Low Frequency Cortical Activity and Neuromodulation in Stroke

What’s the science?

Stroke that affects the brain’s motor cortex can cause motor impairment and disability. Low frequency oscillatory activity (LFO; rhythmic electrical activity in the brain) in the motor cortex is known to be involved in motor movements such as reaching. In particular, LFO is related to movement timing, and may be responsible for fast, accurate movements. The role of LFO in recovery from strokes that affect motor function is not known. This week in Nature Medicine, Ramanathan and colleagues studied LFO in rats and humans to understand their potential role in stroke.

How did they do it?

Four rats were trained to perform a skilled reaching task and then had microwire arrays (arrays of electrodes measuring electrical signal) implanted in their primary motor cortices. Signals were recorded from the electrodes while they performed the reaching task. The authors then performed a distal middle cerebral artery occlusion as a model of stroke (this model results in damage to sensorimotor cortex) and recorded brain activity and reaching behaviour 5 days post-stroke. However, the middle cerebral artery occlusion model of stroke results in widely variable damage to the motor cortex. Therefore, the authors next used a different stroke model (focal photothrombotic stroke) to study damage in a specific area of the motor cortex and how recovery of brain tissue at the edge of a stroke-related lesion (perilesional cortex) might be related to LFO. They did this by using a microwire array placed just anterior to the site of injury. The authors also assessed electrocorticography data in humans (when electrodes are placed on the brain’s surface to record activity – in this case in patients with epilepsy undergoing monitoring) and had them perform a reaching task. Two of the patients were otherwise healthy (‘non-stroke subjects’), while one patient had had a stroke in sensorimotor cortex four years prior (‘stroke subject’). Finally, the authors applied direct current stimulation to the sensorimotor cortex in rats to assess whether this stimulation would change LFO or could improve reaching behaviour.

What did they find?

As expected, LFO was found in rats during the reaching task, both in terms of spiking (action potentials from neurons in the brain), and local field potentials (the summation of local electrical currents around neurons), especially at lower frequencies (~<4Hz). For example, neurons showed coherent spiking at low frequencies prior to the onset of reaching during the task. Five days following the middle cerebral artery occlusion stroke, the animals had impaired motor skills. However, at least some electrodes in the microwire array were in undamaged or viable tissue that was still able to demonstrate reach-related increases in activity similar to pre-stroke activity. Prior to stroke, the strength of local field potentials tracked the phase (phase locking, ie. synchrony of firing) of neuron spiking. However, after stroke, local field potential modulation was reduced and was no longer related to neuron spiking.

This reduction was not related to changes in the speed of reaching movements post-stroke. The results remained unchanged when the event-related potential (changes in local field potentials time locked to the stimulus) were subtracted. These results suggest that LFO was altered after stroke independent of other changes post-stroke. When the authors used the focal photothrombotic stroke model, they found that motor skills were impaired after the injury but improved over time with training. With this recovery, spiking activity and local field potentials returned in perilesional cortex (i.e. cortex near the stroke), and these changes were related to improvement in reaching accuracy. When they examined human electrocorticography data, task-related low frequency activity was found to be increased in the non-stroke subjects during the reaching task, but not in the stroke subject. Low frequency activity in the stroke subject was lower than that in the non-stroke subjects. The results suggest that LFO indicates healthy motor system function in rats and humans. When direct current stimulation was applied at varied times during the reaching task to post-stroke rats (with 1 second pulses), the authors found that reach accuracy was improved when stimulation was applied 500-400 ms prior to the reach. This time period overlaps with the expected LFO, suggesting that direct current stimulation could boost LFO.

What’s the impact?

This is the first study to assess cortical dynamics during stroke recovery and neuromodulation via direct current stimulation. LFO (spiking activity, local field potentials) is reduced following stroke and is related to improved accuracy during recovery. Cortical stimulation improved stroke recovery in rats, suggesting that neuromodulation may be an important clinical target for stroke patients.

Ramanathan et al., Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke. Nature Medicine (2018). Access the original scientific publication here.