Resting state functional connectivity in addiction: Lessons learned and a road ahead

Abstract

Despite intensive scientific investigation and public health imperatives, drug addiction treatment outcomes have not significantly improved in more than 50 years. Non-invasive brain imaging has, over the past several decades, contributed important new insights into the neuroplastic adaptations that result from chronic drug intake, but additional experimental approaches and neurobiological hypotheses are needed to better capture the totality of the motivational, affective, cognitive, genetic and pharmacological complexities of the disease. Recent advances in assessing network dynamics through resting-state functional connectivity (rsFC) may allow for such systems-level assessments. In this review, we first summarize the nascent addiction-related rsFC literature and suggest that in using this tool, circuit connectivity may inform specific neurobiological substrates underlying psychological dysfunctions associated with reward, affective and cognitive processing often observed in drug addicts. Using nicotine addiction as an exemplar, we subsequently provide a heuristic framework to guide future research by linking recent findings from intrinsic network connectivity studies with those interrogating nicotine’s neuropharmacological actions. Emerging evidence supports a critical role for the insula in nicotine addiction. Likewise, the anterior insula, potentially together with the anterior cingulate cortex, appears to pivotally influence the dynamics between large-scale brain networks subserving internal (default-mode network) and external (executive control network) information processing. We suggest that a better understanding of how the insula modulates the interaction between these networks is critical for elucidating both the cognitive impairments often associated with withdrawal and the performance-enhancing effects of nicotine administration. Such an understanding may be usefully applied in the design and development of novel smoking cessation treatments.

Semiological classification of psychogenic nonepileptic seizures

“…We observed that 31% of the patients with generalized motor PNES reported substance abuse, whereas none of the patients with non-motor PNES had such a history. A previous review suggested that brain circuit connectivity may explain specific neurobiological substrates underlying psychological dysfunctions associated with reward, affective and cognitive processing often observed in drug addiction 12 . The temporal relationship between substance abuse and onset of PNES in our patients remains unknown and therefore, we cannot establish a causal relationship.…”

Resting-state Abnormalities in Heroin-dependent Individuals

“…Nucleus Accumbens (NAc) Orbitofrontal Cortex (OFC) Drug addiction or substance dependence (Koob and Le Moal, 2005)is defined as a multifaceted neuropsychiatric disorder resulting from complex interactions between neurobiological, environmental, genetic and pharmacological variables (Sutherland et al, 2012).It affects both cognitive as well as emotional processes . Furthermore, the compulsive seeking and taking of the drug despite the negative consequences, (including downward social mobility (Denier et al, 2013b)), constitutes its behavioral phenotype (Volkow et al, 2003).…”

“…Finally, in need of a contemporary therapya multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games Keywords:Heroin addiction, resting-state, functional and structural connectivity, small-world properties, behavioral traits of heroin-dependent individuals. Radial Diffusivity (RD) 5 Drug addiction or substance dependence (Koob and Le Moal, 2005)is defined as a multifaceted neuropsychiatric disorder resulting from complex interactions between neurobiological, environmental, genetic and pharmacological variables (Sutherland et al, 2012).It affects both cognitive as well as emotional processes . Furthermore, the compulsive seeking and taking of the drug despite the negative consequences, (including downward social mobility (Denier et al, 2013b)), constitutes its behavioral phenotype (Volkow et al, 2003).…”

“…Furthermore, resting-state connectivity provides reliable, quick and straightforward data collection when studying populations with variable attentional, motor and executive control (Sutherland et al, 2012). It enables 7 the detection of underlying neuronal circuitry dysfunctions in numerous neurological disorders including autism ), Alzheimer's disease (Lustig et al, 2003;Greicius et al, 2004;Rombouts et al, 2005;Wang et al, 2006), depression (Anand et al, 2005), attention and hyperactive disorders and multiple sclerosis (Lowe et al, 2002).Thus, resting-state connectivity can serve both as a biomarker of neurological diseases, as well as a helpful diagnostic tool (Sutherland et al, 2012). Furthermore, resting state networks are consistent across time within and between the subjects and can be used as predictor of stimulus related neural responses .…”

“…Moreover, a diminished perfusion in the MPFC of addicted individuals has been involved in emotional and self-disruption (Denier et al, 2013a). Reduced rsFC strength found in the MPFC and amygdale has also been linked to emotional dysregulation Sutherland et al, 2012). On the other hand, the dorsolateral part of PFC is centrally associated with decision-18 making (Krawczyk, 2002;Yuan et al, 2010b) and high-order cognitive tasks such as self-control, planning, working memory and attention focusing (Garavan et al, 2000;Wang et al, 2013), that are all compromised in heroin addiction.…”