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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.
doi:10.1093/alcalc/agq042
PMCID: PMC2930251
PMID: 20729530
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.
doi:10.1016/j.drugalcdep.2005.01.009
PMCID: PMC2270678
PMID: 16002029
Alcohol abuse; Marijuana abuse; fMRI; Adolescents
Aims
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.
Design
Participants performed a verbal paired associates encoding task during fMRI scanning.
Setting
Adolescent subjects were recruited from local public schools and imaged at a University-based fMRI Center.
Participants
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.
Measurements
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.
Findings
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.
Conclusions
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.
doi:10.1111/j.1360-0443.2010.03197.x
PMCID: PMC3423457
PMID: 21134014
adolescence; functional magnetic resonance imaging; verbal learning; cannabis; alcohol; binge drinking
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.
doi:10.1016/j.neuroimage.2011.02.004
PMCID: PMC3066261
PMID: 21316465
alcohol; fMRI; cue reactivity; ventral striatum; dorsal striatum; HLM
Rationale
Exposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence.
Objectives
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).
Methods
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.
Results
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).
Conclusions
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.
doi:10.1007/s00213-008-1436-9
PMCID: PMC2810714
PMID: 19107465
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.
doi:10.3109/10826084.2011.646381
PMCID: PMC3359800
PMID: 22329835
abstinence; cue-reactivity; craving; heroin dependence; fMRI
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.
doi:10.1016/j.neuroimage.2011.09.066
PMCID: PMC3254828
PMID: 22001264
autobiographical memory; retrieval; fMRI; partial least squares
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.
doi:10.1016/j.neuroimage.2010.12.009
PMCID: PMC3032532
PMID: 21147234
fMRI; Dietary restraint; OFC; DLPFC; Bulimia nervosa; Binge eating; Obesity; Dieting; Food pictures; anticipation and receipt; Food intake
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.
doi:10.1016/j.neuropsychologia.2011.04.020
PMCID: PMC3137688
PMID: 21549721
fan effect; left ventrolateral prefrontal cortex (VLPFC); parahippocampal place area (PPA); ACT-R; reactivation
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.
doi:10.1016/j.bandc.2008.05.008
PMCID: PMC2666800
PMID: 18614265
PTSD; Memory; Trauma; Imaging
Purpose
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.
Design/Setting/Participants
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.
Findings
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.
Conclusions
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.
doi:10.1016/j.jadohealth.2010.09.016
PMCID: PMC3058837
PMID: 21185518
fMRI; adolescent nicotine addiction; adolescent smoking; brain imaging
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.
PMCID: PMC3287079
PMID: 22332246
obesity; fMRI; food cues; weight loss; weight maintenance; reward system
McDonald, Carrie R. | Thesen, Thomas | Carlson, Chad | Blumberg, Mark | Girard, Holly M. | Trongnetrpunya, Amy | Sherfey, Jason S. | Devinsky, Orrin | Kuzniecky, Rubin | Dolye, Werner K. | Cash, Sydney S. | Leonard, Matt K. | Hagler, Donald J. | Dale, Anders M. | Halgren, Eric
Repetition priming is a core feature of memory processing whose anatomical correlates remain poorly understood. In this study, we use advanced multimodal imaging (functional magnetic resonance imaging (fMRI) and magnetoencephalography; MEG) to investigate the spatiotemporal profile of repetition priming. We use intracranial electroencephalography (iEEG) to validate our fMRI/MEG measurements. Twelve controls completed a semantic judgment task with fMRI and MEG that included words presented once (new, ‘N’) and words that repeated (old, ‘O’). Six patients with epilepsy completed the same task during iEEG recordings. Blood-oxygen level dependent (BOLD) responses for N vs O words were examined across the cortical surface and within regions of interest. MEG waveforms for N vs O words were estimated using a noise-normalized minimum norm solution, and used to interpret the timecourse of fMRI. Spatial concordance was observed between fMRI and MEG repetition effects from 350–450ms within bilateral occipitotemporal and medial temporal, left prefrontal, and left posterior temporal cortex. Additionally, MEG revealed widespread sources within left temporoparietal regions, whereas fMRI revealed bilateral reductions in occipitotemporal and left superior frontal, and increases in inferior parietal, precuneus, and dorsolateral prefrontal activity. BOLD suppression in left posterior temporal, left inferior prefrontal, and right occipitotemporal cortex correlated with MEG repetition-related reductions. IEEG responses from all three regions supported the timecourse of MEG and localization of fMRI. Furthermore, iEEG decreases to repeated words were associated with decreased gamma power in several regions, providing evidence that gamma oscillations are tightly coupled to cognitive phenomena and reflect regional activations seen in the BOLD signal.
doi:10.1016/j.neuroimage.2010.06.069
PMCID: PMC2930128
PMID: 20620212
fMRI; magnetoencepholography; intracranial EEG; memory; language; gamma
Summary
With no further intervention, relapse rates in detoxified alcoholics are high and usually exceed 80% of all detoxified patients. It has been suggested that stress and exposure to priming doses of alcohol and to alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. This article focuses on neuronal correlates of cue responses in detoxified alcoholics. Current brain imaging studies indicate that dysfunction of dopaminergic, glutamatergic, and opioidergic neurotransmission in the brain reward system (ventral striatum including the nucleus accumbens) can be associated with alcohol craving and functional brain activation in neuronal systems that process attentional relevant stimuli, reward expectancy and experience. Increased functional brain activation elicited by such alcohol-associated cues predicted an increased relapse risk, while high brain activity elicited by affectively positive stimuli may represent a protective factor and was correlated with a decreased prospective relapse risk. These findings are discussed with respect to psychotherapeutic and pharmacological treatment options.
doi:10.1111/j.1369-1600.2008.00136.x
PMCID: PMC2879014
PMID: 18855799
alcohol craving; functional magnetic resonance imaging; relapse; reward system; dopamine; opioids
Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for low or high painful thermal stimulation, and we assessed how cues influenced human subjects’ pain reports and BOLD fMRI responses to matched levels of noxious heat. We used multi-level mediation analysis to identify brain regions that 1) are modulated by predictive cues, 2) predict trial-to-trial variations in pain reports, and 3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pre-task expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing.
doi:10.1523/JNEUROSCI.0057-10.2010
PMCID: PMC2966558
PMID: 20881115
Expectancy; Pain; fMRI; Mediation; orbitofrontal; insula; ventral striatum; prediction; cues; anticipation
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.
doi:10.1016/j.neuroimage.2006.10.031
PMCID: PMC1919407
PMID: 17196398
fMRI; Masked priming; Repetition priming; Picture processing; Repetition suppression
In an uncertain environment, probabilities are key to predicting future events and making adaptive choices. However, little is known about how humans learn such probabilities and where and how they are encoded in the brain, especially when they concern more than two outcomes. During functional magnetic resonance imaging (fMRI), young adults learned the probabilities of uncertain stimuli through repetitive sampling. Stimuli represented payoffs and participants had to predict their occurrence to maximize their earnings. Choices indicated loss and risk aversion but unbiased estimation of probabilities. BOLD response in medial prefrontal cortex and angular gyri increased linearly with the probability of the currently observed stimulus, untainted by its value. Connectivity analyses during rest and task revealed that these regions belonged to the default mode network. The activation of past outcomes in memory is evoked as a possible mechanism to explain the engagement of the default mode network in probability learning. A BOLD response relating to value was detected only at decision time, mainly in striatum. It is concluded that activity in inferior parietal and medial prefrontal cortex reflects the amount of evidence accumulated in favor of competing and uncertain outcomes.
Author Summary
In order to make adaptive choices, people need to gather evidence to predict what will happen next. In general, the more frequently an event is observed, the more likely it will occur in the future. Thus the probability of an event is useful to predict its future occurrence. Previous studies have identified regions in the brain that react to rewarding or surprising events, but not to likely events. In the present study, participants had to predict payoffs by observing their repeated occurrence. Functional imaging showed that brain activity in inferior parietal and medial prefrontal cortex increased if the currently observed payoff had been seen many times before. This suggests that these two cortical regions accumulate evidence to predict future events. Further analyses revealed that they belonged to the larger default mode network. This network is involved in introspection and remembering. The inferior parietal and medial prefrontal cortex might thus support the prediction of future events by activating memories of past events.
doi:10.1371/journal.pcbi.1002895
PMCID: PMC3561043
PMID: 23401673
Stimulus repetition often leads to facilitated processing, resulting in neural decreases (repetition suppression) and faster RTs (repetition priming). Such repetition-related effects have been attributed to the facilitation of repeated cognitive processes and/or the retrieval of previously encoded stimulus–response (S-R) bindings. Although previous research has dissociated these two forms of learning, their interaction in the brain is not fully understood. Utilizing the spatial and temporal resolutions of fMRI and EEG, respectively, we examined a long-lag classification priming paradigm that required response repetitions or reversals at multiple levels of response representation. We found a repetition effect in occipital/temporal cortex (fMRI) that was time-locked to stimulus onset (EEG) and robust to switches in response, together with a repetition effect in inferior pFC (fMRI) that was time-locked to response onset (EEG) and sensitive to switches in response. The response-sensitive effect occurred even when changing from object names (words) to object pictures between repetitions, suggesting that S-R bindings can code abstract representations of stimuli. Most importantly, we found evidence for interference effects when incongruent S-R bindings were retrieved, with increased neural activity in inferior pFC, demonstrating that retrieval of S-R bindings can result in facilitation or interference, depending on the congruency of response between repetitions.
doi:10.1162/jocn_a_00163
PMCID: PMC3601413
PMID: 22066586
Objective
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.
Methods
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.
Results
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.
Conclusions
Individual tendencies to exhibit memory-load dependent oscillations are associated with negative BOLD responses certain brain regions.
Significance
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.
doi:10.1016/j.clinph.2007.07.023
PMCID: PMC2080790
PMID: 17900976
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.
doi:10.1016/j.neuroimage.2007.05.017
PMCID: PMC2093956
PMID: 17574442
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.
doi:10.3389/fnhum.2010.00030
PMCID: PMC2868300
PMID: 20463867
repetition priming; repetition suppression; synchrony; evoked power; MEG; theta; alpha; beta
Prior studies have indicated brain abnormalities underlying social processing in autism, but no fMRI study has specifically addressed the differential processing of direct and averted gaze, a critical social cue. Fifteen adolescents and adults with autism and 14 typically developing comparison participants viewed dynamic virtual-reality videos depicting a simple but realistic social scenario, in which an approaching male figure maintained either direct or averted gaze. Significant group by condition interactions reflecting differential responses to direct versus averted gaze in people with autism relative to typically developing individuals were identified in the right temporoparietal junction, right anterior insula, left lateral occipital cortex, and left dorsolateral prefrontal cortex. Our results provide initial evidence regarding brain mechanisms underlying the processing of gaze direction during simple social encounters, providing new insight into the social deficits in individuals with autism.
doi:10.1007/s10803-011-1197-x
PMCID: PMC3337548
PMID: 21484518
Autism; direct gaze; averted gaze; gaze processing; functional magnetic resonance imaging
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.
doi:10.1111/j.1469-8986.2009.00868.x
PMCID: PMC2875869
PMID: 19674398
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.
doi:10.1016/j.brainres.2007.07.060
PMCID: PMC2288660
PMID: 17889835
attention; cognitive control; advance preparation; feature biasing; conflict; Stroop
We tested for differential brain response to distinct spatial-frequency (SF) components in faces. During an fMRI experiment, participants were presented with ‘hybrid’ faces containing superimposed low and high SF information from different identities. We used a repetition paradigm where faces at either SF range were independently repeated or changed across consecutive trials. In addition, we manipulated which SF band was attended. Our results suggest that repetition and attention affected partly overlapping occipito-temporal regions but did not interact. Changes of high SF faces increased responses of the right inferior occipital gyrus (IOG) and left inferior temporal gyrus (ITG), with the latter response being also modulated additively by attention. In contrast, the bilateral middle occipital gyrus (MOG) responded to repetition and attention manipulations of low SF. A common effect of high and low SF repetition was observed in the right fusiform gyrus (FFG). Follow-up connectivity analyses suggested direct influence of the MOG (low SF), IOG and ITG (high SF) on the FFG responses. Our results reveal that different regions within occipito-temporal cortex extract distinct visual cues at different SF ranges in faces, and that the outputs from these separate processes project forward to the right FFG, where the different visual cues may converge.
doi:10.1093/cercor/bhl180
PMCID: PMC2600423
PMID: 17283203
attention; DCM; fMRI; human; occipito-temporal cortex; repetition