The possibility of deep brain stimulation to treat eating disorders. Andres M Lozano MD PhD Professor and Dan Family Chair of Neurosurgery Canada Research Chair in Neuroscience Toronto Western Hospital University of Toronto
Brain Functions are localized within specific circuits. Dysfunction in circuits leads to Neurologic and Psychiatric disorders
Interventions Drive the activity in underperforming circuitse.g. Alzheimer's Eliminate/Block/Neutralizeabnormal activity Tremor, Epilepsy, Pain, Hallucinations
Neuromodulation Techniques TENS PNS VNS TMS TDCS CORTEX DBS DRUG DELIVERY SPINAL STIMULATION
Neuron 2013 > 30 Published Indications for DBS (established, Investigational, Proposed) Parkinson s Disease Essential and other tremors (post-traumatic, Holmes, MS, etc..) Dystonias Chorea Chronic pain Cluster headache Epilepsy Gilles de la Tourette OCD Major Depression Bipolar disorder Aggressivity /violence Anorexia nervosa Obesity Drug/alcohol/nicotine Addiction Alzheimer Cognitive impairment in PD Minimally conscious state Tinnitus Post-traumatic stress disorder Enhancements (memory) Pleasure Antisocial behaviour / Abnormal morality
Obesity Regulation of Feeding Appetite Hunger Satiety Hypothalamus and Brainstem Behavioral Reward/Salience Motivation/Drive Learning/Memory Self control
OBESITY Appetite control in hypothalamus Ventral medial nucleus satiety Ventrolateral nucleus hunger Animal experiments show hypothalamic stimulation influences feeding behavior Experience with hypothalamotomy for obesity in humans Quaade F. Lancet. 1974 Feb 16;1(7851):267. Stereotaxy for obesity.
LETTER: STEREOTAXY FOR OBESITY QUAADE F. Lancet. 1974 Feb 16;1(7851):267.
DBS IMPLANTATION 53 yo male with lifelong history of morbid obesity (420 lbs, BMI 55.1 kg/m2) DBS electrodes implanted bilaterally in medial or lateral hypothalamus To identify the best site to suppress appetite, the effect of stimulation at each of the 4 four contacts of each of these electrodes was tested in the operating room.
DBS ELECTRODE POSITION
World Neurosurg. 2013 Sep-Oct;80(3-4):S28.e21-31.
One patient with SCC DBS for depression and co-morbid anorexia Significant improvement in depression Improvement in anorexia symptoms Weight restoration
What else do we know about Cg25? local connections SERT S1A S2A D3 GABA Hypothalamus sleep-appetite cortisol Amygdala Motivation Drive anhedonia OMPFC 24 11 25 NA Cd-P DLPFC 10 9 6 4 MOTOR Thal Brainstem 5HT, NE, opiates Sleep, Pain, Diffuse Projections Stress responses Circadian regulation Emotional reactivity Ongur and Price. JCN 1998 VTA SN Haber, J. Neuroscience 2000 Changes in Cg25 may have local and Remote effects throughout the Brain
Study Rationale DBS for anorexia 1. Psychiatric condition with highest mortality rate affecting predominantly young females 2. No effective treatments for most chronic, refractory cases 3. Body of neuroscientific literature pointing at dysfunctional circuits and structures in AN brains 4. Promising experience with deep brain stimulation in conditions such as Depression and Obsessive-Compulsive Disorder 5. Targeting mood and anxiety may be a foot-in-the-door in otherwise treatment refractory patients, helping to convert treatment-nonresponders into treatment-responders
Pilot Trial 2013
Refusal, Fear, Image
Anorexia patient. Stimulation of Left area 25
The Lancet Psychiatry. Feb 24, 2017
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Symptom Counts Graphs show total number of binges and purges in previous 28 days at each time point Some patients are pure restrictors or in program at the time Means: Baseline Binges Binges 1m Binges 3m Binges 6m Binges 12m 48 13 23 5 5 Baseline Purges Purges 1m Purges 3m Purges 6m Purges 12m 107 45 29 10 13
FDG PET in 6 Patients with Anorexia. Changes over 6 months.
Summary study of DBS in chronic anorexia nervosa, suggests that DBS is safe and well-tolerated in these patients DBS is associated with beneficial effects on mood, anxiety and affective regulation DBS influences the metabolism in structures believed to be involved in AN circuitry First study that directly influences AN circuitry Decreased subcallosal and insular activity at 6 months Increased parietal activity at 6 and 12m
Brain targets for Obesity/Anorexia Multiple theoretical targets possible Emphasized DBS but need to consider more targeted and non-electrical approaches drug infusion, gene therapy, other biogical therapies, non-invasive stimulation, optical and magnetic stimulation are possible Single approach/target unlikely to succeed Multiple strategies can be considered who, where and how needs to be determined
Conclusion Brain circuits are accessible and modifiable Neuromodulation changes brain function Opportunity to learn, to test, to discover Multidisciplinary work essential The hope is to help more patients.