Aim: This functional magnetic resonance imaging (fMRI) study examined reactivity to alcohol, polydrug, marijuana and emotional picture cues in students who were referred to a college alcohol and drug assistance program. Methods: The fMRI data of 10 participants (5 females; 5 males) were collected while they viewed standardized emotional and appetitive cues. Results: Positive and negative emotional cues produced greater activity than neutral cues in the expected brain areas. Compared with neutral cues, alcohol cues produced greater brain activation in the right insula, left anterior cingulate, left caudate and left prefrontal cortex (Z = 2.01, 1.86, 1.82, 1.81, respectively; P < 0.05). Drug cues produced significantly greater left prefrontal activity compared with neutral cues, with polydrug cues activating the right insula and marijuana cues activating left anterior cingulate. Conclusions: Students at-risk for alcohol abuse showed neural reactivity to alcohol cues in four brain regions, which is consistent with their greater use of alcohol. Insula activation to appetitive cues may be an early marker of risk for progression to alcohol/drug abuse.
Attenuation of cue-elicited craving with brain stimulation techniques is a growing area of attention in addiction research. This investigation aims to guide these studies by assessing individual variability in the location of peak cortical activity during cue-elicited craving.
Twenty-six nicotine-dependent individuals performed a cue-elicited craving task in a 3T MRI scanner while BOLD signal data was collected. The task included epochs of smoking cues, neutral cues, and rest. The location of peak activity during smoking cues relative to neutral cues (‘hot spot’) was isolated for each individual. The spatial dispersion of the 26 cue-elicited hot spots (1 per participant) was quantified via hierarchical clustering.
When viewing nicotine cues all 26 participants had at least one cluster of significant prefrontal cortex activity (p<0.05, cluster corrected). Only 62% had peak activity in the medial prefrontal cortex cluster (including 100% of the men). In 15% of the participants peak activity was located in either the left lateral prefrontal cortex or left insula cluster. Peak activity in the remaining 23% was dispersed throughout the prefrontal cortex.
There is considerable individual variability in the location of the cue-elicited ‘hot spot’ as measured by BOLD activity. Men appear to have a more uniform location of peak BOLD response to cues than women. Consequently, acquiring individual functional imaging data may be advantageous for either tailoring treatment to the individual or filtering participants before enrollment in treatment.
nicotine; craving; functional MRI; transcranial magnetic stimulation
In functional magnetic resonance imaging (fMRI) studies of alcohol-dependent individuals, alcohol cues elicit activation of the ventral and dorsal aspects of the striatum (VS and DS), which are believed to underlie aspects of reward learning critical to the initiation and maintenance of alcohol dependence. Cue-elicited striatal activation may represent a biological substrate through which treatment efficacy may be measured. However, to be useful for this purpose, VS or DS activation must first demonstrate stability across time. Using hierarchical linear modeling (HLM), this study tested the stability of cue-elicited activation in anatomically and functionally defined regions of interest in bilateral VS and DS. Nine non-treatment-seeking alcohol-dependent participants twice completed an alcohol cue reactivity task during two fMRI scans separated by 14 days. HLM analyses demonstrated that, across all participants, alcohol cues elicited significant activation in each of the regions of interest. At the group level, these activations attenuated slightly between scans, but session-wise differences were not significant. Within-participants stability was best in the anatomically defined right VS and DS and in a functionally defined region that encompassed right caudate and putamen (intraclass correlation coefficients of .75, .81, and .76, respectively). Thus, within this small sample, alcohol cue-elicited fMRI activation had good reliability in the right striatum, though a larger sample is necessary to ensure generalizability and further evaluate stability. This study also demonstrates the utility of HLM analytic techniques for serial fMRI studies, in which separating within-participants variance (individual changes in activation) from between-participants factors (time or treatment) is critical.
alcohol; fMRI; cue reactivity; ventral striatum; dorsal striatum; HLM
Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of concomitant use remains unclear. We previously demonstrated functional magnetic resonance imaging (fMRI) response to spatial working memory (SWM) among teens with alcohol use disorders (AUD) compared to controls, and predicted that adolescents with marijuana and alcohol use disorders would show additional abnormalities.
Participants were three groups of 15−17-year-olds: 19 non-abusing controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid marijuana and alcohol use disorders (MAUD) and minimal other drug experience. After >2 days’ abstinence, participants performed a SWM task during fMRI acquisition.
fMRI brain response patterns differed between groups, despite similar performance on the task. MAUD youths showed less activation in inferior frontal and temporal regions than controls, and more response in other prefrontal regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and temporal activation, but more medial frontal response.
Overall, MAUD youths showed different brain response abnormalities than teens with AUD alone, despite relatively short histories of substance involvement. This pattern could suggest compensation for marijuana-related attention and working memory deficits. However, relatively recent use and premorbid features may influence results, and should be examined in future studies.
Alcohol abuse; Marijuana abuse; fMRI; Adolescents
Models of autobiographical memory propose two routes to retrieval depending on cue specificity. When available cues are specific and personally-relevant, a memory can be directly accessed. However, when available cues are generic, one must engage a generative retrieval process to produce more specific cues to successfully access a relevant memory. The current study sought to characterize the neural bases of these retrieval processes. During functional magnetic resonance imaging (fMRI), participants were shown personally-relevant cues to elicit direct retrieval, or generic cues (nouns) to elicit generative retrieval. We used spatiotemporal partial least squares to characterize the spatial and temporal characteristics of the networks associated with direct and generative retrieval. Both retrieval tasks engaged regions comprising the autobiographical retrieval network, including hippocampus, and medial prefrontal and parietal cortices. However, some key neural differences emerged. Generative retrieval differentially recruited lateral prefrontal and temporal regions early on during the retrieval process, likely supporting the strategic search operations and initial recovery of generic autobiographical information. However, many regions were activated more strongly during direct versus generative retrieval, even when we time-locked the analysis to the successful recovery of events in both conditions. This result suggests that there may be fundamental differences between memories that are accessed directly and those that are recovered via the iterative search and retrieval process that characterizes generative retrieval.
autobiographical memory; retrieval; fMRI; partial least squares
Alcohol and marijuana are the most widely used intoxicants among adolescents, yet their potential unique and interactive influences on the developing brain are not well established. Brain regions subserving learning and memory undergo continued maturation during adolescence, and may be particularly susceptible to substance-related neurotoxic damage. Here, we characterize brain response during verbal learning among adolescent users of alcohol and marijuana.
Participants performed a verbal paired associates encoding task during fMRI scanning.
Adolescent subjects were recruited from local public schools and imaged at a University-based fMRI Center.
Participants were 74 16- to 18-year-olds, divided into four groups: (1) 22 controls with limited alcohol and marijuana experience, (2) 16 binge drinkers, (3) 8 marijuana users, and (4) 28 binge drinking marijuana users.
Diagnostic interview assured that all teens were free from neurologic or psychiatric disorders; urine toxicology and breathalyzer verified abstinence for 22–28 days before scanning; a verbal paired associates task was administered during fMRI.
Groups demonstrated no differences in performance on the verbal encoding task, yet exhibited different brain response patterns. A main effect of drinking pointed to decreased inferior frontal but increased dorsal frontal and parietal fMRI response among binge drinkers (corrected p < .05). There was no main effect of marijuana use. Binge drinking × marijuana interactions were found in bilateral frontal regions (corrected p < .05), where users of either alcohol or marijuana showed greater response than non-users, but users of both substances resembled non-users.
Adolescent substance users demonstrated altered fMRI response relative to nonusing controls, yet binge drinking appeared associated with more differences in activation than marijuana use. Alcohol and marijuana may have interactive effects that alter these differences, particularly in prefrontal brain regions.
adolescence; functional magnetic resonance imaging; verbal learning; cannabis; alcohol; binge drinking
In the present study, we used fMRI to assess patients suffering from post-traumatic stress disorder (PTSD) or depression, and trauma-exposed controls, during an episodic memory retrieval task that included non-trauma-related emotional information. In the study phase of the task neutral pictures were presented in emotional or neutral contexts. Participants were scanned during the test phase, when they were presented with old and new neutral images in a yes/no recognition memory task. fMRI results for the contrast between old and new items revealed activation in a predominantly left-sided network of cortical regions including the left middle temporal, bilateral posterior cingulate, and left prefrontal cortices. Activity common to all three groups when correctly judging pictures encoded in emotional contexts was much more limited. Relative to the control and depressed groups the PTSD group exhibited greater sensitivity to correctly recognised stimuli in the left amygdala/ventral striatum and right occipital cortex, and more specific sensitivity to items encoded in emotional contexts in the right precuneus, left superior frontal gyrus, and bilateral insula. These results are consistent with a substantially intact neural system supporting episodic retrieval in patients suffering from PTSD. Moreover, there was little indication that PTSD is associated with a marked change in the way negatively valenced information, not of personal significance, is processed.
PTSD; Memory; Trauma; Imaging
Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.
attention; cognitive control; advance preparation; feature biasing; conflict; Stroop
This functional magnetic resonance imaging (fMRI) study investigated the role of Broca’s region for selecting semantic, syntactic, and phonological information during picture naming. According to psycholinguistic theory, selection is reflected in speech latency differences, e.g. during priming. Here, homogenous (priming) blocks in which German picture names had the same semantic category, syntactic gender, or initial phoneme alternated with heterogeneous (non-priming) blocks. Speech latencies revealed a negative priming effect. Speech latencies were used as regressors for the fMRI data in order to tap selection processes. In Broca’s region (BA 44), among others, fMRI data showed repetition priming, which was positive for semantic and syntactic but negative for phonological selection. The different effects in area 44 are discussed in terms of psycholinguistic theory. Overall, the activation pattern is in line with the hypothesis that area 44 generally supports selection processes during noun production at several levels of the mental lexicon.
Broca’s region; Area 44; BA 44; Semantic; Phonological; Syntactic gender; fMRI
Exposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence.
In the present study we evaluated the effect of 24-hr smoking abstinence on brain responses to smoking-related cues using functional magnetic resonance imaging (fMRI).
Eighteen adult smokers underwent fMRI scanning following smoking as usual (satiated condition) and following 24-hr abstinence (abstinent condition). During scanning they viewed blocks of photographic smoking and control cues.
Following 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 > 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).
The present findings indicate 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.
cue-reactivity; craving; nicotine dependence; fMRI; smoking; dorsal striatum
Objective: We evaluated the effect of short-term and long-term heroin abstinence on brain responses to heroin-related cues using functional magnetic resonance imaging (fMRI). Methods: Eighteen male heroin addicts following short-term abstinence and 19 male heroin addicts following long-term abstinence underwent fMRI scanning while viewing heroin-related and neutral images. Cue-elicited craving and withdrawal symptoms in the subjects were measured. Results: Following short-term abstinence, greater activation was found in response to heroin cues compared to neutral cues in bilateral temporal, occipital, posterior cingulate, anterior cingulate, thalamus, cerebellum, and left hippocampus. In contrast, activations in bilateral temporal and occipital and deactivations in bilateral frontal, bilateral parietal, left posterior cingulate, insula, thalamus, dorsal striatum, and bilateral cerebellum were observed following long-term abstinence. Direct comparisons between conditions showed greater brain reactivity in response to smoking cues following short-term abstinence. In addition, short-term abstinence had more serious withdrawal symptoms than the long-term. Conclusion: The present findings indicate that compared to short-term, long-term abstinence manifests less serious withdrawal symptoms and significantly decreases neural responses to heroin-related cues in brain regions subserving visual sensory processing, attention, memory, and action planning. These findings suggest that long-term abstinence can decrease the salience of conditioned cues, thereby reducing the risk of relapses. The study's limitations are noted.
abstinence; cue-reactivity; craving; heroin dependence; fMRI
Prospective studies indicate that individuals with elevated dietary restraint scores are at increased risk for future bulimic symptom onset, suggesting that these individuals may show hyper-responsivity of reward regions to food and food cues. Thus, we used functional magnetic resonance imaging (fMRI) to examine the relation of dietary restraint scores to activation of reward-related brain regions in response to receipt and anticipated receipt of chocolate milkshake and exposure to pictures of appetizing foods in 39 female adolescents (mean age = 15.5 ± 0.94). Dietary restraint scores were positively correlated with activation in the right orbitofrontal cortex (OFC) and bilateral dorsolateral prefrontal cortex (DLPFC) in response to milkshake receipt. However, dietary restraint scores did not correlate with activation in response to anticipated milkshake receipt or exposure to food pictures. Results indicate that individuals who report high dietary restraint have a hyper-responsivity in reward-related brain regions when food intake is occurring, which may increase risk for overeating and binge eating.
fMRI; Dietary restraint; OFC; DLPFC; Bulimia nervosa; Binge eating; Obesity; Dieting; Food pictures; anticipation and receipt; Food intake
The aim of this study was to further elucidate the mechanisms of early and automatic object processing using a masked picture priming paradigm with both identity and exemplar repetition in functional MRI (fMRI). Masked repetition priming has been commonly used with words to isolate automatic, rapidly occurring mechanisms involved in visual word recognition; however, studies using the technique of masked priming with rapid presentation of pictures have been limited. This study demonstrates how the masked priming technique can be used to study early, automatic processing of rapidly presented complex objects. Temporal-occipital regions previously found to be sensitive to repetition priming in both masked word and unmasked picture studies were found to show repetition suppression for the identity primes only. Most notably, when divided into anterior and posterior divisions, the fusiform gyrus showed anatomically specific repetition suppression only in the posterior portion. This finding is comparable to that found in a previous study of masked word priming, and the similarity may suggest an overlap in the early identification processes for visual word form and visual object processing in this region. Finally, masked repetition of different exemplar objects did not result in reliable neural effects, suggesting that the underlying mechanisms of the more semantic-based, different exemplar priming may occur later or require the intervention of conscious processes.
fMRI; Masked priming; Repetition priming; Picture processing; Repetition suppression
Reactivity to smoking-related cues may play a role in the maintenance of smoking behavior and may change depending on smoking status. Whether smoking cue-related functional MRI (fMRI) reactivity differs between active smoking and extended smoking abstinence states currently is unknown.
We used fMRI to measure brain reactivity in response to smoking-related versus neutral images in 13 tobacco-dependent subjects prior to a smoking cessation attempt and again during extended smoking abstinence (52 ± 11 days) aided by nicotine replacement therapy.
Pre-quit smoking cue induced fMRI activity patterns paralleled those reported in prior smoking cue reactivity fMRI studies. Greater fMRI activity was detected during extended smoking abstinence than during the pre-quit assessment subcortically in the caudate nucleus and cortically in prefrontal (BA 6, 9, 44, 46), primary somatosensory (BA 1,2,3), temporal (BA 22, 41, 42), parietal (BA 7, 40) anterior cingulate (BA 24, 32), and posterior cingulate (BA 31) cortex.
These data suggest that during extended smoking abstinence, fMRI reactivity to smoking versus neutral stimuli persists in brain areas involved in attention, somatosensory processing, motor planning, and conditioned cue responding. In some brain regions, fMRI smoking cue reactivity is increased during extended smoking abstinence in comparison to the pre-quit state, which may contribute to persisting relapse vulnerability.
abstinence; addiction; caudate nucleus; fMRI; nicotine
As people learn more facts about a concept, those facts become more difficult to remember. This is called the fan effect, where fan refers to the number of facts known about a concept. Increasing fan has been shown to decrease accuracy and increase response time and left ventrolateral prefrontal cortex (VLPFC) activity during retrieval. In this study, participants learned 36 arbitrary person-location pairings and had to recognize them while we recorded brain activity using fMRI. We separately manipulated the fan of each person and location, as well as the training procedure with which each pair was studied. In the person focus condition, participants studied pairs with a picture of the person’s face and used the person as a retrieval cue during training. In the location focus condition, participants studied pairs with a picture of the location and used the location as a retrieval cue during training. We found that the fan of the focused cue had a greater effect on response time, accuracy, and left VLPFC activity during retrieval than the fan of the unfocused cue. We also found that the parahippocampal place area (PPA) was more active during the recognition of pairs studied in the location focus condition, but not when the fan of the location was high. Overall, we found opposite effects of fan on VLPFC and PPA that were modulated by cue focus.
fan effect; left ventrolateral prefrontal cortex (VLPFC); parahippocampal place area (PPA); ACT-R; reactivation
Theta and alpha range EEG oscillations are commonly induced in cognitive tasks, but their possible relationship to the BOLD signal of fMRI is not well understood, and individual variability is high. We explored individual differences in EEG reactivity to determine whether it is positively or negatively correlated with BOLD across subjects.
A Sternberg working memory task with 2, 4, or 6 digits was administered to 18 subjects in separate fMRI and EEG sessions. Memory load dependent theta and alpha reactivity was quantified and used as a regressor to reveal brain areas exhibiting EEG-fMRI correlation across subjects.
Theta increases localized to medial prefrontal cortex, and correlated negatively with BOLD in that region and in other “default mode” areas. Alpha modulation localized to parietal-occipital midline cortex and also correlated negatively with BOLD.
Individual tendencies to exhibit memory-load dependent oscillations are associated with negative BOLD responses certain brain regions.
Positive BOLD responses and increased EEG oscillations do not necessarily arise in the same regions. Negative BOLD responses may also relate to cognitive activity, as traditionally indexed by increased EEG power in the theta band.
default mode; MEG; deactivation; ERS; negative BOLD
Current models of executive function hold that the internal representations of stimuli used during reflective thought are maintained in the same posterior cortical regions initially activated during perception, and that activity in such regions is modulated by top-down signals originating in prefrontal cortex. In an event-related functional magnetic resonance imaging study, we presented participants with two pictures simultaneously, a face and a scene, immediately followed either by a repetition of one of the pictures (perception) or by a cue to think briefly of one of the just-seen, but no longer present, pictures (refreshing, a reflective act). Refreshing faces and scenes modulated activity in the fusiform face area (FFA) and parahippocampal place area (PPA), respectively, as well as other regions exhibiting relative perceptual selectivity for either faces or scenes. Four scene-selective regions (lateral precuneus, retrosplenial cortex, PPA, and middle occipital gyrus) showed an anatomical gradient of responsiveness to top-down reflective influences versus bottom-up perceptual influences. These results demonstrate that a brief reflective act can modulate posterior cortical activity in a stimulus-specific manner, suggesting that such modulatory mechanisms are engaged even during transient ongoing thought. Our findings are consistent with the hypothesis that refreshing is a component of more complex modulatory operations such as working memory and mental imagery, and that refresh-related activity may thus contribute to the common activation patterns seen across different cognitive tasks.
executive function; fMRI; refreshing; top-down control; working memory
Experience with visual objects leads to later improvements in identification speed and accuracy (“repetition priming”), but generally leads to reductions in neural activity in single-cell recording studies in animals and fMRI studies in humans. Here we use event-related, source-localized MEG (ER-SAM) to evaluate the possibility that neural activity changes related to priming in occipital, temporal, and prefrontal cortex correspond to more temporally coordinated and synchronized activity, reflected in local increases in the amplitude of low-frequency activity fluctuations (i.e. evoked power) that are time-locked to stimulus onset. Subjects (N = 17) identified pictures of objects that were either novel or repeated during the session. Tests in two separate low-frequency bands (theta/alpha: 5–15 Hz; beta: 15–35 Hz) revealed increases in evoked power (5–15 Hz) for repeated stimuli in the right fusiform gyrus, with the earliest significant increases observed 100–200 ms after stimulus onset. Increases with stimulus repetition were also observed in striate/extrastriate cortex (15–35 Hz) by 200–300 ms post-stimulus, along with a trend for a similar pattern in right lateral prefrontal cortex (5–15 Hz). Our results suggest that experience-dependent reductions in neural activity may affect improved behavioral identification through more coordinated, synchronized activity at low frequencies, constituting a mechanism for more efficient neural processing with experience.
repetition priming; repetition suppression; synchrony; evoked power; MEG; theta; alpha; beta
This study examined how valence and arousal affect the processes linked to subsequent memory for emotional information. While undergoing an fMRI scan, participants viewed neutral pictures and emotional pictures varying by valence and arousal. After the scan, participants performed a recognition test. Subsequent memory for negative or high arousal information was associated with occipital and temporal activity, while memory for positive or low arousal information was associated with frontal activity. Regression analyses confirmed that for negative or high arousal items, temporal lobe activity was the strongest predictor of later memory whereas for positive or low arousal items, frontal activity corresponded most strongly with later memory. These results suggest that the types of encoding processes relating to memory (e.g., sensory vs. elaborative processing) can differ based on the affective qualities of emotional information.
Behavioral studies have suggested that food cues have stronger motivating effects in obese than in normal-weight individuals, which may be a risk factor underlying obesity. Previous cross-sectional neuroimaging studies have suggested that this difference is mediated by increased reactivity to food cues in parts of the reward system in obese individuals. To date, however, only a few prospective neuroimaging studies have been conducted to examine whether individual differences in brain activation elicited by food cues can predict differences in weight change. We used functional magnetic resonance imaging (fMRI) to investigate activation in reward-system as well as other brain regions in response to viewing high-calorie food vs. control pictures in 25 obese individuals before and after a 12-week psychosocial weight-loss treatment and at 9-mo follow-up. In those obese individuals who were least successful in losing weight during the treatment, we found greater pre-treatment activation to high-calorie food vs. control pictures in brain regions implicated in reward-system processes, such as the nucleus accumbens, anterior cingulate, and insula. We found similar correlations with weight loss in brain regions implicated by other studies in vision and attention, such as superior occipital cortex, inferior and superior parietal lobule, and prefrontal cortex. Furthermore, less successful weight maintenance at 9-mo follow-up was predicted by greater post-treatment activation in such brain regions as insula, ventral tegmental area, putamen, and fusiform gyrus. In summary, we found that greater activation in brain regions mediating motivational and attentional salience of food cues in obese individuals at the start of a weight-loss program was predictive of less success in the program and that such activation following the program predicted poorer weight control over a 9-mo follow-up period.
obesity; fMRI; food cues; weight loss; weight maintenance; reward system
Visual spatial orienting of attention can be investigated with location-cueing paradigms in which a cue provides correct information about the location of the upcoming target. Target detection is facilitated when the target appears at the expected cued location. In this study, we examined the brain activation of the spatial orienting response based on attentional “benefits.” During an fMRI experiment, two types of attentional tasks were used. Both predictive and nonpredictive cues were used and followed by an upcoming target. Behavioral data showed a faster reaction time with the predictive cue when compared with that of the nonpredictive cue. The fMRI results of these two tasks were compared, whereby isolated brain areas activated when the targets appeared at the attended position after a specific spatial expectation was induced by the cue were compared with when equivalent targets appeared after no spatial expectation was induced by the cue. The results showed that the right ventral prefrontal cortex was activated to a similar degree as the dorsal frontoparietal spatial attentional network.
The amygdala, hippocampus, medial prefrontal cortex (mPFC) and brain-stem subregions are implicated in fear conditioning and extinction, and are brain regions known to be sexually dimorphic. We used functional magnetic resonance imaging (fMRI) to investigate sex differences in brain activity in these regions during fear conditioning and extinction.
Subjects were 12 healthy men comparable to 12 healthy women who underwent a 2-day experiment in a 3 T MR scanner. Fear conditioning and extinction learning occurred on day 1 and extinction recall occurred on day 2. The conditioned stimuli were visual cues and the unconditioned stimulus was a mild electric shock. Skin conductance responses (SCR) were recorded throughout the experiment as an index of the conditioned response. fMRI data (blood-oxygen-level-dependent [BOLD] signal changes) were analyzed using SPM8.
Findings showed no significant sex differences in SCR during any experimental phases. However, during fear conditioning, there were significantly greater BOLD-signal changes in the right amygdala, right rostral anterior cingulate (rACC) and dorsal anterior cingulate cortex (dACC) in women compared with men. In contrast, men showed significantly greater signal changes in bilateral rACC during extinction recall.
These results indicate sex differences in brain activation within the fear circuitry of healthy subjects despite similar peripheral autonomic responses. Furthermore, we found that regions where sex differences were previously reported in response to stress, also exhibited sex differences during fear conditioning and extinction.
Sex differences; Fear extinction; Fear conditioning; fMRI; Stress response circuitry
Using fMRI, we examined whether or not adolescents with low levels of nicotine exposure (light smokers) display neural activation in areas shown to be involved with addiction in response to smoking-related stimuli.
Twelve adolescent light smokers (aged 13 to17, smoked 1 to 5 cigarettes per day) and 12 non-smokers (ages 13 to 17, never smoked a cigarette) from the San Francisco Bay Area underwent fMRI scanning. During scanning they viewed blocks of photographic smoking and control cues. Smoking cues consisted of pictures of people smoking cigarettes and smoking-related objects such as lighters and ashtrays. Neutral cues consisted of everyday objects and people engaged in everyday activities.
For smokers, smoking cues elicited greater activation than neutral cues in the mesolimbic reward circuit (left anterior cingulate (T=7.88, p<.001), right hippocampus (T=6.62, p<.001) and right parahippocampal gyrus (T=4.70, p<.001)). We found activation from smoking cues versus neutral cues within both the left and right frontal medial orbital regions (T=5.09, p<.001 and T=3.94, p=.001 respectively), which may be unique to adolescents. Non-smokers showed no significant difference in activation between smoking-related cues and neutral cues.
Our finding that smoking cues produced activation in adolescent light smokers in brain regions seen in adult and heavy teen smokers suggests that even at low levels of smoking, adolescents exhibit heightened reactivity to smoking cues. This paper adds to the existing literature suggesting that nicotine dependence may begin with exposure to low levels of nicotine, underscoring the need for early intervention among adolescent smokers.
fMRI; adolescent nicotine addiction; adolescent smoking; brain imaging
Recent studies have emphasized the importance of dopamine projections to the prefrontal cortex (PFC) for working memory (WM) function, although this system has rarely been studied in humans in vivo. However, dopamine and PFC activity can be directly measured with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), respectively. In this study, we examined WM capacity, dopamine, and PFC function in healthy older participants in order to test the hypothesis that there is a relationship between these 3 factors. We used the PET tracer 6-[18F]fluoro-L-m-tyrosine to measure dopamine synthesis capacity in the striatum (caudate, putamen), and event-related fMRI to measure brain activation during different epochs (cue, delay, probe) of a WM task. Caudate (but not putamen) dopamine correlated positively with WM capacity, whereas putamen (but not caudate) dopamine correlated positively with motor speed. In addition, delay-related fMRI activation in a left inferior prefrontal region was related to both caudate dopamine and task accuracy, suggesting that this may be a critical site for the integration of WM maintenance processes. These results provide new evidence that striatal dopaminergic function is related to PFC-dependent functions, particularly brain activation and behavioral performance during WM tasks.
aging; caudate; fMRI; maintenance; PET; putamen
Intrusive reexperiencing in posttraumatic stress disorder (PTSD) is commonly triggered by stimuli with perceptual similarity to those present during the trauma. Information processing theories suggest that perceptual processing during the trauma and enhanced perceptual priming contribute to the easy triggering of intrusive memories by these cues.
Healthy volunteers (N = 51) watched neutral and trauma picture stories on a computer screen. Neutral objects that were unrelated to the content of the stories briefly appeared in the interval between the pictures. Dissociation and data-driven processing (as indicators of perceptual processing) and state anxiety during the stories were assessed with self-report questionnaires. After filler tasks, participants completed a blurred object identification task to assess priming and a recognition memory task. Intrusive memories were assessed with telephone interviews 2 weeks and 3 months later.
Neutral objects were more strongly primed if they occurred in the context of trauma stories than if they occurred during neutral stories, although the effect size was only moderate (ηp2=.08) and only significant when trauma stories were presented first. Regardless of story order, enhanced perceptual priming predicted intrusive memories at 2-week follow-up (N = 51), but not at 3 months (n = 40). Data-driven processing, dissociation and anxiety increases during the trauma stories also predicted intrusive memories. Enhanced perceptual priming and data-driven processing were associated with lower verbal intelligence.
It is unclear to what extent these findings generalize to real-life traumatic events and whether they are specific to negative emotional events.
The results provide some support for the role of perceptual processing and perceptual priming in reexperiencing symptoms.
► We investigated whether perceptual processing and priming predict intrusive memories. ► Neutral objects were more readily identified if previously seen in a traumatic rather than neutral context. ► Enhanced perceptual priming predicted intrusive memories 2 weeks later. ► Perceptual processing during the stories also predicted intrusive memories. ► The results support the role of perceptual triggers of unwanted trauma memories.
Trauma memories; Enhanced perceptual priming; Posttraumatic stress disorder; Data-driven processing; Dissociation