Q&A: Neuroplasticity after stroke reveals ‘critical’ early period for rehabilitation

A longitudinal study quantifying neuroplasticity in the ipsilesional and contralesional human motor cortex following a stroke demonstrated “a period of enhanced synaptic plasticity” that was strongest about 2 weeks after the event.

The results, which were published in Neurorehabilitation and Neural Repair, provided “the first neurophysiological evidence” for such a period, according to the researchers.

Brenton Hordacre, PhD, a senior lecturer in physiotherapy at the University of South Australia and a National Health and Medical Research Council Early Career Research Fellow, and colleagues aimed to find evidence of changes in synaptic plasticity in the human brain in the weeks and months after an ischemic stroke. They based their research on previous preclinical models that showed greater gains with behavioral training in the early period after a stroke compared with delayed training.

Healio Neurology spoke with Hordacre to learn more about the approach used in the study and the results.

Healio Neurology: What prompted this research?

Hordacre: There was some indication from animal studies that brain changes occur after stroke to provide a period where neuroplasticity is enhanced. This upregulation in neuroplasticity appeared to be associated with accelerated recovery. It is significantly more challenging to test the same phenomenon in humans (as we cannot dissect brains!), but it would be incredibly useful to understand whether a similar period existed. We therefore devised a technique using brain stimulation to test this question.

Healio Neurology: Can you describe the process you used to examine synaptic plasticity?

Hordacre: We used a technique called continuous theta burst stimulation, which is a repetitive transcranial magnetic stimulation protocol. Essentially, it delivers high-frequency electromagnetic stimuli to the brain by holding a coil over the scalp. This particular protocol delivers 600 pulses in 40 seconds. We have good evidence from previous studies that continuous theta burst stimulation suppresses excitability of the brain and represents a synaptic plasticity mechanism known as long-term depression.

At each session, which were conducted at different times after stroke, we would perform this continuous theta burst stimulation and measure the excitability of the motor cortex before and after using single-pulse transcranial magnetic stimulation. This single-pulse transcranial magnetic stimulation activates motor areas of the brain to cause an evoked response in a hand muscle that we measured with surface electromyography. Essentially, what we look for is how the evoked response changes from before to after the continuous theta burst stimulation. As this is a long-term depression type of synaptic plasticity, we would expect the evoked responses to get smaller after continuous theta burst stimulation. The magnitude of this change was used as a measure of the capacity for neuroplasticity at each session.

This is a painless technique and any change in brain activity induced by continuous theta burst stimulation is only temporary, lasting approximately 60 minutes.

Healio Neurology: What did the study results demonstrate?

Hordacre: The key finding was that the response to continuous theta burst stimulation was strongest at 2 weeks after stroke and dissipated over subsequent weeks and months in the non-stroke hemisphere. We did test the stroke-affected hemisphere but did not see any change in the neuroplasticity response over time.

There are two possible reasons for this lack of response in the stroke-affected hemisphere. It might indicate this particular type of synaptic plasticity is not as important here; perhaps it is more likely to respond to long-term potentiation, rather than long-term depression. Additionally, this particular measure activates cortical tissue in the brain. The patients who experienced a stroke in this study did have a lot of cortical damage and it might be this measure is not as responsive when the brain is damaged.

Healio Neurology: How could these findings impact clinical practice?

Hordacre: It emphasizes that therapy early after stroke is critical to take advantage of this heightened capacity for neuroplasticity. Delaying the start of therapy, or delivering too little, is likely to lead to poor recovery outcomes.

Healio Neurology: What are the next steps for this research?

Hordacre: We are looking at methods to reopen or prolong a similar period of enhanced neuroplasticity with this idea that it would further promote recovery in people who have experienced a stroke.

Reference:

Hordacre B, et al. Neurorehabil Neural Repair. 2021;doi: 10.1177/1545968321992330.