CORRESPONDENCE
Effective Deep Brain Stimulation in Heroin Addiction:
A Case Report with Complementary Intracranial
Electroencephalogram
To the Editor:
eep brain stimulation (DBS) treatment consists of perma-
D nently implanted electrodes that deliver electrical pulses
to a target brain region. DBS of the nucleus accumbens
shows encouraging results as treatment for certain therapy-
resistant psychiatric disorders (1,2) and has been suggested for
therapy-resistant addiction (3). Heroin addiction is a chronic
relapsing brain disorder seriously affecting both the individual
and the public (4), and DBS could provide a new intervention for
those patients who do not respond to current treatments. One
central issue in DBS treatment is adaptation of the stimulation
parameters: to achieve effective DBS treatment, an extensive
optimization period is required in which stimulation parame-
ters— such as contact points, current, and pulse width—are
adapted based on clinical observations.
Here we report effective DBS treatment in a patient with therapy-
resistant heroin addiction in whom we also obtained pretreatment
intracranial electroencephalogram (iEEG) recordings from the nucleus
accumbens and adjacent anterior limb of the internal capsule in re-
sponse to drug-related pictures. We argue that pretreatment EEG re-
cordings from the implanted target area might be used to shorten the
optimization procedure and provide a more systematic and empiri-
cally based approach for optimizing the stimulation parameters (1).
Case Report. Patient A is a 47-year-old treatment-refractory
heroin-dependent man who had been using heroin for 22 years at
the time of intake. After he was fully informed and signed informed
consent, he was the first patient to be included in a larger pilot study
that was approved by the medical ethical board of the Academic
Medical Center Amsterdam (Protocol 09/322). The patient had
been treated with all currently available evidence-based interven-
tions, including four long-term inpatient treatments with a detoxi-
fication period— two under full anaesthesia—followed by oral nal-
trexone maintenance treatment and complementary behavioral
therapy and several outpatient psychotherapeutic and substitution
treatments with methadone and buprenorphine. At intake, he
smoked on average .5 g of heroin a day in addition to taking 20 mg of
oral methadone, which was switched to 6 mg buprenorphine during
the current treatment episode. To evaluate the desire for heroin, we
implemented the “desire and intention” scale of the desires for drugs
questionnaire (5) on which the patient scored 33 at intake.
The patient was implanted following standard procedures (3)
with a four contact electrode (model 3387 with contact points 1.5
mm long and separated from adjacent contacts by 1.5 mm;
Medtronic, Minneapolis, Minnesota) in each hemisphere. Elec-
trodes were implanted following the anterior limb of the internal
capsule into the nucleus accumbens. Contact point 0 (most ventral)
was located 7 mm lateral to midline and 4 mm below and 3 mm
anterior to the anterior border of the anterior commissure. Imme-
diately after electrode implantation the patient was exposed to
drug-related and drug-unrelated pictures for which he rated the
arousal, valence, and symptom-inducing properties. During the
presentation of the pictures, concurrent iEEG and scalp EEG were
recorded. On the basis of the ratings, all pictures were classified as
either drug-related or drug-unrelated. Immediately following the EEG
recordings, the electrodes were connected to the stimulator (Activa,
Medtronic), implanted in the chest, and activated 1 week later.
0006-3223/$36.00
Table 1. Average Drug Use and Craving Scores During Different
Stimulation Location Settings
Average Drug Use Average
Stimulation/Contact Points (g/day) Score DI
Before DBS .50 33
No Stimulation
Two Dorsal Contact Pointsa
Two Middle Contact Points
2 Ventral Contact Points
.68
.10
.87
.25
27
18
41
23
DBS, deep brain stimulation; DI, Desire and Intention Scale of the desire
for drugs.
a
Average over time including 4 months reduced drug use and 6 months
abstinence with 14-day relapse.
During the optimization period, several electrode settings were
systematically tested according to a standardized procedure (bilat-
eral, monopolar stimulation with 3.5-V amplitude, 90-␮s pulse
width, and 180-Hz frequency). In general, three combinations of
contact points were tested: two ventral, two middle, and two dorsal
contacts. When improvement was observed on drug use and/or
craving, the stimulation location was conserved, and small changes
in voltage were tested to achieve further improvement. In this
period, the patient was assessed approximately once a week for
heroin use, his intention and desire to use heroin, and possible side
effects. Stimulation of the middle contact points (1 and 2) led to an
increase in drug use and reported craving (see Table 1 for drug use
and craving) and was therefore stopped after 1 week. Stimula-
tion of the ventral contact points (0 and 1) was suboptimal with
limited reduction in heroine use and craving. Stimulation of the
two dorsal contact points (2 and 3), at the border of the internal
capsule and nucleus accumbens, was effective in generating a
significant reduction of drug use and craving. With this dorsal
stimulation (3.5-V amplitude at contact 2 and 3, 90-␮s pulse
width, and 180-Hz frequency), the patient first reduced his use to
the weekends and then succeeded in cessation of his heroin use;
he is currently clean for more than 6 months with the exception
of a 14-day relapse.
During the iEEG recordings, we observed significant differences
in power for drug-related compared to drug-unrelated pictures at
the dorsal contact points (2 and 3) but not at the other contact
points (Figure 1). This difference was significant in the right hemi-
sphere for the gamma band (40 – 60 Hz). To assess the connectivity
of the implanted target and the frontal cortex, we correlated
gamma power with frontal theta (4 – 8 Hz) power on a trial-by-trial
basis (6) and found a lower correlation in response to drug-related
compared with drug-unrelated pictures at the dorsal contact
points, whereas no difference was found for the other contact
points (Figure 1). On the basis of the commonalities of the iEEG
results and the clinical response in the dorsal contact points, we
propose that pretreatment recordings of the implanted target in
response to symptom triggers can help to determine the clinically
most effective location for DBS stimulation.
To the best of our knowledge this is the second report of suc-
cessful DBS in a heroin-dependent patient (7) and the first report on
the association between pretreatment electrophysiologic mea-
surements of the implanted target and DBS effectiveness. Our re-
sults support the existing literature (3), suggesting nucleus accum-
bens and adjacent internal capsule DBS as a promising treatment
for drug addiction and advocating for clinical studies with larger
samples. Additionally, given the observation that clinical outcome
in this patient seemed to be associated with pretreatment EEG
BIOL PSYCHIATRY 2012;71:e35– e37
© 2012 Society of Biological Psychiatry
e36 BIOL PSYCHIATRY 2012;71:e35– e37 Correspondence

Figure 1. Intracranial measurements of drug-related versus drug-unrelated stimuli. (A) Overview of the task. Two hundred stimuli were randomly
presented to provoke affective responses. (B) To increase the specificity of the signal, the intracranial signals were re-referenced to the adjacent
contact point (0 –1, 1–2, 2–3, where 0 is the most ventral contact). We then computed time-frequency representations along the electrodes. Right
bipolar contact point 2–3 showed higher power for drug-related compared with non-drug-related responses in the gamma-band (40 – 60 Hz) based on
permutation-based cluster-level statistics (p ⬍ .05). We then correlated the power time series of all bipolar intracranial electroencephalogram channels
to the time series of the theta range (4 – 8 Hz) of the scalp electrodes on a trial-by-trial basis and converted the correlation coefficients to Fisher Z scores
to make comparisons between conditions. Only the right bipolar contact point showed a significantly lower correlation to frontal theta compared with
the drug-unrelated responses (based on image by Mikael Häggström, reprinted with permission).

recordings, we argue that using such recordings may shorten DBS This work was supported by Geestkracht programme of the Netherlands Organization
optimization and facilitate custom-tailored DBS treatment. How- for Health Research and Development (ZonMw, Grant No. 60-60600-97-168).
PRS received travel grants from Medtronic and occasional consultant fees for edu-
ever, the inclusion of more patients is needed to validate this pro-
cational purposes, DD receives occasional consultant fees from Medtronic for educa-
cedure. tional purposes, WvdM received travel grants from Medtronic. C-EV-A, JL, RS, MXC, NL,
Carlos-Eduardo Valencia-Alfonsoa,b AM, and WvdB reported no biomedical financial interests or potential conflicts of
Judy Luigjesb* interest.
Ruud Smoldersb Authors C-EV-A and JL contributed equally to this work.
Michael X. Cohenc
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a
Department of Neuromodulation and Behavior, Netherlands Institute for Neuroscience; PR, Schippers R, et al. (2011): Deep brain stimulation in addiction: A
b
Psychiatry Department, Academic Medical Center; cPsychology Department, University review of potential brain targets [published online ahead of print Sep-
of Amsterdam; and dNeurosurgery Department, Academic Medical Center, tember 20]. Mol Psychiatry.
Amsterdam, The Netherlands. 4. Hser YI, Hoffman V, Grella CE, Anglin MD (2001): A 33-year follow-up of
*Corresponding author E-mail: judyluigjes@gmail.com. narcotics addicts. Arch Gen Psychiatry 58:503–508.

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doi:10.1016/j.biopsych.2011.12.013

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