John D.E. Gabrieli

YNICL Journal 2023 Journal Article

Altered engagement of the speech motor network is associated with reduced phonological working memory in autism

• Amanda M. O'Brien
• Tyler K. Perrachione
• Lisa Wisman Weil
• Yoel Sanchez Araujo
• Kelly Halverson
• Adrianne Harris
• Irina Ostrovskaya
• Margaret Kjelgaard

Nonword repetition, a common clinical measure of phonological working memory, involves component processes of speech perception, working memory, and speech production. Autistic children often show behavioral challenges in nonword repetition, as do many individuals with communication disorders. It is unknown which subprocesses of phonological working memory are vulnerable in autistic individuals, and whether the same brain processes underlie the transdiagnostic difficulty with nonword repetition. We used functional magnetic resonance imaging (fMRI) to investigate the brain bases for nonword repetition challenges in autism. We compared activation during nonword repetition in functional brain networks subserving speech perception, working memory, and speech production between neurotypical and autistic children. Autistic children performed worse than neurotypical children on nonword repetition and had reduced activation in response to increasing phonological working memory load in the supplementary motor area. Multivoxel pattern analysis within the speech production network classified shorter vs longer nonword-repetition trials less accurately for autistic than neurotypical children. These speech production motor-specific differences were not observed in a group of children with reading disability who had similarly reduced nonword repetition behavior. These findings suggest that atypical function in speech production brain regions may contribute to nonword repetition difficulties in autism.

YNIMG Journal 2022 Journal Article

A large-scale investigation of white matter microstructural associations with reading ability

• Steven L. Meisler
• John D.E. Gabrieli

Reading involves the functioning of a widely distributed brain network, and white matter tracts are responsible for transmitting information between constituent network nodes. Several studies have analyzed fiber bundle microstructural properties to shed insights into the neural basis of reading abilities and disabilities. Findings have been inconsistent, potentially due to small sample sizes and varying methodology. To address this, we analyzed a large data set of 686 children ages 5-18 using state-of-the-art neuroimaging acquisitions and processing techniques. We searched for associations between fractional anisotropy (FA) and single-word and single-nonword reading skills in children with diverse reading abilities across multiple tracts previously thought to contribute to reading. We also looked for group differences in tract FA between typically reading children and children with reading disabilities. FA of the white matter increased with age across all participants. There were no significant correlations between overall reading abilities and tract FAs across all children, and no significant group differences in tract FA between children with and without reading disabilities. There were associations between FA and nonword reading ability in older children (ages 9 and above). Higher FA in the right superior longitudinal fasciculus (SLF) and left inferior cerebellar peduncle (ICP) correlated with better nonword reading skills. These results suggest that letter-sound correspondence skills, as measured by nonword reading, are associated with greater white matter coherence among older children in these two tracts, as indexed by higher FA.

YNICL Journal 2020 Journal Article

Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study

• Yuwen Hung
• Mai Uchida
• Schuyler L. Gaillard
• Hilary Woodworth
• Caroline Kelberman
• James Capella
• Kelly Kadlec
• Mathias Goncalves

Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.

YNICL Journal 2019 Journal Article

Disrupted left fusiform response to print in beginning kindergartners is associated with subsequent reading

• Tracy M. Centanni
• Elizabeth S. Norton
• Ola Ozernov-Palchik
• Anne Park
• Sara D. Beach
• Kelly Halverson
• Nadine Gaab
• John D.E. Gabrieli

Dyslexia is a common neurobiological disorder in which a child fails to acquire typical word reading skills despite adequate opportunity and intelligence. The visual word form area (VWFA) is a region within the left fusiform gyrus that specializes for print over the course of reading acquisition and is often hypoactivated in individuals with dyslexia. It is currently unknown whether atypicalities in this brain region are already present in kindergarten children who will subsequently develop dyslexia. Here, we measured fMRI activation in response to letters and false fonts in bilateral fusiform gyrus in children with and without risk for dyslexia (defined by family history or low scores on assessments of pre-reading skills, such as phonological awareness). We then followed these children longitudinally through the end of second grade to evaluate whether brain activation patterns in kindergarten were related to second-grade reading outcomes. Compared to typical readers who exhibited no risk factors for reading impairment in kindergarten, there was significant hypoactivation to both letters and false-fonts in the left fusiform gyrus in at-risk children who subsequently developed reading impairment, but not in at-risk children who developed typical reading skills. There were no significant differences in letter- or false-font responses in the right fusiform gyrus among the groups. The finding that hypoactivation to print in the VWFA is present in children who subsequently develop reading impairment even prior to the onset of formal reading instruction suggests that atypical responses to print play an early role in the development of reading impairments such as dyslexia.

YNIMG Journal 2019 Journal Article

Speech processing and plasticity in the right hemisphere predict variation in adult foreign language learning

• Zhenghan Qi
• Michelle Han
• Yunxin Wang
• Carlo de los Angeles
• Qi Liu
• Keri Garel
• Ee San Chen
• Susan Whitfield-Gabrieli

Foreign language learning in adulthood often takes place in classrooms where learning outcomes vary widely among students, for both initial learning and long-term retention. Despite the fundamental role of speech perception in first language acquisition, its role in foreign language learning outcomes remains unknown. Using a speech discrimination functional magnetic resonance imaging (fMRI) task and resting-state fMRI before and after an intensive, classroom-based, Mandarin Chinese course, we examined how variations in pre-training organization and pre-to-post reorganization of brain functions predicted successful language learning in male and female native English-speakers. Greater pre-training activation in right inferior frontal gyrus (IFG) to Mandarin speech was associated with better Mandarin attainment at the end of the course. After four weeks of class, learners showed overall increased activation in left IFG and left superior parietal lobule (SPL) to Mandarin speech, but in neither region was variation related to learning outcomes. Immediate attainment was associated with greater pre-to-post reduction of right IFG activation to Mandarin speech but also greater enhancement of resting-state connectivity between this region and both left IFG and left SPL. Long-term retention of Mandarin skills measured three months later was more accurately predicted by models using features of neural preparedness (pre-training activation) and neural plasticity (pre-to-post activation change) than models using behavior preparedness and plasticity features (pre-training speech discrimination accuracy and Mandarin attainment, respectively). These findings suggest that successful holistic foreign language acquisition in human adulthood requires right IFG engagement during initial learning but right IFG disengagement for long-term retention of language skills.

YNIMG Journal 2018 Journal Article

Human aging reduces the neurobehavioral influence of motivation on episodic memory

• Maiya R. Geddes
• Aaron T. Mattfeld
• Carlo de los Angeles
• Anisha Keshavan
• John D.E. Gabrieli

The neural circuitry mediating the influence of motivation on long-term declarative or episodic memory formation is delineated in young adults, but its status is unknown in healthy aging. We examined the effect of reward and punishment anticipation on intentional declarative memory formation for words using an event-related functional magnetic resonance imaging (fMRI) monetary incentive encoding task in twenty-one younger and nineteen older adults. At 24-hour memory retrieval testing, younger adults were significantly more likely to remember words associated with motivational cues than neutral cues. Motivational enhancement of memory in younger adults occurred only for recollection (“remember” responses) and not for familiarity (“familiar” responses). Older adults had overall diminished memory and did not show memory gains in association with motivational cues. Memory encoding associated with monetary rewards or punishments activated motivational (substantia nigra/ventral tegmental area) and memory-related (hippocampus) brain regions in younger, but not older, adults during the target word periods. In contrast, older and younger adults showed similar activation of these brain regions during the anticipatory motivational cue interval. In a separate monetary incentive delay task that did not require learning, we found evidence for relatively preserved striatal reward anticipation in older adults. This supports a potential dissociation between incidental and intentional motivational processes in healthy aging. The finding that motivation to obtain rewards and avoid punishments had reduced behavioral and neural influence on intentional episodic memory formation in older compared to younger adults is relevant to life-span theories of cognitive aging including the dopaminergic vulnerability hypothesis.

YNIMG Journal 2018 Journal Article

Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort

• Xavier Guell
• John D.E. Gabrieli
• Jeremy D. Schmahmann

Delineation of functional topography is critical to the evolving understanding of the cerebellum's role in a wide range of nervous system functions. We used data from the Human Connectome Project (n = 787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen's d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).

YNICL Journal 2016 Journal Article

Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain

• Aaron T. Mattfeld
• Susan Whitfield-Gabrieli
• Joseph Biederman
• Thomas Spencer
• Ariel Brown
• Ronna Fried
• John D.E. Gabrieli

Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

YNICL Journal 2015 Journal Article

Functional and structural brain correlates of risk for major depression in children with familial depression

• Xiaoqian J. Chai
• Dina Hirshfeld-Becker
• Joseph Biederman
• Mai Uchida
• Oliver Doehrmann
• Julia A. Leonard
• John Salvatore
• Tara Kenworthy

Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group) and a group of children of parents without a history of major depression (control group). Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression.

YNIMG Journal 2014 Journal Article

Development of deactivation of the default-mode network during episodic memory formation

• Xiaoqian J. Chai
• Noa Ofen
• John D.E. Gabrieli
• Susan Whitfield-Gabrieli

Task-induced deactivation of the default-mode network (DMN) has been associated in adults with successful episodic memory formation, possibly as a mechanism to focus allocation of mental resources for successful encoding of external stimuli. We investigated developmental changes of deactivation of the DMN (posterior cingulate, medial prefrontal, and bilateral lateral parietal cortices) during episodic memory formation in children, adolescents, and young adults (ages 8–24), who studied scenes during functional magnetic resonance imaging (fMRI). Recognition memory improved with age. We defined DMN regions of interest from a different sample of participants with the same age range, using resting-state fMRI. In adults, there was greater deactivation of the DMN for scenes that were later remembered than scenes that were later forgotten. In children, deactivation of the default-network did not differ reliably between scenes that were later remembered or forgotten. Adolescents exhibited a pattern of activation intermediate to that of children and adults. The hippocampal region, often considered part of the DMN, showed a functional dissociation with the rest of the DMN by exhibiting increased activation for later remembered than later forgotten scene that was similar across age groups. These findings suggest that development of memory ability from childhood through adulthood may involve increased deactivation of the neocortical DMN during learning.

YNIMG Journal 2014 Journal Article

Personality influences temporal discounting preferences: Behavioral and brain evidence

• Joshua Manning
• Trey Hedden
• Nina Wickens
• Susan Whitfield-Gabrieli
• Drazen Prelec
• John D.E. Gabrieli

Personality traits are stable predictors of many life outcomes that are associated with important decisions that involve tradeoffs over time. Therefore, a fundamental question is how tradeoffs over time vary from person to person in relation to stable personality traits. We investigated the influence of personality, as measured by the Five-Factor Model, on time preferences and on neural activity engaged by intertemporal choice. During functional magnetic resonance imaging (fMRI), participants made choices between smaller-sooner and larger-later monetary rewards. For each participant, we estimated a constant-sensitivity discount function that dissociates impatience (devaluation of future consequences) from time sensitivity (consistency with rational, exponential discounting). Overall, higher neuroticism was associated with a relatively greater preference for immediate rewards and higher conscientiousness with a relatively greater preference for delayed rewards. Specifically, higher conscientiousness correlated positively with lower short-term impatience and more exponential time preferences, whereas higher neuroticism (lower emotional stability) correlated positively with higher short-term impatience and less exponential time preferences. Cognitive-control and reward brain regions were more activated when higher conscientiousness participants selected a smaller-sooner reward and, conversely, when higher neuroticism participants selected a larger-later reward. The greater activations that occurred when choosing rewards that contradicted personality predispositions may reflect the greater recruitment of mental resources needed to override those predispositions. These findings reveal that stable personality traits fundamentally influence how rewards are chosen over time.

YNIMG Journal 2012 Journal Article

When the brain is prepared to learn: Enhancing human learning using real-time fMRI

• Julie J. Yoo
• Oliver Hinds
• Noa Ofen
• Todd W. Thompson
• Susan Whitfield-Gabrieli
• Christina Triantafyllou
• John D.E. Gabrieli

The rate of learning or memory formation varies over time for any individual, partly due to moment-to-moment fluctuation of brain state. Functional neuroimaging has revealed the neural correlates of learning and memory, but here we asked if neuroimaging can causally enhance human learning by detection of brain states that reveal when a person is prepared or not prepared to learn. The parahippocampal cortex (PHC) is essential for memory formation for scenes. Here, activation in PHC was monitored in real-time, and scene presentations were triggered when participants entered “good” or “bad” brain states for learning of novel scenes. Subsequent recognition memory was more accurate for scenes presented in “good” than “bad” brain states. These findings show that neuroimaging can identify in real-time brain states that enhance or depress learning and memory formation, and knowledge about such brain states may be useful for accelerating education and training. Further, the use of functional neuroimaging as a causal, rather than correlative, tool to study the human brain may open new insights into the neural basis of human cognition.

YNIMG Journal 2011 Journal Article

Associations and dissociations between default and self-reference networks in the human brain

• Susan Whitfield-Gabrieli
• Joseph M. Moran
• Alfonso Nieto-Castañón
• Christina Triantafyllou
• Rebecca Saxe
• John D.E. Gabrieli

Neuroimaging has revealed consistent activations in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) extending to precuneus both during explicit self-reference tasks and during rest, a period during which some form of self-reference is assumed to occur in the default mode of brain function. The similarity between these two patterns of midline cortical activation may reflect a common neural system for explicit and default-mode self-reference, but there is little direct evidence about the similarities and differences between the neural systems that mediate explicit self-reference versus default-mode self-reference during rest. In two experiments, we compared directly the brain regions activated by explicit self-reference during judgments about trait adjectives and by rest conditions relative to a semantic task without self-reference. Explicit self-reference preferentially engaged dorsal MPFC, rest preferentially engaged precuneus, and both self-reference and rest commonly engaged ventral MPFC and PCC. These findings indicate that there are both associations (shared components) and dissociations between the neural systems underlying explicit self-reference and the default mode of brain function.

YNIMG Journal 2011 Journal Article

Computing moment-to-moment BOLD activation for real-time neurofeedback

• Oliver Hinds
• Satrajit Ghosh
• Todd W. Thompson
• Julie J. Yoo
• Susan Whitfield-Gabrieli
• Christina Triantafyllou
• John D.E. Gabrieli

Estimating moment-to-moment changes in blood oxygenation level dependent (BOLD) activation levels from functional magnetic resonance imaging (fMRI) data has applications for learned regulation of regional activation, brain state monitoring, and brain–machine interfaces. In each of these contexts, accurate estimation of the BOLD signal in as little time as possible is desired. This is a challenging problem due to the low signal-to-noise ratio of fMRI data. Previous methods for real-time fMRI analysis have either sacrificed the ability to compute moment-to-moment activation changes by averaging several acquisitions into a single activation estimate or have sacrificed accuracy by failing to account for prominent sources of noise in the fMRI signal. Here we present a new method for computing the amount of activation present in a single fMRI acquisition that separates moment-to-moment changes in the fMRI signal intensity attributable to neural sources from those due to noise, resulting in a feedback signal more reflective of neural activation. This method computes an incremental general linear model fit to the fMRI time series, which is used to calculate the expected signal intensity at each new acquisition. The difference between the measured intensity and the expected intensity is scaled by the variance of the estimator in order to transform this residual difference into a statistic. Both synthetic and real data were used to validate this method and compare it to the only other published real-time fMRI method.

YNIMG Journal 2011 Journal Article

Connectivity-based segmentation of human amygdala nuclei using probabilistic tractography

• Zeynep M. Saygin
• David E. Osher
• Jean Augustinack
• Bruce Fischl
• John D.E. Gabrieli

The amygdala plays an important role in emotional and social functions, and amygdala dysfunction has been associated with multiple neuropsychiatric disorders, including autism, anxiety, and depression. Although the amygdala is composed of multiple anatomically and functionally distinct nuclei, typical structural magnetic resonance imaging (MRI) sequences are unable to discern them. Thus, functional MRI (fMRI) studies typically average the BOLD response over the entire structure, which reveals some aspects of amygdala function as a whole but does not distinguish the separate roles of specific nuclei in humans. We developed a method to segment the human amygdala into its four major nuclei using only diffusion-weighted imaging and connectivity patterns derived mainly from animal studies. We refer to this new method as Tractography-based Segmentation, or TractSeg. The segmentations derived from TractSeg were topographically similar to their corresponding amygdaloid nuclei, and were validated against a high-resolution scan in which the nucleic boundaries were visible. In addition, nuclei topography was consistent across subjects. TractSeg relies on short scan acquisitions and widely accessible software packages, making it attractive for use in healthy populations to explore normal amygdala nucleus function, as well as in clinical and pediatric populations. Finally, it paves the way for implementing this method in other anatomical regions which are also composed of functional subunits that are difficult to distinguish with standard structural MRI.

YNIMG Journal 2011 Journal Article

Face value: Amygdala response reflects the validity of first impressions

• Nicholas O. Rule
• Joseph M. Moran
• Jonathan B. Freeman
• Susan Whitfield-Gabrieli
• John D.E. Gabrieli
• Nalini Ambady

The human amygdala responds to first impressions of people as judged from their faces, such as normative judgments about the trustworthiness of strangers. It is unknown, however, whether amygdala responses to first impressions can be validated by objective criteria. Here, we examined amygdala responses to faces of Chief Executive Officers (CEOs) where real-world outcomes could be measured objectively by the amounts of profits made by each CEO's company. During fMRI scanning, participants made incidental judgments about the symmetry of each CEO's face. After scanning, participants rated each CEO's face on leadership ability. Parametric analyses showed that greater left amygdala response to the CEOs' faces was associated with higher post-scan ratings of the CEOs' leadership ability. In addition, greater left amygdala response was also associated with greater profits made by the CEOs' companies and this relationship was statistically mediated by external raters' perceptions of arousal. Thus, amygdala response reflected both subjective judgments and objective measures of leadership ability based on first impressions.

YNIMG Journal 2010 Journal Article

Evaluating the validity of volume-based and surface-based brain image registration for developmental cognitive neuroscience studies in children 4 to 11years of age

• Satrajit S. Ghosh
• Sita Kakunoori
• Jean Augustinack
• Alfonso Nieto-Castanon
• Ioulia Kovelman
• Nadine Gaab
• Joanna A. Christodoulou
• Christina Triantafyllou

Understanding the neurophysiology of human cognitive development relies on methods that enable accurate comparison of structural and functional neuroimaging data across brains from people of different ages. A fundamental question is whether the substantial brain growth and related changes in brain morphology that occur in early childhood permit valid comparisons of brain structure and function across ages. Here we investigated whether valid comparisons can be made in children from ages 4 to 11, and whether there are differences in the use of volume-based versus surface-based registration approaches for aligning structural landmarks across these ages. Regions corresponding to the calcarine sulcus, central sulcus, and Sylvian fissure in both the hemispheres were manually labeled on T1-weighted structural magnetic resonance images from 31 children ranging in age from 4. 2 to 11. 2years old. Quantitative measures of shape similarity and volumetric-overlap of these manually labeled regions were calculated when brains were aligned using a 12-parameter affine transform, SPM's nonlinear normalization, a diffeomorphic registration (ANTS), and FreeSurfer's surface-based registration. Registration error for normalization into a common reference framework across participants in this age range was lower than commonly used functional imaging resolutions. Surface-based registration provided significantly better alignment of cortical landmarks than volume-based registration. In addition, registering children's brains to a common space does not result in an age-associated bias between older and younger children, making it feasible to accurately compare structural properties and patterns of brain activation in children from ages 4 to 11.

YNIMG Journal 2010 Journal Article

Live face-to-face interaction during fMRI: A new tool for social cognitive neuroscience

• Elizabeth Redcay
• David Dodell-Feder
• Mark J. Pearrow
• Penelope L. Mavros
• Mario Kleiner
• John D.E. Gabrieli
• Rebecca Saxe

Cooperative social interaction is critical for human social development and learning. Despite the importance of social interaction, previous neuroimaging studies lack two fundamental components of everyday face-to-face interactions: contingent responding and joint attention. In the current studies, functional MRI data were collected while participants interacted with a human experimenter face-to-face via live video feed as they engaged in simple cooperative games. In Experiment 1, participants engaged in a live interaction with the experimenter (“Live”) or watched a video of the same interaction (“Recorded”). During the “Live” interaction, as compared to the Recorded conditions, greater activation was seen in brain regions involved in social cognition and reward, including the right temporoparietal junction (rTPJ), anterior cingulate cortex (ACC), right superior temporal sulcus (rSTS), ventral striatum, and amygdala. Experiment 2 isolated joint attention, a critical component of social interaction. Participants either followed the gaze of the live experimenter to a shared target of attention (“Joint Attention”) or found the target of attention alone while the experimenter was visible but not sharing attention (“Solo Attention”). The right temporoparietal junction and right posterior STS were differentially recruited during Joint, as compared to Solo, attention. These findings suggest the rpSTS and rTPJ are key regions for both social interaction and joint attention. This method of allowing online, contingent social interactions in the scanner could open up new avenues of research in social cognitive neuroscience, both in typical and atypical populations.

YNIMG Journal 2010 Journal Article

Shared and selective neural correlates of inhibition, facilitation, and shifting processes during executive control

• Trey Hedden
• John D.E. Gabrieli

A network of prefrontal and parietal regions has been implicated in executive control processes. However, the extent to which individual regions within this network are engaged in component control processes, such as inhibition of task-irrelevant stimulus attributes or shifting (switching) between attentional foci, remains controversial. Participants (N =17) underwent functional magnetic resonance imaging while performing a global–local task in which the global and local levels could facilitate or interfere with one another. Stimuli were presented in blocks in which participants either constantly shifted between the global and local levels, or consistently responded to one level only. Activations related to inhibition and shifting processes were observed in a large network of bilateral prefrontal, parietal, and basal ganglia regions. Region of interest analyses were used to classify each region within this network as being common to inhibition and shifting, or preferential to one component process. Several regions were classified as being preferential to inhibition, including regions within the dorsolateral and ventrolateral prefrontal cortex, the parietal lobes, and the temporal–parietal junction. A limited set of regions in the parietal lobes and left dorsolateral prefrontal cortex were classified as preferential to shifting. There was a very large set of regions displaying activation common to both inhibition and shifting processes, including regions within the dorsolateral prefrontal cortex, anterior cingulate, and basal ganglia. Several of these common regions were also involved during facilitation, suggesting that they are responsive to the number of task-salient channels of information, rather than purely to demands on control processes.

YNIMG Journal 2008 Journal Article

Cognitive processing speed and the structure of white matter pathways: Convergent evidence from normal variation and lesion studies

• U. Turken
• Susan Whitfield-Gabrieli
• Roland Bammer
• Juliana V. Baldo
• Nina F. Dronkers
• John D.E. Gabrieli

We investigated the relation between cognitive processing speed and structural properties of white matter pathways via convergent imaging studies in healthy and brain-injured groups. Voxel-based morphometry (VBM) was applied to diffusion tensor imaging data from thirty-nine young healthy subjects in order to investigate the relation between processing speed, as assessed with the Digit–Symbol subtest from WAIS-III, and fractional anisotropy, an index of microstructural organization of white matter. Digit–Symbol performance was positively correlated with fractional anisotropy of white matter in the parietal and temporal lobes bilaterally and in the left middle frontal gyrus. Fiber tractography indicated that these regions are consistent with the trajectories of the superior and inferior longitudinal fasciculi. In a second investigation, we assessed the effect of white matter damage on processing speed using voxel-based lesion-symptom mapping (VLSM) analysis of data from seventy-two patients with left-hemisphere strokes. Lesions in left parietal white matter, together with cortical lesions in supramarginal and angular gyri were associated with impaired performance. These findings suggest that cognitive processing speed, as assessed by the Digit–Symbol test, is closely related to the structural integrity of white matter tracts associated with parietal and temporal cortices and left middle frontal gyrus. Further, fiber tractography applied to VBM results and the patient findings suggest that the superior longitudinal fasciculus, a major tract subserving fronto-parietal integration, makes a prominent contribution to processing speed.

YNIMG Journal 2008 Journal Article

Default-mode function and task-induced deactivation have overlapping brain substrates in children

• Moriah E. Thomason
• Catherine E. Chang
• Gary H. Glover
• John D.E. Gabrieli
• Michael D. Greicius
• Ian H. Gotlib

The regions that comprise the functionally connected resting-state default-mode network (DMN) in adults appear to be the same as those that are characterized by task-induced decreases in blood-oxygen-level-dependent (BOLD) signal. Independent component analysis can be used to produce a picture of the DMN as an individual rests quietly in the scanner. Contrasts across conditions in which cognitive load is parametrically modulated can delineate neural structures that have decreases in activation in response to high-demand task conditions. Examination of the degree to which these networks subsume dissociable brain substrates, and of the degree to which they overlap, provides insight concerning their purpose, function, and the nature of their associations. Few studies have examined the DMN in children, and none have tested whether the neural regions that comprise the DMN during a resting condition are the same regions that show reduced activity when children engage in cognitive tasks. In this paper we describe regions that show both task-related decreases and spontaneous intrinsic activity at rest in children, and we examine the co-localization of these networks. We describe ways in which the DMN in 7–12-year-old children is both similar to and different from the DMN in adults; moreover, we document that task-induced deactivations and default-mode resting-state activity in children share common neural substrates. It appears, therefore, that even before adolescence a core aspect of task-induced deactivation involves reallocating processing resources that are active at rest. We describe how future studies assessing the development of these systems would benefit from examining these constructs as part of one continuous system.

YNIMG Journal 2005 Journal Article

Breath holding reveals differences in fMRI BOLD signal in children and adults

• Moriah E. Thomason
• Brittany E. Burrows
• John D.E. Gabrieli
• Gary H. Glover

Application of fMRI to studies of cognitive development is of growing interest because of its sensitivity and non-invasive nature. However, interpretation of fMRI results in children is presently based on vascular dynamics that have been studied primarily in healthy adults. Comparison of the neurological basis of cognitive development is valid to the extent that the neurovascular responsiveness between children and adults is equal. The present study was designed to detect age-related vascular differences that may contribute to altered BOLD fMRI signal responsiveness. We examined BOLD signal changes in response to breath holding, a global, systemic state change in brain oxygenation. Children exhibited greater percent signal changes than adults in grey and white matter, and this was accompanied by an increase in noise. Consequently, the volume of activation exceeding statistical threshold was reduced in children. The reduced activation in children was well modeled by adding noise to adult data. These findings raise the possibility that developmental differences in fMRI findings between children and adults could, under some circumstances, reflect greater noise in the BOLD response in the brains of children than adults. BOLD responses varied across brain regions, but showed similar regional variation in children and adults.

YNIMG Journal 2005 Journal Article

The neural bases of amusement and sadness: A comparison of block contrast and subject-specific emotion intensity regression approaches

• Philippe R. Goldin
• Cendri A.C. Hutcherson
• Kevin N. Ochsner
• Gary H. Glover
• John D.E. Gabrieli
• James J. Gross

Neuroimaging studies have made substantial progress in elucidating the neural bases of emotion. However, few studies to date have directly addressed the subject-specific, time-varying nature of emotional responding. In the present study, we employed functional magnetic resonance imaging to examine the neural bases of two common emotions–amusement and sadness–using both (a) a stimulus-based block contrast approach and (b) a subject-specific regression analysis using continuous ratings of emotional intensity. Thirteen women viewed a set of nine 2-min amusing, sad, or neutral film clips two times. During the first viewing, participants watched the film stimuli. During the second viewing, they made continuous ratings of the intensity of their own amusement and sadness during the first film viewing. For sad films, both block contrast and subject-specific regression approaches resulted in activations in medial prefrontal cortex, inferior frontal gyrus, superior temporal gyrus, precuneus, lingual gyrus, amygdala, and thalamus. For amusing films, the subject-specific regression analysis demonstrated significant activations not detected by the block contrast in medial, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior cingulate, temporal lobes, hippocampus, thalamus, and caudate. These results suggest a relationship between emotion-specific temporal dynamics and the sensitivity of different data analytic methods for identifying emotion-related neural responses. These findings shed light on the neural bases of amusement and sadness, and highlight the value of using emotional film stimuli and subject-specific continuous emotion ratings to characterize the dynamic, time-varying components of emotional responses.

YNIMG Journal 2005 Journal Article

The neural correlates of direct and reflected self-knowledge

• Kevin N. Ochsner
• Jennifer S. Beer
• Elaine R. Robertson
• Jeffrey C. Cooper
• John D.E. Gabrieli
• John F. Kihsltrom
• Mark D'Esposito

Socrates said that in order to lead a balanced life one must, “know thyself. ” In two fMRI experiments, the present study examined the mechanisms mediating two ways in which the self can be known: through direct appraisals (i. e. , an individual's own self-beliefs) and reflected appraisals (i. e. , an individual's perception of how others view him or her). Experiment 1 examined the common and distinct neural bases of direct appraisals of the self, close others, and normative judgments of trait desirability. All three judgment types activated medial prefrontal cortex (MPFC) to a similar degree. Experiment 2 examined the common and distinct neural bases of (1) direct appraisals of self, a close other or a non-close other, and (2) reflected appraisals made from the perspective of a close or a non-close other. Consistent with Experiment 1, all judgment types activated MPFC. Direct appraisals of the self as compared to others more strongly recruited MPFC and right rostrolateral PFC. Direct appraisals as compared to reflected appraisals recruited regions associated with a first-person perspective (posterior cingulate), whereas reflected as compared to direct appraisals recruited regions associated with emotion and memory (insula, orbitofrontal, and temporal cortex). These results support models suggesting that MPFC mediates meta-cognitive processes that may be recruited for direct and reflected self appraisals depending upon the demands of a specific task.

YNIMG Journal 2004 Journal Article

For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion

• Kevin N. Ochsner
• Rebecca D. Ray
• Jeffrey C. Cooper
• Elaine R. Robertson
• Sita Chopra
• John D.E. Gabrieli
• James J. Gross

Functional neuroimaging studies examining the neural bases of the cognitive control of emotion have found increased prefrontal and decreased amygdala activation for the reduction or down-regulation of negative emotion. It is unknown, however, (1) whether the same neural systems underlie the enhancement or up-regulation of emotion, and (2) whether altering the nature of the regulatory strategy alters the neural systems mediating the regulation. To address these questions using functional magnetic resonance imaging (fMRI), participants up- and down-regulated negative emotion either by focusing internally on the self-relevance of aversive scenes or by focusing externally on alternative meanings for pictured actions and their situational contexts. Results indicated (1a) that both up- and down-regulating negative emotion recruited prefrontal and anterior cingulate regions implicated in cognitive control, (1b) that amygdala activation was modulated up or down in accord with the regulatory goal, and (1c) that up-regulation uniquely recruited regions of left rostromedial PFC implicated in the retrieval of emotion knowledge, whereas down-regulation uniquely recruited regions of right lateral and orbital PFC implicated in behavioral inhibition. Results also indicated that (2) self-focused regulation recruited medial prefrontal regions implicated in internally focused processing, whereas situation-focused regulation recruited lateral prefrontal regions implicated in externally focused processing. These data suggest that both common and distinct neural systems support various forms of reappraisal and that which particular prefrontal systems modulate the amygdala in different ways depends on the regulatory goal and strategy employed.

YNIMG Journal 2001 Journal Article

Rostrolateral prefrontal cortex involvement in evaluating self-generated information

• Kalina Christoff
• Leo M.T. Geddes
• John D.E. Gabrieli

YNIMG Journal 2001 Journal Article

Rostrolateral Prefrontal Cortex Involvement in Relational Integration during Reasoning

• Kalina Christoff
• Vivek Prabhakaran
• Jennifer Dorfman
• Zuo Zhao
• James K. Kroger
• Keith J. Holyoak
• John D.E. Gabrieli

Patient and neuroimaging studies indicate that complex reasoning tasks are associated with the prefrontal cortex (PFC). In this study, we tested the hypothesis that the process of relational integration, or considering multiple relations simultaneously, is a component process of complex reasoning that selectively recruits PFC. We used fMRI to examine brain activation during 0-relational, 1-relational, and 2-relational problems adapted from the Raven's Progressive Matrices and hypothesized that PFC would be preferentially recruited by the 2-relational problem type. Event-related responses were modeled by convolving a canonical hemodynamic response function with the response time (RT) associated with each trial. The results across different analyses revealed the same pattern: PFC activation was specific to the comparison between 2- and 1-relational problems and was not observed in the comparison between 1- and 0-relational problems. Furthermore, the process of relational integration was specifically associated with bilateral rostrolateral PFC (RLPFC; lateral area 10) and right dorsolateral PFC (areas 9 and 46). Left RLPFC showed the greatest specificity by remaining preferentially recruited during 2-relational problems even after comparisons were restricted to trials matched for RT and accuracy. The link between RLPFC and the process of relational integration may be due to the associated process of manipulating self-generated information, a process that may characterize RLPFC function.

YNIMG Journal 2000 Journal Article

An fMRI study of cross modal recognition memory

• Allyson C. Rosen
• Chandan J. Vaidya
• John D.E. Gabrieli

YNIMG Journal 1999 Journal Article

Functional Specialization for Semantic and Phonological Processing in the Left Inferior Prefrontal Cortex

• Russell A. Poldrack
• Anthony D. Wagner
• Matthew W. Prull
• John E. Desmond
• Gary H. Glover
• John D.E. Gabrieli

Neuroimaging and neuropsychological studies have implicated left inferior prefrontal cortex (LIPC) in both semantic and phonological processing. In this study, functional magnetic resonance imaging was used to examine whether separate LIPC regions participate in each of these types of processing. Performance of a semantic decision task resulted in extensive LIPC activation compared to a perceptual control task. Phonological processing of words and pseudowords in a syllable-counting task resulted in activation of the dorsal aspect of the left inferior frontal gyrus near the inferior frontal sulcus (BA 44/45) compared to a perceptual control task, with greater activation for nonwords compared to words. In a direct comparison of semantic and phonological tasks, semantic processing preferentially activated the ventral aspect of the left inferior frontal gyrus (BA 47/45). A review of the literature demonstrated a similar distinction between left prefrontal regions involved in semantic processing and phonological/lexical processing. The results suggest that a distinct region in the left inferior frontal cortex is involved in semantic processing, whereas other regions may subserve phonological processes engaged during both semantic and phonological tasks.

YNIMG Journal 1999 Journal Article

Load-Dependent Roles of Frontal Brain Regions in the Maintenance of Working Memory

• Bart Rypma
• Vivek Prabhakaran
• John E. Desmond
• Gary H. Glover
• John D.E. Gabrieli

Brain imaging studies have suggested a critical role for prefrontal cortex in working memory (WM) tasks that require both maintainenance and manipulation of information over time in delayed-response WM tasks. In the present study, functional magnetic resonance imaging (fMRI) was used to examine whether prefrontal areas are activated when only maintenance is required in a delayed-response WM task, without the overt requirement to manipulate the stored information. In two scans, six subjects performed WM tasks in which, on each trial, they (1) encoded 1, 3, or 6 to-be-remembered letters, (2) maintained these letters across a 5-second unfilled delay, and (3) determined whether a single probe letter was or was not part of the memory set. Activation of left caudal inferior frontal gyrus was observed, relative to the 1-letter task, when subjects were required to maintain 3 letters in WM. When subjects were required to maintain 6 letters in WM, additional prefrontal areas, most notably middle and superior frontal gyri, were activated bilaterally. Thus, increasing the amount of to-be-maintained information, without any overt manipulation requirement, resulted in the recruitment of wide-spread frontal-lobe regions. Inferior frontal gyrus activation was left-hemisphere dominant in both the 3- and 6-letter conditions, suggesting that such activation reflected material-specific verbal processes. Activation in middle and superior frontal gyri appeared only in the 6-letter condition and was right-hemisphere dominant, suggesting that such activation reflected material-independent executive processes.

YNIMG Journal 1998 Journal Article

Dissociation of Frontal and Cerebellar Activity in a Cognitive Task: Evidence for a Distinction between Selection and Search

• John E. Desmond
• John D.E. Gabrieli
• Gary H. Glover

Human brain imaging studies have found that increases in functional activation in left-frontal cortex during cognitive tasks are often accompanied by similar increases in right-cerebellar regions. The present study used functional magnetic resonance imaging (fMRI) to investigate the distinctive contributions of these regions using a word stem completion task. Stems with many possible completions (MANY condition) were alternately presented with stems that had few possible completions (FEW condition), and subjects were asked to covertly complete each stem with a word and press a response switch for each successful completion. Prominent increases in activation in the MANY, relative to the FEW, condition were observed in the left middle frontal gyrus (Brodmann areas 9/10) and left caudate nucleus. In contrast, portions of the right-cerebellar hemisphere (posterior quadrangular lobule and superior semilunar lobule) and cerebellar vermis exhibited increases in the FEW, relative to the MANY, condition. This double dissociation suggests that the frontal and cerebellar regions make distinctive contributions to cognitive performance, with left-frontal (and striatal) activations reflecting response selection, which increases in difficulty when there are many appropriate responses, and right-cerebellar activation reflecting the search for responses, which increases in difficulty when even a single appropriate response is hard to retrieve.