Research Projects in fragile X Spectrum
Fragile X Syndrome is the most common cause of inherited mental retardation. It is a genetic disorder resulting from an expanding trinucleotide (CGG) repeat on the X chromosome. When the number of repeats is 200 or more, the fragile X gene is silenced, leading to a lack of FMRP (fragile X mental retardation protein). This protein is thought to be important in the early development of the brain, but researchers are still studying exactly when, how and where it works during development. Males with fragile X usually have mental retardation and often exhibit characteristic physical features and behavior. Affected females exhibit a similar, but usually less severe profile. The cognitive profile of fragile X includes deficits in visuospatial processing and working memory, visual-motor coordination, and poor arithmetic skills.
Visual Processing and Later Cognitive Effects in Infants with fragile X Syndrome (FXS Baby Study)
In collaboration with the M.I.N.D. Institute’s fragile X Research and Treatment Center, we are currently conducting a longitudinal study of the development of visual and cognitive processing in infants with fragile X syndrome. The study includes infants with fragile X syndrome 6-72-months-old, typically developing infants between 6-48-months-old and infants with Down syndrome between 10-48-months-old. During the study we use eye tracking technology to observe the infant's looking patterns to various visual displays presented on a screen as well as complete standardized assessments of the infant's development. The information gained from this research can be utilized in future studies of early interventions using behavioral, medical and education-based treatments.
*Currently enrolling 6-72 month olds with fragile X syndrome. If Interested in participating, please contact the Neurocognitive Development Lab at (530) 754-4508.
In collaboration with the M.I.N.D. Institute’s fragile X Research and Treatment Center, we are currently conducting a longitudinal study of the development of visual and cognitive processing in infants with fragile X syndrome. The study includes infants with fragile X syndrome 6-72-months-old, typically developing infants between 6-48-months-old and infants with Down syndrome between 10-48-months-old. During the study we use eye tracking technology to observe the infant's looking patterns to various visual displays presented on a screen as well as complete standardized assessments of the infant's development. The information gained from this research can be utilized in future studies of early interventions using behavioral, medical and education-based treatments.
*Currently enrolling 6-72 month olds with fragile X syndrome. If Interested in participating, please contact the Neurocognitive Development Lab at (530) 754-4508.
Infant in front of Tobii eye-tracker
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Data showing increased fixation to a novel stimulus (right image)
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TRAX: Longitudinal Study of Brain and Cognition in fragile X Premutation Carriers
Individuals with the FMR1 premutation (55-200 CGG repeats) can pass on the gene in its expanded full mutation form to offspring who will then have fragile X syndrome. Until recently, these “carriers” of fragile X were believed to be unaffected. Recent evidence, however, suggests that these individuals can have significant social, emotional, cognitive and even physical problems. This study examines changes in the brain and cognition associated with aging, in males with and without the fragile X premutation. The study consists of three 2-day visits over the course of five years to observe changes occurring over time. The protocol involves a medical history exam, neuropsychological evaluation, behavioral testing, MRI, and blood draw.
*If Interested in participating, please contact Contact Jessica Famula, at 916-703-0470 or jfamula@ucdavis.edu.
Individuals with the FMR1 premutation (55-200 CGG repeats) can pass on the gene in its expanded full mutation form to offspring who will then have fragile X syndrome. Until recently, these “carriers” of fragile X were believed to be unaffected. Recent evidence, however, suggests that these individuals can have significant social, emotional, cognitive and even physical problems. This study examines changes in the brain and cognition associated with aging, in males with and without the fragile X premutation. The study consists of three 2-day visits over the course of five years to observe changes occurring over time. The protocol involves a medical history exam, neuropsychological evaluation, behavioral testing, MRI, and blood draw.
*If Interested in participating, please contact Contact Jessica Famula, at 916-703-0470 or jfamula@ucdavis.edu.
Brain structural changes associated with FXTAS development and progression
We utilize various magnetic resonance imaging (MRI) techniques to study the range of brain structural changes associated with FXTAS development and progression. Our long-term goal is to decipher pathophysiologic mechanisms underlying FXTAS, which is critical for developing effective treatments and generating relevant biomarkers for diagnosis and prognosis. MRI is the only method that allows non-invasive in vivo examination of the brain. Patients with FXTAS may have severe brain atrophy that makes the segmentation of the brain challenging.
We improve segmentation accuracy by using multi-atlas-based automated segmentation plus machine learning-based error correction. This step is critical for obtaining accurate measurements from various types of MRI scans. The range of brain structural changes we are studying include atrophy, morphological change (such as thinning), white matter hyper-intensities structural connectivity loss, and iron depositions in the brain. We are also conducting postmortem MRI-neuropathology association studies to understand pathophysiology underlying MRI signal changes in patients with FXTAS.
We utilize various magnetic resonance imaging (MRI) techniques to study the range of brain structural changes associated with FXTAS development and progression. Our long-term goal is to decipher pathophysiologic mechanisms underlying FXTAS, which is critical for developing effective treatments and generating relevant biomarkers for diagnosis and prognosis. MRI is the only method that allows non-invasive in vivo examination of the brain. Patients with FXTAS may have severe brain atrophy that makes the segmentation of the brain challenging.
We improve segmentation accuracy by using multi-atlas-based automated segmentation plus machine learning-based error correction. This step is critical for obtaining accurate measurements from various types of MRI scans. The range of brain structural changes we are studying include atrophy, morphological change (such as thinning), white matter hyper-intensities structural connectivity loss, and iron depositions in the brain. We are also conducting postmortem MRI-neuropathology association studies to understand pathophysiology underlying MRI signal changes in patients with FXTAS.
Attention Bias Modification Training (ABMT)
Excessive attention to threat in the environment is linked to the development and maintenance of anxiety disorders. Recent evidence suggests that young children with FXS show a threat-specific attention bias, which may be related to heightened levels of anxiety. The current study uses eye tracking methodology to implement a multisession treatment study to modify attention to threat with the goal of reducing anxiety symptoms. In addition, using EEG/ERP this study examines the underlying neural changes of attention bias to threat and the flexibility of the attention system to shift biases through training.
This study includes children ranging from 3 to 12 years old who are either typically developing or diagnosed with FXS. To evaluate brain response to training, participants complete a pre- and post- training EEG/ERP during which they view images of facial expressions and emotion-eliciting photos while brain activity is recorded. Across 8 sessions of attention training, participants view a brief presentation of two images, one neutral valence and one depicting an emotion (i.e., anger), followed by a probe that is set to draw attention away from the threatening stimuli, towards the neutral image.
Excessive attention to threat in the environment is linked to the development and maintenance of anxiety disorders. Recent evidence suggests that young children with FXS show a threat-specific attention bias, which may be related to heightened levels of anxiety. The current study uses eye tracking methodology to implement a multisession treatment study to modify attention to threat with the goal of reducing anxiety symptoms. In addition, using EEG/ERP this study examines the underlying neural changes of attention bias to threat and the flexibility of the attention system to shift biases through training.
This study includes children ranging from 3 to 12 years old who are either typically developing or diagnosed with FXS. To evaluate brain response to training, participants complete a pre- and post- training EEG/ERP during which they view images of facial expressions and emotion-eliciting photos while brain activity is recorded. Across 8 sessions of attention training, participants view a brief presentation of two images, one neutral valence and one depicting an emotion (i.e., anger), followed by a probe that is set to draw attention away from the threatening stimuli, towards the neutral image.
