Sunday, September 19, 2010

Mania and Artistic 'Surprise' Induced by Deep Brain Stimulation

Fig. 2 (Haq et al., 2010). A painting made following initial ALIC-NA [anterior limb of the internal capsule/nucleus accumbens] DBS activation. It was produced after a night-long effort and was described as a ‘surprise’ for the staff. The religious tone is typical of the patient.

Deep brain stimulation (DBS) is being tested as an experimental treatment for intractable obsessive-compulsive disorder (OCD), as well as for major depression.1 A recent review by Mian et al. (2010) discusses the three main brain regions that are targeted by DBS for OCD:
  • Target 2: the subthalamic nucleus (STN) within the basal ganglia, a major DBS target for Parkinson's disease as well
Haq et al. (2010) reported on the adverse events experienced by a patient receiving DBS in ALIC and the nucleus accumbens (part of the ventral striatum) for severe OCD. A 29 year old woman started experiencing OCD symptoms in early childhood:
...obsessions that centered on a need to be clean and a need to please. At the time of enrollment, her compulsions included counting, bra-snapping, pant-pulling and leg scratching. She completed the 12th grade but subsequently had difficulty remaining employed because of her illness. In addition to her history of OCD, she was also diagnosed as having major depressive disorder. Twice, in the remote past, she had attempted suicide via drug overdose.
Since she had failed to respond to three different classes of drugs, as well as to cognitive behavioral therapy, she was eligible to enroll in the DBS trial. The implantation surgery was uneventful, and the patient was randomized to have activation of the stimulator begin at 30 days post surgery.

In the Introduction, the authors were remarkably honest about how the choice of stimulation parameters can be hit and miss:
The published experience with DBS programming for OCD is limited. Parameters (voltage, pulse width and frequency) are commonly adjusted by trial and error with the aim of deriving the greatest possible clinical efficacy while avoiding uncomfortable side effects. As physicians’ experience with DBS programming in OCD has broadened, the potential for stimulation-induced side effects has become increasingly apparent. Novel targets, such as the anterior limb of the internal capsule/nucleus accumbens (ALIC-NA), have introduced novel stimulation-induced effects.
And Haq et al. (2010) did see some novel stimulation-induced effects that included mania ("hugging" and pressured speech), insomnia, and worsening of OCD symptoms on the first two days of stimulation (as shown below). Oops. The patient was admitted to inpatient psychiatry the next day.

-- click on table for larger image --

Table 1 (modified from Haq et al., 2010). Programming settings and patient behavior. PW=pulse width. Contacts were implanted bilaterally, and the parameters were identical for each.

The initially stimulated contacts were located in the nucleus accumbens (NAcc), considered to be one of the brain's pleasure centres. Not surprisingly, the NAcc is a rational DBS target for depression too, given the common symptom of anhedonia, i.e. the inability to experience pleasure from normally pleasurable life events (see Good News/Bad News Update on Nucleus Accumbens DBS for Treatment-Resistant Depression).

Upon transfer to the psych ward, the patient's medication regimen was extensive: one antidepressant (fluoxetine), three mood stabilizers/anticonvulsants (lamotrigine, pregabalin, topiramate), one benzodiazapine (clonazepam), and one non-benzo sedative/hypnotic (eszopiclone). Nonetheless,
Following this initial adjustment [of DBS stimulation parameters], the patient spent most of the night awake, alternating between cleaning the adjoining room and painting (see Fig. 2 above). Her painting and speech were notable for their hyperreligious content. She also reported that her OCD symptoms were more troublesome than in her preoperative state. She developed bruises on her shins and thighs from obsessively rubbing her legs and reported an increase in her counting behaviors. Her fluoxetine dose was decreased to be sure that it was not exacerbating the mania and her topiramate was discontinued.
Also, her clonazepam dose was doubled and an atypical antipsychotic (quetiapine) was initiated. Not surprisingly, "The patient showed signs of mild sedation after these changes in medication." Fortunately, her condition stabilized after a week. Her symptoms had improved (from extreme to severe) at the one month follow-up, reaching remission after six months of stimulation at the more conservative intensity.

The side effects of mania and hypomania are not uncommon after DBS in NAcc and the ventral capsule (Tsai et al., 2010). As noted by Haq and colleagues (2010):
Stimulation-induced mania may result from spread of the stimulation field from the motor regions of gray matter structures into limbic or frontal territories... The ALIC-NA is more richly connected to limbic and frontal regions than the STN or other basal ganglion targets and (based on limited experience) has a correspondingly higher incidence of postoperative psychiatric side effects. The occurrence of transient hypomania with ALIC-NA DBS has been estimated to be as high as 50–67%...
The abnormal circuitry implicated in OCD is quite complex, and is thought to include fronto-striatal- thalamic-cortical loops (Maia et al., 2008). A clearer understanding of the connectivity of these regions through the use of tractography may improve the choice of target for DBS in a number of psychiatric disorders.


1 David Dobbs has also written extensively about this topic, most recently in his post on Depression’s wiring diagram.

2 In More on Deep Brain Stimulation for OCD, Neuroskeptic explains the ventral capsule/ventral striatum procedure.


Haq, I., Foote, K., Goodman, W., Ricciuti, N., Ward, H., Sudhyadhom, A., Jacobson, C., Siddiqui, M., & Okun, M. (2010). A Case of Mania following Deep Brain Stimulation for Obsessive Compulsive Disorder. Stereotactic and Functional Neurosurgery, 88 (5), 322-328 DOI: 10.1159/000319960

Maia TV, Cooney RE, Peterson BS. (2008). The neural bases of obsessive-compulsive disorder in children and adults. Dev Psychopathol. 20:1251-83.

Mian MK, Campos M, Sheth SA, Eskandar EN. (2010). Deep brain stimulation for obsessive-compulsive disorder: past, present, and future. Neurosurg Focus 29(2):E10.
Tsai HC, Chen SY, Tsai ST, Hung HY, Chang CH. (2010). Hypomania following bilateral ventral capsule stimulation in a patient with refractory obsessive-compulsive disorder. Biol Psychiatry 68:e7-8.

Fig. 3 (Saxena & Rauch, 2000). Model of the pathophysiology of obsessive-compulsive disorder. Obsessive-compulsive disorder symptomatology may be the result of a captured signal in the direct orbitofrontal-subcortical pathway, a positive-feedback loop. This signal could be caused by excess tone in the direct (large arrows) relative to the indirect (small arrows) orbitofrontal-subcortical pathway, resulting in increased activity in the orbitofrontal cortex, ventromedial caudate, and medial dorsal thalamus. This orbitofrontal-subcortical hyperactivity allows for concerns about danger, violence, hygiene, order, and sex to rivet attention to themselves, compel patients to respond with ritualistic behavior, and result in an inability to switch to other behaviors.

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