short-latency afferent inhibition (no task baseline)

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter TMS

Multiple sensorimotor loops converge in the motor cortex to shape pyramidal tract projections to spinal motor neurons and interneurons1. However, how these sensorimotor loops interact to shape corticospinal projections and motor behavior remains an open question. Short-latency afferent inhibition (SAI) provides a tool to probe the functional properties of convergent sensorimotor loops in motor cortex output. SAI combines motor cortical transcranial magnetic stimulation (TMS) with electrical stimulation of the corresponding peripheral afferent nerve.
TMS is a non-invasive method to safely stimulate pyramidal motor neurons trans-synaptically in the human brain2,3. TMS involves passing a large, transient electric current through a coiled wire placed on the scalp. The transient nature of the electrical current creates a rapidly changing magnetic field that induces an electric current in the brain4. In the case of a single TMS stimulus, the induced current activates a series of excitatory inputs to the pyramidal motor neurons5-7. If the strength of the generated excitatory inputs is sufficient, the descending activity elicits a contralateral muscular response known as the motor-evoked potential (MEP). The latency of the MEP reflects the corticomotor conduction time8. The amplitude of the MEP indexes the excitability of the corticospinal neurons9. The single TMS stimulus that elicits the MEP can also be preceded by a conditioning stimulus10,11,12. These paired-pulse paradigms can be used to index the effects of various interneuron pools on the corticospinal output. In the case of SAI, the peripheral electrical conditioning stimulus is used to probe the impact of the afferent volley on the motor cortical excitability11,13,14,15. The relative timing of the TMS stimulus and peripheral electrical stimulation aligns the action of the TMS stimulus on the motor cortex with the arrival of the afferent projections to the motor cortex. For SAI in the distal upper limb muscles, the median nerve stimulus typically precedes the TMS stimulus by 18-24 ms11,13,15,16. At the same time, SAI increases as the strength of the afferent volley induced by the peripheral stimulus increases13,17,18.
Despite its strong association with the extrinsic properties of the afferent projection to the motor cortex, SAI is a malleable phenomenon implicated in many motor control processes. For example, SAI is reduced in task-relevant muscles before an impending movement19,20,21 but is maintained in adjacent task-irrelevant motor representations19,20,22. The sensitivity to task relevancy is hypothesized to reflect a surround inhibition mechanism23 that aims to reduce unwanted effector recruitment. More recently, it was proposed that the reduction in SAI in the task-relevant effector may reflect a movement-related gating phenomenon designed to suppress expected sensory afference21 and facilitate corrections during sensorimotor planning and execution24. Regardless of the specific functional role, SAI is correlated with reductions in manual dexterity and processing efficiency25. Altered SAI is also associated with an increased risk of falling in older adults26 and compromised sensorimotor function in Parkinson&#39;s disease26,27,28 and individuals with focal hand dystonia29.
Clinical and pharmacological evidence indicates that the inhibitory pathways mediating SAI are sensitive to central cholinergic modulation30. For example, administering the muscarinic acetylcholine receptor antagonist scopolamine reduces SAI31. In contrast, increasing the half-life of acetylcholine via acetylcholinesterase inhibitors enhances SAI32,33. Consistent with pharmacological evidence, SAI is sensitive to several cognitive processes with central cholinergic involvement, including arousal34, reward35, the allocation of attention21,36,37, and memory38,39,40. SAI is also altered in clinical populations with cognitive deficits associated with the loss of cholinergic neurons, such as Alzheimer&#39;s disease41,42,43,44,45,46,47, Parkinson&#39;s disease (with mild cognitive impairment)48,49,50, and mild cognitive impairment47,51,52. The differential modulation of SAI by various benzodiazepines with differential affinities for various &#947;-aminobutyric acid type A (GABAA) receptor subunit types suggests that the SAI inhibitory pathways are distinct from pathways mediating other forms of paired-pulse inhibition30. For example, lorazepam decreases SAI but enhances short-interval cortical inhibition (SICI)53. Zolpidem reduces SAI but has little effect on SICI53. Diazepam increases SICI but has little impact on SAI53. The reduction in SAI by these positive allosteric modulators of GABAA receptor function, coupled with the observation that GABA controls the release of acetylcholine in the brain stem and cortex54, has led to the hypothesis that GABA modulates the cholinergic pathway that projects to the sensorimotor cortex to influence SAI55.
Recently, SAI has been used to investigate interactions between the sensorimotor loops that set procedural motor control processes and those that align procedural processes to explicit top-down goals and cognitive control processes21,36,37,38. The central cholinergic involvement in SAI31 suggests that&#160;SAI may index an executive influence over procedural sensorimotor control and learning. Importantly, these studies have begun to identify the unique effects of cognition on specific sensorimotor circuits by assessing SAI using different TMS current directions. SAI studies typically employ posterior-anterior (PA) induced current, while only a handful of SAI studies have employed anterior-posterior (AP) induced current55. However, using TMS to induce AP compared with PA current during SAI assessment recruits distinct sensorimotor circuits16,56. For example, AP-sensitive, but not PA-sensitive, sensorimotor circuits are altered by cerebellar modulation37,56. Furthermore, AP-sensitive, but not PA-sensitive, sensorimotor circuits are modulated by attention load36. Finally, attention and cerebellar influences may converge on the same AP-sensitive sensorimotor circuits, leading to maladaptive alterations in these circuits37.
Advances in TMS technology provide additional flexibility to manipulate the configuration of the TMS stimulus employed during single-pulse, paired-pulse, and repetitive applications57,58. Controllable pulse parameter TMS (cTMS) stimulators are now commercially available for research use worldwide, and these provide flexible control over the pulse width and shape57. The increased flexibility arises from controlling the discharge duration of two independent capacitors, each responsible for a separate phase of the TMS stimulus. The biphasic or monophasic nature of the stimulus is governed by the relative discharge amplitude from each capacitor, a parameter called the M-ratio. cTMS studies have combined pulse width manipulation with different current directions to demonstrate that the fixed pulse widths used by conventional TMS stimulators (70-82 &#181;s)59,60 likely recruit a mix of functionally distinct sensorimotor circuits during SAI56. Therefore, cTMS is an exciting tool to disentangle further the functional significance of various convergent sensorimotor loops in sensorimotor performance and learning.
This manuscript details a unique SAI approach to studying sensorimotor integration that integrates peripheral electrical stimulation with cTMS during sensorimotor behaviors. This approach improves on the typical SAI approach by assessing the effect of afferent projections on select interneuron populations in the motor cortex that govern the corticospinal output during ongoing sensorimotor behavior. Although relatively new, cTMS provides a distinct advantage in studying sensorimotor integration in typical and clinical populations. Furthermore, the current approach can be easily adapted for use with conventional TMS stimulators and to quantify other forms of afferent inhibition and facilitation, such as long-latency afferent inhibition (LAI)13 or short-latency afferent facilitation (SAF)15.

Author Spotlight: Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning  

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning

This technique provides insight into how sensory information is integrated into motor planning and execution. The implementation of controllable pulse parameter TMS enables us to identify specific sensory to motor pathways and how these pathways may be disrupted in neurological disorders. Motor scale acquisition and performance requires a fine balance between the conscious declarative and subconscious procedural process.Short latency afferent inhibition is a potential marker of how cognition may shape different procedural sensory motor circuits in the motor cortex of healthy and clinical populations. afferent inhibition quantifies the impact of afferent inputs on motor cortical output as elicited by transcranial magnetic stimulation. As a measure of sensory motor integration, it compliments functional magnetic resonance imaging and on electroencephalography by probing the contributions of specific neuronal populations on global hemodynamic and electrical responses elicited by skilled motor behavior.The lock parameters of magnetic stimuli generated by traditional transcranial magnetic stimulators recruit a mixture of sensory motor circuits. On the other hand, controllable pulse parameter transcranial magnetic stimulators unlock several stimulus parameters, enhancing the specificity of sensory motor circuits probed by afferent inhibition during skilled behavior. Assessing sensory motor inhibition during performance is critical to establishing markers of skilled and unskilled motor execution.Reliable and valid markers are an important step in developing enhanced models of motor control that will enhance or boost best practices in healthy populations, as well as minimize the impact of movement disorders through effective clinical interventions. Enhanced modeling of sensory motor circuits and the factors that influence their function can help provide objective markers of function and dysfunction that will inform best practices for motor performance, skill acquisition, and rehabilitation in both healthy and neurological populations. Continued definition of psychomotor and pharmacological influences over sensory motor circuits converging in motor cortex is critical.Combining afferent inhibition with electroencephalography provides an exciting opportunity to quantify afferent inhibition in non-motor areas as a marker of movement disorders and neuropsychiatric disorders.

Watch this Scientific Journal Video about Short-Latency Afferent Inhibition No Task Baseline at JoVE.com

Short-Latency Afferent Inhibition (No Task Baseline)  

Attach the coil that will induce the PA current in the brain to the CTMS stimulator. Set the pulse type to monophasic positive, the pulse width to 120 microseconds, and M-ratio to 0.2. Finally, set the stimulus intensity to the one millivolt threshold.After setting the peripheral electrical stimulus intensity, launch the no task software routine on a personal computer or PC 1. Next, set the inter stimulus interval between the peripheral electrical and TMS stimuli to 21 milliseconds. Position the TMS coil over the first dorsal interosseous or FDI motor hotspot and ask the participant to hold a slight contraction of the FDI muscle.Next, run the no task software on PC 1 to trigger the peripheral and CTMS stimulators. Repeat the procedure for the AP 30 current configuration using the coil that induces AP current in the brain.

short-latency-afferent-inhibition-no-task-baseline

Research

JoVE Journal

Neuroscience

81 Views.  University of Waterloo. Attach the coil that will induce the PA current in the brain to the CTMS stimulator. Set the pulse type to monophasic positive, the pulse width to 120 microseconds, and M-ratio to 0.2. Finally, set the stimulus intensity to the one millivolt threshold.After setting the peripheral electrical stimulus intensity, launch the no task software routine on a personal computer or PC 1. Next, set the inter stimulus interval between the peripheral electrical and TMS stimuli to 21 milliseconds. Po...