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Open Access Publications from the University of California

Scholarly Works (13 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2024)

Cognitive and behavioral flexibility necessitate mental and behavioral changes in response to changing environmental demands. Cognitive flexibility, or the mental ability to change from one thought to another, supports positive life outcomes. Individuals diagnosed with autism spectrum disorder (ASD) often face challenges with cognitive flexibility as exhibited by a core symptom of restricted and repetitive interests and behaviors (RRBs) and having poor adaptive behavior skills. ASD is rising each year, with one in 36 children diagnosed annually. Early diagnosis and treatment are critical for improving life outcomes. This makes it even more important to investigate the neural underpinnings of cognitive flexibility during early stages of development and across the lifespan to improve treatments and interventions. This dissertation seeks to understand the neural mechanisms underlying healthy cognitive flexibility development and the cognitive inflexibility observed in ASD. Chapter 1 includes an introduction to the research involved in the following chapters, and provides a review of cognitive flexibility and its neural correlates in typical development and in ASD. Chapter 2 includes a study exploring brain dynamics and cognitive flexibility across the lifespan in a neurotypical population. Using a co-activation pattern analysis method to investigate brain dynamics, brain networks including the salience (SN), default mode (DMN), and central executive networks (CEN) underlie changes in cognitive flexibility across the lifespan. Chapter 3 then explores the neural correlates of shifting in children with and without autism during a task and resting state fMRI. Results of this study further revealed brain dynamics among the SN, DMN and CEN were involved in shifting abilities and abnormalities in these dynamics may underlie differences observed in children with ASD. Chapter 4 then examines early brain dynamics in toddlers with and without ASD and their relationship with flexible behaviors. Findings reveal differences in brain dynamics among the SN, DMN, and CEN in toddlers later diagnosed with ASD compared with non-ASD toddlers. Additionally, brain dynamics among the SN, DMN, and CEN were associated with RRBs and real-world measures of flexible behaviors across all toddlers. Chapter 5 discusses the overall findings of this dissertation, limitations, and future directions. Overall, these data indicate the importance of investigating brain dynamics associated with cognitive flexibility across the lifespan. Further, it has potential implications for autism research, implying that brain network dynamics may be an early indicator for behavioral symptoms.

    Cover page: Brain Dynamics Underlying Cognitive Flexibility in Typical and Atypical Development
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2018)
    Neurodevelopmental disorders are associated with atypical development and maturation of brain networks. A recent focus on human connectomics research and the growing popularity of open science initiatives has created the ideal climate in which to make real progress toward understanding the neurobiology of disorders affecting youth. Here we outline future directions for neuroscience researchers examining brain networks in neurodevelopmental disorders, highlighting gaps in the current literature. We emphasize the importance of leveraging large neuroimaging and phenotypic data sets recently made available to the research community, and we suggest specific novel methodological approaches, including analysis of brain dynamics and structural connectivity, that have the potential to produce the greatest clinical insight. Transdiagnostic approaches will also become increasingly necessary as the Research Domain Criteria framework put forth by the National Institute of Mental Health permeates scientific discourse. During this exciting era of big data and increased computational sophistication of analytic tools, the possibilities for significant advancement in understanding neurodevelopmental disorders are limitless.
      Cover page: Future Directions for Examination of Brain Networks in Neurodevelopmental Disorders
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2005)

      Self-recognition has been demonstrated by a select number of primate species and is often used as an index of self-awareness. Whether a specialized neural mechanism for self-face recognition in humans exists remains unclear. We used event-related fMRI to investigate bra in regions selectively activated by images of one's own face. Ten right-handed normal subjects viewed digital morphs between their own face and a gender-matched familiar other presented in a random sequence. Subjects were instructed to press a button with the right hand if the image looked like their own face, and another button if it looked like a familiar or scrambled face. Contrasting the trials in which images contain more "self" with those containing more familiar "other" revealed signal changes in the right hemisphere (RH) including the inferior parietal lobule, inferior frontal gyrus, and inferior occipital gyros. The opposite contrast revealed voxels with higher signal intensity for images of "other" than for "self" in the medial prefrontal cortex and precuneus. Additional contrasts against baseline revealed that activity in the "self" minus "other" contrasts represent signal increases compared to baseline (null events) in "self" trials, while activity in the "other" minus "self" contrasts represent deactivations relative to baseline during "self" trials. Thus, a unique network involving frontoparietal structures described as part of the "mirror neuron systern" in the RH underlies self-face recognition, while regions comprising the "default/resting state" network deactivate less for familiar others. We provide a model that reconciles these findings and previously published work to account for the modulations in these two networks previously implicated in social cognition. (c) 2004 Elsevier Inc. All rights reserved.

        Cover page: Self-face recognition activates a frontoparietal "mirror" network in the right hemisphere: an event-related fMRI study
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)
        In rare cases of severe and intractable epilepsy, cerebral hemispherectomy is performed to arrest seizure activity and improve quality of life. The remaining hemisphere is often capable of supporting many cognitive functions post-surgery, although the outcome depends on the underlying etiology, hemisphere removed, and age of resection. The mechanisms underlying this massive reorganization are at present unknown. Here we examined intrinsic functional connectivity of putative language brain networks in four children after left cerebral hemispherectomy using resting-state functional magnetic resonance imaging (rsfMRI). We compared these functional systems to intrinsic language networks in 15 neurotypical controls using region-of-interest (ROI)-based functional connectivity analyses. In three out of four hemispherectomy patients, the ROI placed in the right inferior gyrus revealed a functional network that strongly resembled the right-hemisphere intrinsic language network observed in controls. This network typically comprised inferior frontal gyrus, superior temporal sulcus, and premotor regions. Quantitative ROI-to-ROI analyses revealed that functional connectivity between major nodes of the language network was significantly altered in all 4 examined patients. Overall, our data demonstrate that the pattern of functional connectivity within language networks is at least partially preserved in the intact right hemisphere of patients who underwent left hemispherectomy.
          Cover page: Intrinsic functional organization of putative language networks in the brain following left cerebral hemispherectomy.
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2023)

          Background

          Intraindividual variability (IIV) during cognitive task performance is a key behavioral index of attention and a consistent marker of attention-deficit/hyperactivity disorder. In adults, lower IIV has been associated with anticorrelation between the default mode network (DMN) and dorsal attention network (DAN)-thought to underlie effective allocation of attention. However, whether these behavioral and neural markers of attention are 1) associated with each other and 2) can predict future attention-related deficits has not been examined in a developmental, population-based cohort.

          Methods

          We examined relationships at the baseline visit between IIV on 3 cognitive tasks, DMN-DAN anticorrelation, and parent-reported attention problems using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,878 participants, ages 9 to 10 years, female = 47.8%). We also investigated whether behavioral and neural markers of attention at baseline predicted attention problems 1, 2, and 3 years later.

          Results

          At baseline, greater DMN-DAN anticorrelation was associated with lower IIV across all 3 cognitive tasks (B = 0.22 to 0.25). Older age at baseline was associated with stronger DMN-DAN anticorrelation and lower IIV (B = -0.005 to -0.0004). Weaker DMN-DAN anticorrelation and IIV were cross-sectionally associated with attention problems (B = 1.41 to 7.63). Longitudinally, lower IIV at baseline was associated with less severe attention problems 1 to 3 years later, after accounting for baseline attention problems (B = 0.288 to 0.77).

          Conclusions

          The results suggest that IIV in early adolescence is associated with worsening attention problems in a representative cohort of U.S. youth. Attention deficits in early adolescence may be important for understanding and predicting future cognitive and clinical outcomes.
            Cover page: Variability in Cognitive Task Performance in Early Adolescence Is Associated With Stronger Between-Network Anticorrelation and Future Attention Problems
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2008)

            Background

            Autism is a developmental disorder characterized by decreased interest and engagement in social interactions and by enhanced self-focus. While previous theoretical approaches to understanding autism have emphasized social impairments and altered interpersonal interactions, there is a recent shift towards understanding the nature of the representation of the self in individuals with autism spectrum disorders (ASD). Still, the neural mechanisms subserving self-representations in ASD are relatively unexplored.

            Methodology/principal findings

            We used event-related fMRI to investigate brain responsiveness to images of the subjects' own face and to faces of others. Children with ASD and typically developing (TD) children viewed randomly presented digital morphs between their own face and a gender-matched other face, and made "self/other" judgments. Both groups of children activated a right premotor/prefrontal system when identifying images containing a greater percentage of the self face. However, while TD children showed activation of this system during both self- and other-processing, children with ASD only recruited this system while viewing images containing mostly their own face.

            Conclusions/significance

            This functional dissociation between the representation of self versus others points to a potential neural substrate for the characteristic self-focus and decreased social understanding exhibited by these individuals, and suggests that individuals with ASD lack the shared neural representations for self and others that TD children and adults possess and may use to understand others.
              Cover page: Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2014)
              22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal pole. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a 'developmental-disconnection' hypothesis of symptom development in this disorder.
                Cover page: Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2024)
                BACKGROUND: The 22q11.2 deletion syndrome (22qDel) is a genetic copy number variant that strongly increases risk for schizophrenia and other neurodevelopmental disorders. Disrupted functional connectivity between the thalamus and the somatomotor/frontoparietal cortex has been implicated in cross-sectional studies of 22qDel, idiopathic schizophrenia, and youths at clinical high risk for psychosis. Here, we used a novel functional atlas approach to investigate longitudinal age-related changes in network-specific thalamocortical functional connectivity (TCC) in participants with 22qDel and typically developing (TD) control participants. METHODS: TCC was calculated for 9 functional networks derived from resting-state functional magnetic resonance imaging scans collected from 65 participants with 22qDel (63.1% female) and 69 demographically matched TD control participants (49.3% female) ages 6 to 23 years. Analyses included 86 longitudinal follow-up scans. Nonlinear age trajectories were characterized with generalized additive mixed models. RESULTS: In participants with 22qDel, TCC in the frontoparietal network increased until approximately age 13, while somatomotor TCC and cingulo-opercular TCC decreased from age 6 to 23. In contrast, no significant relationships between TCC and age were found in TD control participants. Somatomotor connectivity was significantly higher in participants with 22qDel than in TD control participants in childhood, but lower in late adolescence. Frontoparietal TCC showed the opposite pattern. CONCLUSIONS: 22qDel is associated with aberrant development of functional network connectivity between the thalamus and cortex. Younger individuals with 22qDel have lower frontoparietal connectivity and higher somatomotor connectivity than control individuals, but this phenotype may normalize or partially reverse by early adulthood. Altered maturation of this circuitry may underlie elevated neuropsychiatric disease risk in this syndrome.
                  Cover page: Longitudinal Development of Thalamocortical Functional Connectivity in 22q11.2 Deletion Syndrome.
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2017)
                  22q11.2 Deletion syndrome (22q11DS) is a genetic disorder associated with numerous phenotypic consequences and is one of the greatest known risk factors for psychosis. We investigated intrinsic-connectivity-networks (ICNs) as potential biomarkers for patient and psychosis-risk status in 2 independent cohorts, UCLA (33 22q11DS-participants, 33 demographically matched controls), and Syracuse (28 22q11DS, 28 controls). After assessing group connectivity differences, ICNs from the UCLA cohort were used to train classifiers to distinguish cases from controls, and to predict psychosis risk status within 22q11DS; classifiers were subsequently tested on the Syracuse cohort. In both cohorts we observed significant hypoconnectivity in 22q11DS relative to controls within anterior cingulate (ACC)/precuneus, executive, default mode (DMN), posterior DMN, and salience networks. Of 12 ICN-derived classifiers tested in the Syracuse replication-cohort, the ACC/precuneus, DMN, and posterior DMN classifiers accurately distinguished between 22q11DS and controls. Within 22q11DS subjects, connectivity alterations within 4 networks predicted psychosis risk status for a given individual in both cohorts: the ACC/precuneus, DMN, left executive, and salience networks. Widespread within-network-hypoconnectivity in large-scale networks implicated in higher-order cognition may be a defining characteristic of 22q11DS during adolescence and early adulthood; furthermore, loss of coherence within these networks may be a valuable biomarker for individual prediction of psychosis-risk in 22q11DS.
                    Cover page: Intrinsic Connectivity Network-Based Classification and Detection of Psychotic Symptoms in Youth With 22q11.2 Deletions.
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2020)
                    The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the worlds scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemics consequences and prevent recurrences of similar pandemics.
                      Cover page: The urgent need for integrated science to fight COVID-19 pandemic and beyond.
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