Deep Brain Stimulation of the Internal Capsule Improves Prefrontal Cortex Function

Post by Leigh Christopher

What's the science?

Gold standard treatments for mood and anxiety disorders are often ineffective. Deep brain stimulation (DBS), where electrical current is applied to brain circuits, effectively relieves symptoms in some cases, however, the results are inconsistent. One theory is that this inconsistency is due to the lack of a biomarker to indicate the ‘effective dose’ of electrical stimulation. The ventral internal capsule is affected in both depression and obsessive-compulsive disorder (OCD) and has shown promise as a target for DBS therapy. This region is involved in cognitive control – it regulates theta oscillations in the prefrontal cortex that could act as a biomarker of DBS efficacy. Recently in Nature Communications, Widge and colleagues use DBS to stimulate the ventral internal capsule to assess whether its stimulation alters brain oscillations in the prefrontal cortex and improves cognitive control in patients with depression and OCD.

How did they do it?

Fourteen patients — 12 with major depressive disorder and 2 with OCD participated in the study — these patients previously had a DBS electrode implanted in the ventral internal capsule/ventral striatum. Patients performed the Multi-Source Interference Task – a cognitive control task that includes emotional distractors. During this task, participants had to identify which of a set of three numbers was different than its neighbours, using a key press. In the conflict trail, the target number is out of position (e.g. a number two is not in the second key position). An emotionally distracting image was displayed during certain trials. The participants then played the Effort Expenditure for Rewards task, in which they had to press a button to fill a bar on the screen - they had to choose quickly between easy and hard options in an attempt to receive as high a payoff as possible. The authors used EEG to record the patients’ brain oscillatory activity throughout these tasks while their DBS was turned either on or off. They analyzed response times and how they were affected by cognitive conflict (interference), emotional distraction and DBS treatment using a linear mixed effects model. They used sliding multivariate regression to assess whether theta activity (as recorded by EEG) was associated with cognitive control.

What did they find?

DBS enhanced cognitive control for both interference and control trials of the Multi-Source Interference task – reaction times were 34 seconds faster on average compared to DBS being turned off. The power of theta oscillations (non-phase-locked, or task-evoked) was higher throughout the prefrontal cortex while participants exercised cognitive control during the decision-making portion of the task. DBS stimulation increased this effect for almost the entire decision-making period. In the Effort Expenditure for Rewards task, the response times were slower while DBS was on, suggesting that the DBS effects were specific to the cognitive control tested in the Multi-Source interference task. Button presses were not different when DBS was on vs. off in this task, suggesting that DBS does not impact movement speed. Change in the theta power in the inferior frontal gyrus during the interference task while DBS was on was associated with a reduction in depressive symptoms. The inferior frontal gyrus showed the most drastic change in theta power of any prefrontal region. These changes were specific to the theta frequency, with no other frequency band showing changes during the task.

What's the impact?

This work supports the theory that DBS exerts its therapeutic effects by regulating brain activity in the cortex. Thes study demonstrates that DBS improves cognitive control and that this is related to an increase in theta oscillatory power in the prefrontal cortex. These findings have important clinical implications – clinicians could use change in theta power as a biomarker to assess whether the proper stimulations parameters have been applied during DBS, improving efficacy of the treatment. Further, this study suggests that augmenting cognitive control in general may be an effective treatment strategy for psychiatric illness.

Widge et al. Title. Nature Communications (2019). Deep brain stimulation of the internal capsule enhances human cognitive control and prefrontal cortex function. Access the original scientific publication here.