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.

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.

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.

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.

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.

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.

Association of short- and long-latency afferent inhibition with human behavior.

Transcranial magnetic stimulation (TMS) paired with nerve stimulation evokes short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI), which are non-invasive assessments of the excitability of the sensorimotor system. SAI and LAI are abnormally reduced in various special populations in comparison to healthy controls. However, the relationship between afferent inhibition and human behavior remains unclear. The purpose of this review is to survey the current literature and synthesize observations and patterns that affect the interpretation of SAI and LAI in the context of human behavior. We discuss human behaviour across the motor and cognitive domains, and in special and control populations. Further, we discuss future considerations for research in this field and the potential for clinical applications. By understanding how human behavior is mediated by changes in SAI and LAI, this can allow us to better understand the neurophysiological underpinnings of human motor control.

Biological sex differences in afferent-mediated inhibition of motor responses evoked by TMS.

Sensorimotor integration can be assessed by pairing electrical peripheral nerve stimulation with transcranial magnetic stimulation (TMS). The resulting afferent inhibition is observed when TMS precedes nerve stimulation by âˆ¼ 20-25 ms, termed short-latency afferent inhibition (SAI), or by 200 ms, termed long-latency afferent inhibition (LAI). The purpose of this study was to determine whether biological sex influences the magnitude of SAI or LAI. SAI and LAI were assessed in fifteen males (21.5 ± 2.7 years) and fifteen females (20.2 ± 2.3 years). TMS was delivered to the primary motor cortex (M1) following stimulation of the contralateral median nerve at the wrist or digital nerve of the index finger, and motor-evoked potentials (MEPs) were obtained from the right first dorsal interosseous (FDI) muscle. SAI evoked by median and digital nerve stimulation, and LAI evoked by median nerve stimulation, were not different between males and females. LAI evoked by digital nerve stimulation was increased in females compared to males, but this difference between sexes was no longer present following the removal of datapoints where inhibition was not observed. This study is the first to investigate biological sex differences in afferent inhibition.

The distribution and reliability of TMS-evoked short- and long-latency afferent interactions.

Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) occur when the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) is reduced by the delivery of a preceding peripheral nerve stimulus. The intra-individual variability in SAI and LAI is considerable, and the influence of sample demographics (e.g., age and biological sex) and testing context (e.g., time of day) is not clear. There are also no established normative values for these measures, and their reliability varies from study-to-study. To address these issues and facilitate the interpretation of SAI and LAI research, we pooled data from studies published by our lab between 2014 and 2020 and performed several retrospective analyses. Patterns in the depth of inhibition with respect to age, biological sex and time of testing were investigated, and the relative reliability of measurements from studies with repeated baseline SAI and LAI assessments was examined. Normative SAI and LAI values with respect to the mean and standard deviation were also calculated. Our data show no relationship between the depth of inhibition for SAI and LAI with either time of day or age. Further, there was no significant difference in SAI or LAI between males and females. Intra-class correlation coefficients (ICC) for repeated measurements of SAI and LAI ranged from moderate (ICC = 0.526) to strong (ICC = 0.881). The mean value of SAI was 0.71 ± 0.27 and the mean value of LAI was 0.61 ± 0.34. This retrospective study provides normative values, reliability estimates, and an exploration of demographic and testing influences on these measures as assessed in our lab. To further facilitate the interpretation of SAI and LAI data, similar studies should be performed by other labs that use these measures.

The Influence of Recreational Substance Use in TMS Research.

(1) Background: Transcranial magnetic stimulation (TMS) approaches are widely used to study cortical and corticospinal function. However, responses to TMS are subject to significant intra-and inter-individual variability. Acute and chronic exposure to recreational substances alters the excitability of the sensorimotor system and may contribute to the variability in TMS outcome measures. The increasing prevalence of recreational substance use poses a significant challenge for executing TMS studies, but there is a lack of clarity regarding the influence of these substances on sensorimotor function. (2) Methods: The literature investigating the influence of alcohol, nicotine, caffeine and cannabis on TMS outcome measures of corticospinal, intracortical and interhemispheric excitability was reviewed. (3) Results: Both acute and chronic use of recreational substances modulates TMS measures of excitability. Despite the abundance of research in this field, we identify knowledge gaps that should be addressed in future studies to better understand the influence of these substances on TMS outcomes. (4) Conclusions: This review highlights the need for TMS studies to take into consideration the history of participant substance use and to control for acute substance use prior to testing.

Altered motor system function in post-concussion syndrome as assessed via transcranial magnetic stimulation.

OBJECTIVE: It is unclear why specific individuals incur chronic symptoms following a concussion. This exploratory research aims to identify and characterize any neurophysiological differences that may exist in motor cortex function in post-concussion syndrome (PCS). METHODS: Fifteen adults with PCS and 13 healthy, non-injured adults were tested. All participants completed symptom questionnaires, and transcranial magnetic stimulation (TMS) was used to measure intracortical and transcallosal excitability and inhibition in the dominant motor cortex. RESULTS: Cortical silent period (p = 0.02, g = 0.96) and ipsilateral silent period (p = 0.04, g = 0.78) were shorter in the PCS group compared to the control group which may reflect reduced GABA-mediated inhibition in PCS. Furthermore, increased corticomotor excitability was observed in the left hemisphere but not the right hemisphere. CONCLUSIONS: These data suggest that persistent neurophysiological differences are present in those with PCS. The exact contributing factors to such changes remain to be investigated by future studies. SIGNIFICANCE: This study provides novel evidence of lasting neurophysiological changes in PCS.

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.

Fitness Level Influences White Matter Microstructure in Postmenopausal Women.

Aerobic exercise has both neuroprotective and neurorehabilitative benefits. However, the underlying mechanisms are not fully understood and need to be investigated, especially in postmenopausal women, who are at increased risk of age-related disorders such as Alzheimer's disease and stroke. To advance our understanding of the potential neurological benefits of aerobic exercise in aging women, we examined anatomical and functional responses that may differentiate women of varying cardiorespiratory fitness using neuroimaging and neurophysiology. A total of 35 healthy postmenopausal women were recruited (59 ± 3 years) and cardiorespiratory fitness estimated (22-70 mL/kg/min). Transcranial magnetic stimulation was used to assess -aminobutyric acid (GABA) and glutamate (Glu) receptor function in the primary motor cortex (M1), and magnetic resonance spectroscopy (MRS) was used to quantify GABA and Glu concentrations in M1. Magnetic resonance imaging was used to assess mean cortical thickness (MCT) of sensorimotor and frontal regions, while the microstructure of sensorimotor and other white matter tracts was evaluated through diffusion tensor imaging. Regression analysis revealed that higher fitness levels were associated with improved microstructure in pre-motor and sensory tracts, and the hippocampal cingulum. Fitness level was not associated with MCT, MRS, or neurophysiology measures. These data indicate that, in postmenopausal women, higher cardiorespiratory fitness is linked with preserved selective white matter microstructure, particularly in areas that influence sensorimotor control and memory.

A Single Bout of High-intensity Interval Exercise Increases Corticospinal Excitability, Brain-derived Neurotrophic Factor, and Uncarboxylated Osteolcalcin in Sedentary, Healthy Males.

Exercise induces neuroplasticity in descending motor pathways facilitating motor learning, and as such it could be utilized as an intervention in neurorehabilitation, for example when re-learning motor skills after stroke. To date, however, the neurophysiological and molecular mechanisms underlying exercise-induced neuroplasticity remain largely unknown impeding the potential utilization of exercise protocols as 'motor learning boosters' in clinical and non-clinical settings. Here, we assessed corticospinal excitability, intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS) and serum biochemical markers including brain-derived neurotrophic factor (BDNF), total and precursor cathepsin B (tCTSB, proCTSB), uncarboxylated and carboxylated osteocalcin (unOCN, cOCN) and irisin using ELISA. Measurements were carried out in sedentary, healthy males before and after a single session of high-intensity interval exercise (HIIE) or in individuals who rested and did not perform exercise (No Exercise). We found that HIIE increased corticospinal excitability, BDNF and unOCN, and decreased cOCN. We also determined that greater increases in BDNF were associated with increases in unOCN and irisin and decreases in cOCN only in participants who underwent HIIE, suggesting that unOCN and irisin may contribute to exercise-induced BDNF increases. Conversely, no changes other than a decrease in serum unOCN/tOCN were found in No Exercise participants. The present findings show that a single session of HIIE is sufficient to modulate corticospinal excitability and to increase BDNF and unOCN in sedentary, healthy males.

Human motor cortical organization is influenced by handedness.

Although there is some evidence that handedness is associated with structural and functional differences in the motor cortex, findings remain inconclusive. Here, we evaluated whether handedness influences the location, size and overlap of the cortical representations of upper limb muscles across hemispheres in right- versus left-handed individuals. Using transcranial magnetic stimulation, the cortical representations of abductor pollicis brevis, flexor carpi radialis and biceps brachii muscles were mapped bilaterally with a 6 by 5 grid space. Results indicate that right-handers had more lateral and posterior representations in the non-dominant hemisphere as well as greater overall cortical territory compared to left-handers. Right- and left-handers did not differ in the extent of overlap between muscle representations. Our findings suggest that human motor cortical organization of upper limb muscles is indeed influenced by handedness, specifically with regard to the location of non-dominant cortical muscle representations and the size of cortical territory dedicated to upper limb muscle representations.

Reliability of transcranial magnetic stimulation measures of afferent inhibition.

Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) are well-known transcranial magnetic stimulation (TMS) paradigms used to probe the sensorimotor system. To date, there is a paucity of research examining the reliability of these neurophysiological measures. This information is required to validate the utility of afferent inhibition as a biomarker of neural function. The goal of this study was to quantify the absolute reliability, relative reliability, and smallest detectable change (SDC) of SAI and LAI using a test-retest paradigm. 30 healthy individuals (20.9 ±â€¯2.5 years) participated in two sessions (intersession interval of ~7 days). Reliability was assessed with intraclass correlation coefficients (ICC), standard error of measurement (SEMeas), and SDC. The results show that LAI and SAI had poor-to-moderate relative reliability as determined by the ICC, with digital nerve LAI displaying the highest relative reliability (highest ICC with smallest confidence interval). The %SEMeas indicated a large amount of measurement error in all measures of afferent inhibition, with LAI exhibiting more measurement error than SAI. The SDC was large at the individual level (SDCindiv), but analyses showed that the SDC is significantly reduced at the group-level (SDCgroup). Our results indicate that digital nerve LAI is the most reliable outcome to differentiate between individuals within a sample. Further, results suggest that SAI and LAI are not appropriate indicators of individual neurophysiological change across time but can reliably detect changes in group-averaged data providing sample sizes are sufficient.