Rachel V. Kozink

24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum.

RationaleExposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence.ObjectivesIn the present study, we evaluated the effect of 24-h smoking abstinence on brain responses to smoking-related cues using functional magnetic resonance imaging (fMRI).Materials and methodsEighteen adult smokers underwent fMRI scanning following smoking as usual (satiated condition) and following 24-h abstinence (abstinent condition). During scanning, they viewed blocks of photographic smoking and control cues.ResultsFollowing abstinence, greater activation was found in response to smoking cues compared to control cues in parietal (BA 7/31), frontal (BA 8/9), occipital (BA 19), and central (BA 4) cortical regions and in dorsal striatum (putamen) and thalamus. In contrast, no smoking cue greater than control cue activations were observed following smoking as usual. Direct comparisons between conditions (satiated vs. abstinent) showed greater brain reactivity in response to smoking cues following abstinence. In addition, positive correlations between pre-scan craving in the abstinent condition and smoking cue activation were observed in right dorsomedial prefrontal cortex (dmPFC) including superior frontal gyrus (BA 6/10), anterior cingulate gyrus (BA 32), and supplementary motor area (BA 6).ConclusionsThe present findings indicate that smoking abstinence significantly potentiates neural responses to smoking-related cues in brain regions subserving visual sensory processing, attention, and action planning. Moreover, greater abstinence-induced craving was significantly correlated with increased smoking cue activation in dmPFC areas involved in action planning and decision making. These findings suggest that drug abstinence can increase the salience of conditioned cues, which is consistent with incentive-motivation models of addiction.

Individual Differences in Nicotine Dependence, Withdrawal Symptoms, and Sex Predict Transient fMRI-BOLD Responses to Smoking Cues

Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level–dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerström test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.

Remitted major depression is characterized by reward network hyperactivation during reward anticipation and hypoactivation during reward outcomes

BACKGROUND Although functional brain imaging has established that individuals with unipolar major depressive disorder (MDD) are characterized by frontostriatal dysfunction during reward processing, no research to date has examined the chronometry of neural responses to rewards in euthymic individuals with a history of MDD. METHOD A monetary incentive delay task was used during fMRI scanning to assess neural responses in frontostriatal reward regions during reward anticipation and outcomes in 19 participants with remitted major depressive disorder (rMDD) and in 19 matched control participants. RESULTS During the anticipation phase of the task, the rMDD group was characterized by relatively greater activation in bilateral anterior cingulate gyrus, in right midfrontal gyrus, and in the right cerebellum. During the outcome phase of the task, the rMDD group was characterized by relatively decreased activation in bilateral orbital frontal cortex, right frontal pole, left insular cortex, and left thalamus. Exploratory analyses indicated that activation within a right frontal pole cluster that differentiated groups during reward anticipation predicted the number of lifetime depressive episodes within the rMDD group. LIMITATIONS Replication with larger samples is needed. CONCLUSIONS Results suggest a double dissociation between reward network reactivity and temporal phase of the reward response in rMDD, such that rMDD is generally characterized by reward network hyperactivation during reward anticipation and reward network hypoactivation during reward outcomes. More broadly, these data suggest that aberrant frontostriatal response to rewards may potentially represent a trait marker for MDD, though future research is needed to evaluate the prospective utility of this functional neural endophenotype as a marker of MDD risk.

DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues

RationaleA dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism has been related to reactivity to smoking cues among smokers, but the effect of this genetic variation on brain responses to smoking cues has not been evaluated.ObjectivesThe present study evaluated the relationship between carrying the DRD4 VNTR 7-repeat allele and transient functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent responses to smoking cues among adult dependent cigarette smokers.Materials and methodsSmokers (n = 15) underwent fMRI scanning after 2-h abstinence. During scanning, they viewed visual smoking and control cues. A blood sample was assayed for the DRD4 VNTR polymorphism, and participants were categorized based on whether they carried one or two copies of the 7-repeat allele (DRD4 L, n = 7) or not (DRD4 S, n = 8).ResultsContrasts in brain cue-reactivity (smoking minus control cues) between DRD4 groups were conducted using SPM2. Smoking cues as compared to control cues elicited transient brain responses in right superior frontal gyrus (BA 8/9/10/32), left anterior cingulate gyrus (BA 32), and right cuneus (BA 19). Exposure to smoking cues resulted in greater activation of right superior frontal gyrus (BA 10) and right insula in DRD4 L compared to DRD4 S individuals. By contrast, exposure to smoking cues among DRD4 S individuals resulted in no significant increases in activation compared to DRD4 L individuals.ConclusionsThese brain imaging results suggest that DRD4 VNTR polymorphism is related to transient brain responses to smoking cues in regions subserving executive and somatosensory processes.

Meditation-State Functional Connectivity (msFC): Strengthening of the Dorsal Attention Network and Beyond.

Meditation practice alters intrinsic resting-state functional connectivity (rsFC) in the default mode network (DMN). However, little is known regarding the effects of meditation on other resting-state networks. The aim of current study was to investigate the effects of meditation experience and meditation-state functional connectivity (msFC) on multiple resting-state networks (RSNs). Meditation practitioners (MPs) performed two 5-minute scans, one during rest, one while meditating. A meditation naïve control group (CG) underwent one resting-state scan. Exploratory regression analyses of the relations between years of meditation practice and rsFC and msFC were conducted. During resting-state, MP as compared to CG exhibited greater rsFC within the Dorsal Attention Network (DAN). Among MP, meditation, as compared to rest, strengthened FC between the DAN and DMN and Salience network whereas it decreased FC between the DAN, dorsal medial PFC, and insula. Regression analyses revealed positive correlations between the number of years of meditation experience and msFC between DAN, thalamus, and anterior parietal sulcus, whereas negative correlations between DAN, lateral and superior parietal, and insula. These findings suggest that the practice of meditation strengthens FC within the DAN as well as strengthens the coupling between distributed networks that are involved in attention, self-referential processes, and affective response.

Association between the oxytocin receptor ( OXTR ) gene and mesolimbic responses to rewards

BackgroundThere has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI).MethodsThe moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task.ResultsT homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes.ConclusionsThis preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation.

Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition

Smoking withdrawal is associated with significant deficits in the ability to initiate and maintain attention for extended periods of time (i.e. sustained attention; SA). However, the effects of smoking abstinence on the temporal dynamics of neurocognition during SA have not been evaluated. Twenty adult smokers underwent functional magnetic resonance imaging scans following smoking as usual and after 24‐hours abstinence. During scanning they completed a SA task with two levels of task difficulty, designed to measure both sustained (i.e. over the duration of the task) and transient (i.e. event‐related) activation. Smoking abstinence significantly decreased task accuracy regardless of task difficulty. Compared to smoking as usual, abstinence resulted in decreased sustained activation in right inferior and middle frontal gyri but increased transient activation across dispersed cortical areas including precuneus and right superior frontal gyrus. Greater task difficulty was associated with even greater transient activation during abstinence in mostly right hemisphere regions including right inferior frontal gyrus. These findings suggest smoking withdrawal shifts the temporal and spatial dynamics of neurocognition from sustained, right prefrontal activation reflecting proactive cognitive control ( Braver, Gray & Burgess 2009 ) to more dispersed and transient activation reflecting reactive control.

Nicotine withdrawal modulates frontal brain function during an affective Stroop task

BackgroundAmong nicotine-dependent smokers, smoking abstinence disrupts multiple cognitive and affective processes including conflict resolution and emotional information processing (EIP). However, the neurobiological basis of abstinence effects on resolving emotional interference on cognition remains largely uncharacterized. In this study, functional magnetic resonance imaging (fMRI) was used to investigate smoking abstinence effects on emotion–cognition interactions.MethodsSmokers (n = 17) underwent fMRI while performing an affective Stroop task (aST) over two sessions: once following 24-h abstinence and once following smoking as usual. The aST includes trials that serially present incongruent or congruent numerical grids bracketed by neutral or negative emotional distractors and view-only emotional image trials. Statistical analyses were conducted using a statistical threshold of p < 0.05 cluster corrected.ResultsSmoking abstinence increased Stroop blood-oxygenation-level-dependent response in the right middle frontal and rostral anterior cingulate gyri. Moreover, withdrawal-induced negative affect was associated with less activation in frontoparietal regions during negative emotional information processing; whereas, during Stroop trials, negative affect predicted greater activation in frontal regions during negative, but not neutral emotional distractor trials.ConclusionHyperactivation in the frontal executive control network during smoking abstinence may represent a need to recruit additional executive resources to meet task demands. Moreover, abstinence-induced negative affect may disrupt cognitive control neural circuitry during EIP and place additional demands on frontal executive neural resources during cognitive demands when presented with emotionally distracting stimuli.

Smoking Withdrawal Modulates Right Inferior Frontal Cortex but not Presupplementary Motor Area Activation During Inhibitory Control

Smokers exhibit decrements in inhibitory control (IC) during withdrawal. The objective of this study was to investigate the neural basis of these effects in critical substrates of IC—right inferior frontal cortex (rIFC) and presupplementary motor area (pre-SMA). Smokers were scanned following smoking as usual and after 24-h smoking abstinence. During scanning they completed a Go/No-Go task that required inhibiting responses to infrequent STOP trials. Event-related brain activation in response to successfully inhibited STOP trials was evaluated in two regions of interest: rIFC (10 mm sphere, x=40, y=30, z=26) and pre-SMA (10 mm sphere, x=2, y=18, z=40). Smoking abstinence robustly increased errors of commission on STOP trials (37.1 vs 24.8% in the satiated condition, p<0.001) while having no effects on GO trial accuracy or reaction time (RT). In rIFC, smoking abstinence was associated with a significantly increased event-related BOLD signal (p=0.026). Pre-SMA was unaffected by smoking condition. The results of this preliminary study suggest that successful IC during withdrawal is associated with increased processing demands on a cortical center associated with attention to inhibitory signals.

Smoking Abstinence and Depressive Symptoms Modulate the Executive Control System During Emotional Information Processing

Smoking abstinence disrupts affective and cognitive processes. In this study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of smoking abstinence on emotional information processing. Smokers (n = 17) and non‐smokers (n = 18) underwent fMRI while performing an emotional distractor oddball task in which rare targets were presented following negative and neutral task‐irrelevant distractors. Smokers completed two sessions: once following 24‐hour abstinence and once while satiated. The abstinent versus satiated states were compared by evaluating responses to distractor images and to targets following each distractor valence within frontal executive and limbic brain regions. Regression analyses were done to investigate whether self‐reported negative affect influences brain response to images and targets. Exploratory regression analyses examined relations between baseline depressive symptoms and smoking state on brain function. Smoking state affected response to target detection in the right inferior frontal gyrus (IFG). During satiety, activation was greater in response to targets following negative versus neutral distractors; following abstinence, the reverse was observed. Withdrawal‐related negative affect was associated with right insula activation to negative images. Finally, depression symptoms were associated with abstinence‐induced hypoactive response to negative emotional distractors and task‐relevant targets following negative distractors in frontal brain regions. Neural processes related to novelty detection/attention in the right IFG may be disrupted by smoking abstinence and negative stimuli. Reactivity to emotional stimuli and the interfering effects on cognition are moderated by the magnitude of smoking state‐dependent negative affect and baseline depressive symptoms.