Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis-dependent males

Abstract

The transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral-dorsal striatal control of behavior; however, this shift has not been directly examined in humans. The present resting state functional magnetic resonance imaging (fMRI) study employed a two-step approach to: (a) precisely map striatal alterations using a novel, data-driven network classification strategy combining intrinsic connectivity contrast with multivoxel pattern analysis and, (b) to determine whether a ventral to dorsal striatal shift in connectivity with reward and regulatory control regions can be observed in abstinent (28 days) male cannabis-dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto-limbic regions that have been consistently involved in reward processing (rostral anterior cingulate cortex [ACC]) and executive/regulatory functions (dorsomedial prefrontal cortex [PFC]). Specifically, in the cannabis-dependent subjects, connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together, these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.

Keywords: addiction; anterior cingulate; cannabis; cognitive control; data-driven; functional connectivity; intrinsic connectivity contrast; prefrontal cortex; reward; striatum.

Figure 1

Striatum regions discriminating cannabis‐dependent subjects and nonusing controls. Images are thresholded at accuracy > = 0.75 (approximate p < .001, uncorrected) and cluster size >5 for display purpose

Figure 2

Brain regions showing significant main effect of seed on functional connectivity. (a) and (b) Results from data‐driven seeds. (c) and (d) Results from validation seeds. Red color indicated stronger functional connectivity with VS than DS and blue color indicated stronger functional connectivity with DS than VS. All images were thresholded at p < .05, TFCE corrected

Figure 3

Brain regions showing significant group (control vs user) by seed (ventral vs dorsal striatum) functional connectivity interaction. (a) and (b) Results from data‐driven seeds. (c) and (d) Results from validation seeds. All images are thresholded at p < .05, TFCE corrected

Figure 4

Patterns of functional connectivity associated with a significant group (control vs user) by seed (VS vs. DS) interaction. (a) and (c) Results from data‐driven seeds and (b) and (d) Results from validation seeds. Error bars reflect the SEM. *p < .05; **p < .01; VS: Ventral striatum; DS: Dorsal striatum; dmPFC: Dorsomedial prefrontal cortex; rACC: Rostral anterior cingulate cortex

Figure 5

Word cloud showing the correlation strength between the ROIs and the meta‐analytic map. (a) The top 25 terms associated with dmPFC based on Neurosynth decoding and font size represents relative correlation strength of that term to dmPFC. (b) The same information for rACC