Addiction and Brain-Neurosurgical Perspective

Invited Review Article 


Addiction and Brain-Neurosurgical Perspective 



V.K.S. Gautam 

Assistant Professor, Neurosurgery, IHBAS, Delhi 

Address for Correspondence: Email: drvksg@gmail.com 


ABSTRACT 

Drug addiction remains a significant public health concern, with significant morbidity and mortality. Current therapies for drug addiction have a high rate of relapse. In the past 15 years, the newer therapeutic option was tried in such refractory cases. Functional neurosurgery was done in some cases with the use of deep brain stimulation (DBS) surgery.  Functional  neurosurgery involves precise  surgical  targeting  of anatomic structures to modulate neurologic function. It can be done by either open neurosurgical procedure or deep brain stimulation (DBS) surgery. DBS is a potentially valuable role in  the management of  otherwise intractable  addictive  disorders  of  the brain.  The neurobiology study of drug addiction suggests the cause of drug addiction is neuroplastic changes in nucleus accumbens, a key structure in the brain reward system. Deep brain stimulation (DBS) surgery involves the neuroimaging of the brain by Magnetic Resonance Imaging (MRI). Neuroimaging identifies the location of the nucleus accumbens. Stereo tactically placed electelectrotrodes influence the neuronal activity and achieve desired therapeutic effect. DBS is a safe, convenient and effective therapy for managing refractory 

cases of substance abuse. 

Keywords: Deep Brain Stimulation, drug addiction, functional neurosurgery, substance abuse, Nucleus Accumbens  


INTRODUCTION 

Drug  addiction  represents  a  significant public health  concern that  has  a  high rate  of relapse  despite  optimal  medical  therapy  and rehabilitation  support.  Given  the  current treatments-consisting of  psychosocial  and/or pharmacological interventions for drug addiction have  relapse  rates  as  high  as  50%  to  70%, additional  treatments  are  needed.  Newer therapeutic options were applied in last 15 years and  now  numerous  publications  of  the application of DBS in drug addiction is available (Wang et al., 2018). Neurosurgical procedures, particularly  deep  brain  stimulation,  have  a potentially valuable role in the management of otherwise intractable addiction disorders (Ma et al., 2020). For DBS, the most common target is the nucleus accumbens (Wang et al., 2018). 

Drug  addiction  is  a  chronic  psychiatric disorder  characterized  by  compulsive  drug- seeking  behavior.  Deep brain stimulation is a novel treat-ment for psychiatric disease and has gradually gained popularity in the treatment of addiction. The concept of treating drug addiction by  DBS  is  based  on  the  premise  that  drug addiction  is  due  the  long  term  neuroplastic changes in the brain and if the electrophysiology of such structures is altered or modulated there will be functional change in the function of any area of the brain. DBS was very successful in the treatment of movement disorders, especially dystonia and Parkinson disease. Although there may be different theories about the reasons for developing drug addiction in some people and why a  lot of  people do not  suffer  from drug addiction despite tasting alcohol or nicotine or opioids  occasionally.  But  the  neuroanatomic structures which control or influence the drug seeking behavior have been identified. So, if this area is surgically reached with precision and there is some mechanism to stimulate or modulate this nucleus or area then there will be change in the electrophysiological signaling and after that there will be change in the behavior of the person. This procedure is known as functional neurosurgery. These days very minute electrodes can be placed in  the  desired  location  of  the  brain  under stereotactic guidance. 

Image  1: Photograph showing stereotactic frame  applied over the skull of the patient (Fymat, 2020) 

The neurobiology of drug addiction 


Image  2 : X ray of the skull of the patient showing electrodes in the brain of the patient (Source- By Jmarchn- own work) 

The development of drug addiction over time is usually predictable  and  has  a  pattern. The etiology and pathogenesis of drug addiction are related to altered functioning of multiple brain systems. It  is widely  accepted  that the initial reinforcing effects of drug abuse are mediated by  large  and  rapid  increases  in  the  level  of dopamine  in  the  nucleus  accumbens.  Drug addiction develops through a series of stages, the first of which is binge or intoxication stage. Sense of reward is mediated by dopamine increases in the  mesolimbic  system.  The  mesolimbic dopaminergic  system  is  a  reward  circuit composed of medial forebrain  bundle,  which connects  the  ventral  tegmental  area  and hypothalamus with the olfactory tubercle and nucleus accumbens (NAc). With continued drug use,  prolonged  and  unregulated  release  of dopamine results in synaptic changes including elevation in mesolimbic dopaminergic excitability. This enhanced excitability is short lived  because  repeated  drug  use  leads  to  an attenuation of mesolimbic dopamine activity, i.e., decreases in dopamine at the NAc in response to drug use. As a result, increasing amounts of drug must be used to attain that amounts to a declining reward, or in other words, tolerance develops. It  is the beginning of the second stage. 

Withdrawal/Negative affect stage 

Decreased mesolimbic dopaminergic activity is hypothesized to be responsible for anhedonia and  psychomotor  depression. This  negative emotional state is mediated by the activation of the  extended  amygdala,  which  includes  the central nucleus of the amygdala, bed nucleus of the stria terminalis and the medial portion (or shell) of the NAc and is potentiated by increases in corticotrophin-releasing factor, norepinephrine and  dynorphin.  These  neurotransmitters additionally activate stress responses which can produce significant anxiety and irritability during withdrawal.  Soon  a  conditioned  negative response to withdrawal is formed, mediated by the extended amygdala and hippocampus. This learned  negative response during  withdrawal coupled  with  tolerance,  further  feeds  into compulsive drug seeking behavior. This marks the  third  and  final  stage  of  addiction;  the preoccupation/anticipation (craving) stage. Here, the amygdale – a critical player in the withdrawal/ negative affect stage-projects to the prefrontal cortex (PFC). 

The PFc, an area including the dorsolateral PFC,  anterior  cingulate  gyrus,  and  medial orbitofrontal  cortex  is  postulated  to  be responsible  impulse control. However, during prolonged drug use, neuroplastic changes in the reward  and  memory  circuit  mediated  by dopamine and glutamate can produce a hypo- functioning PFC, demonstrated by diminished impulse control. So, in addiction the mesolimbic reward  pathway  undergoes  a  series  of neuroplastic  changes.  Diminished  impulse control can explain those with addiction relapse despite known negative consequences, or  why relapse may occur even after prolonged periods of drug abstinence. 

This addiction cycle continues. In late stages, apart from PFC, widespread multiple areas of the  brain  are  affected  such  as  striatum, hippocampus,  insula  and  habenula.  Neuro- imaging,  especially  Positron  Imaging Tomo- graphy (PET), has also demonstrated the critical role of the PFC in addiction (Chang et al., 2022). 

Interruption of Pathological Neural Oscillations 

Abnormal neural oscillation will affect the communication function of the brain. Rhythmic DBS  interrupts  the  pathological  neural oscillations in the target nucleus and connected circuit and normalizes dysfunctional information flow to improve brain function. The impact of DBS  has  also  been  explained  at  the  neural network rather than the cellular level. In DBS, electrophysiology can be modulated according to the response of the patient after surgery. So, it offers titrability and reversibility. 

Image  3: Prefrontal cortex and Nucleus Accumbens (Isabel, 2023) 


CONCLUSION 

Drug  addiction  is  a  chronic  psychiatric disorder  characterized  by  compulsive  drug seeking  and  drug  using  behavior  and  a tremendous  socioeconomic  burden  to society. Addiction  is  characterized  by  neuroplastic changes in the Nucleus Accumbens (NAc), a key structure in brain reward system (Chang et al., 2022). Approximately, 11.8 million deaths occur each year, which is more than cancer deaths in a year. About 85% of addicts relapse within 1 year after abstinence. We are currently in the midst  of a public health emergency, with opioid-related deaths  skyrocketing  over  the  past  15  years. Beyond  opioid  addiction,  alcohol,  nicotine, Methamphetamine and  cocaine addiction  also account for significant morbidity and mortality. 

Functional neurosurgery entered a new era with the introduction of modern-day deep brain stimulation  in  the  late  1980s.  Following successful  subthalamic  DBS  for  Parkinson disease and other movement disorders its uses are gradually expanding. DBS uses technology to  accurately  target NAc  using  intracranially implanted  electrodes  connected  to  pectorally implanted  battery  and  pulse  generators. Electrodes  influence  neuronal  activity  and achieve desired therapeutic effect. So, from a neurosurgical perspective, drug addiction can be treated  by  surgically  targeting  the  nucleus accumbens. DBS had been used as a treatment for  addiction to psychoactive substances  such as  nicotine,  alcohol,  cocaine,  opioid,  and methamphetamine/amphetamine. 

DBS has the characteristics of reversibility, titrability, controllability and cost effectiveness. It is a safe procedure, and it will be established as  a  treatment  option  for  the  management of people with substance abuse. Most people require empathy  and  support  and  care  as  much  as patients  with  other  diseases.  Advising Neurosurgical  intervention  in refractory drug addiction cases will lead to the paradigm shift in manage-ment approach of all stakeholders (Ali et al., 2016; Luiggs et al., 2015). Since last 15 years many neurosurgeons have performed DBS sur- gery for patients with drug addiction and reported  good surgical outcome (Wang et al., 2015). So, DBS has emerged as an effective way to treat  addiction to psychoactive substances, providing novel options for patients with high relapse risks after traditional  treatments have failed. 

Conflicting Interests The authors declared no potential conflicts of interest. 

Funding: Nil. 

 

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