Parallel modulation of interhemispheric inhibition and the size of a cortical hand muscle representation during active contraction.

Interhemispheric inhibition (IHI) between motor cortexes is thought to suppress unwanted mirror movements during voluntary behaviors and can be assessed using paired-pulse transcranial magnetic stimulation (TMS). The magnitude of IHI may be related to the size of the cortical representation for a given muscle as a mechanism for facilitating unimanual control. To date, the relationship between IHI and cortical muscle representations remains unknown. Fifteen healthy, right-handed individuals participated in the present study. IHI was examined in the right first dorsal interosseous (FDI) muscle by delivering conditioning TMS to ipsilateral (right) primary motor cortex (M1) followed by a test TMS pulse to contralateral (left) M1. The size of the FDI representation in M1 was determined by delivering suprathreshold TMS over a 5 × 5-cm grid centered on the FDI motor hotspot of the left M1. Both IHI and cortical territory were obtained during three conditions: rest, contralateral (right) FDI contraction, and ipsilateral (left) FDI contraction. Results indicate a significant association between IHI and the size of the FDI representation only in the context of contraction and not when the FDI muscle was relaxed. Specifically, reduced IHI corresponded to larger cortical FDI representations during both contralateral and ipsilateral contraction. These data demonstrate that, for a muscle of the hand, the magnitude of IHI and the cortical territory are associated within the context of muscle contraction. NEW & NOTEWORTHY This study provides evidence from noninvasive brain stimulation that communication between the motor cortexes of the two hemispheres plays a role in shaping the motor cortical map that outputs to a hand muscle during active contraction of that muscle. This relationship exists only when the hand muscle is contracted. The findings presented further our understanding of motor control during unilateral movement and may inform future research targeting clinical populations that exhibit impaired unilateral control.

Effects of lorazepam and baclofen on short- and long-latency afferent inhibition.

KEY POINTS: Short-latency afferent inhibition (SAI) is modulated by GABAA receptor activity, whereas the pharmacological origin of long-latency afferent inhibition remains unknown. This is the first study to report that long-latency afferent inhibition (LAI) is reduced by the GABAA positive allosteric modulator lorazepam, and that both SAI and LAI are not modulated by the GABAB agonist baclofen. These findings advance our understanding of the neural mechanisms underlying afferent inhibition. ABSTRACT: The afferent volley evoked by peripheral nerve stimulation has an inhibitory influence on transcranial magnetic stimulation induced motor evoked potentials. This phenomenon, known as afferent inhibition, occurs in two phases: short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI). SAI exerts its inhibitory influence via cholinergic and GABAergic activity. The neurotransmitter receptors that mediate LAI remain unclear. The present study aimed to determine whether LAI is contributed by GABAA and/or GABAB receptor activity. In a double-blinded, placebo-controlled study, 2.5 mg of lorazepam (GABAA agonist), 20 mg of baclofen (GABAB agonist) and placebo were administered to 14 males (mean age 22.7 ± 1.9 years) in three separate sessions. SAI and LAI, evoked by stimulation of the median nerve and recorded from the first dorsal interosseous muscle, were quantified before and at the peak plasma concentration following drug ingestion. Results indicate that lorazepam reduced LAI by ∼40% and, in support of previous work, reduced SAI by ∼19%. However, neither SAI, nor LAI were altered by baclofen. In a follow-up double-blinded, placebo-controlled study, 10 returning participants received placebo or 40 mg of baclofen (double the dosage used in Experiment 1). The results obtained indicate that SAI and LAI were unchanged by baclofen. This is the first study to show that LAI is modulated by GABAA receptor activity, similar to SAI, and that afferent inhibition does not appear to be a GABAB mediated process.

Modulation of long-latency afferent inhibition by the amplitude of sensory afferent volley.

Long-latency afferent inhibition (LAI) is the inhibition of the transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) by the sensory afferent volley following electrical stimulation of a peripheral nerve. It is unknown how the activation of sensory afferent fibers relates to the magnitude of LAI. This study investigated the relationship between LAI and the sensory nerve action potentials (SNAP) from the median nerve (MN) and the digital nerves (DN) of the second digit. LAI was obtained by delivering nerve stimulation 200 ms before a TMS pulse delivered over the motor cortex. Experiment 1 assessed the magnitude of LAI following stimulation of the contralateral MN or DN using nerve stimulus intensities relative to the maximum SNAP (SNAPmax) of that nerve and two TMS intensities (0.5- and 1-mV MEP). Results indicate that MN LAI is maximal at ~50% SNAPmax, when presumably all sensory afferents are recruited for TMS of 0.5-mV MEP. For DN, LAI appears at ~50% SNAPmax and does not increase with further recruitment of sensory afferents. Experiment 2 investigated the magnitude of LAI following ipsilateral nerve stimulation at intensities relative to SNAPmax Results show minimal LAI evoked by ipsilateral MN and no LAI following ipsilateral DN stimulation. Implications for future studies investigating LAI include adjusting nerve stimulation to 50% SNAPmax to obtain maximal LAI. Additionally, MN LAI can be used as a marker for neurological disease or injury by using a nerve stimulation intensity that can evoke a depth of LAI capable of increasing or decreasing.NEW & NOTEWORTHY This is the first investigation of the relationship between long-latency afferent inhibition (LAI) and the sensory afferent volley. Differences exist between median and digital nerve LAI. For the median nerve, LAI increases until all sensory fibers are presumably recruited. In contrast, digital nerve LAI does not increase with the recruitment of additional sensory fibers but rather is present when a given volume of sensory afferent fibers is recruited (~50% of maximum sensory nerve action potential). This novel data provide practical guidelines and contribute to our understanding of the mechanisms underlying LAI.

Acute high-intensity and moderate-intensity interval exercise do not change corticospinal excitability in low fit, young adults.

Previous research has demonstrated a lack of neuroplasticity induced by acute exercise in low fit individuals, but the influence of exercise intensity is unclear. In the present study, we assessed the effect of acute high-intensity (HI) or moderate-intensity (MOD) interval exercise on neuroplasticity in individuals with low fitness, as determined by a peak oxygen uptake (VO2peak) test (n = 19). Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability via area under the motor evoked potential (MEP) recruitment curve before and following training. Corticospinal excitability was unchanged after HI and MOD, suggesting no effect of acute exercise on neuroplasticity as measured via TMS in sedentary, young individuals. Repeated bouts of exercise, i.e., physical training, may be required to induce short-term changes in corticospinal excitability in previously sedentary individuals.

Exercise-Induced Neuroplasticity: A Mechanistic Model and Prospects for Promoting Plasticity.

Aerobic exercise improves cognitive and motor function by inducing neural changes detected using molecular, cellular, and systems level neuroscience techniques. This review unifies the knowledge gained across various neuroscience techniques to provide a comprehensive profile of the neural mechanisms that mediate exercise-induced neuroplasticity. Using a model of exercise-induced neuroplasticity, this review emphasizes the sequence of neural events that accompany exercise, and ultimately promote changes in human performance. This is achieved by differentiating between neuroplasticity induced by acute versus chronic aerobic exercise. Furthermore, this review emphasizes experimental considerations that influence the opportunity to observe exercise-induced neuroplasticity in humans. These include modifiable factors associated with the exercise intervention and nonmodifiable factors such as biological sex, ovarian hormones, genetic variations, and fitness level. To maximize the beneficial effects of exercise in health, disease, and following injury, future research should continue to explore the mechanisms that mediate exercise-induced neuroplasticity. This review identifies some fundamental gaps in knowledge that may serve to guide future research in this area.

The Effects of Biological Sex and Ovarian Hormones on Exercise-Induced Neuroplasticity.

Acute aerobic exercise induces short-term neuroplasticity, although it remains unknown whether biological sex and ovarian hormones influence this response. The present study investigated the effects of biological sex and ovarian hormones on short-term neuroplasticity induced by acute aerobic exercise. Young active adults (n = 17 males and n = 17 females; 21 ±â€¯2 years) participated in two sessions in which transcranial magnetic stimulation (TMS) measures were acquired immediately before and after a 20-min bout of moderate-intensity cycling at 65-70% of maximal heart rate. Females were tested in the follicular (~day 7) and luteal (~day 21) phases of the menstrual cycle. Males were tested on two sessions separated by ~14 days. Measures of motor-evoked potential (MEP) recruitment curves and short-interval intracortical inhibition (SICI) were obtained using TMS. Estradiol, progesterone, testosterone, brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) were measured in venous blood samples obtained prior to exercise. MEP recruitment curves increased and SICI decreased after exercise in both sexes, regardless of menstrual cycle phase. BDNF and IGF-1 were not different between sexes or across the menstrual cycle. Females had a greater estradiol to progesterone ratio (E:P) in the follicular phase compared to the luteal phase, while males had similar testosterone levels on both occasions. We conclude that biological sex and ovarian hormones do not impact short-term neuroplasticity induced by acute exercise. SIGNIFICANCE STATEMENT: Acute exercise induces short-term changes indicative of neuroplasticity within the primary motor cortex and corticospinal pathway. This research reveals that increases in corticospinal excitability and decreases in intracortical inhibition occur similarly in males and females, and that female hormones do not influence these changes. These findings may be used to assist with developing exercise interventions aimed at promoting neuroplasticity in both sexes.

Alterations in Motor Cortical Representation of Muscles Following Incomplete Spinal Cord Injury in Humans.

(1) Background: The primary motor cortex (M1) experiences reorganization following spinal cord injury (SCI). However, there is a paucity of research comparing bilateral M1 organization in SCI and questions remain to be answered. We explored the presence of somatotopy within the M1 representation of arm muscles, and determined whether anatomical shifts in these representations occur, and investigated the symmetry in organization between the two hemispheres.; (2) Methods: Transcranial magnetic stimulation (TMS) was used to map the representation of the biceps, flexor carpi radialis and abductor pollicis brevis (APB) bilaterally in nine individuals with chronic incomplete cervical spinal cord injury and nine aged- and handed-matched uninjured controls. TMS was delivered over a 6 × 5 point grid that encompassed M1 using an intensity specific to the resting motor threshold for each muscle tested.; (3) Results: Results indicate that, compared to controls, muscle representations in SCI are shifted medially but preserve a general somatotopic arrangement, and that territory dedicated to the APB muscle is greater.; (4) Conclusions: These findings demonstrate differences in the organization of M1 between able-bodied controls and those with incomplete cervical SCI. This altered organization may have future implications in understanding the functional deficits observed in SCI and rehabilitation techniques aimed at restoring function.

Short- and long-latency afferent inhibition; uses, mechanisms and influencing factors.

Transcranial magnetic stimulation (TMS) is an ideal technique for non-invasively stimulating the brain and assessing intracortical processes. By delivering electrical stimuli to a peripheral nerve prior to a TMS pulse directed to the motor cortex, the excitability and integrity of the sensorimotor system can be probed at short and long time intervals (short latency afferent inhibition, long latency afferent inhibition). The goal of this review is to detail the experimental factors that influence the magnitude and timing of afferent inhibition in the upper limb and these include the intensity of nerve and TMS delivery, and the nerve composition. Second, the neural mechanisms of SAI are discussed highlighting the lack of existing knowledge pertaining to LAI. Third, the usage of SAI and LAI as a tool to probe cognition and sensorimotor function is explored with suggestions for future avenues of research.

Exploring Behavioral Correlates of Afferent Inhibition.

(1) Background: Afferent inhibition is the attenuation of the muscle response evoked from transcranial magnetic stimulation (TMS) by a prior conditioning electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of afferent inhibition relates to sensation and movement; (2) Methods: 24 healthy, young adults were tested. Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were obtained following median and digital nerve stimulation. Temporal tactile acuity was assessed with a temporal order judgement (TOJ) task, spatial tactile acuity was assessed using a grating orientation task (GOT), and fine manual dexterity was assessed with the Pegboard task; (3) Results: Correlation analyses revealed no association between the magnitude of SAI or LAI with performance on the TOJ, GOT, or Pegboard tasks; (4) Conclusion: The magnitude of SAI and LAI does not relate to performance on the sensory and motor tasks tested. Future studies are needed to better understand whether the afferent inhibition phenomenon relates to human behavior.

Physical activity levels determine exercise-induced changes in brain excitability.

Emerging evidence suggests that regular physical activity can impact cortical function and facilitate plasticity. In the present study, we examined how physical activity levels influence corticospinal excitability and intracortical circuitry in motor cortex following a single session of moderate intensity aerobic exercise. We aimed to determine whether exercise-induced short-term plasticity differed between high versus low physically active individuals. Participants included twenty-eight young, healthy adults divided into two equal groups based on physical activity level determined by the International Physical Activity Questionnaire: low-to-moderate (LOW) and high (HIGH) physical activity. Transcranial magnetic stimulation was used to assess motor cortex excitability via motor evoked potential (MEP) recruitment curves for the first dorsal interosseous (FDI) muscle at rest (MEPREST) and during tonic contraction (MEPACTIVE), short-interval intracortical inhibition (SICI) and facilitation (SICF), and intracortical facilitation (ICF). All dependent measures were obtained in the resting FDI muscle, with the exception of AMT and MEPACTIVE recruitment curves that were obtained during tonic FDI contraction. Dependent measures were acquired before and following moderate intensity aerobic exercise (20 mins, ~60% of the age-predicted maximal heart rate) performed on a recumbent cycle ergometer. Results indicate that MEPREST recruitment curve amplitudes and area under the recruitment curve (AURC) were increased following exercise in the HIGH group only (p = 0.002 and p = 0.044, respectively). SICI and ICF were reduced following exercise irrespective of physical activity level (p = 0.007 and p = 0.04, respectively). MEPACTIVE recruitment curves and SICF were unaltered by exercise. These findings indicate that the propensity for exercise-induced plasticity is different in high versus low physically active individuals. Additionally, these data highlight that a single session of aerobic exercise can transiently reduce inhibition in the motor cortex regardless of physical activity level, potentially priming the system for plasticity induction.

Transcranial Magnetic Stimulation with Intermittent Theta Burst Stimulation Alters Corticospinal Output in Patients with Chronic Incomplete Spinal Cord Injury.

Intermittent theta burst stimulation (iTBS) is intended primarily to alter corticospinal excitability, creating an attractive opportunity to alter neural output following incomplete spinal cord injury (SCI). This study is the first to assess the effects of iTBS in SCI. Eight individuals with chronic incomplete SCI were studied. Sham or real iTBS was delivered (to each participant) over primary motor and somatosensory cortices in separate sessions. Motor-evoked potential (MEP) recruitment curves were obtained from the flexor carpi radialis muscle before and after iTBS. Results indicate similar responses for iTBS to both motor and somatosensory cortex and reduced MEPs in 56.25% and increased MEPs in 25% of instances. Sham stimulation exceeded real iTBS effects in the remaining 18.25%. It is our opinion that observing short-term neuroplasticity in corticospinal output in chronic SCI is an important advance and should be tested in future studies as an opportunity to improve function in this population. We emphasize the need to re-consider the importance of the direction of MEP change following a single session of iTBS since the relationship between MEP direction and motor function is unknown and multiple sessions of iTBS may yield very different directional results. Furthermore, we highlight the importance of including sham control in the experimental design. The fundamental point from this pilot research is that a single session of iTBS is often capable of creating short-term change in SCI. Future sham-controlled randomized trials may consider repeat iTBS sessions to promote long-term changes in corticospinal excitability.

Active and resting motor threshold are efficiently obtained with adaptive threshold hunting.

Transcranial magnetic studies typically rely on measures of active and resting motor threshold (i.e. AMT, RMT). Previous work has demonstrated that adaptive threshold hunting approaches are efficient for estimating RMT. To date, no study has compared motor threshold estimation approaches for measures of AMT, yet this measure is fundamental in transcranial magnetic stimulation (TMS) studies that probe intracortical circuits. The present study compared two methods for acquiring AMT and RMT: the Rossini-Rothwell (R-R) relative-frequency estimation method and an adaptive threshold-hunting method based on maximum-likelihood parameter estimation by sequential testing (ML-PEST). AMT and RMT were quantified via the R-R and ML-PEST methods in 15 healthy right-handed participants in an experimenter-blinded within-subject study design. AMT and RMT estimations obtained with both the R-R and ML-PEST approaches were not different, with strong intraclass correlation and good limits of agreement. However, ML-PEST required 17 and 15 fewer stimuli than the R-R method for the AMT and RMT estimation, respectively. ML-PEST is effective in reducing the number of TMS pulses required to estimate AMT and RMT without compromising the accuracy of these estimates. Using ML-PEST to estimate AMT and RMT increases the efficiency of the TMS experiment as it reduces the number of pulses to acquire these measures without compromising accuracy. The benefits of using the ML-PEST approach are amplified when multiple target muscles are tested within a session.