Retraining Reflexes: Clinical Translation of Spinal Reflex Operant Conditioning

Eftekhar, Amir; Norton, James C.; McDonough, Christine M.; Wolpaw, Jonathan R.

doi:10.1007/s13311-018-0643-2

Cited by 15 publications

(9 citation statements)

References 175 publications

(223 reference statements)

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“…However, H-reflex and M-wave measurements are equally clinically useful in the upper extremities, where the process of separating the responses is more challenging. In the flexor carpi radialis, for example, the M-wave and H-reflex often overlap [41,42]. It would be necessary to modify the present algorithm for application to different muscle targets.…”

Section: Discussionmentioning

confidence: 99%

Methods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications

McKinnon¹,

Hill

Carp

et al. 2023

J. Neural Eng.

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Objective: Surface EMG measurements of the Hoffmann (H-) reflex are essential in a wide range of neuroscientific and clinical applications. One promising emerging therapeutic application is H-reflex operant conditioning, whereby a person is trained to modulate the H-reflex, with generalized beneficial effects on sensorimotor function in chronic neuromuscular disorders. Both traditional diagnostic and novel realtime therapeutic applications rely on accurate definitions of the H-reflex and M-wave temporal bounds, which currently depend on expert case-by-case judgment. The current study automates such judgments.Approach: Our novel wavelet-based algorithm automatically determines temporal extent and amplitude of the human soleus H-reflex and M-wave. In each of 20 participants, the algorithm was trained on data from a preliminary 3- or 4-minute recruitment-curve measurement. Output was evaluated on parametric fits to subsequent sessions' recruitment curves (92 curves across all participants) and the conditioning protocol’s subsequent baseline trials (∼1200 per participant) performed near Hmax. Results were compared against the original temporal bounds estimated at the time, and against retrospective estimates made by an expert 6 years later.Main results: Automatic bounds agreed well with manual estimates: 95% lay within ±2.5 ms. The resulting H-reflex magnitude estimates showed excellent agreement (97.5% average across participants) between automatic and retrospective bounds regarding which trials would be considered successful for operant conditioning. Recruitment-curve parameters also agreed well between automatic and manual methods: 95% of the automatic estimates of the current required to elicit Hmax fell within ±1.4% of the retrospective estimate; for the “threshold” current that produced an M-wave 10% of maximum, this value was ±3.5%.Significance: Such dependable automation of M-wave and H-reflex definition should make both established and emerging H-reflex protocols considerably less vulnerable to inter-personnel variability and human error, increasing translational potential.

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Section: Discussionmentioning

confidence: 99%

Methods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications

McKinnon¹,

Hill

Carp

et al. 2023

J. Neural Eng.

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“…The protocol will also need to be adapted according to the muscle that is being conditioned. For example, when targeting the flexor carpi radialis muscle 24 , 25 : a lower current setting is generally used; the Voluntary Contraction mode should be used to establish a scale for the background-EMG limits; and greater care must be taken both during optimization of electrode placement, and during optimization of posture, which must then be kept constant across trials.…”

Section: Discussionmentioning

confidence: 99%

The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders

Hill

Gupta

Eftekhar

et al. 2022

JoVE

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The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle responses in people with neuromuscular disorders, which in turn can improve sensorimotor function when applied appropriately. EPOCS monitors the state of specific target muscles-e.g., from surface electromyography (EMG) while standing, or from gait cycle measurements while walking on a treadmill-and automatically triggers calibrated stimulation when pre-defined conditions are met. It provides two forms of feedback that enable a person to learn to modulate the targeted pathway's excitability.First, it continuously monitors ongoing EMG activity in the target muscle, guiding the person to produce a consistent level of activity suitable for conditioning. Second, it provides immediate feedback of the response size following each stimulation and indicates whether it has reached the target value.To illustrate its use, this article describes a protocol through which a person can learn to decrease the size of the Hoffmann reflex-the electrically-elicited analog of the spinal stretch reflex-in the soleus muscle. Down-conditioning this pathway's excitability can improve walking in people with spastic gait due to incomplete spinal cord injury.The article demonstrates how to set up the equipment; how to place stimulating and recording electrodes; and how to use the free software to optimize electrode placement, measure the recruitment curve of direct motor and reflex responses, measure the response without operant conditioning, condition the reflex, and analyze the resulting data. It illustrates how the reflex changes over multiple sessions and how walking improves. It also discusses how the system can be applied to other kinds of evoked responses and to other kinds of stimulation, e.g., motor evoked potentials to

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“…There is a rich literature on motor neuron plasticity in this preparation, some of which reports PKC-dependent mechanisms (Cai et al, 2008; Fulton et al, 2008; Glanzman, 2008; Villareal et al, 2009; Reissner et al, 2010; Jin et al, 2011; Bougie et al, 2012; Choi et al, 2014; Hu et al, 2015, 2017a; Ferguson et al, 2019; Alexandrescu and Carew, 2020). Also in mammals (including humans) motor neuron plasticity in the spinal cord is a readily observable phenomenon in non-clinical and clinical settings (Wolpaw and Lee, 1989; Wolpaw et al, 1989; Carp and Wolpaw, 1994; Carp et al, 2001; Wang et al, 2006; Wolpaw, 2012; Eftekhar et al, 2018; Kaneko et al, 2022; Rochat et al, 2022; Simonyan et al, 2022). The discovery of aPKC-dependent plasticity in Drosophila motor neurons expands this body of literature to a genetically tractable organism and inasmuch as clinical practice relies on motor neuron plasticity, may even help instruct the development of clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Wings of Change: aPKC/FoxP-dependent plasticity in steering motor neurons underlies operant selflearning inDrosophila

Ehweiner

Brembs

2022

Preprint

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Motor learning is not only a key invention of the many new animals evolving new body plans during the Cambrian, it is also central to human existence such as in learning to speak or walk, rehabilitation after injury, or sports. Evidence suggests that all forms of motor learning may share an evolutionary conserved molecular plasticity pathway. Here we present novel insights into the molecular processes underlying a kind of motor learning in the fruit fly Drosophila, operant self-learning. We have discovered that the Forkhead Box gene FoxP is not required in the fly brain for this type of learning. Instead, atypical protein kinase C (aPKC) appears to be a central component in a plasticity process that takes place in FoxP-expressing motor neurons in the ventral nerve cord. Using CRISPR/Cas9 to knock out canonical aPKC interaction partners bazooka and the kidney and brain gene (KIBRA) in adult animals, we found that aPKC likely acts via non-canonical pathways in this form of learning. We also found that 14 but not 7 days after CRISPR/Cas9-mediated knockout of FoxP in adult animals, learning is impaired, suggesting that adult FoxP expression is required for operant self-learning.

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Retraining Reflexes: Clinical Translation of Spinal Reflex Operant Conditioning

Cited by 15 publications

References 175 publications

Methods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications

Methods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications

The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders

Wings of Change: aPKC/FoxP-dependent plasticity in steering motor neurons underlies operant selflearning inDrosophila

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