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1.  Lower subcortical gray matter volume in both younger smokers and established smokers relative to non-smokers 
Addiction biology  2014;21(1):185-195.
Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non-smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error-corrected clusters, P < 0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre-existing differences in these areas may predispose individuals to the development of nicotine dependence.
PMCID: PMC4326619  PMID: 25125263
Gray matter; nicotine; smoking; voxel-based morphometry
2.  Typical and atypical neurodevelopment for face specialization: An fMRI study 
Individuals with Autism Spectrum Disorder (ASD) and their relatives process faces differently from typically developed (TD) individuals. In an fMRI face-viewing task, TD and undiagnosed sibling (SIB) children (5–18 years) showed face specialization in the right amygdala and ventromedial prefrontal cortex (vmPFC), with left fusiform and right amygdala face specialization increasing with age in TD subjects. SIBs showed extensive antero-medial temporal lobe activation for faces that was not present in any other group, suggesting a potential compensatory mechanism. In ASD, face specialization was minimal but increased with age in the right fusiform and decreased with age in the left amygdala, suggesting atypical development of a frontal-amygdala-fusiform system which is strongly linked to detecting salience and processing facial information.
PMCID: PMC4442764  PMID: 25479816
Face processing; typical development; Autism Spectrum Disorder; undiagnosed siblings; fMRI
3.  Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle 
Neuroreport  2015;26(14):814-819.
Mental rotation is a visuo-spatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional magnetic resonance imaging. Ten pre-menopausal women were tested on a 3D mental rotation task during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the LF than the EF phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuo-spatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.
PMCID: PMC4549195  PMID: 26222958
menstrual cycle; estradiol; functional lateralization; fMRI
4.  Pruning or tuning? Maturational profiles of face specialization during typical development 
Brain and Behavior  2016;6(6):e00464.
Face processing undergoes significant developmental change with age. Two kinds of developmental changes in face specialization were examined in this study: specialized maturation, or the continued tuning of a region to faces but little change in the tuning to other categories; and competitive interactions, or the continued tuning to faces accompanied by decreased tuning to nonfaces (i.e., pruning).
Using fMRI, in regions where adults showed a face preference, a face‐ and object‐specialization index were computed for younger children (5–8 years), older children (9–12 years) and adults (18–45 years). The specialization index was scaled to each subject's maximum activation magnitude in each region to control for overall age differences in the activation level.
Although no regions showed significant face specialization in the younger age group, regions strongly associated with social cognition (e.g., right posterior superior temporal sulcus, right inferior orbital cortex) showed specialized maturation, in which tuning to faces increased with age but there was no pruning of nonface responses. Conversely, regions that are associated with more basic perceptual processing or motor mirroring (right middle temporal cortex, right inferior occipital cortex, right inferior frontal opercular cortex) showed competitive interactions in which tuning to faces was accompanied by pruning of object responses with age.
The overall findings suggest that cortical maturation for face processing is regional‐specific and involves both increased tuning to faces and diminished response to nonfaces. Regions that show competitive interactions likely support a more generalized function that is co‐opted for face processing with development, whereas regions that show specialized maturation increase their tuning to faces, potentially in an activity‐dependent, experience‐driven manner.
PMCID: PMC4907975  PMID: 27313976
Development; face perception; fMRI
5.  Developmental changes in analytic and holistic processes in face perception 
Frontiers in Psychology  2015;6:1165.
Although infants demonstrate sensitivity to some kinds of perceptual information in faces, many face capacities continue to develop throughout childhood. One debate is the degree to which children perceive faces analytically versus holistically and how these processes undergo developmental change. In the present study, school-aged children and adults performed a perceptual matching task with upright and inverted face and house pairs that varied in similarity of featural or 2nd order configural information. Holistic processing was operationalized as the degree of serial processing when discriminating faces and houses [i.e., increased reaction time (RT), as more features or spacing relations were shared between stimuli]. Analytical processing was operationalized as the degree of parallel processing (or no change in RT as a function of greater similarity of features or spatial relations). Adults showed the most evidence for holistic processing (most strongly for 2nd order faces) and holistic processing was weaker for inverted faces and houses. Younger children (6–8 years), in contrast, showed analytical processing across all experimental manipulations. Older children (9–11 years) showed an intermediate pattern with a trend toward holistic processing of 2nd order faces like adults, but parallel processing in other experimental conditions like younger children. These findings indicate that holistic face representations emerge around 10 years of age. In adults both 2nd order and featural information are incorporated into holistic representations, whereas older children only incorporate 2nd order information. Holistic processing was not evident in younger children. Hence, the development of holistic face representations relies on 2nd order processing initially then incorporates featural information by adulthood.
PMCID: PMC4528094  PMID: 26300838
holistic; configural; featural; similarity; face inversion; children; perceptual matching; serial; parallel
6.  Process- and Domain-Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation 
Journal of cognitive neuroscience  2012;24(12):2428-2444.
The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. The present study parametrically varied demands on featural, first-order configural or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing) or reflected generalized perceptual differentiation (i.e. differentiation that crosses category and processing type boundaries). Regions of interest were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process-specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex, and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain-specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.
PMCID: PMC4527533  PMID: 22849402
7.  Influence of neurobehavioral incentive valence and magnitude on alcohol drinking behavior 
NeuroImage  2014;104:373-385.
The monetary incentive delay (MID) task is a widely used probe for isolating neural circuitry in the human brain associated with incentive motivation. In the present functional magnetic resonance imaging (fMRI) study, 82 young adults, characterized along dimensions of impulsive sensation seeking, completed a MID task. fMRI and behavioral incentive functions were decomposed into incentive valence and magnitude parameters, which were used as predictors in linear regression to determine whether mesolimbic response is associated with problem drinking and recent alcohol use. Alcohol use was best explained by higher fMRI response to anticipation of losses and feedback on high gains in the thalamus. In contrast, problem drinking was best explained by reduced sensitivity to large incentive values in meso-limbic regions in the anticipation phase and increased sensitivity to small incentive values in the dorsal caudate nucleus in the feedback phase. Altered fMRI responses to monetary incentives in mesolimbic circuitry, particularly those alterations associated with problem drinking, may serve as potential early indicators of substance abuse trajectories.
PMCID: PMC4257498  PMID: 25261001
monetary incentive delay; fMRI; sensation seeking; impulsivity; problem drinking; alcohol use
8.  The relationship between years of cocaine use and brain activation to cocaine and response inhibition cues 
Addiction (Abingdon, England)  2014;109(12):2062-2070.
Functional Magnetic Resonance Imaging research has attempted to elucidate the neurobehavioral underpinnings of cocaine dependence by evaluating differences in brain activation to cocaine and response inhibition cues between cocaine dependent individuals and controls. Less research has investigated associations between task-related brain activation and cocaine use characteristics; the present study was designed to address this gap in the literature.
The Center for Brain Imaging at the Medical University of South Carolina.
51 cocaine users (41 dependent).
Brain activation to cocaine-cue exposure and go no-go tasks in six a priori selected brain regions of interest and cocaine use characteristics (i.e., cocaine dependence status, years of cocaine use, cocaine use in the past 90 days) assessed via standardized interviews.
Participants demonstrated elevated activation to cocaine (bilateral ventral striatum, dorsal caudate, amygdala; mean F=19.00, mean p<.001) and response inhibition (bilateral anterior cingulate, insula, inferior frontal gyrus; mean F=7.01, mean p=.02) cues in all hypothesized brain regions. Years of cocaine use was associated with task-related brain activation, with more years of cocaine use associated with greater activation to cocaine cues in right (F=7.97,p=.01) and left (F=5.47,p=.02) ventral striatum and greater activation to response inhibition cues in left insula (F=5.10,p=.03) and inferior frontal gyrus (F=4.12,p=.05) controlling for age, cocaine dependence status, and cocaine use in the past 90 days.
Years of cocaine use may be more centrally related to cocaine cue and response inhibition brain activation as compared to cocaine dependence diagnosis or amount of recent use.
PMCID: PMC4229403  PMID: 24938849
fMRI; cue; go no-go; years of use; cocaine; response inhibition
9.  The changing landscape of functional brain networks for face processing in typical development 
NeuroImage  2012;63(3):1223-1236.
Greater expertise for faces in adults than in children may be achieved by a dynamic interplay of functional segregation and integration of brain regions throughout development. The present study examined developmental changes in face network functional connectivity in children (5–12 years) and adults (18–43 years) during face-viewing using a graph-theory approach. A face-specific developmental change involved connectivity of the right occipital face area (ROFA). During childhood, this node increased in strength and within-module clustering based on positive connectivity. These changes reflect an important role of the ROFA in segregation of function during childhood. In addition, strength and diversity of connections within a module that included primary visual areas (left and right calcarine) and limbic regions (left hippocampus and right inferior orbitofrontal cortex) increased from childhood to adulthood, reflecting increased visuo-limbic integration. This integration was pronounced for faces but also emerged for natural objects. Taken together, the primary face-specific developmental changes involved segregation of a posterior visual module during childhood, possibly implicated in early stage perceptual face processing, and greater integration of visuo-limbic connections from childhood to adulthood, which may reflect processing related to development of perceptual expertise for individuation of faces and other visually homogenous categories.
PMCID: PMC3637657  PMID: 22906788
Face Processing; Development; Functional Connectivity; Social Neuroscience
10.  Too little, too late or too much, too early? Differential hemodynamics of response inhibition in high and low sensation seekers 
Brain research  2012;1481:1-12.
High sensation seeking is associated with strong approach behaviors and weak avoidance responses. The present study used functional magnetic resonance imaging (fMRI) to further characterize the neurobiological underpinnings of this behavioral profile using a Go/No-go task. Analysis of brain activation associated with response inhibition (No-go) versus response initiation and execution (Go) revealed the commonly reported right lateral prefrontal, insula, cingulate, and supplementary motor area network. However, right lateral activation was associated with greater No-go than Go responses only in low sensation seekers. High sensation seekers showed no differential activation in these regions but a more pronounced Go compared to No-go response in several other regions that are involved in salience detection (insula), motor initiation (anterior cingulate) and attention (inferior parietal cortex). Temporal analysis of the hemodynamic response for Go and No-go conditions revealed that the stronger response to Go than No-go trials in high sensation seekers occurred in in the earliest time window in the right middle frontal gyrus, right mid-cingulate and right precuneus. In contrast, the greater No-go than Go response in low sensation seekers occurred in the later time window in these same regions. These findings indicate that high sensation seekers more strongly attend to or process Go trials and show delayed or minimal inhibitory responses on No-go trials in regions that low sensation seekers use for response inhibition. Failure to engage such regions for response inhibition may underlie some of the risky and impulsive behaviors observed in high sensation seekers.
PMCID: PMC3637656  PMID: 22902769
Functional magnetic resonance imaging; cognitive control; personality
11.  Influence of estradiol on functional brain organization for working memory 
Neuroimage  2011;59(3):2923-2931.
Working memory is a cognitive function that is affected by aging and disease. To better understand the neural substrates for working memory, the present study examined the influence of estradiol on working memory using functional magnetic resonance imaging. Pre-menopausal women were tested on a verbal n-back task during the early (EF) and late follicular (LF) phases of the menstrual cycle. Although brain activation patterns were similar across the two phases, the most striking pattern that emerged was that estradiol had different associations with the two hemispheres. Increased activation in left frontal circuitry in the LF phase was associated with increased estradiol levels and decrements in working memory performance. In contrast, increased activation in right hemisphere regions in the LF phase was associated with improved task performance. The present study showed that better performance in the LF than the EF phase was associated with a pattern of reduced recruitment of the left-hemisphere and increased recruitment of the right-hemisphere in the LF compared to EF phase. We speculate that estradiol interferes with left-hemisphere working-memory processing in the LF phase, but that recruitment of the right hemisphere can compensate for left-hemisphere interference. This may be related to the proposal that estradiol can reduce cerebral asymmetries by modulating transcallosal communication (Hausmann, 2005).
PMCID: PMC3392124  PMID: 21985908
functional magnetic resonance imaging; n-back; menstrual cycle; performance; hemispheric lateralization
12.  Neural Correlates of Emotional Reactivity in Sensation Seeking 
Psychological science  2009;20(2):215-223.
High sensation seeking has been linked to increased risk for drug abuse and other negative behavioral outcomes. This study explored the neurobiological basis of this personality trait using functional magnetic resonance imaging (fMRI). High sensation seekers (HSSs) and low sensation seekers (LSSs) viewed high- and low-arousal pictures. Comparison of the groups revealed that HSSs showed stronger fMRI responses to high-arousal stimuli in brain regions associated with arousal and reinforcement (right insula, posterior medial orbitofrontal cortex), whereas LSSs showed greater activation and earlier onset of fMRI responses to high-arousal stimuli in regions involved in emotional regulation (anterior medial orbitofrontal cortex, anterior cingulate). Furthermore, fMRI response in anterior medial orbitofrontal cortex and anterior cingulate was negatively correlated with urgency. Finally, LSSs showed greater sensitivity to the valence of the stimuli than did HSSs. These distinct neurobiological profiles suggest that HSSs exhibit neural responses consistent with an overactive approach system, whereas LSSs exhibit responses consistent with a stronger inhibitory system.
PMCID: PMC3150539  PMID: 19222814
13.  Neural Correlates of Decision-Making Under Ambiguity and Conflict 
HIGHLIGHTS We use a simple gambles design in an fMRI study to compare two conditions: ambiguity and conflict.Participants were more conflict averse than ambiguity averse.Ambiguity aversion did not correlate with conflict aversion.Activation in the medial prefrontal cortex correlated with ambiguity level and ambiguity aversion.Activation in the ventral striatum correlated with conflict level and conflict aversion.
Studies of decision making under uncertainty generally focus on imprecise information about outcome probabilities (“ambiguity”). It is not clear, however, whether conflicting information about outcome probabilities affects decision making in the same manner as ambiguity does. Here we combine functional magnetic resonance imaging (fMRI) and a simple gamble design to study this question. In this design the levels of ambiguity and conflict are parametrically varied, and ambiguity and conflict gambles are matched on expected value. Behaviorally, participants avoided conflict more than ambiguity, and attitudes toward ambiguity and conflict did not correlate across participants. Neurally, regional brain activation was differentially modulated by ambiguity level and aversion to ambiguity and by conflict level and aversion to conflict. Activation in the medial prefrontal cortex was correlated with the level of ambiguity and with ambiguity aversion, whereas activation in the ventral striatum was correlated with the level of conflict and with conflict aversion. These novel results indicate that decision makers process imprecise and conflicting information differently, a finding that has important implications for basic and clinical research.
PMCID: PMC4661279  PMID: 26640434
decision making; uncertainty; ambiguity; conflict; fMRI
14.  Mid-fusiform Activation during Object Discrimination Reflects the Process of Differentiating Structural Descriptions 
Journal of cognitive neuroscience  2008;20(9):1711-1726.
The present study explored constraints on mid-fusiform activation during object discrimination. In three experiments, participants performed a matching task on simple line configurations, nameable objects, three dimensional (3-D) shapes, and colors. Significant bilateral mid-fusiform activation emerged when participants matched objects and 3-D shapes, as compared to when they matched two-dimensional (2-D) line configurations and colors, indicating that the mid-fusiform is engaged more strongly for processing structural descriptions (e.g., comparing 3-D volumetric shape) than perceptual descriptions (e.g., comparing 2-D or color information). In two of the experiments, the same mid-fusiform regions were also modulated by the degree of structural similarity between stimuli, implicating a role for the mid-fusiform in fine differentiation of similar visual object representations. Importantly, however, this process of fine differentiation occurred at the level of structural, but not perceptual, descriptions. Moreover, mid-fusiform activity was more robust when participants matched shape compared to color information using the identical stimuli, indicating that activity in the mid-fusiform gyrus is not driven by specific stimulus properties, but rather by the process of distinguishing stimuli based on shape information. Taken together, these findings further clarify the nature of object processing in the mid-fusiform gyrus. This region is engaged specifically in structural differentiation, a critical component process of object recognition and categorization.
PMCID: PMC2675283  PMID: 18345986
15.  Perceptual Specialization and Configural Face Processing in Infancy 
Adults’ face processing expertise includes sensitivity to second-order configural information (spatial relations among features, such as distance between eyes). Prior research indicates that infants process this information in female faces. In the current experiments, 9-month-olds discriminated spacing changes in upright human male and monkey faces but not in inverted faces. However, they failed to process matching changes in upright house stimuli. A similar pattern of performance was exhibited by 5-month-olds. Thus, 5- and 9-month-olds exhibited specialization by processing configural information in upright primate faces but not in houses or inverted faces. This finding suggests that, even early in life, infants treat faces in a special manner by responding to changes in configural information more readily in faces than in non-face stimuli. However, previously reported differences in infants’ processing of human versus monkey faces at 9 months of age (but not at younger ages), which have been associated with perceptual narrowing, were not evident in the current study. Thus, perceptual narrowing is not absolute in the sense of loss of the ability to process information from other species’ faces at older ages.
PMCID: PMC3796849  PMID: 23994509
16.  Perfusion Network Shift during Seizures in Medial Temporal Lobe Epilepsy 
PLoS ONE  2013;8(1):e53204.
Medial temporal lobe epilepsy (MTLE) is associated with limbic atrophy involving the hippocampus, peri-hippocampal and extra-temporal structures. While MTLE is related to static structural limbic compromise, it is unknown whether the limbic system undergoes dynamic regional perfusion network alterations during seizures. In this study, we aimed to investigate state specific (i.e. ictal versus interictal) perfusional limbic networks in patients with MTLE.
We studied clinical information and single photon emission computed tomography (SPECT) images obtained with intravenous infusion of the radioactive tracer Technetium- Tc 99 m Hexamethylpropyleneamine Oxime (Tc-99 m HMPAO) during ictal and interictal state confirmed by video-electroencephalography (VEEG) in 20 patients with unilateral MTLE (12 left and 8 right MTLE). Pair-wise voxel-based analyses were used to define global changes in tracer between states. Regional tracer uptake was calculated and state specific adjacency matrices were constructed based on regional correlation of uptake across subjects. Graph theoretical measures were applied to investigate global and regional state specific network reconfigurations.
A significant increase in tracer uptake was observed during the ictal state in the medial temporal region, cerebellum, thalamus, insula and putamen. From network analyses, we observed a relative decreased correlation between the epileptogenic temporal region and remaining cortex during the interictal state, followed by a surge of cross-correlated perfusion in epileptogenic temporal-limbic structures during a seizure, corresponding to local network integration.
These results suggest that MTLE is associated with a state specific perfusion and possibly functional organization consisting of a surge of limbic cross-correlated tracer uptake during a seizure, with a relative disconnection of the epileptogenic temporal lobe in the interictal period. This pattern of state specific shift in metabolic networks in MTLE may improve the understanding of epileptogenesis and neuropsychological impairments associated with MTLE.
PMCID: PMC3544909  PMID: 23341932
17.  Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures 
It has been hypothesised that seizure induced neuronal loss and axonal damage in medial temporal lobe epilepsy (MTLE) may lead to the development of aberrant connections between limbic structures and eventually result in the reorganisation of the limbic network. In this study, limbic structural connectivity in patients with MTLE was investigated, using diffusion tensor MRI, probabilistic tractography and graph theory based network analysis.
12 patients with unilateral MTLE and hippocampal sclerosis (five left and seven right MTLE) and 26 healthy controls were studied. The connectivity of 10 bilateral limbic regions of interest was mapped with probabilistic tractography, and the probabilistic fibre density between each pair of regions was used as the measure of their weighted structural connectivity. Binary connectivity matrices were then obtained from the weighted connectivity matrix using a range of fixed density thresholds. Graph theory based properties of nodes (degree, local efficiency, clustering coefficient and betweenness centrality) and the network (global efficiency and average clustering coefficient) were calculated from the weight and binary connectivity matrices of each subject and compared between patients and controls.
MTLE was associated with a regional reduction in fibre density compared with controls. Paradoxically, patients exhibited (1) increased limbic network clustering and (2) increased nodal efficiency, degree and clustering coefficient in the ipsilateral insula, superior temporal region and thalamus. There was also a significant reduction in clustering coefficient and efficiency of the ipsilateral hippocampus, accompanied by increased nodal degree.
These results suggest that MTLE is associated with reorganisation of the limbic system. These results corroborate the concept of MTLE as a network disease, and may contribute to the understanding of network excitability dynamics in epilepsy and MTLE.
PMCID: PMC3415309  PMID: 22764263
18.  Progressive and regressive developmental changes in neural substrates for face processing: Testing specific predictions of the Interactive Specialization account 
Developmental science  2011;14(2):227-241.
Face processing undergoes a fairly protracted developmental time course but the neural underpinnings are not well understood. Prior fMRI studies have only examined progressive changes (i.e., increases in specialization in certain regions with age), which would be predicted by both the Interactive Specialization (IS) and maturational theories of neural development. To differentiate between these accounts, the present study also examined regressive changes (i.e., decreases in specialization in certain regions with age), which is predicted by the IS but not maturational account. The fMRI results show that both progressive and regressive changes occur, consistent with IS. Progressive changes mostly occurred in occipital-fusiform and inferior frontal cortex whereas regressive changes largely emerged in parietal and lateral temporal cortices. Moreover, inconsistent with the maturational account, all of the regions involved in face viewing in adults were active in children, with some regions already specialized for face processing by 5 years of age and other regions activated in children but not specifically for faces. Thus, neurodevelopment of face processing involves dynamic interactions among brain regions including age-related increases and decreases in specialization and the involvement of different regions at different ages. These results are more consistent with IS than maturational models of neural development.
PMCID: PMC3050484  PMID: 21399706
19.  Prefrontal Cortex and Drug Abuse Vulnerability: Translation to Prevention and Treatment Interventions 
Brain research reviews  2010;65(2):124-149.
Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and primates. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences factors (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals.
PMCID: PMC3005953  PMID: 20837060
Anterior cingulate cortex; Dopamine; Drug abuse; GABA; Glutamate; Impulsivity; Lateral prefrontal cortex; Medial prefrontal cortex; Norepinephrine; Orbitofrontal cortex; Serotonin
20.  Human experience seeking correlates with hippocampus volume: convergent evidence from manual tracing and voxel-based morphometry 
Neuropsychologia  2007;45(12):2874-2881.
Experience-seekers continuously pursue novel environmental stimuli, a tendency linked to genetic variation in mesolimbic dopamine transmission. However, the neuroantomical basis accompanying these genetic and neurochemical associations is unknown. Animal and human experimental results suggest a central role for the hippocampus in processing novel stimuli. Here, we explored whether differences in human experience seeking are related to variations in hippocampal volume. High resolution anatomic MR images were analyzed in 40 individuals who ranged from low through high on a validated experience seeking personality scale. Manual tracing analysis demonstrated positive correlation between right hippocampal volumes and scores on the experience seeking scale. A separate voxel-based morphometric analysis confirmed these results and localized the significant increase to the anterior portion of right hippocampal grey matter. We tested and were able to reject the possibility that results were mediated by a personality trait related to, but distinct from, experience seeking. The present data provide the first direct evidence for a relationship between human experience seeking and brain structure. In addition, these results provide new ecologically relevant evidence for a link between right anterior hippocampus and novelty processing.
PMCID: PMC2971547  PMID: 17603086
21.  Brain responses to repeated visual experience among low and high sensation seekers: role of boredom susceptibility 
Psychiatry research  2009;173(2):100-106.
To better understand individual differences in sensation seeking and its components, including boredom susceptibility and experience seeking, we examined brain responses of high and low sensation seekers during repeated visual experience. Individuals scoring in the top and bottom quartiles from a college-aged population on the Brief Sensation-Seeking Scale (BSSS) participated in an event-related potentials (ERPs) experiment. Line drawings of common objects were randomly intermixed and presented 1–3 times. Sixty-four channel ERP responses were recorded while participants classified items as “man-made” or “not man-made” in a repetition priming task. The two groups showed different ERP responses at frontal electrode sites after seeing a visual stimulus for 400–800 ms. The frontal late positive components (LPC) showed different habituation of ERP responses to new and studied repeated objects between high and low sensation seekers. Source localization analysis (LORETA) indicated that during visual stimulus adaptation the left ventral pre-frontal cortex showed lack of frontal involvement among high sensation seekers. Furthermore, frontal LPC latencies during repeated visual exposure correlated with boredom susceptibility and experience seeking subscales. The distinct profiles of brain responses to repeated visual experience in high and low sensation seekers provide evidence that individual differences in neural adaptation can be linked to personality dimensions.
PMCID: PMC2774088  PMID: 19560906
sensation seeking; repetition effect; EEG/ERP; priming; LORETA; LPC

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