Neural Adaptation After Tendon Transfer and Training in Tetraplegia

Restoring upper limb function is rated among the highest priorities for individuals with
tetraplegia. Re-establishing active grasp and pinch strength to the hand can be accomplished
by tendon transfer procedures in which the tendon of a strong proximal muscle is surgically
re-attached to the tendon of a paralyzed muscle. A common procedure to restore lateral (key)
pinch is to transfer the distal tendon of one of the three elbow flexor muscles, the
brachioradialis (Br) to the tendon of the paralyzed thumb flexor, the flexor pollicis longus
(FPL). Recovery of functional pinch depends on how well the patient learns to activate the Br
to flex the thumb through its new distal attachment, and also to control flexion at the elbow
through its proximal attachment. The investigators' previous work shows that Br to FPL
recipients do not activate the transferred Br fully and may not reach optimal functional
status on their own or with traditional therapies. The investigators propose that
participation in a postoperative task-based training program will drive cortical changes that
impact functional (pinch) ability.

Recent studies of individuals with cervical SCI show substantial cortical reorganization can
occur after the injury, but neural substrates of motor learning after tendon transfer have
not been studied. For these patients, very little is known about what functional brain
changes accompany improved performance in response to additional intervention. The Br to FPL
transfer alters the central feedback from the periphery and may permit new or adaptive neural
pathways that can achieve greater functional use of the tendon transfer. Neuroimaging
techniques, such as functional magnetic resonance imaging (fMRI) have become important tools
for understanding plasticity in the neuromuscular system and for assessing the neural
underpinnings of successful novel interventions. The objective of the proposed study is to
identify the neural pattern that is associated with the best functional outcomes (highest
pinch force) after Br to FPL transfer. The investigators will use fMRI and functional
performance measures to find neural predictors and correlates of muscle re-education. That
is, the investigators expect that successful postoperative muscle re-education will depend on
increased cortical drive to the transferred Br in combination with new synergists, and this
will be reflected in the neural imaging results.

The purpose of the study is to evaluate neural activity from Br to FPL transfer recipients
after conventional therapy and in response to an additional task-based training home program
that aims to improve voluntary activation of the transferred Br in functional pinch tasks.
The 10-week training program is under evaluation in RRD Pilot (B0583P) study and includes
producing pinch force in different upper limb postures, biofeedback from a pinch dynamometer,
and practicing selected pinch tasks. The investigators anticipate that increases in the
amplitude and distribution of fMRI blood oxygen level dependent (BOLD) responses in
sensorimotor cortices will underlie improved motor control post-surgically and following
successful intervention to promote motor relearning.

Specific Aims

1. Define the cortical representation of pre-training pinch function in SCI patients. The
investigators will quantify the pattern (location, volume and intensity) of cortical
activation associated with voluntary pinch in individuals who are one-year post Br to
FPL tendon transfer surgery and a conventional therapy program. The investigators
hypothesize (H1) greater volume and intensity of brain activation will correlate to
better pinch function measured by pinch strength and the magnitude Br activation in
pinch. Secondary analyses will determine if the location of the brain activation varies
with pinch function (force) and specificity relative to voluntary elbow flexion.

2. Evaluate the cortical response to the task-based home therapy program. Correlates of
task-based adaptation from pre- to post-training will be assessed using fMRI. H2:
Greater activation (intensity and volume) in the primary motor cortex (M1) and sensory
cortex will translate to increased voluntary activation of the transferred Br in pinch
compared to elbow flexion. Task-based training outcome measures will include isometric
pinch force magnitude, EMG quantification of Br activation in pinch and elbow flexion.

3. Determine neural signatures of surgical and training induced motor improvements. H3:
After directed task-based training, brain activity during voluntary pinch will extend to
adjacent areas (larger representation, greater activity), in sensorimotor brain areas,
facilitating the ability to voluntarily increase the transferred Br activation in pinch.
Secondary analyses will contrast size and activation level of brain changes with pinch
activation in patients who receive training relative to non-impaired and non-surgical
participants.

The postoperative therapy protocols after tendon transfer procedures are not well defined,
inconsistently applied, and lack evidence for their effectiveness. The study proposed here
will investigate cortical change to assess outcome dependent plasticity. Thus, it may be
possible to predict why some individuals do not re-train the transferred muscle as well as
others. Establishing this relationship can lead to understanding the mechanisms of successful
interventions and may identify brain based dynamics that could become the focus of future
treatments (e.g. biofeedback, brain stimulation, etc.).

Inclusion Criteria:

- Individuals with a clinical diagnosis of SCI cervical level 4-7, complete or
incomplete injuries, who have completed conventional therapy and be at least 1-year
post-surgery, are eligible for the study.

- Participants must have had Br to FPL tendon transfer, be willing to participate in a
10 week exercise program, have adequate assistance or be independent in setting up
exercise equipment (weight cuffs, functional tasks), and be available for two
measurement sessions.

- Women and minorities may be included in the study if they meet the inclusion criteria.

- Non-Veteran participants who meet the selection criteria will be included to expand
the available number of subjects.

Exclusion Criteria:

- More than one tendon transfer to the thumb to restore pinch but not if they have other
tendon transfer procedures on the same upper limb.

- Other exclusion criteria include pain that would limit their ability to perform the
activities, spasticity in the upper limb, or spinal cord injury level above C4 or
below C7 as their pattern of weakness will be substantially different.

- Subjects who are participating in other research studies that include exercise
programs for the upper limb or drug studies that affect their response to exercise
will also be excluded.