Role of anterior cingulate cortex and insula in Cigarette smoking and treatment with Neurofeedback: A new approach

 

Cigarette smoking, which is an addictive behavior, is the most common cause of morbidity and mortality in the developed world 1.  However, many smokers find it difficult to quit even while knowing that the consequences of continuing can be grave 2-3.  Quitting smoking can be quite difficult, and even after quitting, the relapse rate is high due to the cravings they experience.  The reason for this difficulty in quitting and the high relapse rate appears to be due to long-term changes in specific neural subsystems within the brain.  Animal models have shown that changes in regions such as the amygdale, the nucleus acumens, and the mesotelendephalic dopamine system promote the self-administration of harmful drugs4-5-6. Since the cravings are a key factor leading to relapse among smokers who are trying to quit controlling these cravings may be help stopping smoking.

 

The anterior cingulate cortex (ACC) is a part of the brain’s limbic system.   Based on lesion studies in animals and humans this region has been related to affect, on the basis of lesion studies in humans and in animals.

Based on EEG studies a focal negativity develops after an error response leading to the theory that the ACC may be involved in the brain’s error detection and control7

Neuropsychological studies show that the cognitive version of the Counting Stroop activates the cognitive subdivision of the Emotional Counting Stroop activated the affective subdivision. The cognitive subdivision is part of a distributed attentional network which maintains strong reciprocal interconnections with the lateral prefrontal cortex (BA 46/9), parietal cortex (BA 7), and premotor and supplementary motor areas.  The affective division on the other hand (ACad) is activated by affect related tasks as seen in normal volunteer studies of emotional processing and in psychiatric disorders (anxiety, simple phobia and obsessive–compulsive disorder) when their symptoms are provoked.  It has also been activated repeatedly by induced sadness in normal subjects and in individuals with major depression. The affective subdivision is connected to the amygdala, periaqueductal gray, nucleus accumbens, hypothalamus, anterior insula, hippocampus and orbitofrontal cortex.

                                  

                                      

According to functional imaging studies show that areas such as the cingulated cortex, the anterior cingulate cortex, the orbitofrontal cortex, and the insula activate in the presence of drug-associated cures 8-9.

The insula is particularly interesting due to its potential role in conscious urges.  This area has been proposed to function in conscious emotional feelings, through its role in the representation of bodily (interoceptive) states10-11-12. Subjective drug urges induced by a cue has been shown to correlate with activity within the insula on both sides of the brain during a simple decision-making task associated with relapse to drug use 13-14 -15 . During a simple decision-making task a high amount of activity in the right insula has been observed which has been associated with drug use16.

It is interesting to note that damage to the insula may lead to a loss of the urge to smoke.  According to Dr. Antoine Bechara of the University of Southern California and the University of Iowa, and his colleagues have patients with insula damage were able to quit smoking immediately, easily, and without relapse in comparison to patients with other types of brain injuries.

There are numerous methods available to quit smoking.  They range from nicotine replacement therapy to psychotherapy to different self-help and behavior modification programs.  However, the success rates for them have been quite low.  To achieve total abstinence may take several attempts and even then persons who have quit may have problems staying smoke-free.  Although 70% of smokers report wanting to quit, only 5% report being able to do so.  The relapse rate is more than 70%17.  Daily pressures, environmental factors such as the smell of smoke, and other environmental factors and triggers may induce strong cravings as well as fond memories of smoking which may be difficult to resist.  That is why most tobacco cessation programs encourage people to avoid triggers, reduce stress, and find alternatives to cigarettes.

One method that has been found to be effective in altering dependence behavior is neurofeedback.  NF is an operant conditioning paradigm whereby patients are given contingent audio/visual rewards for producing specific patterns of brain wave activity.  Since the 1960s, studies have shown that through NF patients can be taught to promote normal functioning of the brain by normalizing dysfunctional brainwave patterns characterized by excessive slow wave activity 18-19 or by normalizing patterns which deviate from corresponding age related norms.

NF Presents the user with real-time feedback on brain wave activity, typically in the form of a video display and sound. The aim is to provide real-time information to the Central Nervous System (CNS) as to its current activity. For instance, people are asked to increase beta or sensorimotor rhythm (SMR) and decrease delta and theta. When the desired paradigmis accomplished, the patient is rewarded with a moving display and/or a sound. This is operant conditioning.

Studies using EEG neurofeedback were shown to have positive effects on drug use, treatment compliance, and cue reactivity in patients with cocaine and alcohol dependence20-21-22-23-24.

Neurofeedback, delivered via real-time functional magnetic resonance imaging (rtfMRI), can facilitate self-regulation of internal states by providing feedback from localized regions of interest (ROIs) to individuals while performing a task25-26 -27 -28 -29.   In recent years, rtfMRI feedback has demonstrated therapeutic potential by facilitating modulation of brain activation associated with pain30, depression31, and ADHD32-33

By using neurofeedback (NF) from the anterior cingulated cortex (ACC), a key craving region, Cantebery et al. 34, were able to reduce craving related to brain activation and self-reported craving in one visit35.  In another study feedback from a craving related region of interest (ROI) in the ACC was more effective than multiple sessions of simultaneous resistant related feedback of an ROI over the medial prefrontal cortex36.  This shows that in order to quit smokers can use feedback methods to effectively modulate the responses of their brain and behavior to smoking cues and that decreasing activity in areas involved in cravings (e.g. ventral anterior cingulate cortex (vACC)) is more effective than increasing activity in regions involved in resisting them (e.g. dorsal medial prefrontal cortex (dmPFC)) because dependence severity, for example, is associated with craving and smoking cessation outcomes37-38  and has been linked with ACC activation during exposure to smoking cues 29- 40. This shows that the severity of nicotine dependence may influence the response to neurofeedback where low-to-moderate nicotine dependent smokers can use neurofeedback targeting the ACC to decrease craving-related activation18-19-20.

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