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. 2015 Feb;52(2):249-62.
doi: 10.1111/psyp.12303. Epub 2014 Sep 2.

Do You Feel Alright? Attenuated Neural Processing of Aversive Interoceptive Stimuli in Current Stimulant Users

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Free PMC article

Do You Feel Alright? Attenuated Neural Processing of Aversive Interoceptive Stimuli in Current Stimulant Users

Jennifer L Stewart et al. Psychophysiology. .
Free PMC article

Abstract

Inability to appropriately process afferent interoceptive stimuli may contribute to initiation and/or escalation of substance use. An aversive interoceptive stimulus probed neural processing in problem stimulant users (PSU; n = 19), 18 desisted stimulant users (DSU; n = 18), and healthy comparison subjects (CTL; n = 21). Participants completed a continuous performance task while they anticipated and experienced 40 cm H2 O/L/sec inspiratory breathing loads during fMRI. PSU exhibited lower left dorsolateral prefrontal cortex and inferior frontal gyrus (IFG) activation than DSU and CTL across trials. Greater lifetime drug use due to stimulants was also linked to lower activation in these regions. In addition, PSU displayed lower right IFG and insula activation during breathing load than DSU and CTL. Findings suggest that transition to stimulant use disorders is marked by weakened attentional salience of aversive stimuli.

Keywords: Interoception; Substance abuse; fMRI/PET/MRI.

Figures

Figure 1
Figure 1
Timeline of subject recruitment. Occasional stimulant users were followed up 3 years later to determine which individuals escalated stimulant use (Problem Stimulant Users; PSU) or desisted stimulant use (Desisted Stimulant Users; DSU). Age and education-matched stimulant-naïve healthy comparison subjects (CTL) were also recruited.
Figure 2
Figure 2
Illustration of continuous performance task (CPT) with breathing load. A: Participants wore a nose clip and respired through a breathing tube while reclining in the scanner. Subjects were instructed to press a button corresponding to the direction pointed by an arrow on the screen left arrow = left button, right arrow = right button). Each trial lasted 3 s; the arrows appeared for 2.5 s and the subject was allowed to respond during the entire 3-s interval. The background color of the arrow served as a cue to the impending presentation of the breathing load; change of color indicated a 25% chance of load presence. Group analysis consisted of four conditions: (1) baseline: subject performs the CPT with a color background signifying no cue; (2) anticipation: a change in color background (cue) signals 25% chance of an impending resistive loaded breathing period; (3) breathing load: 25% of the periods following the anticipation condition, subject continues to view the colored cue and experiences 40-s period of resistive loaded breathing (plug at 40 cm H2O/L/sec); (4) post anticipation: 75% of the periods following the anticipation condition, subject performs the task with the original color background present (no cue). B: Depiction of condition regressors of interest (anticipation, breathing load, post anticipation) that were compared to the baseline condition (% signal change from baseline) in linear mixed model analysis. MRI repetition time (TR) was 2 s; thus, each trial consisted of 1.5 TRs. Subjects experienced 24 periods of anticipation, 8 periods of the breathing load, and 16 periods of post anticipation.
Figure 3
Figure 3
Results for the group main effect indicate that problem stimulant users (PSU) exhibited lower activation than desisted stimulant users (DSU) and healthy comparison subjects (CTL) in three regions: left middle frontal gyrus/dorsolateral prefrontal cortex (MFG/DLPFC), left inferior frontal gyrus (IFG), and right medial frontal gyrus (MedFG). Furthermore, PSU and DSU groups both displayed lower activation than CTL in six regions: left MFG/frontal pole (FP), right MFG/DLPFC, bilateral thalamus, left middle insula, left lentiform nucleus, and left postcentral gyrus. Error bars display ±1 standard error.
Figure 4
Figure 4
Findings for the condition main effect show that breathing load was associated with greater bilateral anterior and posterior insula (peak coordinates: left insula x = 42, y = 15, z = 8; right insula x = 30, y = 15, z = 12) and anterior cingulate cortex (ACC; peak coordinates: x = 6, y = 39, z = 24) activation than the anticipation condition. Bilateral insula activation was also greater for anticipation than post anticipation. Error bars display ±1 standard error.
Figure 5
Figure 5
Results for the Group × Condition interaction demonstrate that problem stimulant users (PSU) displayed lower right inferior frontal gyrus (IFG) and right anterior insula activation than desisted stimulant users (DSU) and healthy comparison subjects (CTL) during breathing load (peak coordinates : x = 42, y = 15, z = 4). Groups did not differ in activation during anticipation or post anticipation. Error bars display ±1 standard error.
Figure 6
Figure 6
Greater percentage of lifetime drug use attributable to stimulants (amphetamine and cocaine as opposed to marijuana) was associated with lower left middle frontal gyrus/dorsolateral prefrontal cortex (MFG/DLPFC; r = .36, p = .03) and left inferior frontal gyrus (IFG; (r = .40, p = .02) activation across problem stimulant user (PSU) and desisted stimulant user (DSU) subjects, as well as lower left IFG activation within the PSU group alone (r = .52, p = .02).
Figure 7
Figure 7
Robust regression findings across problem stimulant user (PSU) and desisted stimulant user (DSU) subjects demonstrated that higher lifetime amphetamine use was uniquely associated with lower left middle frontal gyrus/dorsolateral prefrontal cortex (MFG/DLPFC) and left thalamus activation during the experience of breathing load. Bottom: Activation in these regions also differentiated groups, such that PSU exhibited lower neural responses during breathing load than DSU and healthy comparison subjects (CTL). Error bars display ±1 standard error.

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