Translational interdisciplinary researcher investigating neurocognitive correlates and potential biomarkers of neurodevelopmental disorders, especially autism spectrum disorders and fragile X syndrome, with the goal of advancing clinical care and health policy.
Honors & Awards
Young Investigator Award, National Fragile X Foundation (2018)
CNI Seed-grant Award, Stanford Center for Cognitive and Neurobiological Imaging (2016)
National Institute of Mental Health T32 postdoctoral training funding, Stanford University (2012)
Helena Anna Henzl Gabor Young Women in Science Fellowship, Stanford University (2009)
Morkovin Graduate School Fellowship, University of Southern California (2007-2008)
Dissertation Award, University of Southern California (2007)
Fellowship for advanced graduate study, Developmental Area, Psychology Department, University of Southern California (2006-2007)
Postdoctoral Fellowship, Stanford University, Cognitive Neuroscience (2014)
Doctor of Philosophy, University of Southern California, Developmental Psychology (2008)
M.A., University of Southern California, Developmental Psychology (2005)
B.A., Temple University, Psychology (2002)
Current Research and Scholarly Interests
Dr. Bruno is a translational researcher at the interface of developmental cognitive neuropsychology and neurobiology. Her research is aimed at understanding the neural basis of intellectual and developmental disorders with goals of improving early diagnosis using biomarkers and designing and testing targeted interventions. Current research projects include longitudinal investigations of neurobiological and behavioral outcomes in Fragile X Syndrome and autism spectrum disorders. Dr. Bruno is also developing adaptable non-constraining functional near-infrared spectroscopy (fNIRS) paradigms to assess the neural circuitry underlying cognition in healthy typically developing individuals and in individuals with neurodevelopmental disorders. Working towards the goal of informing the design of targeted treatments while providing important outcome and progress metrics, Dr. Bruno's research includes infant developmental studies to uncover early, objective biomarkers and epidemiological studies to investigate brain functioning correlates in populations.
Closing the Gender Gap in Fragile X Syndrome: Review on Females with FXS and Preliminary Research Findings.
2019; 9 (1)
Fragile X syndrome (FXS) is a genetic condition known to increase the risk of cognitive impairment and socio-emotional challenges in affected males and females. To date, the vast majority of research on FXS has predominantly targeted males, who usually exhibit greater cognitive impairment compared to females. Due to their typically milder phenotype, females may have more potential to attain a higher level of independence and quality of life than their male counterparts. However, the constellation of cognitive, behavioral, and, particularly, socio-emotional challenges present in many females with FXS often preclude them from achieving their full potential. It is, therefore, critical that more research specifically focuses on females with FXS to elucidate the role of genetic, environmental, and socio-emotional factors on outcome in this often-overlooked population.
View details for DOI 10.3390/brainsci9010011
View details for PubMedID 30642066
Mind over motor mapping: Driver response to changing vehicle dynamics.
Human brain mapping
Improvements in vehicle safety require understanding of the neural systems that support the complex, dynamic task of real-world driving. We used functional near infrared spectroscopy (fNIRS) and pupilometry to quantify cortical and physiological responses during a realistic, simulated driving task in which vehicle dynamics were manipulated. Our results elucidate compensatory changes in driver behavior in response to changes in vehicle handling. We also describe associated neural and physiological responses under different levels of mental workload. The increased cortical activation we observed during the late phase of the experiment may indicate motor learning in prefrontal-parietal networks. Finally, relationships among cortical activation, steering control, and individual personality traits suggest that individual brain states and traits may be useful in predicting a driver's response to changes in vehicle dynamics. Results such as these will be useful for informing the design of automated safety systems that facilitate safe and supportive driver-car communication.
View details for DOI 10.1002/hbm.24220
View details for PubMedID 29885097
- Altered Brain Network Segregation in Fragile X Syndrome Revealed by Structural Connectomics CEREBRAL CORTEX 2017; 27 (3): 2249-2259
Longitudinal identification of clinically distinct neurophenotypes in young children with fragile X syndrome.
Proceedings of the National Academy of Sciences of the United States of America
Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability. The cognitive, behavioral, and neurological phenotypes observed in affected individuals can vary considerably, making it difficult to predict outcomes and determine the need for interventions. We sought to examine early structural brain growth as a potential marker for identification of clinically meaningful subgroups. Participants included 42 very young boys with FXS who completed a T1-weighted anatomical MRI and cognitive/behavioral assessment at two longitudinal time points, with mean ages of 2.89 y and 4.91 y. Topological data analysis (TDA), an unsupervised approach to multivariate pattern analysis, was applied to the longitudinal anatomical data to identify coherent but heretofore unknown subgroups. TDA revealed two large subgroups within the study population based solely on longitudinal MRI data. Post hoc comparisons of cognition, adaptive functioning, and autism severity scores between these groups demonstrated that one group was consistently higher functioning on all measures at both time points, with pronounced and significant unidirectional differences (P < 0.05 for time point 1 and/or time point 2 for each measure). These results support the existence of two longitudinally defined, neuroanatomically distinct, and clinically relevant phenotypes among boys with FXS. If confirmed by additional analyses, such information may be used to predict outcomes and guide design of targeted therapies. Furthermore, TDA of longitudinal anatomical MRI data may represent a useful method for reliably and objectively defining subtypes within other neuropsychiatric disorders.
View details for DOI 10.1073/pnas.1620994114
View details for PubMedID 28923933
View details for PubMedCentralID PMC5635864
The cognitive developmental profile associated with fragile X syndrome: A longitudinal investigation of cognitive strengths and weaknesses through childhood and adolescence.
Development and psychopathology
2016; 28 (4): 1457-1469
Few studies have investigated developmental strengths and weaknesses within the cognitive profile of children and adolescents with fragile X syndrome (FXS), a single-gene cause of inherited intellectual impairment. With a prospective longitudinal design and using normalized raw scores (Z scores) to circumvent floor effects, we measured cognitive functioning of 184 children and adolescents with FXS (ages 6 to 16) using the Wechsler Scale of Intelligence for Children on one to three occasions for each participant. Participants with FXS received lower raw scores relative to the Wechsler Scale of Intelligence for Children normative sample across the developmental period. Verbal comprehension, perceptual organization, and processing speed Z scores were marked by a widening gap from the normative sample, while freedom from distractibility Z scores showed a narrowing gap. Key findings include a relative strength for verbal skills in comparison with visuospatial-constructive skills arising in adolescence and a discrepancy between working memory (weakness) and processing speed (strength) in childhood that diminishes in adolescence. Results suggest that the cognitive profile associated with FXS develops dynamically from childhood to adolescence. Findings are discussed within the context of aberrant brain morphology in childhood and maturation in adolescence. We argue that assessing disorder-specific cognitive developmental profiles will benefit future disorder-specific treatment research.
View details for PubMedID 26648140
Altered Brain Network Segregation in Fragile X Syndrome Revealed by Structural Connectomics
View details for DOI 10.1093/cercor/bhw055
Specific effect of the fragile-X mental retardation-1 gene (FMR1) on white matter microstructure
BRITISH JOURNAL OF PSYCHIATRY
2015; 207 (2): 143-148
Background Fragile-X syndrome (FXS) is a neurodevelopmental disorder associated with intellectual disability and neurobiological abnormalities including white matter microstructural differences. White matter differences have been found relative to neurotypical individuals. Aims To examine whether FXS white matter differences are related specifically to FXS or more generally to the presence of intellectual disability. Method We used voxel-based and tract-based analytic approaches to compare individuals with FXS (n = 40) with gender- and IQ-matched controls (n = 30). Results Individuals with FXS had increased fractional anisotropy and decreased radial diffusivity values compared with IQ-matched controls in the inferior longitudinal, inferior fronto-occipital and uncinate fasciculi. Conclusions The genetic variation associated with FXS affects white matter microstructure independently of overall IQ. White matter differences, found in FXS relative to IQ-matched controls, are distinct from reported differences relative to neurotypical controls. This underscores the need to consider cognitive ability differences when investigating white matter microstructure in neurodevelopmental disorders.
View details for DOI 10.1192/bjp.bp.114.151654
View details for Web of Science ID 000359180800009
View details for PubMedID 25792692
- Aberrant Face and Gaze Habituation in Fragile X Syndrome AMERICAN JOURNAL OF PSYCHIATRY 2014; 171 (10): 1099-1106
- Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study JOURNAL OF NEURODEVELOPMENTAL DISORDERS 2013; 5
Phonological processing is uniquely associated with neuro-metabolic concentration
2013; 67: 175-181
Reading is a complex process involving recruitment and coordination of a distributed network of brain regions. The present study sought to establish a methodologically sound evidentiary base relating specific reading and phonological skills to neuro-metabolic concentration. Single voxel proton magnetic resonance spectroscopy was performed to measure metabolite concentration in a left hemisphere region around the angular gyrus for 31 young adults with a range of reading and phonological abilities. Correlation data demonstrated a significant negative association between phonological decoding and normalized choline concentration and as well as a trend toward a significant negative association between sight word reading and normalized choline concentration, indicating that lower scores on these measures are associated with higher concentrations of choline. Regression analyses indicated that choline concentration accounted for a unique proportion of variance in the phonological decoding measure after accounting for age, cognitive ability and sight word reading skill. This pattern of results suggests some specificity for the negative relationship between choline concentration and phonological decoding. To our knowledge, this is the first study to provide evidence that choline concentration in the angular region may be related to phonological skills independently of other reading skills, general cognitive ability, and age. These results may have important implications for the study and treatment of reading disability, a disorder which has been related to deficits in phonological decoding and abnormalities in the angular gyrus.
View details for DOI 10.1016/j.neuroimage.2012.10.092
View details for Web of Science ID 000314144600017
View details for PubMedID 23147236
Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors
NEUROBIOLOGY OF DISEASE
2012; 48 (3): 329-338
Many women with breast cancer, especially those treated with chemotherapy, experience cognitive decline due in part to neurotoxic brain injury. Recent neuroimaging studies suggest widespread brain structural abnormalities pointing to disruption of large-scale brain networks. We applied resting state functional magnetic resonance imaging and graph theoretical analysis to examine the connectome in breast cancer survivors treated with chemotherapy relative to healthy comparison women. Compared to healthy females, the breast cancer group displayed altered global brain network organization characterized by significantly decreased global clustering as well as disrupted regional network characteristics in frontal, striatal and temporal areas. Breast cancer survivors also showed significantly increased self-report of executive function and memory difficulties compared to healthy females. These results suggest that topological organization of both global and regional brain network properties may be disrupted following breast cancer and chemotherapy. This pattern of altered network organization is believed to result in reduced efficiency of parallel information transfer. This is the first report of alterations in large-scale functional brain networks in this population and contributes novel information regarding the neurobiologic mechanisms underlying breast cancer-related cognitive impairment.
View details for DOI 10.1016/j.nbd.2012.07.009
View details for Web of Science ID 000309694000007
View details for PubMedID 22820143
View details for PubMedCentralID PMC3461109
Sensitivity to orthographic familiarity in the occipito-temporal region
2008; 39 (4): 1988-2001
The involvement of the left hemisphere occipito-temporal (OT) junction in reading has been established, yet there is current controversy over the region's specificity for reading and the nature of its role in the reading process. Recent neuroimaging findings suggest that the region is sensitive to orthographic familiarity [Kronbichler, M., Bergmann, J., Hutzler, F., Staffen, W., Mair, A., Ladurner, G., Wimmer, H. 2007. Taxi vs. Taksi: on orthographic word recognition in the left ventral occipito-temporal cortex. Journal of Cognitive Neuroscience 19, 1-11], and the present study tested that hypothesis. Using fMRI, the OT region and other regions in the reading network were localized in 28 adult, right-handed participants. The BOLD signal in these regions was measured during a phonological judgment task (i.e., "Does it sound like a word?"). Stimuli included words, pseudohomophones (phonologically familiar yet orthographically unfamiliar), and pseudowords (phonologically and orthographically unfamiliar) that were matched on lexical properties including sublexical orthography. Relative to baseline, BOLD signal in the OT region was greater for pseudohomophones than for words, suggesting that the region is sensitive to orthographic familiarity at the whole-word level. Further contrasts of orthographic frequency within the word condition revealed increased BOLD signal for low- than high-frequency words. Specialization in the OT region for recognition of frequent letter strings may support the development of reading expertise. Additionally, BOLD signal in the OT region correlates positively with reading efficiency, supporting the idea that this region is a skill zone for reading printed words. BOLD signal in the IFG and STG correlates negatively with reading efficiency, indicating that processing effort in these classic phonological regions is inversely related to reading efficiency.
View details for DOI 10.1016/j.neuroimage.2007.10.044
View details for Web of Science ID 000253241800047
View details for PubMedID 18180168
Auditory word identification in dyslexic and normally achieving readers
JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY
2007; 97 (3): 183-204
The integrity of phonological representation/processing in dyslexic children was explored with a gating task in which children listened to successively longer segments (gates) of a word. At each gate, the task was to decide what the entire word was. Responses were scored for overall accuracy as well as the children's sensitivity to coarticulation from the final consonant. As a group, dyslexic children were less able than normally achieving readers to detect coarticulation present in the vowel portion of the word, particularly on the most difficult items, namely those ending in a nasal sound. Hierarchical regression and path analyses indicated that phonological awareness mediated the relation of gating and general language ability to word and pseudoword reading ability.
View details for DOI 10.1016/j.jecp.2007.01.005
View details for Web of Science ID 000247704900002
View details for PubMedID 17359994
fNIRS measurement of cortical activation and functional connectivity during a visuospatial working memory task.
2018; 13 (8): e0201486
Demands on visuospatial working memory are a ubiquitous part of everyday life. As such, significant efforts have been made to understand how the brain responds to these demands in real-world environments. Multiple brain imaging studies have highlighted a fronto-parietal cortical network that underlies visuospatial working memory, is modulated by cognitive load, and that appears to respond uniquely to encoding versus retrieval components. Furthermore, multiple studies have identified functional connectivity in regions of the fronto-parietal network during working memory tasks. Together, these findings have helped outline important aspects of the neural architecture that underlies visuospatial working memory. Here, we provide results from the first fNIRS-based investigation of fronto-parietal signatures of cortical activation and functional connectivity during a computer-based visuospatial working memory task. Our results indicate that the local maxima of cortical activation and functional coherence do not necessarily overlap spatially, and that cortical activation is significantly more susceptible to task-specific demands compared to functional connectivity. These results highlight important and novel information regarding neurotypical signatures of cortical activation and functional connectivity during visuospatial working memory. Our findings also demonstrate the utility of fNIRS for interrogating these cognitive processes.
View details for DOI 10.1371/journal.pone.0201486
View details for PubMedID 30071072
Neural, physiological, and behavioral correlates of visuomotor cognitive load
Visuomotor ability is quite crucial for everyday functioning, particularly in driving and sports. While there is accumulating evidence regarding neural correlates of visuomotor transformation, less is known about the brain regions that accommodate visuomotor mapping under different cognitive demands. We concurrently measured cortical activity and pupillary response, using functional near infrared spectroscopy (fNIRS) and eye-tracking glasses, to examine the neural systems linked to pupil dilation under varying cognitive demands. Twenty-three healthy adults performed two sessions of a navigation task, in which the cognitive load was manipulated by either reversing the visuomotor mapping or increasing the speed of the moving object. We identified a region in the right superior parietal lobule that responded to both types of visuomotor load and its activity was associated with larger pupillary response and better performance in the task. Our multimodal analyses suggest that activity in this region arises from the need for increased attentional effort and alertness for visuomotor control and is an ideal candidate for objective measurement of visuomotor cognitive load. Our data extend previous findings connecting changes in pupil diameter to neural activity under varying cognitive demand and have important implications for examining brain-behavior associations in real-world tasks such as driving and sports.
View details for DOI 10.1038/s41598-017-07897-z
View details for PubMedCentralID PMC5562732
Estimating individual contribution from group-based structural correlation networks.
2015; 120: 274-284
Coordinated variations in brain morphology (e.g., cortical thickness) across individuals have been widely used to infer large-scale population brain networks. These structural correlation networks (SCNs) have been shown to reflect synchronized maturational changes in connected brain regions. Further, evidence suggests that SCNs, to some extent, reflect both anatomical and functional connectivity and hence provide a complementary measure of brain connectivity in addition to diffusion weighted networks and resting-state functional networks. Although widely used to study between-group differences in network properties, SCNs are inferred only at the group-level using brain morphology data from a set of participants, thereby not providing any knowledge regarding how the observed differences in SCNs are associated with individual behavioral, cognitive and disorder states. In the present study, we introduce two novel distance-based approaches to extract information regarding individual differences from the group-level SCNs. We applied the proposed approaches to a moderately large dataset (n=100) consisting of individuals with fragile X syndrome (FXS; n=50) and age-matched typically developing individuals (TD; n=50). We tested the stability of proposed approaches using permutation analysis. Lastly, to test the efficacy of our method, individual contributions extracted from the group-level SCNs were examined for associations with intelligence scores and genetic data. The extracted individual contributions were stable and were significantly related to both genetic and intelligence estimates, in both typically developing individuals and participants with FXS. We anticipate that the approaches developed in this work could be used as a putative biomarker for altered connectivity in individuals with neurodevelopmental disorders.
View details for DOI 10.1016/j.neuroimage.2015.07.006
View details for PubMedID 26162553
Cognitive outcomes in pediatric heart transplant recipients bridged to transplantation with ventricular assist devices
JOURNAL OF HEART AND LUNG TRANSPLANTATION
2013; 32 (2): 212-220
Ventricular assist devices (VADs) have been associated with high rates of neurologic injury in pediatric patients during the period of support, but the delayed consequences of this type of injury have not been described in the literature.In this study we assess cognitive outcomes with indices of general intellectual functioning, including working memory, processing speed, perceptual reasoning and verbal comprehension, for pediatric heart transplant recipients who required VAD support as a bridge to transplant (n = 9). We present an aggregate of these VAD patients combined with heart transplant recipients who did not require mechanical circulatory support (n = 11), and compare the performance of all transplant patients (n = 20) to typically developing, healthy comparators (n = 12). We also present a post hoc analysis of those transplant recipients with significant medical morbidity in the first year of life, referred to as the "high-risk" transplant group (n = 5), and compare them with the "low-risk" transplant group (n = 15) and the typically developing comparators (n = 12).The mean performance of the VAD patients was in the average range for each of the examined indices of cognitive functioning. A total of 11% of the VAD patients performed in the impaired range and 78% performed in the average range, with 11% in the superior range on measures of general intellectual functioning. The typically developing participants performed significantly better than the aggregated transplant recipients on all indices except verbal comprehension. Lower cognitive performance in the combined transplant group appears to be associated with medical morbidity in the first year of life.Despite significant neurologic risk factors, this cohort of pediatric patients who were bridged to transplant with VAD demonstrated resiliency in terms of cognitive outcomes. In this heterogeneous population, it is likely that multiple factors contributed to the cognitive outcomes. As VAD use becomes more common in pediatric patients, a prospective evaluation of cognitive outcomes is warranted.
View details for DOI 10.1016/j.healun.2012.11.006
View details for Web of Science ID 000314445800006
View details for PubMedID 23352393
- Neuroimaging in Genetic Disorders Handbook of Neurodevelopmental and Genetic Disorders in Children Gilford Press. 2010; 2