Deep brain stimulation (DBS) is a rapidly developing therapeutic approach for severe psychiatric disorders. A recent study from Texas Children’s Hospital and Baylor College of Medicine identified a specific neural activity pattern as a novel biomarker to accurately predict and monitor the clinical status of individuals with OCD who have undergone DBS. The study, which was co-directed by Drs. Nicole Provenza, Sandy Reddy, and Anthony Allam and headed by Drs. Sameer Sheth and Wayne Goodman.
Their findings were published in the journal Nature Medicine.
Recent advances in surgical neuromodulation have enabled long-term continuous monitoring of brain activity in OCD patients during their everyday lives,
We used this novel opportunity to identify key neural signatures that can act as predictors of clinical state in twelve individuals with treatment-resistant OCD who were receiving DBS therapy.
Dr. Nicole Provenza
Two to three per cent of people worldwide suffer from OCD, a prevalent and debilitating mental illness. OCD affects over two million people in the United States. In extreme situations, patients put in a remarkable amount of time engaging in monotonous, apparently pointless compulsions and enduring intrusive thoughts. OCD severely impairs the quality of life and general well-being of patients as well as carers. It can also make it difficult to keep up relationships and a job. While most afflicted persons respond well to psychotherapy and medication, between 20–40% of severe OCD sufferers are not responsive to these traditional therapies.
DBS treatment has been utilised to alter neural activity in particular brain areas associated with OCD symptoms since the early 2000s. Many of the patients who are eligible for this treatment have not benefited enough from traditional therapies. After DBS, over two-thirds of individuals in this treatment-resistant population exhibit a significant reduction in their OCD symptoms.
DBS devices control electrical activity in the brain like how pacemaker devices control electrical activity in the heart. DBS systems use two thin leads, or cables, to transmit electrical impulses from the generator, which is usually implanted in the upper chest, to certain target areas in the brain. Accurate adjustment of the stimulation parameters enables the electrical pulses to rectify an unhealthy brain circuit.
DBS is an FDA-approved procedure that is increasingly being utilised to treat severe OCD in addition to being frequently used to treat movement disorders such as tremors and Parkinson’s disease.
We have seen remarkable progress in the field of DBS research, a technology that has been used for decades to treat movement disorders,
The advance reported here represents just one on a growing list of success stories where the BRAIN Initiative has helped develop a new generation of DBS technologies, bringing treatments for conditions like OCD closer to the clinic.
Dr. John Ngai
For mental diseases such as OCD, defining the appropriate dosage is frequently more challenging than for movement disorders.
In patients with movement disorders, it is more obvious when stimulation delivery and tuning is correct because abnormal movements such as tremors or stiffness decrease right away,
However, it is much more difficult to achieve this level of precise DBS programming for OCD and other psychiatric disorders because there is a long delay between stimulation initiation and symptom improvement. It is difficult to know what particular adjustment led to a particular change months later. Our goal in undertaking this study was therefore to find a reliable neural biomarker to guide us during DBS management, and to remotely monitor changes in our patients’ symptoms. This is particularly important because several of our patients travel long distances from around the country or world to get DBS treatment, which for OCD is currently offered only in very few specialized centers.
Dr. Sheth
The scientists concentrated on pathological avoidance, which is one of the most defining behaviours of OCD, to find the best target for creating a biomarker. A difficult-to-control avoidance of possible damage or suffering is a common symptom of OCD. They are frequently troubled by intrusive thoughts and illogical concerns (obsessions) while attempting to avoid such imagined risks in daily life, which results in strict routines and repetitive behaviours (compulsions).
The researchers set out to investigate how patients with severe, treatment-resistant OCD differed in low-frequency brain oscillations in the theta (4-8 Hz) to alpha (8-12 Hz) range, which has been established by a substantial body of scientific literature to play a key role in cognitive processes. They achieved this by utilising a cutting-edge function of contemporary DBS devices: the capacity to capture and deliver brain activity.
Studies that track patterns of brain activity are often planned as short bursts of time that are carried out while subjects complete a particular cognitive task. This study is distinctive, though, since the researchers were able to continually track patterns of brain activity in the backdrop of daily tasks using the DBS system. This aspect of the study allowed the research to be conducted in the participants’ everyday lives as opposed to being restricted to artificial laboratory environments.
Recordings began as soon as the DBS system was installed. The scientists were able to quantify brain activity patterns in the highly symptomatic condition since stimulation usually started days or weeks later. It’s interesting to note that they discovered a strong diurnal rhythm in the neuronal activity of the ventral striatum at 9 Hz (theta-alpha boundary), which varied throughout the 24-hour cycle.
Before DBS, we saw an extremely predictable and periodic neural activity pattern in all participants,
However, after DBS activation, as individuals began responding and improving symptomatically, we saw a breakdown in this predictable pattern. This is a very interesting phenomenon and we have a theory to explain it. Individuals with OCD have a limited repertoire of responses to any given situation. They often perform the same rituals repeatedly and seldom vary their routines or engage in new activities, which may result in high predictability of activity in this brain region. However, after DBS activation, their behavioral repertoire is expanded; they might respond more flexibly to situations and not be just driven by a strong desire to avoid OCD triggers. This expanded repertoire may be a reflection of the more diverse brain activity pattern. Thus, we think this loss of a highly predictable neural activity indicates that the participants engaged in fewer repetitive and compulsive OCD behaviors.
Dr. Goodman
In summary, we have identified a neurophysiological biomarker that can serve as a reliable indicator of improvements in mood and behaviors in OCD patients after DBS treatment. We anticipate these findings to transform how patients are monitored throughout DBS therapy.
Dr. Sheth
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Incorporating this information into a clinician-facing dashboard, for example, could help guide therapy delivery, thus demystifying the process of DBS programming for OCD and making the therapy more accessible to a greater number of clinicians and patients. Moreover, we are excited by the potential possibility that such similar neural activity signatures may underlie other neuropsychiatric disorders and could serve as biomarkers to diagnose, predict, and monitor those conditions.
Dr. Nicole Provenza
Source: Baylor College of Medicine News.
Journal Reference: Provenza, Nicole R., et al. “Disruption of Neural Periodicity Predicts Clinical Response After Deep Brain Stimulation for Obsessive-compulsive Disorder.” Nature Medicine, 2024, pp. 1-11, https://doi.org/10.1038/s41591-024-03125-0.
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