS for 30 and 60 min and sham for 30 min. Single and paired-pulse transcranial magnetic stimulation was delivered over the right M1 to evaluate motor-evoked potentials. Adverse events, heart rate and blood pressure measures were evaluated. Participant blinding effectiveness was assessed via guesses about group allocation. There was an increase in short-interval intracortical inhibition (F = 7.006, p = .002) and a decrease in short-interval intracortical facilitation (F = 4.602, p = .014) after 60 min of taVNS, but not 30 min, compared to sham. taVNS was tolerable and safe. Heart rate and blood pressure were not modified by taVNS (p > .05). Overall, 96% of participants detected active stimulation and 22% detected sham stimulation. taVNS modifies cortical excitability in M1 and its effect depends on stimulation duration in middle-aged and older adults. taVNS increased GABAAergic inhibition and decreased glutamatergic activity. Sham taVNS protocol is credible but there is an imbalance in beliefs about group allocation.

Acute physiological responses to steady-state arm cycling ergometry with and without blood flow restriction.

PURPOSE: To compare heart rate (HR), oxygen consumption (VO2), blood lactate (BL), and ratings of perceived exertion (RPE) during arm cycling with and without a blood flow restriction (BFR). METHODS: Twelve healthy males (age: 23.9 ± 3.75 years) completed four, randomized, 15-min arm cycling conditions: high-workload (HW: 60% maximal power output), low-workload (LW: 30% maximal power output), low-workload with BFR (LW-BFR), and BFR with no exercise (BFR-only). In the BFR conditions, cuff pressure to the proximal biceps brachii was set to 70% of occlusion pressure. HR, VO2, and RPE were recorded throughout the exercise, and BL was measured before, immediately after, and five minutes post-exercise. Within-subject repeated-measures ANOVA was used to evaluate condition-by-time interactions. RESULTS: HW elicited the greatest responses in HR (91% of peak; 163.3 ± 15.8 bpm), VO2 (71% of peak; 24.0 ± 3.7 ml kg-1 min-1), BL (7.7 ± 2.5 mmol L-1), and RPE (14 ± 1.7) and was significantly different from the other conditions (p < 0.01). The LW and LW-BFR conditions did not differ from each other in HR, VO2, BL, and RPE mean of conditions: ~ 68%, 41%, 3.5 ± 1.6 mmol L-1, 10.4 ± 1.6, respectively; p > 0.05). During the BFR-only condition, HR increased from baseline by ~ 15% (on average) (p < 0.01) without any changes in VO2, BL, and RPE (p > 0.05). CONCLUSIONS: HW arm cycling elicited the largest and most persistent physiological responses compared to LW arm cycling with and without a BFR. As such, practitioners who prescribe arm cycling for their clients should be advised to augment the demands of exercise via increases in exercise intensity (i.e., power output), rather than by adding BFR.

Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex.

PURPOSE: Acute intermittent hypoxia (AIH) is a safe and non-invasive treatment approach that uses brief, repetitive periods of breathing reduced oxygen air alternated with normoxia. While AIH is known to affect spinal circuit excitability, the effects of AIH on cortical excitability remain largely unknown. We investigated the effects of AIH on cortical excitability within the primary motor cortex. METHODS: Eleven healthy, right-handed participants completed two testing sessions: (1) AIH (comprising 3 min in hypoxia [fraction of inspired oxygen ~ 10%] and 2 min in normoxia repeated over five cycles) and (2) normoxia (NOR) (equivalent duration to AIH). Single- and paired-pulse transcranial magnetic stimulations were delivered to the primary motor cortex, before and 0, 25, and 50 min after AIH and normoxia. RESULTS: The mean nadir in arterial oxygen saturation was lower (p < 0.001) during the cycles of AIH (82.5 ± 4.9%) than NOR (97.8 ± 0.6%). There was no significant difference in corticospinal excitability, intracortical facilitation, or intracortical inhibition between AIH and normoxia conditions at any time point (all p > 0.05). There was no association between arterial oxygen saturation and changes in corticospinal excitability after AIH (r = 0.05, p = 0.87). CONCLUSION: Overall, AIH did not modify either corticospinal excitability or excitability of intracortical facilitatory and inhibitory circuits within the primary motor cortex. Future research should explore whether a more severe or individualised AIH dose would induce consistent, measurable changes in corticospinal excitability.

Premovement inhibition can protect motor actions from interference by response-irrelevant sensory stimulation.

KEY POINTS: Suppression of corticospinal excitability is reliably observed during preparation for a range of motor actions, leading to the belief that this preparatory inhibition is a physiologically obligatory component of motor preparation. The neurophysiological function of this suppression is uncertain. We restricted the time available for participants to engage in preparation and found no evidence for preparatory inhibition. The function of preparatory inhibition can be inferred from our findings that sensory stimulation can disrupt motor output in the absence of preparatory inhibition, but enhance motor output when inhibition is present. These findings suggest preparatory inhibition may be a strategic process which acts to protect prepared actions from external interference. Our findings have significant theoretical implications for preparatory processes. Findings may also have a pragmatic benefit in that acoustic stimulation could be used therapeutically to facilitate movement, but only if the action can be prepared well in advance. ABSTRACT: Shortly before movement initiation, the corticospinal system undergoes a transient suppression. This phenomenon has been observed across a range of motor tasks, suggesting that it may be an obligatory component of movement preparation. We probed whether this was also the case when the urgency to perform a motor action was high, in a situation where little time was available to engage in preparatory processes. We controlled the urgency of an impending motor action by increasing or decreasing the foreperiod duration in an anticipatory timing task. Transcranial magnetic stimulation (TMS; experiment 1) or a loud acoustic stimulus (LAS; experiment 2) were used to examine how corticospinal and subcortical excitability were modulated during motor preparation. Preparatory inhibition of the corticospinal tract was absent when movement urgency was high, though motor actions were initiated on time. In contrast, subcortical circuits were progressively inhibited as the time to prepare increased. Interestingly, movement force and vigour were reduced by both TMS and the LAS when movement urgency was high, and enhanced when movement urgency was low. These findings indicate that preparatory inhibition may not be an obligatory component of motor preparation. The behavioural effects we observed in the absence of preparatory inhibition were induced by both TMS and the LAS, suggesting that accessory sensory stimulation may disrupt motor output when such stimulation is presented in the absence of preparatory inhibition. We conclude that preparatory inhibition may be an adaptive strategy which can serve to protect the prepared motor action from external interference.

Reduced SMA-M1 connectivity in older than younger adults measured using dual-site TMS.

With advancing age comes a decline in voluntary movement control. Growing evidence suggests that an age-related decline in effective connectivity between the supplementary motor area and primary motor cortex (SMA-M1) might play a role in an age-related decline of bilateral motor control. Dual-site transcranial magnetic stimulation (TMS) can be used to measure SMA-M1 effective connectivity. In the current study, we aimed to (1) replicate previous dual-site TMS research showing reduced SMA-M1 connectivity in older than younger adults and (2) examine whether SMA-M1 connectivity is associated with bilateral motor control in independent samples of younger (n = 30) and older adults (n = 30). SMA-M1 connectivity was measured using dual-site TMS with interstimulus intervals of 6, 7 and 8 ms, and bilateral motor control was measured using the Purdue Pegboard, Four Square Step Test and the Timed Up and Go task. Findings from this study showed that SMA-M1 connectivity was reduced in older than in younger adults, suggesting that the direct excitatory connections between SMA and M1 had reduced efficacy in older than younger adults. Furthermore, greater SMA-M1 connectivity was associated with better bimanual motor control in older adults. Thus, SMA-M1 connectivity in older adults might underpin, in part, the age-related decline in bilateral motor control. These findings contribute to our understanding of age-related declines in motor control and provide a physiological basis for the development of interventions to improve bimanual and bilateral motor control.

Examining motor evoked potential amplitude and short-interval intracortical inhibition on the up-going and down-going phases of a transcranial alternating current stimulation (tacs) imposed alpha oscillation.

Many brain regions exhibit rhythmical activity thought to reflect the summed behaviour of large populations of neurons. The endogenous alpha rhythm has been associated with phase-dependent modulation of corticospinal excitability. However, whether exogenous alpha rhythm, induced using transcranial alternating current stimulation (tACS) also has a phase-dependent effect on corticospinal excitability remains unknown. Here, we triggered transcranial magnetic stimuli (TMS) on the up- or down-going phase of a tACS-imposed alpha oscillation and measured motor evoked potential (MEP) amplitude and short-interval intracortical inhibition (SICI). There was no significant difference in MEP amplitude or SICI when TMS was triggered on the up- or down-going phase of the tACS-imposed alpha oscillation. The current study provides no evidence of differences in corticospinal excitability or GABAergic inhibition when targeting the up-going (peak) and down-going (trough) phase of the tACS-imposed oscillation.

Good test-retest reliability of a paired-pulse transcranial magnetic stimulation protocol to measure short-interval intracortical facilitation.

Transcranial magnetic stimulation (TMS) is used frequently to study human physiology, including the indirect-wave (I-wave) circuits generating short-interval intracortical facilitation (SICF). Growing evidence implicates SICF in plasticity and motor learning, suggesting that SICF is likely of functional relevance in both health and disease. To date, test-retest reliability has not been established for measures of SICF: given the clear potential of SICF to be used as a diagnostic tool, it is critical to establish the reliability of the paired-pulse TMS protocol to measure SICF. We investigated the test-retest reliability of SICF measured using paired-pulse TMS. SICF was measured in two sessions in 20 young adults using single- and paired-pulse TMS. Single-pulse TMS was set at an intensity that elicited MEPs of 1 mV (SI1mV) and paired-pulse TMS was set with the first stimulus at SI1mV, the second stimulus (S2) 90% of resting motor threshold (RMT), and a total of 20 interstimulus intervals (ISI; 1.1-4.9 ms with a 0.2 ms step). Large intraclass correlation coefficients (ICC) indicate good test-retest reliability between sessions for all SICF peaks (ICCs ranging from 0.73 to 0.79). The ISI at which SICF was maximal within individuals was consistent at all three peaks across both experimental sessions. Results showed good test-retest reliability of SICF at all three peaks when using a standard paired-pulse protocol to measure SICF. This finding suggests that paired-pulse TMS can be used to reliably probe the excitability of the interneuronal circuits that generate SICF. This provides a strong platform for future research to investigate the functional role of I-wave circuitry, including the role of I-wave circuitry in motor control decline in healthy older adults and individuals with movement disorders.

Corticospinal excitability is modulated by distinct movement patterns during action observation.

It is well established that excitability of the primary motor cortex increases during action observation. However, the modulation of motor cortex excitability during observation of different actions, with distinct movement patterns, is not fully understood. The aim of the current study was to examine time-dependent changes in corticospinal excitability during observation of two actions with different levels of complexity. We developed videos of two distinct actions (a point and a reach-and-grasp), that were matched in video length, action onset, and onset of kinematics. Single-pulse transcranial magnetic stimulation was used to investigate time-dependent changes in primary motor cortex excitability during observation of the two actions. Motor evoked potentials (MEP) were recorded from two intrinsic hand muscles, namely first dorsal interosseous (FDI) and abductor digiti minimi. Results showed no difference in MEP amplitude during observation of a static hand compared to observation of the actions. When comparing the point to the grasp action, there were two key findings showing time-dependent changes in motor cortex excitability: first, greater MEP amplitude in FDI during observation of the point than the grasp action at an early time-point (index finger extension) and second, greater MEP amplitude in FDI during observation of the grasp than the point action at a later time-point (hand opening to form a grasp). These results show that excitability of the primary motor cortex is differentially modulated during observation of a point and grasp action, suggesting that the action observation network is engaged in a time-dependent manner during action observation.

Differential plasticity of extensor and flexor motor cortex representations following visuomotor adaptation.

Representations within the primary motor cortex (M1) are capable of rapid functional changes following motor learning, known as use-dependent plasticity. GABAergic inhibition plays a role in use-dependent plasticity. Evidence suggests a different capacity for plasticity of distal and proximal upper limb muscle representations. However, it is unclear whether the motor cortical representations of forearm flexor and extensor muscles also have different capacities for plasticity. The current study used transcranial magnetic stimulation to investigate motor cortex excitability and inhibition of forearm flexor and extensor representations before and after performance of a visuomotor adaptation task that primarily targeted flexors and extensors separately. There was a decrease in extensor and flexor motor-evoked potential (MEP) amplitude after performing the extensor adaptation, but no change in flexor and extensor MEP amplitude after performing the flexor adaptation. There was also a decrease in motor cortical inhibition in the extensor following extensor adaptation, but no change in motor cortical inhibition in the flexor muscle following flexor adaptation or either of the non-prime mover muscles. Findings suggest that the forearm extensor motor cortical representation exhibits plastic change following adaptive motor learning, and broadly support the distinct neural control of forearm flexor and extensor muscles.

The neural bases of different levels of action understanding.

Many have recently questioned whether all levels of actions understanding, from lower kinematic levels to the higher goal or intention levels of action understanding, are processed in the action observation network (a network of neurons that are active during action execution and observation). A recent study by Wurm and Lingnau (J Neurosci 35: 7727-7735, 2015) gave evidence to the contrary, by showing that higher levels of action understanding are processed in the lateral occipitotemporal cortex. An important next step is to differentiate between the role of the lateral occipitotemporal cortex in processing the visual form of an observed action and the goal of an observed action.

Combined transcranial alternating current stimulation and continuous theta burst stimulation: a novel approach for neuroplasticity induction.

Non-invasive brain stimulation can induce functionally relevant plasticity in the human cortex, making it potentially useful as a therapeutic tool. However, the induced changes are highly variable between individuals, potentially limiting research and clinical utility. One factor that might contribute to this variability is the level of cortical inhibition at the time of stimulation. The alpha rhythm (~ 8-13 Hz) recorded with electroencephalography (EEG) is thought to reflect pulsatile cortical inhibition; therefore, targeting non-invasive brain stimulation to particular phases of the alpha rhythm may provide an approach to enhance plasticity induction. Transcranial alternating current stimulation (tACS) has been shown to entrain cortical oscillations in a frequency-specific manner. We investigated whether the neuroplastic response to continuous theta burst stimulation (cTBS) was enhanced by timing bursts of stimuli to the peak or the trough of a tACS-imposed alpha rhythm. While motor evoked potentials (MEPs) were unaffected when cTBS was applied in-phase with the peak of the tACS-imposed oscillation, MEP depression was enhanced when cTBS was applied in-phase with the trough. This enhanced MEP depression was dependent on the individual peak frequency of the endogenous alpha rhythm recorded with EEG prior to stimulation, and was strongest in those participants classified as non-responders to standard cTBS. These findings suggest that tACS may be used in combination with cTBS to enhance the plasticity response. Furthermore, the peak frequency of endogenous alpha, as measured with EEG, may be used as a simple marker to pre-select those individuals likely to benefit from this approach.

Can noninvasive brain stimulation enhance function in the ageing brain?

Advancing age is associated with cognitive and motor performance deficits and a reduced capacity for plasticity. Zimerman and colleagues (Zimerman M, Nitsch M, Giraux P, Gerloff C, Cohen LG, Hummel FC. Ann Neurol 73: 10-15, 2013) have recently shown that noninvasive brain stimulation can enhance behavioral improvements following training on a motor sequence task in older adults. The work is of high clinical importance given the rapidly growing ageing population and the accompanying costs to health systems globally.

Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain.

The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this, its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from five time points on four sessions across nine healthy researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days, we hypothesized that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (df: 1, 148.24; F: 10.41; p = 0.002). As the magnitude of the CAR is regulated by the "master" circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral "slave" CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity.

The impact of burn injury on the central nervous system.

Burn injuries can be devastating, with life-long impacts including an increased risk of hospitalization for a wide range of secondary morbidities. One area that remains not fully understood is the impact of burn trauma on the central nervous system (CNS). This review will outline the current findings on the physiological impact that burns have on the CNS and how this may contribute to the development of neural comorbidities including mental health conditions. This review highlights the damaging effects caused by burn injuries on the CNS, characterized by changes to metabolism, molecular damage to cells and their organelles, and disturbance to sensory, motor and cognitive functions in the CNS. This damage is likely initiated by the inflammatory response that accompanies burn injury, and it is often long-lasting. Treatments used to relieve the symptoms of damage to the CNS due to burn injury often target inflammatory pathways. However, there are non-invasive treatments for burn patients that target the functional and cognitive damage caused by the burn, including transcranial magnetic stimulation and virtual reality. Future research should focus on understanding the mechanisms that underpin the impact of a burn injury on the CNS, burn severity thresholds required to inflict damage to the CNS, and acute and long-term therapies to ameliorate deleterious CNS changes after a burn.

Functional Brain Changes Following Burn Injury: A Narrative Review.

BACKGROUND: Burn injuries cause significant motor and sensory dysfunctions that can negatively impact burn survivors' quality of life. The underlying mechanisms of these burn-induced dysfunctions have primarily been associated with damage to the peripheral neural architecture, however, evidence points to a systemic influence of burn injury. Central nervous system (CNS) reorganizations due to inflammation, afferent dysfunction, and pain could contribute to persistent motor and sensory dysfunction in burn survivors. Recent evidence shows that the capacity for neuroplasticity is associated with self-reported functional recovery in burn survivors. OBJECTIVE: This review first outlines motor and sensory dysfunctions following burn injury and critically examines recent literature investigating the mechanisms mediating CNS reorganization following burn injury. The review then provides recommendations for future research and interventions targeting the CNS such as non-invasive brain stimulation to improve functional recovery. CONCLUSIONS: Directing focus to the CNS following burn injury, alongside the development of non-invasive methods to induce functionally beneficial neuroplasticity in the CNS, could advance treatments and transform clinical practice to improve quality of life in burn survivors.

Chronic tension-type headache is associated with impaired motor learning.

BACKGROUND: Supraspinal activity-dependent neuroplasticity may be important in the transition from acute to chronic pain. We examined neuroplasticity in a cortical region not considered to be a primary component of the central pain matrix in chronic tension-type headache (CTTH) patients. We hypothesised that neuroplasticity would be exaggerated in CTTH patients compared to healthy controls, which might explain (in part) the development of chronic pain in these individuals. METHODS: Neuroplasticity was examined following a ballistic motor training task in CTTH patients and control subjects (CS). Changes in peak acceleration (motor learning) and motor-evoked potential (MEP) amplitude evoked by single-pulse transcranial magnetic stimulation were compared. RESULTS: CTTH patients showed significantly less motor learning on the training task than CS (mean acceleration increase 87% CTTH, 204% CS, P < .05), and CS but not CTTH patients showed a significant increased MEP amplitude following training (CS: F = 2.9, P < .05; CTTH: F = 1.6, P > .05). CONCLUSIONS: These findings suggest a deficit in use-dependent neuroplasticity within networks responsible for task performance in CTTH patients which might reflect reciprocal influences between primary motor cortex and interconnected pain processing networks. These findings may help explain the positive effects of facilitatory non-invasive brain stimulation targeting motor areas on chronic pain and help elucidate the mechanisms mediating chronic pain.

Finding synaptic couplings from a biophysical model of motor evoked potentials after theta-burst transcranial magnetic stimulation.

OBJECTIVE: We aimed to use measured input-output (IO) data to identify the best fitting model for motor evoked potentials. METHODS: We analyzed existing IO data before and after intermittent and continuous theta-burst stimulation (iTBS & cTBS) from a small group of subjects (18 for each). We fitted individual synaptic couplings and sensitivity parameters using variations of a biophysical model. A best performing model was selected and analyzed. RESULTS: cTBS gives a broad reduction in MEPs for amplitudes larger than resting motor threshold (RMT). Close to threshold, iTBS gives strong potentiation. The model captures individual IO curves. There is no change to the population average synaptic weights post TBS but the change in excitatory-to-excitatory synaptic coupling is strongly correlated with the experimental post-TBS response relative to baseline. CONCLUSIONS: The model describes population-averaged and individual IO curves, and their post-TBS change. Variation among individuals is accounted for with variation in synaptic couplings, and variation in sensitivity of neural response to stimulation. SIGNIFICANCE: The best fitting model could be applied more broadly and validation studies could elucidate underlying biophysical meaning of parameters.

Increase in flexor but not extensor corticospinal motor outputs following ischemic nerve block.

Human motor cortex is capable of rapid and long-lasting reorganization, evident globally, as shifts in body part representations, and at the level of individual muscles as changes in corticospinal excitability. Representational shifts provide an overview of how various body parts reorganize relative to each other but do not tell us whether all muscles in a given body part reorganize in the same manner and to the same extent. Transcranial magnetic stimulation (TMS) provides information about individual muscles and can therefore inform us about the uniformity of plastic changes within a body part. We used TMS to investigate changes in corticospinal excitability of forearm flexors and extensors after inflation of a tourniquet around the wrist. Motor evoked potential (MEP) amplitudes and input/output (I/O) curves were obtained from wrist flexors and extensors simultaneously before and during block. TMS was delivered to the optimal site for eliciting MEPs in flexors in experiment 1, extensors in experiment 2, and both flexors and extensors in experiment 3. In all experiments flexor MEP amplitude increased during block while extensor MEP amplitude showed no systematic change, and the slope of flexor but not extensor I/O curves increased. Flexor H-reflex amplitude normalized to maximal M wave showed negligible changes during block, suggesting that the increase in corticospinal excitability in the flexors cannot be completely explained by increased excitability at the spinal cord level. These findings show that forearm flexors and extensors differ in their potential for plastic changes, highlight the importance of investigating how experimentally induced plasticity affects anatomically close, but functionally distinct, muscle groups, and suggest that rehabilitation interventions aiming to alter cortical organization should consider the differential sensitivity of various muscle groups to plasticity processes.