Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine Relapse

Abstract

BACKGROUND Cocaine-induced neuroplastic changes may result in a heightened propensity for relapse. Using regional cerebral blood flow (rCBF) as a marker of basal neuronal activity, this study assessed alterations in rCBF and related resting state functional connectivity (rsFC) to prospectively predict relapse in patients following treatment for cocaine use disorder (CUD). METHODS Pseudocontinuous arterial spin labeling functional magnetic resonance imaging and resting blood oxygen level-dependent functional magnetic resonance imaging data were acquired in the same scan session in abstinent participants with CUD before residential treatment discharge and in 20 healthy matched control subjects. Substance use was assessed twice weekly following discharge. Relapsed participants were defined as those who used stimulants within 30 days following treatment discharge (n = 22); early remission participants (n = 18) did not. RESULTS Voxel-wise, whole-brain analysis revealed enhanced rCBF only in the left posterior hippocampus (pHp) in the relapsed group compared with the early remission and control groups. Using this pHp as a seed, increased rsFC strength with the posterior cingulate cortex (PCC)/precuneus was seen in the relapsed versus early remission subgroups. Together, both increased pHp rCBF and strengthened pHp-PCC rsFC predicted relapse with 75% accuracy at 30, 60, and 90 days following treatment. CONCLUSIONS In CUD participants at risk of early relapse, increased pHp basal activity and pHp-PCC circuit strength may reflect the propensity for heightened reactivity to cocaine cues and persistent cocaine-related ruminations. Mechanisms to mute hyperactivated brain regions and delink dysregulated neural circuits may prove useful to prevent relapse in patients with CUD.

A hypo‐status in drug‐dependent brain revealed by multi‐modal MRI

“…Low insular perfusion indicates a hypo-status induced by the over-stimulation of drug to those involved brain functionalities. We didn’t find hypoperfusion in parahippocampus, which is the only suprathreshold region shown in (Adinoff et al, 2015). This discrepancy may reflect a difference in inter-subject variances between our study and theirs.…”

“…In drug addiction, we have used ASL MRI to probe the cue-induced activation and abstinence-induced activation in smoking (Franklin et al, 2011; Franklin et al, 2007; Wang et al, 2007b; Wang et al, 2008b), but ASL MRI still remains underexplored in cocaine addiction studies (Question No. 3) with only two publications (Adinoff et al, 2015; Adinoff et al, 2016) which found hypoperfusion only in the parahippocampus.…”

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

“…In fMRI studies, hippocampal activation and network connectivity has been shown to predict cocaine relapse. 12 Limbic connectivity between the hippocampus and the amygdala is also associated with reduced adaptive emotional processing in maltreated individuals with methamphetamine dependence.…”

“…10 Connectivity between the amygdala and the hippocampus is associated with maladaptive emotional processing, 11 and alterations in hippocampal network activation and connectivity have been shown to predict relapse. 12 The prefrontal cortex has extensive connections with subcortical structures that regulate emotional processing, including the amygdala. 13 Alcohol and drug exposure impairs emotion regulation in this region, with interconnected medial and cingulate networks showing enhanced reactivity to arousing stimuli and reduced capacity to suppress negative affect.…”

“…We sought to determine the effects of naltrexone at standard dose (50 mg) during negative emotional processing between groups dependent on alcohol alone, dependent on alcohol and drugs (both in abstinence) and healthy control volunteers. On the basis of previous research showing altered activation in limbic and cortical networks during negative emotional processing in substance-dependent individuals, 1,[10][11][12][13][14][15] including the processing of evocative 16 and negative emotional images, 38,39 we hypothesized that the dependent groups would show increased activation in the amygdala, the mPFC and the hippocampus in response to aversive images. In light of preclinical evidence, 29 we further hypothesized that these effects would be modulated by naltrexone depending on the degree of childhood adversity experienced.…”