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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