Investigating the effects of dopamine on short- and long-latency afferent inhibition.

Short- and long-latency afferent inhibition (SAI and LAI respectively) are phenomenon whereby the motor evoked potential induced by transcranial magnetic stimulation (TMS) is inhibited by a sensory afferent volley consequent to nerve stimulation. It remains unclear whether dopamine participates in the genesis or modulation of SAI and LAI. The present study aimed to determine if SAI and LAI are modulated by levodopa (l-DOPA). In this placebo-controlled, double-anonymized study Apo-Levocarb (100 mg l-DOPA in combination with 25 mg carbidopa) and a placebo were administered to 32 adult males (mean age 24 ± 3 years) in two separate sessions. SAI and LAI were evoked by stimulating the median nerve and delivering single-pulse TMS over the motor hotspot corresponding to the first dorsal interosseous muscle of the right hand. SAI and LAI were quantified before and 1 h following ingestion of drug or placebo corresponding to the peak plasma concentration of Apo-Levocarb. The results indicate that Apo-Levocarb increases SAI and does not significantly alter LAI. These findings support literature demonstrating increased SAI following exogenous dopamine administration in neurodegenerative disorders. KEY POINTS: Short- and long-latency afferent inhibition (SAI and LAI respectively) are measures of corticospinal excitability evoked using transcranial magnetic stimulation. SAI and LAI are reduced in conditions such as Parkinson's disease which suggests dopamine may be involved in the mechanism of afferent inhibition. 125 mg of Apo-Levocarb (100 mg dopamine) increases SAI but not LAI. This study increases our understanding of the pharmacological mechanism of SAI and LAI.

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.

Short-latency afferent inhibition determined by the sensory afferent volley.

Short-latency afferent inhibition (SAI) is characterized by the suppression of the transcranial magnetic stimulation motor evoked potential (MEP) by the cortical arrival of a somatosensory afferent volley. It remains unknown whether the magnitude of SAI reflects changes in the sensory afferent volley, similar to that observed for somatosensory evoked potentials (SEPs). The present study investigated stimulus-response relationships between sensory nerve action potentials (SNAPs), SAI, and SEPs and their interrelatedness. Experiment 1 (n = 23, age 23 ± 1.5 yr) investigated the stimulus-response profile for SEPs and SAI in the flexor carpi radialis muscle after stimulation of the mixed median nerve at the wrist using ∼25%, 50%, 75%, and 100% of the maximum SNAP and at 1.2× and 2.4× motor threshold (the latter equated to 100% of the maximum SNAP). Experiment 2 (n = 20, age 23.1 ± 2 yr) probed SEPs and SAI stimulus-response relationships after stimulation of the cutaneous digital nerve at ∼25%, 50%, 75%, and 100% of the maximum SNAP recorded at the elbow. Results indicate that, for both nerve types, SAI magnitude is dependent on the volume of the sensory afferent volley and ceases to increase once all afferent fibers within the nerve are recruited. Furthermore, for both nerve types, the magnitudes of SAI and SEPs are related such that an increase in excitation within somatosensory cortex is associated with an increase in the magnitude of afferent-induced MEP inhibition.

Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively.

Short- and Long-Intracortical Inhibition in Incomplete Spinal Cord Injury.

BACKGROUND: Short- (SICI) and long-interval intracortical inhibition (LICI) are involved in the control of movement and movement initiation. Alterations to the two circuits can result in direct alterations to the physiology of the muscles and can be used to explain the physiological changes to individuals with spinal cord injury (SCI). OBJECTIVE: To probe changes in GABAergic function by characterizing the recruitment curves of SICI and LICI interval intracortical inhibition in an upper limb muscle in chronic SCI participants with injury between C3 and C7. METHODS: Recruitment curves were elicited with conditioning stimulus intensities determined as a percentage of active motor threshold (AMT) (SICI, 60% to 110% AMT; LICI, 90% to 130% AMT) and recorded from the flexor carpi radialis muscle during an isometric contraction equal to 15% to 20% of maximum voluntary contraction. RESULTS: AMT was greater and motor-evoked potential sizes were lower in SCI compared with uninjured controls. SICI magnitude was not different between groups, although the range of conditioning stimulus intensities to evoke SICI was unique to each group. LICI was reduced in the control group during active contraction and remained present in SCI. DISCUSSION: LICI was increased in the actively contracted flexor carpi radialis muscle in individuals with SCI compared with age-matched controls. These findings indicate that GABAB function mediating LICI is different in SCI versus controls. CONCLUSIONS: Increased LICI in SCI may be attributed to the medication baclofen or to changes in the neural mechanisms controlling contraction-related modulation of the LICI circuit.

Repetitive Transcranial Magnetic Stimulation with Sensorimotor Training for the Treatment of Complex Regional Pain Syndrome Type 2 of the Upper Limb Case Report.

This case report describes the use of repetitive transcranial magnetic stimulation (rTMS) combined with sensorimotor training (SMT) to treat an individual with complex regional pain syndrome (CRPS) type 2 with allodynia of the right hand/wrist. After the 9-week intervention, there was a clinically meaningful reduction in pain intensity which continued to 3 months after intervention. Further, clinically meaningful improvements in wrist and hand function and allodynia were observed. Although the use of rTMS for CRPS has been reported, this unique report provides valuable insight into the clinical utility of rTMS plus SMT for the treatment of CRPS and related symptoms.

Continuous theta-burst stimulation modulates tactile synchronization.

BACKGROUND: Temporal order judgement (TOJ) is the ability to detect the order of occurrence of two sequentially delivered stimuli. Previous research has shown that TOJ in the presence of synchronized periodic conditioning stimuli impairs TOJ performance, and this phenomenon is suggested to be mediated by GABAergic interneurons that cause perceptual binding across the two skin sites. Application of continuous theta-burst repetitive TMS (cTBS) over primary somatosensory cortex (SI) alters temporal and spatial tactile perception. The purpose of this study was to examine TOJ perception in the presence and absence of synchronized periodic conditioning stimuli before and after cTBS applied over left-hemisphere SI. A TOJ task was administered on the right index and middle finger (D2 and D3) in two separate sessions in the presence and absence of conditioning stimuli (a background low amplitude sinusoidal vibration). RESULTS: CTBS reduced the impact of the conditioning stimuli on TOJ performance for up to 18 minutes following stimulation while sham cTBS did not affect TOJ performance. In contrast, the TOJ task performed in the absence of synchronized conditioning stimulation was unaltered following cTBS. CONCLUSION: We conclude that cTBS suppresses inhibitory networks in SI that mediate perceptual binding during TOJ synchronization. CTBS offers one method to suppress cortical excitability in the cortex and potentially benefit clinical populations with altered inhibitory cortical circuits. Additionally, TOJ measures with conditioning stimuli may provide an avenue to assess sensory processing in neurologically impaired patient populations.

Experimental environment improves the reliability of short-latency afferent inhibition.

Evidence indicates attention can alter afferent inhibition, a Transcranial Magnetic Stimulation (TMS) evoked measure of cortical inhibition following somatosensory input. When peripheral nerve stimulation is delivered prior to TMS, a phenomenon known as afferent inhibition occurs. The latency between the peripheral nerve stimulation dictates the subtype of afferent inhibition evoked, either short latency afferent inhibition (SAI) or long latency afferent inhibition (LAI). While afferent inhibition is emerging as a valuable tool for clinical assessment of sensorimotor function, the reliability of the measure remains relatively low. Therefore, to improve the translation of afferent inhibition within and beyond the research lab, the reliability of the measure must be improved. Previous literature suggests that the focus of attention can modify the magnitude of afferent inhibition. As such, controlling the focus of attention may be one method to improve the reliability of afferent inhibition. In the present study, the magnitude and reliability of SAI and LAI was assessed under four conditions with varying attentional demands focused on the somatosensory input that evokes SAI and LAI circuits. Thirty individuals participated in four conditions; three conditions were identical in their physical parameters and varied only in the focus of directed attention (visual attend, tactile attend, non- directed attend) and one condition consisted of no external physical parameters (no stimulation). Reliability was measured by repeating conditions at three time points to assess intrasession and intersession reliability. Results indicate that the magnitude of SAI and LAI were not modulated by attention. However, the reliability of SAI demonstrated increased intrasession and intersession reliability compared to the no stimulation condition. The reliability of LAI was unaffected by the attention conditions. This research demonstrates the impact of attention/arousal on the reliability of afferent inhibition and has identified new parameters to inform the design of TMS research to improve reliability.

Investigating the intra-session reliability of short and long latency afferent inhibition.

Objective: To establish the intrasession relative and absolute reliability of Short (SAI) and Long-Latency Afferent Inhibition (LAI). These findings will allow us to guide future explorations of changes to these measures. Methods: 31 healthy individuals (21.06 ±â€¯2.85 years) had SAI and LAI obtained thrice at 30-minute intervals in one session. To identify the minimum number of trials required to reliably elicit SAI and LAI, relative reliability was assessed at running intervals of 5 trials. Results: SAI had moderate-high, and LAI had high-excellent relative reliability. Both SAI and LAI had high amounts of measurement error. LAI had high relative reliability when only 5 frames of data were included, whereas SAI required ∼20-30 frames of data for the same. For both SAI and LAI, individual smallest detectable change was large but was reduced at the group level. Conclusions: SAI and LAI can be used for both diagnostic purposes and to assess group level change but have limited utility in assessing within-individual changes. Significance: These results can be used to inform future work regarding the utility of SAI and LAI, particularly in terms of their ability to identify particularly high or low values of afferent inhibition.

Tactile sensorimotor training does not alter short- and long-latency afferent inhibition.

Sensorimotor integration refers to the process of combining incoming sensory information with outgoing motor commands to control movement. Short-latency afferent inhibition (SAI), and long-latency afferent inhibition (LAI) are neurophysiological measures of sensorimotor integration collected using transcranial magnetic stimulation. No studies to date have investigated the influence of tactile discrimination training on these measures. This study aimed to determine whether SAI and LAI are modulated following training on a custom-designed tactile discrimination maze task. Participants performed a 'high difficulty' and 'low difficulty' maze training condition on separate visits. On an additional visit, no maze training was performed to serve as a control condition. Despite evidence of performance improvements during training, there were no significant changes in SAI or LAI following training in either condition. The total number of errors during maze training was significantly greater in the high-difficulty condition compared with the low-difficulty condition. These findings suggest that sensorimotor maze training for 30 min is insufficient to modify the magnitude of SAI and LAI.

Theta burst repetitive transcranial magnetic stimulation attenuates somatosensory evoked potentials from the lower limb.

BACKGROUND: Continuous theta burst stimulation (cTBS) is a form of repetitive transcranial magnetic stimulation which has been shown to alter cortical excitability in the upper limb representation of primary somatosensory cortex (SI). However, it is unknown whether cTBS modulates cortical excitability within the lower limb representation in SI. The present study investigates the effects of cTBS over the SI lower limb representation on cortical somatosensory evoked potentials (SEPs) and Hoffmann reflex (H-reflex) following tibial nerve stimulation at the knee. SEPs and H-reflex were recorded before and in four time blocks up to 30 minutes following cTBS targeting the lower limb representation within SI. RESULTS: Following cTBS, the P1-N1 first cortical potential was significantly decreased at 12-16 minutes. CTBS also suppressed the P2-N2 second cortical potential for up to 30 minutes following stimulation. The H-reflex remained statistically unchanged following cTBS although there was a modest suppression observed. CONCLUSION: We conclude that cTBS decreases cortical excitability of the lower limb representation of SI as evidenced by suppressed SEP amplitude. The duration and magnitude of the cTBS after effects are similar to those observed in upper limb studies.

Dopamine alters tactile perception in Parkinson's disease.

BACKGROUND: Abnormal somatosensory processing may contribute to motor impairments observed in Parkinson's disease (PD). Dopaminergic medications have been shown to alter somatosensory processing such that tactile perception is improved. In PD, it remains unclear whether the temporal sequencing of tactile stimuli is altered and if dopaminergic medications alter this perception. METHODS: Somatosensory tactile perception was investigated using temporal order judgment in patients with Parkinson's disease on and off dopaminergic medications and in aged-matched healthy controls. Measures of temporal order judgment were acquired using computer controlled stimulation to digits 2 and 3 on the right hand and subjects were required to determine which stimuli occurred first. Two experimental tasks were compared, temporal order judgment without and with synchronization whereby digits 2 and 3 were vibrated synchronously in advance of the temporal order judgment sequence of stimuli. RESULTS: Temporal order judgment in PD patients of and on medications were similar to controls. Temporal order judgment preceded by synchronous vibration impaired tactical acuity in controls and in PD patients off medications to similar degrees, but this perceptual impairment by synchronous vibration was not present in PD patients on medications. CONCLUSIONS: These findings suggest that dopamine in PD reduces cortico-cortical connectivity with SI and this leads to changes in tactical sensitivity.

Case report: The feasibility of rTMS with intrathecal baclofen pump for the treatment of unresolved neuropathic pain following spinal cord injury.

The main objective of this study was to assess the efficacy and safety of 10 Hz repetitive transcranial magnetic stimulation (rTMS) for the treatment of unresolved neuropathic pain in an individual with spinal cord injury and an intrathecal baclofen pump. A 62-year-old male presented with drug resistant neuropathic pain as a result of a complete spinal cord lesion at T8 level. Pain was classified into four types: pressure pain in the left foot, burning pain in buttocks, burning pain in sternum, and electrical attacks in the trunk. The treatment period involved 6 weeks of rTMS stimulation performed 5 days per week, a 6-week follow up period with no stimulation, and an 8-week top up session period which began 5-weeks after the end of the follow up period. 2004 pulses were delivered at 10Hz over the right-hand representation of the left primary motor cortex at 80% resting motor threshold during each session. Assessments were based on the numerical rating scale (NRS), neuropathic pain scale (NPS), Hamilton Depression and Anxiety rating scales. Following the treatment period there was a 30, 13, and 29% reduction in sternum, buttocks, and left foot pain respectively, as reported by the NRS. During this time, electrical attacks were abolished following the third week of treatment. These changes corresponded to a 38% decrease in NPS scores and a 65 and 25% reduction in anxiety and depressions scores respectively. The changes in sternum, buttocks, and left foot pain reported on the NRS persisted for 1 week following treatment. Top up sessions delivered 11 weeks after the end of the treatment period were unsuccessful in reducing pain to the level achieved during the treatment period. A 13% reduction in NPS was seen during these 8-weeks. Anxiety and depression scores decreased 78 and 67% respectively. The frequency of electrical attacks was zero during this time. rTMS stimulation delivered throughout this study did not cause any interference with the functioning of the intrathecal baclofen pump. This case study illustrates that rTMS may be effective at reducing drug resistant neuropathic pain with certain pain types exhibiting greater propensity for change.

The Combined Influences of Exercise, Diet and Sleep on Neuroplasticity.

Neuroplasticity refers to the brain's ability to undergo structural and functional adaptations in response to experience, and this process is associated with learning, memory and improvements in cognitive function. The brain's propensity for neuroplasticity is influenced by lifestyle factors including exercise, diet and sleep. This review gathers evidence from molecular, systems and behavioral neuroscience to explain how these three key lifestyle factors influence neuroplasticity alone and in combination with one another. This review collected results from human studies as well as animal models. This information will have implications for research, educational, fitness and neurorehabilitation settings.

Intensity matters: protocol for a randomized controlled trial exercise intervention for individuals with chronic stroke.

RATIONALE: Cardiovascular exercise is an effective method to improve cardiovascular health outcomes, but also promote neuroplasticity during stroke recovery. Moderate-intensity continuous cardiovascular training (MICT) is an integral part of stroke rehabilitation, yet it may remain a challenge to exercise at sufficiently high intensities to produce beneficial adaptations to neuroplasticity. High-intensity interval training (HIIT) could provide a viable alternative to achieve higher intensities of exercise by using shorter bouts of intense exercise interspersed with periods of recovery. METHODS AND DESIGN: This is a two-arm, parallel-group multi-site RCT conducted at the Jewish Rehabilitation Hospital (Laval, Québec, Canada) and McMaster University (Hamilton, Ontario, Canada). Eighty participants with chronic stroke will be recruited at both sites and will be randomly allocated into a HIIT or MICT individualized exercise program on a recumbent stepper, 3 days per week for 12 weeks. Outcomes will be assessed at baseline, at 12 weeks post-intervention, and at an 8-week follow-up. OUTCOMES: The primary outcome is corticospinal excitability, a neuroplasticity marker in brain motor networks, assessed with transcranial magnetic stimulation (TMS). We will also examine additional markers of neuroplasticity, measures of cardiovascular health, motor function, and psychosocial responses to training. DISCUSSION: This trial will contribute novel insights into the effectiveness of HIIT to promote neuroplasticity in individuals with chronic stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03614585 . Registered on 3 August 2018.

Transcranial magnetic stimulation in different current directions activates separate cortical circuits.

Transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) produces a series of corticospinal descending waves, with a direct (D) wave followed by several indirect (I) waves. TMS inducing posterior-anterior (PA) current in the brain predominantly recruits the early I1-wave, whereas anterior-posterior (AP) directed current preferentially recruits the late I3-wave. However, it is not known whether I-waves elicited by different current directions are mediated by the same neuronal populations. We studied the neuronal mechanisms mediating I-waves by examining the influence of short-latency afferent inhibition (SAI) on various I-waves. SAI was tested with electrical median nerve stimulation at the wrist followed by TMS to the contralateral M1 at different current directions. Surface electromyograms and single motor units were recorded from the first dorsal interosseous muscle. SAI was weaker for the AP compared with that for the PA current direction. With increasing median nerve stimulation intensities, SAI increased for the PA direction but showed a U-shaped relationship for the AP direction. SAI produced more inhibition of late I-waves generated by PA than those generated by AP current direction. We conclude that late I-waves generated by PA and AP current directions are mediated by different neuronal mechanisms.

Current Methodological Pitfalls and Caveats in the Assessment of Exercise-Induced Changes in Peripheral Brain-Derived Neurotrophic Factor: How Result Reproducibility Can Be Improved.

Neural mechanisms, such as enhanced neuroplasticity within the motor system, underpin exercise-induced motor improvements. Being a key mediator of motor plasticity, brain-derived neurotrophic factor (BDNF) is likely to play an important role in mediating exercise positive effects on motor function. Difficulties in assessing brain BDNF levels in humans have drawn attention to quantification of blood BDNF and raise the question of whether peripheral BDNF contributes to exercise-related motor improvements. Methodological and non-methodological factors influence measurements of blood BDNF introducing a substantial variability that complicates result interpretation and leads to inconsistencies among studies. Here, we discuss methodology-related issues and approaches emerging from current findings to reduce variability and increase result reproducibility.

Transcranial Magnetic Stimulation to Assess Exercise-Induced Neuroplasticity.

Aerobic exercise facilitates neuroplasticity and has been linked to improvements in cognitive and motor function. Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to quantify changes in neurophysiology induced by exercise. The present review summarizes the single- and paired-pulse TMS paradigms that can be used to probe exercise-induced neuroplasticity, the optimal stimulation parameters and the current understanding of the neurophysiology underlying each paradigm. Further, this review amalgamates previous research exploring the modulation of these paradigms with exercise-induced neuroplasticity in healthy and clinical populations and highlights important considerations for future TMS-exercise research.