Researchers find a way to reduce the side effects of deep brain stimulation


Deep brain stimulation (DBS) has emerged as an effective therapy for severe, treatment-resistant obsessive-compulsive disorder (trOCD) and has received approval under a humanitarian device exemption from the U.S. FDA. However, there are adverse side effects associated with this procedure. While working on a recent case, a team led by Dr. Wayne Goodman, D.C. and Irene Ellwood Chair of Psychiatry and professor at Baylor College of Medicine, and Dr. Sameer Sheth, director of the Cain Foundation Labs in the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital and professor at Baylor, found a way to reduce potential side effects associated with this procedure. The study was published in Brain Stimulation.

ALIC is an important DBS target for OCD and other psychiatric disorders

The anterior limb of the internal capsule (ALIC) is a fiber pathway that connects the prefrontal cortex with the deep brain regions of the thalamus and brainstem. Neural activity flowing through this brain super-highway is critical for processing different aspects of emotion, motivation, cognition, and decision-making. Activity patterns in this region are abnormal in several psychiatric illnesses, and therefore, the ALIC is an important DBS target to treat trOCD and other psychiatric disorders.

Over the past two decades, the location of this DBS target has evolved and is currently close to another deep gray matter region, the bed nucleus of the stria terminalis (BNST). Although this location has been found effective in a number of treatment-resistant OCD cases, stimulation here may result in certain side effects such as rapid weight gain, fatigue, cold/heat intolerance, all likely due to off-target activation of surrounding tissue and functionally connected structures.

Adverse effects of OCD are likely due to off-target stimulation

In this report, Sheth, Goodman, and colleagues tested the hypothesis that this unusual constellation of adverse side effects originates from the off-target effects of BNST stimulation. They used electrical current-steering with segmented DBS leads on a patient who underwent BNST DBS for trOCD. Before DBS, the patient suffered from severe obsessive (perfectionism, symmetry, contamination) and compulsive (re-arranging, mental rituals, cleaning) behavioral symptoms that were resistant to standard drugs and therapies like cognitive behavioral therapy.

The team used a robot-assisted method to implant two segmented DBS leads. When they stimulated the ventral two levels on both leads, they observed a positive affective response which they had recently demonstrated was a good predictor of longer-term OCD improvement. Consistent with the intraoperative results, within two weeks of surgery, they noticed that activation of the deepest contacts on both leads elicited a positive affect response characterized by spontaneous smiling, increased energy, and improved mood along with dramatic improvements in OCD symptoms to the point that the patient met the criteria for remission.

Unfortunately, over the next two months, the patient developed a number of side effects including heat/cold intolerance, marked weight gain with increased appetite, gastrointestinal distress, restlessness, and marked fatigue.

Finding the best electrode placement to reduce side effects

The team hypothesized that these side effects indicated inadvertent stimulation of the hypothalamus, causing a disturbance in the regulation of these functions. The hypothalamus borders the BNST, and its sub-nuclei regulate temperature, satiety, and circadian rhythm, among other homeostatic functions. Their estimation of the electrical field produced by the stimulation parameters added further confidence to this hypothesis.

To determine whether the stimulation fields overlapped with the hypothalamus, they generated computer models that reconstructed the volume of tissue activated to visualize anatomical overlap. Based on these imaging estimates, they reasoned that steering the field in a lateral and superior direction would avoid the hypothalamus and hopefully, reduce the side effects. Using these models, they investigated different stimulation configurations within the DBS lead to steer the electrical field in the desired direction.

Soon after doing so, the patient’s side effects reduced substantially, while the obsessive-compulsive symptoms still remained under control. Their success highlights the importance of considering off-target stimulation during surgical planning and programming for BNST DBS.

In conclusion, while current steering techniques cannot correct overtly mal-positioned leads, this study showed slight directional adjustments can reduce side effects. Moreover, it also underscored the need for close monitoring of DBS patients for many months after DBS surgery, as the time course of behavioral responses to parameter adjustments can continue to evolve for long periods of time.

Others involved in the study were Huy Q. Dang, Nicole R. Provenza, Garrett, P. Banks, Nisha Giridharan, Michelle Avendano-Ortega, Sarah A. McKay, Ethan Devara, Ben Shofty, and Eric A. Storch. Their institutional affiliations and funding sources can be found here.

Sameer A. Sheth, M.D., Ph.D.

Wayne Goodman, M.D.