Basic Rules Identified for Therapeutic Intracranial Stimulation of the Human Brain

Direct electrical stimulation of the brain can relieve symptoms of several neuropsychiatric diseases, including Parkinson's disease, obsessive-compulsive disorder, and epilepsy. However, its efficacy is quite variable and unpredictable, probably because stimulation interacts differently with the target brain network in different patients.

Subscribe to the latest updates from Neuroscience Advances in Motion

Thank you for subscribing!

Error: Please enter a valid email address.

Email Address Submit

Angelique C. Paulk, PhD, instructor in the Department of Neurology at Massachusetts General Hospital, G. Rees Cosgrove, MD, director of epilepsy and functional neurosurgery at Brigham and Women's Hospital, Ziv M. Williams, MD, a neurosurgeon in the Department of Neurosurgery, Sydney Cash, MD, PhD, co-director of the Center for Neurotechnology and Neurorecovery at Mass General, and colleagues have completed one of the few studies to systematically examine intracranial neurophysiological effects of invasive brain stimulation in humans.

In Brain Stimulation, they describe patterns of responses to different stimulation parameters that could become key to planning treatment with deep brain stimulation, particularly in subcortical regions.

Methods

The researchers performed direct electrical stimulation while recording from intracranial leads in 52 patients. The patients had been implanted with stereoEEG depth electrodes to determine seizure foci. Stimulation was given at 719 sites, and recordings were made at more than 6,500 sites at various distances from the stimulation sites (15–50 mm).

To investigate both local and distant responses, the team also varied the stimulation duration, amplitude, and location relative to grey and white matter.

Results

The principal findings were that:

• Increasing the duration of stimulation led to larger responses both locally and distally
• Responses to stimulation varied non-linearly both near the stimulation site and at a distance; specifically, increasing stimulation from 1 to ~5 mA linearly increased the response, but beyond ~5 mA the response plateaued or even decreased
• Stimulation at the grey–white boundary and particularly in white matter resulted in the largest responses; this effect was observed across brain regions but was most striking in the lateral frontal cortex
• Local responses were largest when stimulation occurred at the grey–white boundary, particularly in the lateral temporal lobe
• Distant responses were best induced with stimulation entirely in white matter

Moving Beyond "One Parameter Set Fits All"

These results suggest it may be possible to tailor therapeutic deep brain stimulation for individual patients with a wide range of neuropsychological disorders. The relationships between stimulation parameters (location, amplitude, duration, and frequency) and the desired neural responses are complex but seem to be knowable and mappable.

Some examples:

• If large, local responses are needed to reach a neurophysiological and behaviorally relevant therapeutic goal, then it might be best to target stimulation across the grey–white junction
• When a therapeutic goal is to induce widespread, network-level changes (e.g., when treating certain forms of epilepsy), it may be preferable to target white matter in the lateral frontal cortex
• If the aim is to produce highly localized responses or induce small circuit changes (e.g., when using microstimulation to affect memory formation), then targeting grey matter might be useful, such as in the cingulate

view original journal article Subscription may be required

Learn more about the Center for Neurotechnology and Neurorecovery

Refer a patient to the Department of Neurology