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.

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.

The Effects of Exercise on Synaptic Plasticity in Individuals With Mild Cognitive Impairment: Protocol for a Pilot Intervention Study.

BACKGROUND: Mild cognitive impairment (MCI) is a syndrome preceding more severe impairment characterized by dementia. MCI affects an estimated 15% to 20% of people older than 65 years. Nonpharmacological interventions including exercise are recommended as part of overall MCI management based on the positive effects of exercise on cognitive performance. Interval training involves brief intermittent bouts of exercise interspersed with short recovery periods. This type of exercise promotes cognitive improvement and can be performed in individuals with MCI. Synaptic plasticity can be assessed in vivo by the neurophysiological response to repetitive transcranial magnetic stimulation (rTMS). A method to assess synaptic plasticity uses an intermittent theta burst stimulation (iTBS), which is a patterned form of rTMS. Individuals with MCI have decreased responses to iTBS, reflecting reduced synaptic plasticity. It is unknown whether interval training causes changes in synaptic plasticity in individuals living with MCI. OBJECTIVE: This research will determine whether interval training performed using a cycle ergometer enhances synaptic plasticity in individuals with MCI. The three aims are to (1) quantify synaptic plasticity after interval training performed at a self-determined intensity in individuals with MCI; (2) determine whether changes in synaptic plasticity correlate with changes in serum brain-derived neurotrophic factor, osteocalcin, and cognition; and (3) assess participant compliance to the exercise schedule. METHODS: 24 individuals diagnosed with MCI will be recruited for assignment to 1 of the 2 equally sized groups: exercise and no exercise. The exercise group will perform exercise 3 times per week for 4 weeks. Synaptic plasticity will be measured before and following the 4-week intervention. At these time points, synaptic plasticity will be measured as the response to single-pulse TMS, reflected as the percent change in the average amplitude of 20 motor-evoked potentials before and after an iTBS rTMS protocol, which is used to induce synaptic plasticity. In addition, individuals will complete a battery of cognitive assessments and provide a blood sample from the antecubital vein to determine serum brain-derived neurotrophic factor and osteocalcin. RESULTS: The study began in September 2023. CONCLUSIONS: The proposed research is the first to assess whether synaptic plasticity is enhanced after exercise training in individuals with MCI. If exercise does indeed modify synaptic plasticity, this will create a new avenue by which we can study and manipulate neural plasticity in these individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05663918; https://clinicaltrials.gov/study/NCT05663918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50030.

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.