Increased error-related thalamic activity during early compared to late cocaine abstinence

Abstract

Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task (Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE>SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control.

Figure 1

(a) Stop signal paradigm. In “go” trials (75%) observers responded to the go signal (a circle) and in “stop” trials (25%) they had to withhold the response when they saw the stop signal (an X). In both trials the go signal appeared after a randomized time interval between 1 to 5 s (the fore-period or FP) following the appearance of the fixation point. The stop signal followed the go signal by a time delay – the stop signal delay (SSD). The SSD was updated according to a staircase procedure, whereby it increased and decreased by 64 ms following a stop success (SS) and stop error (SE) trial, respectively.

Figure 2

Error-related regional brain activations of all 26 patients with cocaine dependence. BOLD contrasts were overlaid on a T1 structural image in axial sections. Images are in neurological orientation: R=R; Color bar represents voxel T value.

Figure 3

Patients with cocaine dependence (PCD) who were scanned during early abstinence showed greater error-related activation in the thalamus (SE>SS), compared to PCD who were scanned during late abstinence. Color bar represents voxel T value; p<0.001, uncorrected.

Figure 4

At a lowered threshold, p<0.005, uncorrected, bilateral posterior insula also showed greater activation in PCD scanned during early abstinence compared to PCD scanned during late abstinence. BOLD contrasts were superimposed on a T1 structural image in axial sections. Images are in neurological orientation: R=R; Color bar represents voxel T value.

Figure 5

Linear correlation of error-related thalamic activation with (a) cocaine craving as assessed by the Cocaine Craving Questionnaire (CCQ) and with (b) loss of self control as assessed by the Difficulty in Emotion Regulation Scale (DERS). Note that DERS data were missing in three patients and that the correlation with CCQ was significant only after the outlier was removed (dashed line).