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1.  Neurovascular coupling in normal aging: A combined optical, ERP and fMRI study 
NeuroImage  2013;85(0 1):10.1016/j.neuroimage.2013.04.113.
Brain aging is characterized by changes in both hemodynamic and neuronal responses, which may be influenced by the cardiorespiratory fitness of the individual. To investigate the relationship between neuronal and hemodynamic changes, we studied the brain activity elicited by visual stimulation (checkerboard reversals at different frequencies) in younger adults and in older adults varying in physical fitness. Four functional brain measures were used to compare neuronal and hemodynamic responses obtained from BA17: two reflecting neuronal activity (the event-related optical signal, EROS, and the C1 response of the ERP), and two reflecting functional hemodynamic changes (functional magnetic resonance imaging, fMRI, and near-infrared spectroscopy, NIRS). The results indicated that both younger and older adults exhibited a quadratic relationship between neuronal and hemodynamic effects, with reduced increases of the hemodynamic response at high levels of neuronal activity. Although older adults showed reduced activation, similar neurovascular coupling functions were observed in the two age groups when fMRI and deoxy-hemoglobin measures were used. However, the coupling between oxy-and deoxy-hemoglobin changes decreased with age and increased with increasing fitness. These data indicate that departures from linearity in neurovascular coupling may be present when using hemodynamic measures to study neuronal function.
PMCID: PMC3791333  PMID: 23664952
Neurovascular coupling; aging; fitness; Event-related optical signal (EROS); Near-infrared spectroscopy (NIRS); Functional magnetic resonance imaging (fMRI); Event-related brain potentials (ERPs)
2.  The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one-year exercise intervention 
Human brain mapping  2012;34(11):2972-2985.
Cerebral white matter degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to white matter integrity in the context of a one-year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training-induced changes in white matter integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group-level change in white matter integrity, executive function, or short-term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in white matter integrity in the frontal and temporal lobes, and greater improvement in short-term memory. Increases in white matter integrity, however, were not associated with short-term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training-induced aerobic fitness, white matter integrity, and cognition among healthy older adults.
PMCID: PMC4096122  PMID: 22674729
Diffusion tensor imaging; Anisotropy; Cerebrum; Cognition; Physical fitness; Aging
3.  Local mechanical properties of white matter structures in the human brain 
NeuroImage  2013;79:145-152.
The noninvasive measurement of the mechanical properties of brain tissue using magnetic resonance elastography (MRE) has emerged as a promising method for investigating neurological disorders. To date, brain MRE investigations have been limited to reporting global mechanical properties, though quantification of the stiffness of specific structures in the white matter architecture may be valuable in assessing the localized effects of disease. This paper reports the mechanical properties of the corpus callosum and corona radiata measured in healthy volunteers using MRE and atlas-based segmentation. Both structures were found to be significantly stiffer than overall white matter, with the corpus callosum exhibiting greater stiffness and less viscous damping than the corona radiata. Reliability of both local and global measures was assessed through repeated experiments, and the coefficient of variation for each measure was less than 10%. Mechanical properties within the corpus callosum and corona radiata demonstrated correlations with measures from diffusion tensor imaging pertaining to axonal microstructure.
PMCID: PMC3676712  PMID: 23644001
elastography; brain; white matter; corpus callosum; microstructure
4.  An In Vivo Three-Dimensional Magnetic Resonance Imaging-Based Averaged Brain Collection of the Neonatal Piglet (Sus scrofa) 
PLoS ONE  2014;9(9):e107650.
Due to the fact that morphology and perinatal growth of the piglet brain is similar to humans, use of the piglet as a translational animal model for neurodevelopmental studies is increasing. Magnetic resonance imaging (MRI) can be a powerful tool to study neurodevelopment in piglets, but many of the MRI resources have been produced for adult humans. Here, we present an average in vivo MRI-based atlas specific for the 4-week-old piglet. In addition, we have developed probabilistic tissue classification maps. These tools can be used with brain mapping software packages (e.g. SPM and FSL) to aid in voxel-based morphometry and image analysis techniques. The atlas enables efficient study of neurodevelopment in a highly tractable translational animal with brain growth and development similar to humans.
PMCID: PMC4177841  PMID: 25254955
5.  Magnetic Resonance Elastography of the Brain using Multi-Shot Spiral Readouts with Self-Navigated Motion Correction 
MRE has been introduced in clinical practice as a possible surrogate for mechanical palpation, but its application to study the human brain in vivo has been limited by low spatial resolution and the complexity of the inverse problem associated with biomechanical property estimation. Here, we report significant improvements in brain MRE data acquisition by reporting images with high spatial resolution and signal-to-noise ratio as quantified by octahedral shear strain metrics. Specifically, we have developed a sequence for brain MRE based on multi-shot, variable-density spiral imaging and three-dimensional displacement acquisition, and implemented a correction scheme for any resulting phase errors. A Rayleigh damped model of brain tissue mechanics was adopted to represent the parenchyma, and was integrated via a finite element-based iterative inversion algorithm. A multi-resolution phantom study demonstrates the need for obtaining high-resolution MRE data when estimating focal mechanical properties. Measurements on three healthy volunteers demonstrate satisfactory resolution of grey and white matter, and mechanical heterogeneities correspond well with white matter histoarchitecture. Together, these advances enable MRE scans that result in high-fidelity, spatially-resolved estimates of in vivo brain tissue mechanical properties, improving upon lower resolution MRE brain studies which only report volume averaged stiffness values.
PMCID: PMC3529970  PMID: 23001771
magnetic resonance elastography; brain; high-resolution; multi-shot; spiral; phase error; Rayleigh damping
6.  Including Spatial Information in Nonlinear Inversion MR Elastography Using Soft Prior Regularization 
IEEE transactions on medical imaging  2013;32(10):1901-1909.
Tissue displacements required for mechanical property reconstruction in magnetic resonance elastography (MRE) are acquired in a magnetic resonance imaging (MRI) scanner, therefore, anatomical information is available from other imaging sequences. Despite its availability, few attempts to incorporate prior spatial information in the MRE reconstruction process have been reported. This paper implements and evaluates soft prior regularization (SPR), through which homogeneity in predefined spatial regions is enforced by a penalty term in a nonlinear inversion strategy. Phantom experiments and simulations show that when predefined regions are spatially accurate, recovered property values are stable for SPR weighting factors spanning several orders of magnitude, whereas inaccurate segmentation results in bias in the reconstructed properties that can be mitigated through proper choice of regularization weighting. The method was evaluated in vivo by estimating viscoelastic mechanical properties of frontal lobe gray and white matter for five repeated scans of a healthy volunteer. Segmentations of each tissue type were generated using automated software, and statistically significant differences between frontal lobe gray and white matter were found for both the storage modulus and loss modulus (p < 10−6). Provided homogeneous property assumptions are reasonable, SPR produces accurate quantitative property estimates for tissue structures which are finer than the resolution currently achievable with fully distributed MRE.
PMCID: PMC4107367  PMID: 23797239
Brain; magnetic resonance elastography (MRE); nonlinear inversion; soft prior
7.  More IMPATIENT: A Gridding-Accelerated Toeplitz-based Strategy for Non-Cartesian High-Resolution 3D MRI on GPUs 
Journal of parallel and distributed computing  2013;73(5):10.1016/j.jpdc.2013.01.001.
Several recent methods have been proposed to obtain significant speed-ups in MRI image reconstruction by leveraging the computational power of GPUs. Previously, we implemented a GPU-based image reconstruction technique called the Illinois Massively Parallel Acquisition Toolkit for Image reconstruction with ENhanced Throughput in MRI (IMPATIENT MRI) for reconstructing data collected along arbitrary 3D trajectories. In this paper, we improve IMPATIENT by removing computational bottlenecks by using a gridding approach to accelerate the computation of various data structures needed by the previous routine. Further, we enhance the routine with capabilities for off-resonance correction and multi-sensor parallel imaging reconstruction. Through implementation of optimized gridding into our iterative reconstruction scheme, speed-ups of more than a factor of 200 are provided in the improved GPU implementation compared to the previous accelerated GPU code.
PMCID: PMC3652469  PMID: 23682203
MRI; non-Cartesian; GPU; CUDA; gridding; Toeplitz
8.  Emotion disrupts neural activity during selective attention in psychopathy 
Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes.
PMCID: PMC3594718  PMID: 22210673
psychopathy; fearless-dominance; impulsive-antisociality; emotional distraction; fMRI
9.  Culture-related differences in default network activity during visuo-spatial judgments 
Studies on culture-related differences in cognition have shown that Westerners attend more to object-related information, whereas East Asians attend more to contextual information. Neural correlates of these different culture-related visual processing styles have been reported in the ventral-visual and fronto-parietal regions. We conducted an fMRI study of East Asians and Westerners on a visuospatial judgment task that involved relative, contextual judgments, which are typically more challenging for Westerners. Participants judged the relative distances between a dot and a line in visual stimuli during task blocks and alternated finger presses during control blocks. Behaviorally, East Asians responded faster than Westerners, reflecting greater ease of the task for East Asians. In response to the greater task difficulty, Westerners showed greater neural engagement compared to East Asians in frontal, parietal, and occipital areas. Moreover, Westerners also showed greater suppression of the default network—a brain network that is suppressed under condition of high cognitive challenge. This study demonstrates for the first time that cultural differences in visual attention during a cognitive task are manifested both by differences in activation in fronto-parietal regions as well as suppression in default regions.
PMCID: PMC3575716  PMID: 22114080
culture; default network; fMRI; visuo-spatial processing
10.  Cardiorespiratory fitness mediates the effects of aging on cerebral blood flow 
The brain's vasculature is likely to be subjected to the same age-related physiological and anatomical changes affecting the rest of the cardiovascular system. Since aerobic fitness is known to alleviate both cognitive and volumetric losses in the brain, it is important to investigate some of the possible mechanisms underlying these beneficial changes. Here we investigated the role that estimated cardiorespiratory fitness (eCRF) plays in determining the relationship between aging and cerebral blood flow (CBF) in a group of older adults (ages 55–85). Using arterial spin labeling to quantify CBF, we found that blood flow in the gray matter was positively correlated with eCRF and negatively correlated with age. Subsequent analyses revealed that eCRF fully mediated the effects of age on CBF in the gray matter, but not in the white matter. Additionally, regional measures of CBF were related to regional measures of brain volume. These findings provide evidence that age-related effects on cerebrovascular health and perfusion in older adults are largely influenced by their eCRF levels.
PMCID: PMC3985032  PMID: 24778617
cardiorespiratory fitness; aging; arterial spin labeling; cerebral blood flow; vascular health; perfusion
11.  Investigation and validation of intersite fMRI studies using the same imaging hardware 
To provide a between site comparison of functional MRI (fMRI) signal reproducibility in two laboratories equipped with identical imaging hardware and software. Many studies have looked at within subject reliability and more recent efforts have begun to calibrate responses across sites, magnetic field strengths, and software. By comparing identical imaging hardware and software, we provide a benchmark for future multi-site comparisons.
Materials and Methods
We evaluated system compatibility based on noise and stability properties of phantom scans and contrast estimates from repeated runs of a blocked motor and visual task on the same four subjects at both sites.
ANOVA and ROI analysis confirmed that site did not play a significant role in explaining variance in our large fMRI data set. Effect size analysis shows that between-subject differences account for nearly ten times more variance than site effects.
We show that quantitative comparisons of contrast estimates derived from cognitive experiments can reliably be compared across two sites. This allows us to establish an effective platform for comparing group differences between two sites using fMRI when group effects are potentially confounded with site, as in the study of neurocultural differences between countries or multi-center clinical trials.
PMCID: PMC2785504  PMID: 18581342
functional MRI; reproducibility; intersite comparisons; effect size; cultural neuroscience
12.  Anxiety type modulates immediate versus delayed engagement of attention-related brain regions 
Brain and Behavior  2013;3(5):532-551.
Background Habituation of the fear response, critical for the treatment of anxiety, is inconsistently observed during exposure to threatening stimuli. One potential explanation for this inconsistency is differential attentional engagement with negatively valenced stimuli as a function of anxiety type. Methods The present study tested this hypothesis by examining patterns of neural habituation associated with anxious arousal, characterized by panic symptoms and immediate engagement with negatively valenced stimuli, versus anxious apprehension, characterized by engagement in worry to distract from negatively valenced stimuli. Results As predicted, the two anxiety types evidenced distinct patterns of attentional engagement. Anxious arousal was associated with immediate activation in attention-related brain regions that habituated over time, whereas anxious apprehension was associated with delayed activation in attention-related brain regions that occurred only after habituation in a worry-related brain region. Conclusions Results further elucidate mechanisms involved in attention to negatively valenced stimuli and indicate that anxiety is a heterogeneous construct with regard to attention to such stimuli.
PMCID: PMC3869982  PMID: 24392275
Anxiety; anxious apprehension; anxious arousal; attention; fMRI; habituation; negative valence
13.  Trait motivation moderates neural activation associated with goal pursuit 
Research has indicated that regions of left and right dorsolateral prefrontal cortex (DLPFC) are involved in integrating the motivational and executive function processes related to, respectively, approach and avoidance goals. Given that sensitivity to pleasant and unpleasant stimuli is an important feature of conceptualizations of approach and avoidance motivation, it is possible that these regions of DLPFC are preferentially activated by valenced stimuli. The present study tested this hypothesis by using a task in which goal pursuit was threatened by distraction from valenced stimuli while functional magnetic resonance imaging data were collected. The analyses examined whether the impact of trait approach and avoidance motivation on the neural processes associated with executive function differed depending on the valence or arousal level of the distractor stimuli. The present findings support the hypothesis that the regions of DLPFC under investigation are involved in integrating motivational and executive function processes, and they also indicate the involvement of a number of other brain areas in maintaining goal pursuit. However, DLPFC did not display differential sensitivity to valence.
PMCID: PMC3345955  PMID: 22460723
Approach and avoidance motivation; Dorsolateral prefrontal cortex; Emotion; Goal pursuit; Cognitive control; Amygdala; Basal ganglia
14.  Span, CRUNCH, and Beyond: Working Memory Capacity and the Aging Brain 
Journal of cognitive neuroscience  2010;22(4):655-669.
Neuroimaging data emphasize that older adults often show greater extent of brain activation than younger adults for similar objective levels of difficulty. A possible interpretation of this finding is that older adults need to recruit neuronal resources at lower loads than younger adults, leaving no resources for higher loads, and thus leading to performance decrements [Compensation-Related Utilization of Neural Circuits Hypothesis; e.g., Reuter-Lorenz, P. A., & Cappell, K. A. Neurocognitive aging and the compensation hypothesis. Current Directions in Psychological Science, 17, 177–182, 2008]. The Compensation-Related Utilization of Neural Circuits Hypothesis leads to the prediction that activation differences between younger and older adults should disappear when task difficulty is made subjectively comparable. In a Sternberg memory search task, this can be achieved by assessing brain activity as a function of load relative to the individual’s memory span, which declines with age. Specifically, we hypothesized a nonlinear relationship between load and both performance and brain activity and predicted that asymptotes in the brain activation function should correlate with performance asymptotes (corresponding to working memory span). The results suggest that age differences in brain activation can be largely attributed to individual variations in working memory span. Interestingly, the brain activation data show a sigmoid relationship with load. Results are discussed in terms of Cowan’s [Cowan, N. The magical number 4 in short-term memory: A reconsideration of mental storage capacity. Behavioral and Brain Sciences, 24, 87–114, 2001] model of working memory and theories of impaired inhibitory processes in aging.
PMCID: PMC3666347  PMID: 19320550
15.  Localized Blood Flow Imaging Using Quantitative FENSI 
Magnetic Resonance in Medicine  2011;67(3):660-668.
FENSI was previously introduced as a novel functional imaging method for measuring changes in localized blood flow in response to a stimulus. However, FENSI was limited to a qualitative functional MRI tool, due to magnetization transfer (MT) effects and different tagging plane profiles between tag and control images. In this work, a revised FENSI acquisition is proposed to enable quantitative imaging, which is capable of providing absolute localized blood flow maps free from MT and slice profile errors. The feasibility and accuracy of measuring microvascular (arteriole, capillary, venule) blood flow by using quantitative FENSI was validated by our phantom studies. Additionally, localized cerebral blood flow, 366±45 μL/min/cm2 in gray matter and 153±23 μL/min/cm2 in white matter, was measured in healthy subjects during resting state, while a flow change of 73±13% was detected during a visual task.
PMCID: PMC3184373  PMID: 21713979
FENSI; perfusion; localized blood flow; blood flux; magnetization transfer
16.  Cortical organization of inhibition-related functions and modulation by psychopathology 
Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.
PMCID: PMC3680711  PMID: 23781192
inhibition; anxiety; depression; DLPFC; attentional control
17.  Pseudo-Continuous Transfer Insensitive Labeling Technique 
Transfer insensitive labeling technique (TILT) was previously applied to acquire multi-slice cerebral blood flow (CBF) maps as a pulsed arterial spin labeling (PASL) method. The magnetization transfer (MT) effect with TILT is well controlled by using concatenated radiofrequency pulses. However, use of TILT has been limited by several challenges, including slice profile errors, sensitivity to arterial transit time and intrinsic low signal-to-noise ratio (SNR). In this work, we propose to address these challenges by making the original TILT method into a novel pseudo-continuous ASL approach, named pseudo-continuous transfer insensitive labeling technique (pTILT). pTILT improves perfusion acquisitions by 1) realizing pseudo-continuous tagging with non-adiabatic pulses, 2) being sensitive to slow flows in addition to fast flows, and 3) providing flexible labeling geometries. Perfusion maps during both resting state and functional tasks are successfully demonstrated in healthy volunteers with pTILT. A comparison with typical SNR values from other perfusion techniques shows that although pTILT provides less SNR than inversion-based pseudo-continuous ASL techniques, the modified sequence provides similar SNR to inversion-based PASL techniques.
PMCID: PMC3137722  PMID: 21381103
arterial spin labeling; pseudo-continuous ASL; transfer insensitive labeling technique; pseudo-continuous TILT
18.  Sustained happiness? Lack of repetition suppression in right-ventral visual cortex for happy faces 
Emotional stimuli have been shown to preferentially engage initial attention but their sustained effects on neural processing remain largely unknown. The present study evaluated whether emotional faces engage sustained neural processing by examining the attenuation of neural repetition suppression to repeated emotional faces. Repetition suppression of neural function refers to the general reduction of neural activity when processing a repeated stimulus. Preferential processing of emotional face stimuli, however, should elicit sustained neural processing such that repetition suppression to repeated emotional faces is attenuated relative to faces with no emotional content. We measured the reduction of functional magnetic resonance imaging signals associated with immediate repetition of neutral, angry and happy faces. Whereas neutral faces elicited the greatest suppression in ventral visual cortex, followed by angry faces, repetition suppression was the most attenuated for happy faces. Indeed, happy faces showed almost no repetition suppression in part of the right-inferior occipital and fusiform gyri, which play an important role in face-identity processing. Our findings suggest that happy faces are associated with sustained visual encoding of face identity and thereby assist in the formation of more elaborate representations of the faces, congruent with findings in the behavioral literature.
PMCID: PMC3150853  PMID: 20584720
emotion; faces; repetition suppression; sustained processing; ventral visual cortex
19.  Neural Mechanisms of Attentional Control Differentiate Trait and State Negative Affect 
The present research examined the hypothesis that cognitive processes are modulated differentially by trait and state negative affect (NA). Brain activation associated with trait and state NA was measured by fMRI during an attentional control task, the emotion-word Stroop. Performance on the task was disrupted only by state NA. Trait NA was associated with reduced activity in several regions, including a prefrontal area that has been shown to be involved in top-down, goal-directed attentional control. In contrast, state NA was associated with increased activity in several regions, including a prefrontal region that has been shown to be involved in stimulus-driven aspects of attentional control. Results suggest that NA has a significant impact on cognition, and that state and trait NA disrupt attentional control in distinct ways.
PMCID: PMC3424055  PMID: 22934089
negative affect; attentional control; prefrontal cortex; emotion; fMRI
20.  Brain Structure in Young and Old East Asians and Westerners: Comparisons of Structural Volume and Cortical Thickness 
Journal of Cognitive Neuroscience  2010;23(5):1065-1079.
There is an emergent literature suggesting that East Asians and Westerners differ in cognitive processes because of cultural biases to process information holistically (East Asians) or analytically (Westerners). To evaluate the possibility that such differences are accompanied by differences in brain structure, we conducted a large comparative study on cognitively matched young and old adults from two cultural/ethnic groups—Chinese Singaporeans and non-Asian Americans—that involved a total of 140 persons. Young predominantly White American adults were found to have higher cortical thickness in frontal, parietal, and medial-temporal polymodal association areas in both hemispheres. These findings were replicated using voxel-based morphometry applied to the same data set. Differences in cortical thickness observed between young volunteers were not significant in older subjects as a whole. However, group differences were evident when high-performing old were compared. Although the observed differences in gray matter may be rooted in strategic differences in cognition arising from ethnic/cultural differences, alternative explanations involving genetic heritage and environmental factors are also considered.
PMCID: PMC3361742  PMID: 20433238
21.  Trait Approach and Avoidance Motivation: Lateralized Neural Activity Associated with Executive Function 
NeuroImage  2010;54(1):661-670.
Motivation and executive function are both necessary for the completion of goal-directed behavior. Research investigating the manner in which these processes interact is beginning to emerge and has implicated middle frontal gyrus (MFG) as a site of interaction for relevant neural mechanisms. However, this research has focused on state motivation, and it has not examined functional lateralization. The present study examined the impact of trait levels of approach and avoidance motivation on neural processes associated with executive function. Functional magnetic resonance imaging was conducted while participants performed a color-word Stroop task. Analyses identified brain regions in which trait approach and avoidance motivation (measured by questionnaires) moderated activation associated with executive control. Approach was hypothesized to be associated with left-lateralized MFG activation, whereas avoidance was hypothesized to be associated with right-lateralized MFG activation. Results supported both hypotheses. Present findings implicate areas of middle frontal gyrus in top-down control to guide behavior in accordance with motivational goals.
PMCID: PMC2962704  PMID: 20728552
Approach; Avoidance; Motivation; Executive Function; Laterality; fMRI
22.  Beyond vascularization: aerobic fitness is associated with N-acetylaspartate and working memory 
Brain and Behavior  2012;2(1):32-41.
Aerobic exercise is a promising form of prevention for cognitive decline; however, little is known about the molecular mechanisms by which exercise and fitness impacts the human brain. Several studies have postulated that increased regional brain volume and function are associated with aerobic fitness because of increased vascularization rather than increased neural tissue per se. We tested this position by examining the relationship between cardiorespiratory fitness and N-acetylaspartate (NAA) levels in the right frontal cortex using magnetic resonance spectroscopy. NAA is a nervous system specific metabolite found predominantly in cell bodies of neurons. We reasoned that if aerobic fitness was predominantly influencing the vasculature of the brain, then NAA levels should not vary as a function of aerobic fitness. However, if aerobic fitness influences the number or viability of neurons, then higher aerobic fitness levels might be associated with greater concentrations of NAA. We examined NAA levels, aerobic fitness, and cognitive performance in 137 older adults without cognitive impairment. Consistent with the latter hypothesis, we found that higher aerobic fitness levels offset an age-related decline in NAA. Furthermore, NAA mediated an association between fitness and backward digit span performance, suggesting that neuronal viability as measured by NAA is important in understanding fitness-related cognitive enhancement. Since NAA is found exclusively in neural tissue, our results indicate that the effect of fitness on the human brain extends beyond vascularization; aerobic fitness is associated with neuronal viability in the frontal cortex of older adults.
PMCID: PMC3343297  PMID: 22574272
Aging; brain; exercise; fitness; human; N-acetylaspartate; working memory
23.  Culture differences in neural processing of faces and houses in the ventral visual cortex 
Behavioral and eye-tracking studies on cultural differences have found that while Westerners have a bias for analytic processing and attend more to face features, East Asians are more holistic and attend more to contextual scenes. In this neuroimaging study, we hypothesized that these culturally different visual processing styles would be associated with cultural differences in the selective activity of the fusiform regions for faces, and the parahippocampal and lingual regions for contextual stimuli. East Asians and Westerners passively viewed face and house stimuli during an functional magnetic resonance imaging experiment. As expected, we observed more selectivity for faces in Westerners in the left fusiform face area (FFA) reflecting a more analytic processing style. Additionally, Westerners showed bilateral activity to faces in the FFA whereas East Asians showed more right lateralization. In contrast, no cultural differences were detected in the parahippocampal place area (PPA), although there was a trend for East Asians to show greater house selectivity than Westerners in the lingual landmark area, consistent with more holistic processing in East Asians. These findings demonstrate group biases in Westerners and East Asians that operate on perceptual processing in the brain and are consistent with previous eye-tracking data that show cultural biases to faces.
PMCID: PMC2894673  PMID: 20558408
ventral-visual; selectivity; culture; faces; houses
24.  The Impact of Increased Relational Encoding Demands on Frontal and Hippocampal Function in Older Adults 
In the present study, we manipulated the cognitive effort in an associative encoding task using fMRI. Older and younger adults were presented with two objects that were either semantically related or unrelated, and were required to form a relationship between the items. Both groups self-reported greater difficulty in completing the unrelated associative encoding task providing independent evidence of the associative difficulty manipulation. On both the low and high difficulty tasks, older adults showed a typical pattern of increased right inferior frontal recruitment relative to younger adults. Of particular interest was the finding that both groups showed increased activation as task difficulty increased in the left inferior frontal and left hippocampus. Overall, the results suggest that the aging brain is characterized by greater prefrontal processing, but that as cognitive demand increases, the networks used by older and younger adults are the largely the same.
PMCID: PMC2826535  PMID: 19709652
Aging; Relational Memory; Prefrontal Cortex; Hippocampus; Encoding
25.  Effects of Adult Attachment and Emotional Distractors on Brain Mechanisms of Cognitive Control 
Psychological science  2010;21(12):1818-1826.
Using data from 34 participants who completed an emotion-word Stroop task during functional magnetic resonance imaging, we examined the effects of adult attachment on neural activity associated with top-down cognitive control in the presence of emotional distractors. Individuals with lower levels of secure-base-script knowledge—reflected in an adult’s inability to generate narratives in which attachment-related threats are recognized, competent help is provided, and the problem is resolved—demonstrated more activity in prefrontal cortical regions associated with emotion regulation (e.g., right orbitofrontal cortex) and with top-down cognitive control (left dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus). Less efficient performance and related increases in brain activity suggest that insecure attachment involves a vulnerability to distraction by attachment-relevant emotional information and that greater cognitive control is required to attend to task-relevant, nonemotional information. These results contribute to the understanding of mechanisms through which attachment-related experiences may influence developmental adaptation.
PMCID: PMC3056541  PMID: 21098213
attachment; secure-base-script knowledge; cognitive control; emotion regulation; Stroop; fMRI

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