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1.  Longitudinal study of striatal activation to reward and loss anticipation from mid-adolescence into late adolescence/early adulthood 
Brain and cognition  2014;89:51-60.
Adolescent risk-taking behavior has been associated with age-related changes in striatal activation to incentives. Previous cross-sectional studies have shown both increased and decreased striatal activation to incentives for adolescents compared to adults. The monetary incentive delay (MID) task, designed to assess functional brain activation in anticipation of reward, has been used extensively to examine striatal activation in both adult and adolescent populations. The current study used this task with a longitudinal approach across mid-adolescence and late adolescence/early adulthood. Twenty-two participants (13 male) were studied using the MID task at two time-points, once in mid-adolescence (mean age = 16.11; SD = 1.44) and a second time in late adolescence/early adulthood (mean age = 20.14; SD = .67). Results revealed greater striatal activation with increased age in high- compared to low-incentive contexts (incentive magnitude), for gain as well as for loss trials (incentive valence). Results extend cross-sectional findings and show reduced striatal engagement in adolescence compared to adulthood during preparation for action in an incentive context.
doi:10.1016/j.bandc.2013.12.003
PMCID: PMC4113563  PMID: 24485273
Reward; Striatal; Longitudinal; Development; fMRI; Monetary Incentive Delay Task (MID)
2.  Social Anhedonia and Medial Prefrontal Response to Mutual Liking in Late Adolescents 
Brain and cognition  2014;89:39-50.
Anhedonia, a cardinal symptom of depression defined as difficulty experiencing pleasure, is also a possible endophenotype and prognostic factor for the development of depression. The onset of depression typically occurs during adolescence, a period in which social status and affiliation are especially salient. The medial prefrontal cortex (mPFC), a region implicated in reward, self-relevant processing, and social cognition, exhibits altered function in adults with anhedonia, but its association with adolescent anhedonia has yet to be investigated. We examined neural response to social reward in 27 late adolescents, 18–21 years old, who varied in social anhedonia. Participants reported their social anhedonia, completed ratings of photos of unfamiliar peers, and underwent a functional magnetic resonance imaging task involving feedback about being liked. Adolescents with higher social anhedonia exhibited greater mPFC activation in response to mutual liking (i.e., being liked by someone they also liked) relative to received liking (i.e., being liked by someone whom they did not like). This association held after controlling for severity of current depressive symptoms, although depressive severity was also associated with greater mPFC response. Adolescents with higher levels of social anhedonia also had stronger positive connectivity between the nucleus accumbens and the mPFC during mutual versus received liking. These results, the first on the pathophysiology of adolescent anhedonia, support altered neural reward-circuit response to social reward in young people with social anhedonia.
doi:10.1016/j.bandc.2013.12.004
PMCID: PMC4090287  PMID: 24412087
Anhedonia; Reward; Social Cognition; Adolescence; Medial Prefrontal Cortex; Depression
3.  Pubertal Status Associations with Reward and Threat Sensitivities and Subcortical Brain Volumes during Adolescence 
Brain and cognition  2014;89:15-26.
Adolescence is characterized by complex developmental processes that impact behavior, biology, and social functioning. Two such adolescence-specific processes are puberty and increases in reward sensitivity. Relations between these processes are poorly understood. The present study focused on examining unique effects of puberty, age, and sex on reward and threat sensitivities and volumes of subcortical brain structures relevant for reward/threat processing in a healthy sample of 9 to 18 year-olds. Unlike age, pubertal status had a significant unique positive relationship with reward sensitivity. In addition, there was a trend for adolescent females to exhibit higher threat sensitivity with more advanced pubertal development and higher reward and threat sensitivity with older age. Similarly, there were significant puberty by sex interaction effects on striatal volumes, i.e., left nucleus accumbens and right pallidum. The present pattern of results suggests that pubertal development, independent of chronological age, is uniquely associated with reward hypersensitivity and with structural differences in striatal regions implicated in reward processing.
doi:10.1016/j.bandc.2014.01.007
PMCID: PMC4125562  PMID: 24512818
Puberty; adolescence; reward sensitivity; behavioral approach system (BAS); behavioral inhibition system (BIS)
4.  The triadic model perspective for the study of adolescent motivated behavior 
Brain and cognition  2014;89:104-111.
The triadic neural systems model is a heuristic tool, which was developed with the goal of providing a framework for neuroscience research into motivated behaviors. Unlike dual models that highlight dynamics between approach systems centered on striatal function and control systems centered on prefrontal cortex, the triadic model also includes an avoidance system, centered on amygdala-related circuits. A first application of this model has been to account for adolescent behavior.
doi:10.1016/j.bandc.2014.01.006
PMCID: PMC4248307  PMID: 24556507
Systems model; Motivation; Regulation; Reward; Avoidance; Cognitive control striatum
5.  Developmental imaging genetics: linking dopamine function to adolescent behavior 
Brain and cognition  2013;89:27-38.
Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to noninvasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach.
doi:10.1016/j.bandc.2013.09.011
PMCID: PMC4226044  PMID: 24139694
6.  Reward feedback processing in children and adolescents: Medial frontal theta oscillations 
Brain and cognition  2013;89:79-89.
We examined event-related electroencephalography (EEG) oscillations, including event-related spectral perturbations (ERSP) and intertrial coherence (ITC), to compare feedback processing during a chance-based reward vs. non-reward task in groups of 10-12-year-old (n = 42), 13-14-year-old (n = 34) and 15-17-year-olds (n = 32). Because few, if any studies have applied these analytic methods to examine feedback processing in children or adolescents, we used a fine-grained approach that explored one half hertz by 16 ms increments during feedback (no win vs. win events) in the theta (4-8 Hz) frequency band. Complex wavelet frequency decomposition revealed that no win feedback was associated with enhanced theta power and phase coherence. We observed condition and age-based differences for both ERSP and ITC, with stronger effects for ITC. The transition from childhood to early adolescence (13-14 yrs.) was a point of increased differentiation of ITC favoring no win vs. wins feedback and also compared to children or older adolescents, a point of heightened ITC for no win feedback (quadratic effect).
doi:10.1016/j.bandc.2013.11.011
PMCID: PMC4062620  PMID: 24360036
theta oscillations; reward; adolescence; event-related spectral analysis; inter-trial phase coherence
7.  The Association between Aerobic Fitness and Language Processing in Children: Implications for Academic Achievement 
Brain and cognition  2014;87:140-152.
Event-related brain potentials (ERPs) have been instrumental for discerning the relationship between children’s aerobic fitness and aspects of cognition, yet language processing remains unexplored. ERPs linked to the processing of semantic information (the N400) and the analysis of language structure (the P600) were recorded from higher and lower aerobically fit children as they read normal sentences and those containing semantic or syntactic violations. Results revealed that higher fit children exhibited greater N400 amplitude and shorter latency across all sentence types, and a larger P600 effect for syntactic violations. Such findings suggest that higher fitness may be associated with a richer network of words and their meanings, and a greater ability to detect and/or repair syntactic errors. The current findings extend previous ERP research explicating the cognitive benefits associated with greater aerobic fitness in children and may have important implications for learning and academic performance.
doi:10.1016/j.bandc.2014.03.016
PMCID: PMC4036460  PMID: 24747513
ERP; N400; semantic processing; P600; syntactic processing
9.  A Search for the Optimal Stimulus 
Brain and cognition  1998;37(3):439-459.
How do stimulus size and item number relate to the magnitude and direction of error on center estimation and line cancellation tests? How might this relationship inform theories concerning spatial neglect? These questions were addressed by testing twenty patients with right hemisphere lesions, eleven with left hemisphere lesions and eleven normal control subjects on multiple versions of center estimation and line cancellation tests. Patients who made large errors on these tests also demonstrated an optimal or pivotal stimulus value, i.e., a particular size center estimation test or number of lines on cancellation that either minimized error magnitude relative to other size stimuli (optimal) or marked the boundary between normal and abnormal performance (pivotal). Patients with right hemisphere lesions made increasingly greater errors on the center estimation test as stimuli were both larger and smaller than the optimal value, whereas those with left hemisphere lesions made greater errors as stimuli were smaller than a pivotal value. In normal subjects, the direction of errors on center estimation stimuli shifted from the right of true center to the left as stimuli decreased in size (i.e., the crossover effect). Right hemisphere lesions exaggerated this effect, whereas left hemisphere lesions diminished and possibly reversed the direction of crossover. Error direction did not change as a function of stimulus value on cancellation tests. The demonstration of optimal and pivotal stimulus values indicates that performances on center estimation and cancellation tests in neglect are only relative to the stimuli used. In light of other studies, our findings indicate that patients with spatial neglect grossly overestimate the size of small stimuli and underestimate the size of large stimuli, that crossover represents an “apparent” shift in error direction that actually results from normally occurring errors in size perception, and that the left hemisphere is specialized for one aspect of size estimation, whereas the right performs dual roles.
doi:10.1006/brcg.1998.1007
PMCID: PMC4447308  PMID: 9733559
10.  Crossover by Line Length and Spatial Location 
Brain and cognition  2001;47(3):412-422.
It is well known that line length has a systematic influence on line bisection error in neglect. Most patients with neglect misbisect long lines on the same side of true center as their brain lesion but then cross over on short lines, misbisecting them on the opposite side (i.e., crossover by line length). What is less recognized is that the spatial location of lines relative to the viewer can similarly induce a crossover effect when one considers line bisection error scores that have been averaged across individual line lengths. Patients with right hemisphere injury and neglect classically make averaged line bisection errors that fall right of true center on lines located either at midline or to the left of the viewer; however, we observed that the averaged line bisection error can fall left of true center when lines are located to the right of the viewer (i.e., crossover by spatial location). We hypothesized that crossover by both line length and spatial location stem from systematic errors in magnitude estimation, i.e., perceived line length. We tested predictions based on this hypothesis by examining how the crossover effect by line length is altered by the spatial location of lines along a horizontal axis relative to the viewer. Participants included patients with unilateral lesions of the right and left cerebral hemispheres and age-appropriate normal subjects. All groups demonstrated a crossover effect by line length at the midline location but the effect was altered by placing lines to the right and left of the viewer. In particular, patients with right hemisphere injury and neglect crossed-over across a hroader range of line lengths when the lines were located to the right of the viewer rather than at either midline or left of the viewer. It is proposed that mental representations of stimulus magnitude are altered in neglect, in addition to mental representations of space, and that traditional accounts of neglect can be enhanced by including the psychophysical concept of magnitude estimation.
doi:10.1006/brcg.2001.1317
PMCID: PMC4442675  PMID: 11748897
hemispace; neglect; line bisection; magnitude estimation; mental representation
11.  Neural activation underlying cognitive control in the context of neutral and affectively charged pictures in children 
Brain and cognition  2012;79(3):181-187.
The neural correlates of cognitive control for typically developing nine-year-old children were examined using dense-array ERPs and estimates of cortical activation (LORETA) during a go/no-go task with two conditions: a neutral picture condition and an affectively charged picture condition. Activation was estimated for the entire cortex after which data were exported for four regions of interest (ROIs): ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulated cortex (dACC), dorsolateral prefrontal cortex (DLPFC), and orbitofrontal/ventromedial prefrontal cortex (OFC/VMPFC). Results revealed faster reaction times, greater N2 activation, and greater prefrontal activation for the affectively charged picture condition than the neutral picture condition. The findings are discussed in reference to the impact of affective stimuli on recruitment of specific brain regions involved in cognitive control.
doi:10.1016/j.bandc.2012.02.013
PMCID: PMC4418661  PMID: 22542842
cognitive control; negative emotion; children; N2; go/no-go; source analysis
12.  Criterion learning in rule-based categorization: Simulation of neural mechanism and new data 
Brain and cognition  2015;95:19-34.
In perceptual categorization, rule selection consists of selecting one or several stimulus-dimensions to be used to categorize the stimuli (e.g, categorize lines according to their length). Once a rule has been selected, criterion learning consists of defining how stimuli will be grouped using the selected dimension(s) (e.g., if the selected rule is line length, define ‘long’ and ‘short’). Very little is known about the neuroscience of criterion learning, and most existing computational models do not provide a biological mechanism for this process. In this article, we introduce a new model of rule learning called Heterosynaptic Inhibitory Criterion Learning (HICL). HICL includes a biologically-based explanation of criterion learning, and we use new category-learning data to test key aspects of the model. In HICL, rule selective cells in prefrontal cortex modulate stimulus-response associations using pre-synaptic inhibition. Criterion learning is implemented by a new type of heterosynaptic error-driven Hebbian learning at inhibitory synapses that uses feedback to drive cell activation above/below thresholds representing ionic gating mechanisms. The model is used to account for new human categorization data from two experiments showing that: (1) changing rule criterion on a given dimension is easier if irrelevant dimensions are also changing (Experiment 1), and (2) showing that changing the relevant rule dimension and learning a new criterion is more difficult, but also facilitated by a change in the irrelevant dimension (Experiment 2). We conclude with a discussion of some of HICL’s implications for future research on rule learning.
doi:10.1016/j.bandc.2015.01.009
PMCID: PMC4385499  PMID: 25682349
rule-based categorization; criterion learning; prefrontal cortex; pre-synaptic inhibition; Hebbian learning
13.  Does degree of handedness in a group of right-handed individuals affect language comprehension? 
Brain and cognition  2014;86:98-103.
The impact of handedness on language processing has been studied extensively and the results indicate that there is a relationship between the two variables; however, the nature of the relationship is not at all clear. In the current study we explored degree of handedness (DH) opposed to direction in a group of right-handed individuals. fMRI was used to explore the impact of DH on the sentence comprehension network. The results revealed that during sentence comprehension activation in regions linked to semantic memory (e.g., anterior temporal cortex) were modulated by DH. Also, unexpectedly the precuneus/posterior cingulate gyrus which has been linked to episodic memory was also affected by DH. These results extend those reported previously by showing that the neural architecture that supports sentence comprehension is modulated by DH. More specifically, together the results presented here support the hypothesis proposed by Townsend et al. (2001) that DH interacts with the language system and impacts the strategy used during sentence comprehension.
doi:10.1016/j.bandc.2014.02.002
PMCID: PMC4006107  PMID: 24607732
degree of handedness; fMRI; comprehension
14.  Change in intraindividual variability over time as a key metric for defining performance-based cognitive fatigability 
Brain and cognition  2014;85:251-258.
Cognitive fatigability is conventionally quantified as the increase over time in either mean reaction time (RT) or error rate from two or more time periods during sustained performance of a prolonged cognitive task. There is evidence indicating that these mean performance measures may not sufficiently reflect the response characteristics of cognitive fatigue. We hypothesized that changes in intraindividual variability over time would be a more sensitive and ecologically meaningful metric for investigations of fatigability of cognitive performance. To test the hypothesis fifteen young adults were recruited. Trait fatigue perceptions in various domains were assessed with the Multidimensional Fatigue Index (MFI). Behavioral data were then recorded during performance of a three-hour continuous cued Stroop task. Results showed that intraindividual variability, as quantified by the coefficient of variation of RT, increased linearly over the course of three hours and demonstrated a significantly greater effect size than mean RT or accuracy. Change in intraindividual RT variability over time was significantly correlated with relevant subscores of the MFI including reduced activity, reduced motivation and mental fatigue. While change in mean RT over time was also correlated with reduced motivation and mental fatigue, these correlations were significantly smaller than those associated with intraindividual RT variability. RT distribution analysis using an ex-Gaussian model further revealed that change in intraindividual variability over time reflects an increase in the exponential component of variance and may reflect attentional lapses or other breakdowns in cognitive control. These results suggest that intraindividual variability and its change over time provide important metrics for measuring cognitive fatigability and may prove useful for inferring the underlying neuronal mechanisms of both perceptions of fatigue and objective changes in performance.
doi:10.1016/j.bandc.2014.01.004
PMCID: PMC3980793  PMID: 24486386
Fatigability; Stroop; Fatigue; Intraindividual variability; Cognition
15.  Evidence for specificity of ERP abnormalities during response inhibition in ADHD children: A comparison with Reading Disorder children without ADHD 
Brain and cognition  2009;72(2):228-237.
Executive function and working memory deficits are not only present in ADHD, but also in Reading Disorder (RD). Here, high-density ERPs were recorded during the Stop Signal Task in 53 children and adolescents: An ADHD-combined type group, a group with RD, and a healthy control group. The ADHD-C group displayed unique abnormalities of the frontal N200. Both healthy controls and RD groups showed a success-related right frontal N200 modulation, which was absent in the ADHD group. Second, for Success Inhibition trials, the ADHD-C had smaller right frontal N200 waves relative to healthy controls, while the RD group didn't. In contrast, NoGo-P3 abnormalities were present both in the ADHD-C and RD groups. Impaired early response inhibition mechanisms, indexed by the frontal N200, appear to be limited to ADHD-C. In contrast, deficits in later cognitive control and error monitoring mechanisms, indexed by the NoGo-P3, appear to be present in both conditions.
doi:10.1016/j.bandc.2009.09.007
PMCID: PMC4321824  PMID: 19850394
ADHD; Reading Disorder; Event-Related Potentials; Stop Signal Task; Inhibitory Control; N200; NoGo-P3
16.  [No title available] 
PMCID: PMC3926098  PMID: 24355545
17.  Measuring Attention in the Hemispheres: The Lateralized Attention Network Test (LANT) 
Brain and cognition  2007;66(1):21-31.
The Attention Network Test (ANT) is a brief computerized battery measuring three independent behavioral components of attention: Conflict resolution (ability to overcome distracting stimuli), spatial Orienting (the benefit of valid spatial pre-cues), and Alerting (the benefit of temporal pre-cues). Imaging, clinical, and behavioral evidence demonstrate hemispheric asymmetries in these attentional networks. We constructed a lateralized version of the ANT (LANT), with brief targets flashed in one or the other visual hemifield. We also modified the tests by including invalid spatial cues in order to measure the cost component of Orienting. In a series of experiments, we investigated the efficiency of the attention networks separately in each hemisphere. Participants exhibited significant estimates of all networks measured by the LANT, comparable to the ANT. The three networks were represented in each hemisphere separately and were largely comparable across the two hemispheres. We suggest that the LANT is an informative extension of the original ANT, allowing for measurement of the three attention networks in each hemisphere separately.
doi:10.1016/j.bandc.2007.05.003
PMCID: PMC4283820  PMID: 17590491
attention; conflict; executive; orienting; vigilance; hemispheric specialization; hemispheric independence
18.  Neural processing of intentional biological motion in unaffected siblings of children with autism spectrum disorder: an fMRI study 
Brain and cognition  2013;83(3):10.1016/j.bandc.2013.09.007.
Despite often showing behaviorally typical levels of social cognitive ability, unaffected siblings of children with autism spectrum disorder have been found to show similar functional and morphological deficits within brain regions associated with social processing. They have also been reported to show increased activation to biological motion in these same regions, such as the posterior superior temporal sulcus (pSTS), relative to both children with autism and control children. It has been suggested that this increased activation may represent a compensatory reorganization of these regions as a result of the highly heritable genetic influence of autism. However, the response patterns of unaffected siblings in the domain of action perception are unstudied, and the phenomenon of compensatory activation has not yet been replicated. The present study used functional magnetic resonance imaging to determine the neural responses to intentional biological actions in 22 siblings of children with autism and 22 matched controls. The presented actions were either congruent or incongruent with the actor’s emotional cue. Prior studies reported that typically developing children and adults, but not children with autism, show increased activation to incongruent actions (relative to congruent), within the pSTS and dorsolateral prefrontal cortex. We report that unaffected siblings did not show a compensatory response, or a preference for incongruent over congruent trials, in any brain region. Moreover, interaction analyses revealed a sub-region of the pSTS in which control children showed an incongruency preference to a significantly greater degree than siblings, which suggests a localized deficit in siblings. A sample of children with autism also did not show differential activation in the pSTS, providing further evidence that it is an area of selective disruption in children with autism and siblings. While reduced activation to both conditions was unique to the autism sample, lack of differentiation to incongruent and congruent intentional actions was common to both children with ASD and unaffected siblings.
doi:10.1016/j.bandc.2013.09.007
PMCID: PMC3869032  PMID: 24128657
action perception; autism; endophenotype; superior temporal sulcus; fMRI
19.  Impact of negative affectively charged stimuli and response style on cognitive-control-related neural activation: An ERP study 
Brain and cognition  2013;83(2):10.1016/j.bandc.2013.07.012.
The canonical AX-CPT task measures two forms of cognitive control: sustained goal-oriented control (“proactive” control) and transient changes in cognitive control following unexpected events (“reactive” control). We modified this task by adding negative and neutral International Affective Picture System (IAPS) pictures to assess the effects of negative emotion on these two forms of cognitive control. Proactive and reactive control styles were assessed based on measures of behavior and electrophysiology, including the N2 event-related potential component and source space activation (Low Resolution Tomography [LORETA]). We found slower reaction-times and greater DLPFC activation for negative relative to neutral stimuli. Additionally, we found that a proactive style of responding was related to less prefrontal activation (interpreted to reflect increased efficiency of processing) during actively maintained previously cued information and that a reactive style of responding was related to less prefrontal activation (interpreted to reflect increased efficiency of processing) during just-in-time environmentally triggered information. This pattern of results was evident in relatively neutral contexts, but in the face of negative emotion, these associations were not found, suggesting potential response style-by-emotion interaction effects on prefrontal neural activation
doi:10.1016/j.bandc.2013.07.012
PMCID: PMC3854958  PMID: 24021156
emotion; AX-CPT; reactive control; proactive control; N2; LORETA; prefrontal neural activation
20.  Musical experts recruit action-related neural structures in harmonic anomaly detection: Evidence for embodied cognition in expertise 
Brain and cognition  2013;83(2):10.1016/j.bandc.2013.07.002.
Humans are extremely good at detecting anomalies in sensory input. For example, while listening to a piece of Western-style music, an anomalous key change or an out-of-key pitch is readily apparent, even to the non-musician. In this paper we investigate differences between musical experts and non-experts during musical anomaly detection. Specifically, we analyzed the electroencephalograms (EEG) of five expert cello players and five non-musicians while they listened to excerpts of J.S. Bach’s Prelude from Cello Suite No.1. All subjects were familiar with the piece, though experts also had extensive experience playing the piece. Subjects were told that anomalous musical events (AMEs) could occur at random within the excerpts of the piece and were told to report the number of AMEs after each excerpt. Furthermore, subjects were instructed to remain still while listening to the excerpts and their lack of movement was verified via visual and EEG monitoring. Experts had significantly better behavioral performance (i.e. correctly reporting AME counts) than non-experts, though both groups had mean accuracies greater than 80%. These group differences were also reflected in the EEG correlates of key-change detection post-stimulus, with experts showing more significant, greater magnitude, longer periods of and earlier peaks in condition-discriminating EEG activity than novices. Using the timing of the maximum discriminating neural correlates, we performed source reconstruction and compared significant differences between cellists and non-musicians. We found significant differences that included a slightly right lateralized motor and frontal source distribution. The right lateralized motor activation is consistent with the cortical representation of the left hand – i.e. the hand a cellist would use, while playing, to generate the anomalous key-changes. In general, these results suggest that sensory anomalies detected by experts may in fact be partially a result of an embodied cognition, with a model of the action for generating the anomaly playing a role in its detection.
doi:10.1016/j.bandc.2013.07.002
PMCID: PMC3877747  PMID: 24056235
electroencephalography (EEG); expertise; single-trial analysis; pattern recognition; perceptual decision-making
21.  Aberrant neural mediation of verbal fluency in Autism Spectrum Disorders 
Brain and cognition  2013;83(2):10.1016/j.bandc.2013.08.003.
Objective:
Contrasts of verbal fluency and automatic speech provide an opportunity to evaluate the neural underpinnings of generativity and flexibility in autism spectrum disorders (ASD).
Method:
We used functional magnetic resonance imaging (fMRI) to contrast brain activity in high functioning ASD (n=17, mean verbal IQ=117) and neurotypical (NT; n=20, mean verbal IQ=112) adolescent and young adult males (12-23 years). Participants responded to three word generation conditions: automatic speech (reciting months), category fluency, and letter fluency.
Results:
Our paradigm closely mirrored behavioral fluency tasks by requiring overt, free recall word generation while controlling for differences in verbal output between the groups and systematically increasing the task demand. The ASD group showed reduced neural response compared to the NT participants during fluency tasks in multiple regions of left anterior and posterior cortices, and sub-cortical structures. Six of these regions fell in corticostriatal circuits previously linked to repetitive behaviors (Langen, et al, 2011), and activity in two of them (putamen and thalamus) was negatively correlated with autism repetitive behavior symptoms in the ASD group. In addition, response in left inferior frontal gyrus was differentially modulated in the ASD, relative to the NT, group as a function of task demand.
Conclusions:
These data indicate a specific, atypical brain response in ASD to demanding generativity tasks that may have relevance to repetitive behavior symptoms in ASD as well as to difficulties generating original verbal responses.
doi:10.1016/j.bandc.2013.08.003
PMCID: PMC3829693  PMID: 24056237
autism; verbal fluency; fMRI; executive function; left inferior frontal gyrus
22.  Functional connectivity abnormalities vary by amygdala subdivision and are associated with psychiatric symptoms in unilateral temporal epilepsy 
Brain and cognition  2013;83(2):10.1016/j.bandc.2013.08.001.
The amygdala has been described as a structure affected by mesial temporal lobe epilepsy (MTLE). Indeed, it is suggested that amygdala abnormalities are related to the co-morbid depression and anxiety reported in MTLE. In this context, we investigated the relation between functional connectivity (FC) emerging from this structure in fMRI and depression and anxiety levels reported in MTLE patients. We focused on resting-state BOLD activity and evaluated whether FC differences emerge from each of three amygdala subdivisions (laterobasal, centromedial and superficial) in left and right MTLE groups, compared with healthy controls. Results revealed significant differences between patient groups and controls. Specifically, the left MTLE group showed abnormal FC for the left-sided seeds only. Furthermore, regardless of the seed, we observed more reliable differences between the right MTLE group and controls. Further analysis of these results revealed correlations between these impaired connectivities and psychiatric symptoms in both MTLE groups. Opposite relations, however, were highlighted: the more depressed or anxious the right MTLE patients, the closer their FC values approached controls; whereas the less anxious the left MTLE patients, the closer their FC values were normative. These results highlight how MTLE alter FC emerging from the limbic system. Overall, our data demonstrate that right TLE has a more maladaptive impact on emotion-related networks, in ways specific to the amygdala region, and the emotion symptom involved, than left TLE.
doi:10.1016/j.bandc.2013.08.001
PMCID: PMC3864635  PMID: 24036129
resting state functional connectivity; amygdala; depression; anxiety; epilepsy
23.  Sex differences in the IQ-white matter microstructure relationship: A DTI study 
Brain and Cognition  2014;91:71-78.
Sex differences in the relationship between general intelligence and brain structure are a topic of increasing research interest. Early studies focused mainly on gray and white matter differences using voxel-based morphometry, while more recent studies investigated neural fiber tracts using diffusion tensor imaging (DTI) to analyze the white matter microstructure. In this study we used tract-based spatial statistics (TBSS) on DTI to test how intelligence is associated with brain diffusion indices and to see whether this relationship differs between men and women. 63 Men and women divided into groups of lower and higher intelligence were selected. Whole-brain DTI scans were analyzed using TBSS calculating maps of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The results reveal that the white matter microstructure differs between individuals as a function of intelligence and sex. In men, higher intelligence was related to higher FA and lower RD in the corpus callosum. In women, in contrast, intelligence was not related to the white matter microstructure. The higher values of FA and lower values of RD suggest that intelligence is associated with higher myelination and/or a higher number of axons particularly in men. This microstructural difference in the corpus callosum may increase cognitive functioning by reducing inter-hemispheric transfer time and thus account for more efficient brain functioning in men.
doi:10.1016/j.bandc.2014.08.006
PMCID: PMC4245721  PMID: 25238623
Corpus callosum; DTI; Intelligence; Sex; TBSS
24.  Differential roles of the frontal and parietal cortices in the control of saccades 
Brain and cognition  2013;83(1):1-9.
Although externally as well as internally-guided eye movements allow us to flexibly explore the visual environment, their differential neural mechanisms remain elusive. A better understanding of these neural mechanisms will help us to understand the control of action and to elucidate the nature of cognitive deficits in certain psychiatric populations (e.g. schizophrenia) that show increased latencies in volitional but not visually-guided saccades. Both the superior precentral sulcus (sPCS) and the intraparietal sulcus (IPS) are implicated in the control of eye movements. However, it remains unknown what differential contributions the two areas make to the programming of visually-guided and internally-guided saccades. In this study we tested the hypotheses that sPCS and IPS distinctly encode internally-guided saccades and visually-guided saccades. We scanned subjects with fMRI while they generated visually-guided and internally-guided delayed saccades. We used multi-voxel pattern analysis to test whether patterns of cue related, preparatory and saccade related activation could be used to predict the direction of the planned eye movement. Results indicate that patterns in the human sPCS predicted internally-guided saccades but not visually-guided saccades in all trial periods and patterns in the IPS predicted internally-guided saccades and visually-guided saccades equally well. The results support the hypothesis that the human sPCS and IPS make distinct contributions to the control of volitional eye movements.
doi:10.1016/j.bandc.2013.06.005
PMCID: PMC3954743  PMID: 23867736
action control; fMRI; MVPA; saccades; volition
25.  Lifespan changes in working memory in fragile X premutation males 
Brain and cognition  2008;69(3):551-558.
Fragile X syndrome is the world’s most common hereditary cause of developmental delay in males and is now well characterized at the biological, brain and cognitive levels. The disorder is caused by the silencing of a single gene on the X chromosome, the FMR1 gene. The premutation (carrier) status, however, is less well documented but has an emerging literature that highlights a more subtle profile of executive cognitive deficiencies that mirror those reported in fully affected males. Rarely, however, has the issue of age-related declines in cognitive performance in premutation males been addressed. In the present study we focus specifically on the cognitive domain of working memory and its sub-components (verbal, spatial and central executive memory) and explore performance across a broad sample of premutation males aged 18–69 years matched on age and IQ to unaffected comparison males. We further tease apart the premutation status into those males with symptoms of the newly identified neurodegenerative disorder, the fragile X-associated tremor/ataxia syndrome (FXTAS) and those males currently symptom-free. Our findings indicate a specific vulnerability in premutation males on tasks that require simultaneous manipulation and storage of new information, so-called executive control of memory. Furthermore, this vulnerability appears to exist regardless of the presence of FXTAS symptoms. Males with FXTAS symptoms demonstrated a more general impairment encompassing phonological working memory in addition to central executive working memory. Among asymptomatic premutation males, we observed the novel finding of a relationship between increased CGG repeat size and impairment to central executive working memory.
doi:10.1016/j.bandc.2008.11.006
PMCID: PMC4158922  PMID: 19114290
Fragile X syndrome; Fragile X tremor and ataxia syndrome; premutation status; working memory; central executive; phonological loop; visual-spatial sketchpad; development; aging

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