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Deep brain stimulation for Addiction

Deep brain stimulation for Addiction. Alexander Taghva , M.D. Orange County Neurosurgical Associates Ohio State University December 6, 2012. Disclosures. Medtronic fellow in neuromodulation at Ohio State University 2010-2011. Objectives.

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Deep brain stimulation for Addiction

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  1. Deep brain stimulation for Addiction Alexander Taghva, M.D. Orange County Neurosurgical Associates Ohio State University December 6, 2012

  2. Disclosures • Medtronic fellow in neuromodulation at Ohio State University 2010-2011

  3. Objectives • 1. Discuss quantifiable behavioral aspects of substance-dependent individuals, especially delay discounting. • 2. Propose a neurobiological explanation for these deficits to support a role for deep brain stimulation . • 3. Briefly review available clinical data on DBS for addiction.

  4. Ongoing research at OSU: TBI, obesity, Alzheimer’s • Ongoing Phase I trials for neurobehavioral deficits for Alzheimer’s, traumatic brain injury, obesity • Many of these patients have problems with behavioral self-regulation, including addictions • Too soon to make claims, but anecdotally, behavioral self-regulation improves in some of these patients with DBS

  5. Claims I will try to support (simplified) • Addiction is essentially a disorder of increased impulsivity. • Prefer immediate gratification despite long-term consequences • Different brain regions respond differently to immediate versus delayed rewards • Ventral and dorsal CSPTC circuits • Addiction arises from imbalances or dysfunction of these circuits

  6. Addiction can be seen as a disorder of increased impulsivity (Claim 1)

  7. Neuroeconomics • Neuroeconomics studies the calculations involved in decision making • “Delay-discounting” refers to the process by which immediate rewards are worth more than delayed rewards. • This can be quantified by the “indifference point.”

  8. Example: Delay discounting • If I offer you $1000 right now versus giving you $1000 one month from now, you would take the money now • What if I offer you $900 now versus $1000 in one month? • How about $800, etc….?

  9. Example: Indifference point • If the preference switches to take $1000 in one month versus $800 now, the amount discounted in one month is 20%. • That is, the indifference point is 80%

  10. Increased discounting in addictive behaviors • Drug addicts, gamblers, alcoholics tend to discount more than non-afflicted people • This is also the case with obese individuals. • In other words, lower-value immediate rewards are more valuable than higher value rewards later. • Translates to impulsive behavior

  11. Heroin abusers

  12. Smokers and EtOH discount more than controls (Businelle et al 2010)

  13. Obese women discount more (higher impulsivity) than control women. (Weller et al. 2008, Appetite)

  14. Different brain regions respond differently to immediate vs. delayed rewards (Claim 2)

  15. Immediate versus delayed rewards • McClure et al in 2004 demonstrated that certain brain circuits react differently to immediate rewards versus delayed rewards. • Immediate-reward (limbic) circuit consists of ventromedially placed structures • VTA, ventral striatum, ventral pallidum, nucleus accumbens, amygdala, anterior and subgenual cingulate gyrus, medial OFC

  16. Immediate reward (McClure 2004)

  17. Delayed-reward (associative) circuits • Structures involved in response to delayed-rewards are more dorsolaterally placed • Dorsolateral prefrontal cortex (DLPFC), lateral orbitofrontal cortex (lOFC), central striatum

  18. Delayed-reward structures

  19. “Limbic” CSPTC loop Corticostriatal circuits exist for limbic, cognitive, and motor circuits. Limbic – emotional value Cognitive – control of emotions Motor – complete action These circuits interface at ventral striatum (and other cortical regions) to provide a link from emotion to action.

  20. “Cognitive” or “Associative” circuit Provides top-down control of impulses

  21. Ventral striatum limbic to motor (Haber et al 2000)

  22. Overlap in ventral striatum Anatomic basis for interface between different circuits (Haber and Knutson)

  23. Areas of interaction of dorsolateral circuits with ventromedial circuits The reward circuit: linking primate anatomy and human imaging. Haber SN, Knutson B. Neuropsychopharmacology. 2010 Jan;35(1):4-26. Epub . Review.

  24. Frontostriatal DTI predicts impulsive behavior Olson EA et al. White matter integrity predicts delay discounting behavior in 9- to 23-year-olds: a diffusion tensor imaging study. J Cogn Neurosci. 2009 Jul;21(7):1406-21.

  25. Addiction results from imbalance or dysfunction of these circuits Claim 3

  26. Magnitude of reward vs. delay Impulsive individuals have more cortical deactivation to delay and less mesolimbic activation to delayed rewards. (Ballard and Knutson 2008)

  27. This dysfunction is also seen in drug abusers Not only the balance but magnitude of activation given a delay may be dysfunctional. Complex picture. NIAAA

  28. Delayed reward in drug abuse NIAAA

  29. Increased limbic activity to reward (Bjork et al 2008)

  30. Decreased dorsal activation with risk taking in drug abuse Bjork 2008

  31. Imaging from obesity • Neuroimaging also supports the fact that delayed-reward circuits are underactive as compared to immediate reward circuits in obesity

  32. Increased activation of reward circuitry in obesity L.E. Stoeckel et al. / Brain Research Bulletin 79 (2009) 388–395

  33. Decreased dorsal activation proportional to BMI (Batterink et al)

  34. Decreased dorsal activation proportional to BMI (Batterink et al)

  35. The emotional brain overrides the rational brain (Arnsten 2009)

  36. Animal data

  37. DBS of NAcc shell attenuates cocaine reinstatement DBS of shell attenuates reinstatement of cocaine DBS of dorsal striatum does not work

  38. DBS NAcc decreases alcohol consumption in rats Current through shell of nucleus accumbens had dose dependent response

  39. DBS decreases EtOH consumption in rats

  40. Clinical data on DBS Addiction • Target primarily used is nucleus accumbens

  41. Smoking cessation and weight loss DBS Nucleus accumbens Mantione et al Neurosurgery 2010

  42. Lesioning study 5-year nonrelapse rate 58% Side effects – lack of sexual desire, poor concentration, loss of interest Lesioning of nucleus accumbens attenuates opiate addiction

  43. DBS leading to smoking cessation in anxiety population

  44. Improvement in craving for EtOH addiction

  45. Mechanisms of Action of DBS • Local inhibition • Local excitation • Regulation of impulses • Desynchronization of impulses • Changes in gene expression

  46. Frontostriatal modulation occurs… But the data are somewhat hard to interpret. (Bourne et al 2012)

  47. Increase in “error related negativity” on EEG Anterior mid-cingulate cortex implicated

  48. Thank you. • Questions?

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