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.

Keywords: Cocaine dependence; Functional MRI; Functional connectivity; Hippocampus; Limbic system; Regional cerebral blood flow.

Figure 1

Basal neuronal activity and connectivity alterations as a function of treatment outcome (relapsed vs. early remission) in cocaine-dependent and healthy control individuals. Top panel: (A) Regional cerebral blood in the left posterior hippocampus (pHp) significantly differed between healthy control subjects and cocaine-dependent individuals who relapsed 30 days before and after completion of residential treatment (pHp: −29, −38, −4; 729 mm³; peak F_2,55 = 11.5). (B) Left pHp normalized regional cerebral blood flow (rCBF_n) group means and standard deviations. Post hoc voxel-wise analysis showed left pHp rCBF_n was significantly higher in the relapsed group relative to control subjects (p < .05). (C) Using the left pHp in (A) as a seed to assess group differences in resting state functional connectivity (FC), pHp-posterior cingulate cortex (PCC) connectivity strength significantly differed between the three groups (PCC: −5, −41, 45; 2052 mm³; peak F_2,55 = 6.8). (D) Left (L) pHp-PCC connectivity strength group means and standard deviations. Post hoc voxel-wise contrasts revealed significantly increased circuit strength in the relapsed group relative to the early remission participants (p < .05).

Figure 2

Relationship between left hippocampal gray matter volume and left posterior hippocampal (pHp) neuronal activity (regional cerebral blood flow). The relationship between left posterior hippocampal normalized regional cerebral blood flow (rCBF_n) and hippocampal gray matter volume was significant only in the healthy control group (r = .62, p = .004, left panel) but not the relapsed (r = −.20, p = .36, middle panel) or early remission (r = .03, p = .90, right panel) groups.

Figure 3

Receiver operator curves of posterior hippocampal (pHp) regional cerebral blood flow and pHp-posterior cingulate cortex functional connectivity strength in predicting cocaine relapse. The receiver operator curves illustrate the sensitivity and specificity of pHp regional cerebral blood flow and pHp-posterior cingulate cortex functional connectivity strength in predicting relapse at 30-day intervals following completion of residential treatment.