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1.  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.
doi:10.1016/j.neuroimage.2012.08.021
PMCID: PMC3637657  PMID: 22906788
Face Processing; Development; Functional Connectivity; Social Neuroscience
2.  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.
doi:10.1016/j.brainres.2012.08.004
PMCID: PMC3637656  PMID: 22902769
Functional magnetic resonance imaging; cognitive control; personality
3.  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.
doi:10.1111/j.1467-9280.2009.02283.x
PMCID: PMC3150539  PMID: 19222814
4.  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.
doi:10.1162/jocn.2008.20116
PMCID: PMC2675283  PMID: 18345986
5.  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).
doi:10.1016/j.neuroimage.2011.09.067
PMCID: PMC3392124  PMID: 21985908
functional magnetic resonance imaging; n-back; menstrual cycle; performance; hemispheric lateralization
6.  Perfusion Network Shift during Seizures in Medial Temporal Lobe Epilepsy 
PLoS ONE  2013;8(1):e53204.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1371/journal.pone.0053204
PMCID: PMC3544909  PMID: 23341932
7.  Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1136/jnnp-2012-302476
PMCID: PMC3415309  PMID: 22764263
8.  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.
doi:10.1111/j.1467-7687.2010.00963.x
PMCID: PMC3050484  PMID: 21399706
9.  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.
doi:10.1016/j.brainresrev.2010.09.001
PMCID: PMC3005953  PMID: 20837060
Anterior cingulate cortex; Dopamine; Drug abuse; GABA; Glutamate; Impulsivity; Lateral prefrontal cortex; Medial prefrontal cortex; Norepinephrine; Orbitofrontal cortex; Serotonin
10.  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.
doi:10.1016/j.neuropsychologia.2007.05.009
PMCID: PMC2971547  PMID: 17603086
11.  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.
doi:10.1016/j.pscychresns.2008.09.012
PMCID: PMC2774088  PMID: 19560906
sensation seeking; repetition effect; EEG/ERP; priming; LORETA; LPC

Results 1-11 (11)