Neuroimaging in Addiction
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Neuroimaging in Alcohol and Drug Dependence
Abstract In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. About the article Corresponding author. Received : Accepted : Published Online : Published in Print : Citing Articles Here you can find all Crossref-listed publications in which this article is cited. DOI: The emerging discipline of behavioral neuroimaging. Effect of deactivation of activity patterns related to smoking cue reactivity on nicotine addiction. Incremental benefits of EEG informed fMRI in the study of disorders related to meso-corticolimbic dopamine pathway dysfunction: A systematic review of recent literature.
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The prefrontal dysfunction in individuals with Internet gaming disorder: a meta-analysis of functional magnetic resonance imaging studies. Individual differences underlying susceptibility to addiction: Role for the endogenous oxytocin system. Femke T. Anterior INS, connected to IFG and dorsal striatum, is implicated in awareness of bodily feeling states as well as the learning and implementation of goal-directed actions that can be conceptually linked to cognitive control processes, whereas ventral INS is more strongly connected to AMG and VS and is thought to be involved in emotional salience and affective feeling states.
In contrast, middle and posterior INS are connected with somatosensory regions sensory and parietal cortices associated with the processing of bodily feeling states, including pain signals 31 , Dorsolateral PFC is thought to work with ACC to regulate goal-directed behavior, wherein it is argued that dorsal ACC processes the value and difficulty of behavior change via its connections with dorsolateral PFC as well as AMG, dorsal striatum, and primary motor cortex Within the context of stress, cognitive control functions in frontocingulate and anterior INS regions are argued to be hijacked by AMG connections.
For example, although the dorsolateral PFC is thought to play an active role in pain suppression 34 , within the context of aversive events, heightened AMG signals activate neurochemical stress reactions that serve to downregulate dorsolateral PFC in favor of salience-driven habitual, impulsive responses instantiated via dorsal striatum Moreover, greater functional and structural links between basolateral AMG and anterior INS are associated with higher state and trait anxiety 36 , instantiating aversive feeling states accompanying stress.
Deficits in the brain circuitry outlined above are present in conjunction with aberrant timing and allocation of neural resources to drug and non-drug related stimuli, consistent with the Three-Stage Model of Addiction. In the following sections, specific neuroimaging tools related to magnetic resonance imaging MRI , functional near-infrared spectroscopy fNIRs , electroencephalography EEG , event related potentials ERP , repetitive transcranial magnetic stimulation rTMS and deep brain stimulation DBS are briefly explained and cross-sectional and longitudinal OUD-relevant literature is summarized for each technique.
Figure 2 illustrates brain regions and processes of interest that are described in more detail below. Figure 2.
Figure 3. Figure 4. With its high spatial resolution typically in order of 1 mm3 , sMRI offers ways to differentiate different brain tissues, such as gray and white matter, and to quantify gray and white matter volume within various brain regions. Gray matter consists of cell bodies, dendrites, unmyelinated axons, and synapses that facilitate specialized information processing in cortical and subcortical regions, whereas white matter consists of myelinated axons that relay signals from one brain region to another.
Moreover, within individuals on opioid maintenance treatment for OUD, lower VS volume is associated with higher depression symptoms, whereas lower AMG volume is linked to greater daily opioid dose Gray matter reductions within orbito-medial prefrontal cortex and bilateral globus pallidus are also associated with increased cognitive impulsivity among individuals on opioid maintenance treatment With respect to abstinence, higher compulsive behavior reported by sober individuals with OUD is linked to lower white matter surrounding VS and rostral ACC when compared to that of active OUD users and healthy controls For instance, VS attenuation may reflect the capacity for heightened drug tolerance and reduced euphoric effects of drug consumption.
Active neurons in the brain require oxygenated blood to replenish energy; BOLD fMRI is affected by the differences in magnetic susceptibility between deoxygenated and oxygenated blood, and by local increases in blood flow and volume, signaling brain regions that are more active during one particular condition, stimulus, response, or timeframe vs.
Researchers often quantify brain changes by computing the percent signal change between an active condition and a baseline condition. It is argued that the characterization of spontaneous or intrinsic brain signals during a resting state e. Only a few studies have examined brain mechanisms involved in responses to negative stimuli, limiting interpretability. Studies of spontaneous fMRI often focus on coherence or connectivity of signals across multiple spatially distinct cortical and subcortical brain regions.
OUD is associated with weak frontocingulate functional connectivity with subcortical regions, but strong functional connectivity within subcortical regions such as striatum and AMG 48 , findings consistent with a reward-control imbalance in OUD [stronger reward-stress connectivity paired with weaker cognitive control connectivity; 49 ]. Finally, research indicates that individuals with OUD exhibit attenuated ACC activity and reduced connectivity with PFC and striatal regions; moreover, lower ACC signal within this context is linked to greater drug cue-induced craving 51 , OUD is marked by frontocingulate and striatal hyperactivation to drug cues, particularly within active users up to a few hours sober , with degree of response decreasing as a function of longer abstinence i.
Compared to non-substance using individuals, those with OUD show frontal attenuation to pleasant non-drug stimuli such as food, pornography, and interactive social situations 54 , 63 , although this pattern may dissipate as a function of abstinence [3 years; 54 ]. One study demonstrates no difference in ACC activation between users with OUD on opioid replacement therapy buprenorphine or methadone and non-users during behavioral control.
However, users do not show a positive correlation between ACC activation and behavioral performance as seen in non-users, indicating a notable discrepancy between brain signaling and behavior 70 ; these findings suggest that even when recruited, these regions may not function as effectively for OUD. However, the literature is far from conclusive and mixed results may be due, in part, to variability in opiate use chronicity and recency across studies On the whole, very limited research suggests that OUD is characterized by blunted brain responses to negatively valenced stimuli as well as punishing outcomes in the absence of drug cues.
Two fMRI studies report hypoactive AMG responses to negative and positive as opposed to neutral stimuli in OUD individuals who are abstinent 2—5 months 71 as well as current users with OUD; it is important to note that these results are based on samples with comorbid borderline personality disorder who are also on opioid replacement therapy Thus, findings may not easily generalize to other OUD samples. These reports of blunted AMG signals are the opposite of what would be predicted by the Negative Reinforcement stage, which suggests that AMG responses should be intensified as a function of aversive cues.
More specifically, when active OUD users are administered saline as opposed to opioids, they display greater AMG activation than healthy individuals to fearful faces, a pattern that is linked to elevated state anxiety Similarly, newly detoxified individuals with OUD exhibit hyperactive AMG responses to drug as opposed to neutral films, a pattern correlated with heightened craving Furthermore, OUD patients on methadone replacement exhibit greater INS and AMG activation to opioid cues before as opposed to after ingestion of their daily methadone dose On the whole, these findings are accordant with the Negative Reinforcement stage.
Non-imaging data indicate that active OUD is associated with exaggerated self-reported arousal to negative non-drug images 77 , suggesting that additional brain-behavior research is needed to determine whether patterns of AMG response to emotional stimuli change as a function of abstinence. Greater negative affect induced by film clips still increases drug craving in OUD users without the presence of drug cues, congruent with the Negative Reinforcement stage of addiction; furthermore, this relationship is stronger for users with high as opposed to low anxiety sensitivity Moderation by anxiety sensitivity points to the importance of measuring individual differences in users' perceptions and awareness of bodily sensations, as these may intensify stress responses that hijack abstinence efforts.
Lastly, OUD is linked to difficulty differentiating punishing vs. The fNIRs technology employs near-infrared light attenuation to quantify concentration of oxy- and deoxy-hemoglobin. EEG, the continuous recording of ongoing brain electrical activity via scalp electrodes, possesses high temporal resolution order of milliseconds Resting state EEG recordings measure the brain's pseudo-periodic oscillatory activity due to coherent activity from many neurons synchronized in time and space.
Frequencies most studied in OUD samples include those segmented within theta, alpha, beta, and gamma bands. Theta band 4—7 Hz activity is implicated in cognitive control processes including working memory and error monitoring 86 — Decreases in alpha band 8—13 Hz activity are associated with increases in active information processing involving attention 89 , whereas beta band 13—30 Hz decreases signal an impending voluntary motor action Finally, gamma band 30— Hz activity is theorized to reflect the comparison of a stimulus with information held in memory to determine a match or mismatch EEG power the square of the EEG magnitude of the signal amplitude within a particular band is often calculated to compare between clinical groups or conditions.
In addition, EEG coherence metrics are calculated to reflect how strongly oscillations between two or more measuring electrodes reflecting and mapping into synchronized brain regions activities within a particular frequency band.
Neuroimaging and biomarkers in addiction treatment. - Abstract - Europe PMC
Although EEG frequencies can be measured within the context of a particular task, resting-state EEG studies investigating frequency band differences as a function of OUD are the norm. On the whole, this literature indicates that EEG power and coherence are disrupted in chronic OUD users compared to healthy individuals, although findings are inconsistent as to directionality which group is higher or lower as well as which frequency band, hemisphere, or specific brain region is affected and whether these patterns normalize as a function of abstinence or methadone maintenance 92 , The most consistent finding is that individuals with OUD whether actively using, maintained on methadone for at least 6 months, or in the early stages of abstinence exhibit greater beta power than healthy individuals [91— With respect to longer abstinence duration, one study reports no difference in beta power between healthy controls and OUD users abstinent 1—6 months, whereas another study indicates that beta power decreases as a function of longer OUD abstinence As beta power increases are thought to reflect decreased need for future motor actions, these results suggest that active opioid users can be characterized by reduced behavioral activation, at least during intrinsic processing.
Perhaps beta power changes as a function of prolonged abstinence can track stages of recovery, although longitudinal studies are warranted to test this hypothesis. For theta band activity, active OUD users either exhibit lower 95 or higher 93 power than healthy individuals. However, OUD users abstinent 1—6 months display similar theta power as control subjects 97 , findings suggestive of a state-like change in theta power as a function of current drug use.
With regard to EEG coherence within and across regions of the brain, active OUD exhibit local hyperconnectivity in alpha and beta frequency bands, a pattern that does not change as a function of early 2-week abstinence. However, remote alpha and beta hypoconnectivity evident in active OUD users does appear to normalize during the early stages of sobriety 99 , Finally, gamma band findings indicate that active OUD as well as OUD on prolonged methadone treatment display greater gamma power than healthy individuals 50 , and OUD abstinent at least 2 weeks exhibit greater fronto-occipital gamma band coherence within the left hemisphere than CTL, although the significance of this greater coherence is not well-understood ERPs are averaged periods of EEG recordings interpreted within the time domain that are elicited by a particular stimulus or a response.
Unlike fMRI studies suggesting that faulty cognitive control circuitry may normalize as a function of OUD abstinence, ERP studies provide mixed results, suggesting that this may not be the case 95 , — , although greater opioid use chronicity does appear to be associated with greater frontocingulate reductions Details regarding timing and proposed function of various ERP components, including early posterior negativity EPN , N, P, slow positive wave SPW and error related negativity ERN , are provided below within the context of various paradigms, including cognitive control, cue reactivity, working memory, attention and emotion tasks.
During an emotional Stroop task involving positive, negative, neutral, and opioid images, OUD users abstinent an average of 9 months show larger EPN amplitude to opioid images than healthy participants in the absence of behavioral differences between groups These results indicate that even with prolonged sobriety, perception of drug cues is prioritized.