The duration of motor responses evoked with intracortical microstimulation in rats is primarily modulated by stimulus amplitude and train duration

Microstimulation of brain tissue plays a key role in a variety of sensory prosthetics, clinical therapies and research applications, however the effects of stimulation parameters on the responses they evoke remain widely unknown. In particular, the effects of parameters when delivered in the form of a stimulus train as opposed to a single pulse are not well understood despite the prevalence of stimulus train use. We aimed to investigate the contribution of each parameter of a stimulus train to the duration of the motor responses they evoke in forelimb muscles. We used constant-current, biphasic, square wave pulse trains in acute terminal experiments under ketamine anaesthesia. Stimulation parameters were systematically tested in a pair-wise fashion in the caudal forelimb region of the motor cortex in 7 Sprague-Dawley rats while motor evoked potential (MEP) recordings from the forelimb were used to quantify the influence of each parameter in the train. Stimulus amplitude and train duration were shown to be the dominant parameters responsible for increasing the total duration of the MEP, while interphase interval had no effect. Increasing stimulus frequency from 100200 Hz or pulse duration from 0.18-0.34 ms were also effective methods of extending response durations. Response duration was strongly correlated with peak time and amplitude. Our findings suggest that motor cortex intracortical microstimulations are often conducted at a higher frequency rate and longer train duration than necessary to evoke maximal response duration. We demonstrated that the temporal properties of the evoked response can be both predicted by certain response metrics and modulated via alterations to the stimulation signal parameters

Somesthetic, Visual, and Auditory Feedback and Their Interactions Applied to Upper Limb Neurorehabilitation Technology: A Narrative Review to Facilitate Contextualization of Knowledge

Reduced hand dexterity is a common component of sensorimotor impairments for individuals after stroke. To improve hand function, innovative rehabilitation interventions are constantly developed and tested. In this context, technology-based interventions for hand rehabilitation have been emerging rapidly. This paper offers an overview of basic knowledge on post lesion plasticity and sensorimotor integration processes in the context of augmented feedback and new rehabilitation technologies, in particular virtual reality and soft robotic gloves. We also discuss some factors to consider related to the incorporation of augmented feedback in the development of technology-based interventions in rehabilitation. This includes factors related to feedback delivery parameter design, task complexity and heterogeneity of sensory deficits in individuals affected by a stroke. In spite of the current limitations in our understanding of the mechanisms involved when using new rehabilitation technologies, the multimodal augmented feedback approach appears promising and may provide meaningful ways to optimize recovery after stroke. Moving forward, we argue that comparative studies allowing stratification of the augmented feedback delivery parameters based upon different biomarkers, lesion characteristics or impairments should be advocated (e.g., injured hemisphere, lesion location, lesion volume, sensorimotor impairments). Ultimately, we envision that treatment design should combine augmented feedback of multiple modalities, carefully adapted to the specific condition of the individuals affected by a stroke and that evolves along with recovery. This would better align with the new trend in stroke rehabilitation which challenges the popular idea of the existence of an ultimate good-for-all intervention

Predicting Individual Treatment Response to rTMS for Motor Recovery After Stroke: A Review and the CanStim Perspective

BackgroundRehabilitation is critical for reducing stroke-related disability and improving quality-of-life post-stroke. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique used as stand-alone or adjunct treatment to physiotherapy, may be of benefit for motor recovery in subgroups of stroke patients. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) seeks to advance the use of these techniques to improve post-stroke recovery through clinical trials and pre-clinical studies using standardized research protocols. Here, we review existing clinical trials for demographic, clinical, and neurobiological factors which may predict treatment response to identify knowledge gaps which need to be addressed before implementing these parameters for patient stratification in clinical trial protocols.ObjectiveTo provide a review of clinical rTMS trials of stroke recovery identifying factors associated with rTMS response in stroke patients with motor deficits and develop research perspectives for pre-clinical and clinical studies.MethodsA literature search was performed in PubMed, using the Boolean search terms stroke AND repetitive transcranial magnetic stimulation OR rTMS AND motor for studies investigating the use of rTMS for motor recovery in stroke patients at any recovery phase. A total of 1,676 articles were screened by two blinded raters, with 26 papers identified for inclusion in this review.ResultsMultiple possible factors associated with rTMS response were identified, including stroke location, cortical thickness, brain-derived neurotrophic factor (BDNF) genotype, initial stroke severity, and several imaging and clinical factors associated with a relatively preserved functional motor network of the ipsilesional hemisphere. Age, sex, and time post-stroke were generally not related to rTMS response. Factors associated with greater response were identified in studies of both excitatory ipsilesional and inhibitory contralesional rTMS. Heterogeneous study designs and contradictory data exemplify the need for greater protocol standardization and high-quality controlled trials.ConclusionClinical, brain structural and neurobiological factors have been identified as potential predictors for rTMS response in stroke patients with motor impairment. These factors can inform the design of future clinical trials, before being considered for optimization of individual rehabilitation therapy for stroke patients. Pre-clinical models for stroke recovery, specifically developed in a clinical context, may accelerate this process

Stimulation signal and motor evoked potential responses.

<p>Part (a) depicts the parameters of the constant-current, biphasic square waveform stimulus. Part (b) depicts the MEP onset and offset definition and the scale in part b applies to parts b-i. Parts b-i demonstrate that a variety of signal envelopes were evoked by the stimulus parameter ranges tested. The duration of the response was determined by subtracting the signal onset time from the offset time. The response onset was defined as the first instance where ten sequential sample points of the MEP signal remained above the trial’s baseline level. Similarly, the response offset was the last instance in which the MEP signal returned to the baseline level and remained there until the end of the trial.</p

Summary of Parameter Influence on Response Duration.

<p>Summary of Parameter Influence on Response Duration.</p

MEP main response duration (mean ± SE) as a function of stimulus train duration.

<p>The effects of train duration paired with three current amplitudes (a), frequencies (b), pulse durations (c) and interphase intervals (d) are depicted. Square symbols represent conditions with an insufficient number of responding sites (n<5) and were not included in statistical analyses. Circular symbols represent conditions with reliable responses (n = 5–14). Control values for each parameter were: A = 50 μA, F = 303 Hz, P = 0.2 ms, I = 0 ms, T = 43 ms. A = amplitude, F = frequency, P = pulse duration, I = interphase interval, T = train duration, SE = standard error.</p

Parameter Test Values.

<p>Parameter Test Values.</p

MEP main response duration (mean ± SE) as a function of stimulus interphase interval.

<p>The effects of interphase interval paired with three amplitude levels (a), frequencies (b), pulse durations (c) and train durations (d) are depicted. Note the difference in scale for trials involving train duration (part d). Square symbols represent conditions with an insufficient number of responding sites (n<5) and were not included in statistical analyses. Circular symbols represent conditions with reliable responses (n = 5–14). Control values for each parameter were: A = 50 μA, F = 303 Hz, P = 0.2 ms, I = 0 ms, T = 43 ms. A = amplitude, F = frequency, P = pulse duration, I = interphase interval, T = train duration, SE = standard error.</p