Motor practice is an essential part of upper limb motor recovery following stroke. To be effective, it must be intensive with a high number of repetitions. Despite the time and effort required, gains made from practice alone are often relatively limited, and substantial residual impairment remains. Using non-invasive brain stimulation to modulate cortical excitability prior to practice could enhance the effects of practice and provide greater returns on the investment of time and effort. However, determining which cortical area to target is not trivial. The implications of relevant conceptual frameworks such as Interhemispheric Competition and Bimodal Balance Recovery are discussed. In addition, we introduce the STAC (Structural reserve, Task Attributes, Connectivity) framework, which incorporates patient-, site-, and task-specific factors. An example is provided of how this framework can assist in selecting a cortical region to target for priming prior to reaching practice poststroke. We suggest that this expanded patient-, site-, and task-specific approach provides a useful model for guiding the development of more successful approaches to neuromodulation for enhancing motor recovery after stroke.
Poststroke Arm Impairment
Upper limb motor impairment following stroke is highly prevalent and often persists even after intensive rehabilitation efforts (1–4). It is also one of the most disabling of stroke sequela, limiting functional independence and precluding return to work and other roles (5).
Upper extremity motor control relies heavily on input transmitted via the corticospinal tract (CST). The CST descends through the posterior limb of the internal capsule, an area vulnerable to middle cerebral artery stroke and in which CST fibers are densely packed. Thus, even a small lesion in this location can have devastating effects on motor function (6–9). A loss of voluntary wrist and finger extension is particularly common and appears to be related to the extent of CST damage (10). There is also evidence that those who retain wrist extension and have considerable CST sparing are more likely to be responsive to existing therapies (7, 8, 11).
However, even individuals who lack voluntary wrist and finger extension often retain some ability to move the shoulder and elbow. Unfortunately, only a few stereotyped movement patterns can be performed and these are often not functional. The combination of shoulder flexion with elbow extension that is required for most functional reaching tasks, for example, is frequently lost. Nevertheless, previous studies have demonstrated that reaching practice with trunk restraint can improve unconstrained reaching ability, even in patients who lack wrist and finger extension (12–15). Still, a great deal of time and effort is required and the improvements are relatively small.
Non-Invasive Brain Stimulation
Non-invasive brain stimulation offers a potential method of enhancing the effects of practice and thus giving patients greater returns on their investment of time and effort. Approaches to non-invasive brain stimulation are rapidly expanding but generally fall into two major categories: transcranial magnetic stimulation (TMS) and transcranial electrical stimulation [TES; see Ref. (16) for overview of non-invasive techniques for neuromodulation]. These modalities are applied to the scalp overlying a specific cortical area that is being targeted. The level of spatial specificity varies depending on many factors including the modality used (TMS is generally more precise than TES), the stimulation intensity (higher intensity results in a more widespread effect), and the architecture of the underlying tissue. The excitability of the underlying pool of neurons can be modulated by varying stimulation parameters such as the frequency and temporal pattern of the stimuli. Therefore, stimulation can be used to temporarily inhibit or facilitate the underlying cortical area for a sustained period of time after the stimulation ends (usually 20–40 min). In this way, non-invasive brain stimulation could be used to “prime” relevant cortical areas before a bout of practice, potentially enhancing the effects of practice. However, there is little guidance for how such cortical sites might be selected and in which direction (inhibition or facilitation) their activity should be modulated. Conceptual models that could offer such guidance are considered below.