Wavelet-transformed temporal cerebral blood flow signals during attempted inhibition of cue-induced cocaine craving distinguish prognostic phenotypes

Abstract

Background: Cocaine addicted patients with positive cocaine urine status at treatment entry are far less likely to have a successful treatment outcome. This work aims to identify brain substrates that can distinguish this group of patients from their cocaine-negative counterparts in order to better understand this clinical phenotype. Going a step beyond conventional functional connectivity, we used wavelet transform coherence (WTC) to determine in which ways the temporal pattern of fMRI cerebral blood flow (CBF) signals during attempted inhibition of cue-induced cocaine craving may differ between these two groups.

Methods: Using a critical node in motivational circuitry, amygdala, as a seed, whole brain correlations for the entire sample revealed a functional connection with the dorsal cingulate. Next, WTC maps of CBF were constructed for each individual, characterizing the temporal patterns between these two regions during craving inhibition.

Results: As revealed by WTC, during attempted craving inhibition, the cocaine-negative subjects had significantly stronger and longer negative coherence between the amygdala and the dorsal cingulate, as compared to the cocaine-positive subjects. This relationship was neither evident in the resting state nor between two regions unrelated to inhibition processes.

Conclusions: The duration and strength of negative coherence calculated from wavelet-transformed CBF provide an objective and well-defined way to characterize brain responses during attempted inhibition of cue-induced craving, at the level of the individual. The stronger and sustained negative coherence in CBF between motivational (amygdala) and modulatory (dorsal cingulate) regions in cocaine-negative subjects may be a critical brain strength that fosters improved craving inhibition and thus, better clinical outcome.