From Prison to Possibility: How Thalamic Stimulation Can Help after a Motor Cortex Stroke

You had a stroke in your motor cortex. Now you can’t move, trapped in your own body, a prison from which you yourself cannot escape. However, doctors can help.

If the damage was partial and some of the motor cortex (M1), and its axons descending down the corticospinal tract (CST), remain intact, there is hope. Many motor neurons may be dead or disconnected and cannot contribute to the collective dynamics of M1. This makes it hard for the remaining M1 neurons to communicate and sustain activity during movement. The doctors’ goal is to boost the signals coming from the surviving M1 neurons so that, together, they can rewire and relearn to support motor activity.

Even when a substantial number of neurons are lost, the remaining neurons can change their collective behavior. If their likelihood of firing is increased, weaker inputs can make it easier for the neurons to communicate and fire. In turn, these surviving neurons can re-establish patterns of activity that underlie movement. In other words, we try to make the neurons that are still there work harder and talk to one another more effectively so the network can sustain the activity needed for voluntary movement.

New work from Dr. Pirondini’s lab and collaborators shows that boosting the signal that reaches M1 via the thalamus is a key part of this strategy. To understand why, we need a bit of anatomy. The thalamus is a relay station that connects many brain regions with the cortex. The motor thalamus, a collection of nuclei and tracts, receives input from several brain areas and sends excitatory input to the motor cortex, helping drive motor neurons to fire.

Figure 1a from the paper. Shows how stimulating the motor thalamus excites M1 neurons, many who have lost connections. 

By implanting a DBS electrode into the VLL part of the thalamus (the thalamic region that mostly connects to cortex), clinicians can stimulate thalamic neurons to fire. This stimulation does not force every M1 neuron to fire at once; rather, it raises their excitability, it makes them more likely to fire in response to inputs. Thus, the few remaining M1 neurons have an easier time communicating with one another and sustaining the activity patterns necessary to escape paralysis.

Readers familiar with DBS may remember that thalamic stimulation is also used to treat essential tremor by interrupting the connection between the cerebellum and M1. That’s true, but the functional effect depends strongly on the stimulation frequency. Lower-to-mid frequencies (about 50–80 Hz) appear to potentiate or enhance motor cortex activity and are best for supporting M1. In contrast, high-frequency stimulation (around 200 Hz) tends to block transmission and suppress the signal. Choosing the correct stimulation frequency is therefore critical to producing a therapeutic effect rather than silencing the pathway.

Figure 5b. This shows how 50 and 80 Hz potentiate movement the most, while 200 suppresses its firing. It is important to note this is measured from the perspective of the muscles membrane potential.

Armed with these insights, Dr. Pirondini has started a clinical trial testing thalamic DBS to boost motor cortical activity in patients with partial M1 damage. The idea is not to replace the motor cortex but to amplify and shape the signals that surviving neurons can give, encouraging the network to reorganize and regain function.

A stroke in M1 can feel like a prison. But when some circuitry survives, it may be possible to open the cell door a crack. By carefully boosting thalamic input, at the right frequency and to the right thalamic target, clinicians aim to give the remaining motor neurons the boost they need to rewire, sustain activity, and restore movement. In that narrow beam of light, there is a path out of paralysis.


Author: Alexander J. White


Origin: Ho, J. C., Grigsby, E. M., Damiani, A., Liang, L., Balaguer, J. M., Kallakuri, S., ... & Pirondini, E. (2024). Potentiation of cortico-spinal output via targeted electrical stimulation of the motor thalamus. Nature Communications, 15(1), 8461.

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