Susan M Rivera

University of California, Davis | UCD · Department of Psychology

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations...

Prior studies suggest that habituation of sensory responses is reduced in autism and that diminished habituation could be related to atypical autistic sensory experiences, for example, by causing brain responses to aversive stimuli to remain strong over time instead of being suppressed. While many prior studies exploring habituation in autism have...

Background Men with fragile X-associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross-sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal stu...

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder associated with the FMR1 premutation. Currently, it is not possible to determine when and if individual premutation carriers will develop FXTAS. Thus, with the aim to identify biomarkers for early diagnosis, development, and progression of FXTAS, along with associat...

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region, and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X premutation-associated conditions (FXPAC) include co-transcriptional R loop formatio...

Premutation alleles with 55–200 CGG repeats in FMR1 can lead to fragile X‐associated tremor/ataxia syndrome (FXTAS). In this case study, we report uncontrolled gout in a 68‐year‐old male with FXTAS with multiple sites of involvement including a rare gouty tophus in the nasal region. This is the first documentation of immune dysregulation manifestin...

This study uses factor mixture modelling of the Short Sensory Profile (SSP) at two time points to describe subgroups of young autistic and typically-developing children. This approach allows separate SSP subscales to influence overall SSP performance differentially across subgroups. Three subgroups were described, one including almost all typically...

Most prior studies of multisensory integration (MSI) in autism have measured MSI in only a single combination of modalities – typically audiovisual integration. The present study used onset reaction times (RTs) and 125-channel electroencephalography (EEG) to examine different forms of bimodal and trimodal MSI based on combinations of auditory (nois...

The current study examines attentional biases toward male and female emotional faces in a sample of infants and young children. Participants were 110 infants and young children who were between 9 and 48 months. These children watched a passive version of a dot probe task that included emotional (happy and angry) male and female faces. Results indic...

Background: Quantitative measurement of eye movements can reveal subtle progression in neurodegenerative diseases. Objective: To determine if quantitative measurements of eye movements may reveal subtle progression of fragile X-associated tremor and ataxia (FXTAS). Methods: Prosaccade (PS) and antisaccade (AS) behavior was analyzed in 25 contr...

Background Carriers of the FMR1 premutation are at increased risk of developing a late-onset progressive neurodegenerative disease, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by intention tremor, gait ataxia, and cognitive decline. Cross-sectional studies to date have provided evidence that neuropsychological changes, such a...

Background: Fragile X premutation carriers (55-200 CGG triplets) may develop a progressive neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), after the age of 50. The neuroradiologic markers of FXTAS are hyperintense T2-signals in the middle cerebellar peduncle-the MCP sign. We recently noticed abnormal T2-signals in...

One of the most universally accepted facts about autism is that it is heterogenous. Individuals diagnosed with autism spectrum disorder have a wide range of behavioral presentations and a variety of co-occurring medical and mental health conditions. The identification of more homogenous subgroups is likely to lead to a better understanding of etiol...

Background Reconciling results obtained using different types of sensory measures is a challenge for autism sensory research. The present study used questionnaire, psychophysical, and neurophysiological measures to characterize autistic sensory processing in different measurement modalities.Methods Participants were 46 autistic and 21 typically-dev...

Objective Although prior studies have compared sensory ERP responses between groups of autistic and typically-developing participants, it is unclear how heterogeneity contributes to the results of these studies. The present study used examined individual differences in these responses. Method 130 autistic children and 81 typically-developing child...

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder that affects movement and cognition in male and female carriers of a premutation allele (55–200 CGG repeats; PM) in the fragile X mental retardation ( FMR1 ) gene. It is currently unknown how the observed brain changes are associated with metabolic...

Background: Children with FMR1 gene expansions are known to experience a range of developmental challenges, including fragile X syndrome. However, little is known about early development and symptom onset, information that is critical to guide earlier identification, more accurate prognoses, and improved treatment options. Methods: Data from 8 u...

Limited research has investigated the development of auditory ERPs in young children, and particularly how stimulus intensity may affect these auditory ERPs. Previous research has also yielded inconsistent findings regarding differences in the development of auditory ERPs in autism and typical development. Furthermore, stimulus intensity may be of...

Fragile X‐associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder associated with the FMR1 premutation. It is currently unknown when, and if, individual premutation carriers will develop FXTAS. Thus, with the aim of identifying biomarkers for early diagnosis, development, and progression of FXTAS, we performed global metabolomic p...

Background Prior longitudinal investigations of trajectories of sensory features in Autism Spectrum Development (ASD) have not explored heterogeneity. The present study explores initial levels and trajectories of sensory features in ASD as well as, for comparison, typical development. Method Growth mixture modelling was used to explore classes of...

Fragile X associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder that affects movement and cognition in male and female carriers of a premutation allele of 55–200 CGG repeats in the Fragile X mental retardation (FMR1) gene. It is currently unknown if and when an individual carrier of a premutation allele will dev...

Background: Autistic individuals exhibit atypical patterns of sensory processing that are known to be related to quality of life, but which are also highly heterogeneous. Previous investigations of this heterogeneity have ordinarily used questionnaires and have rarely investigated sensory processing in typical development (TD) alongside autism spe...

Background: Autistic individuals exhibit atypical patterns of sensory processing that are known to be related to quality of life, but which are also highly heterogeneous. Previous investigations of this heterogeneity have ordinarily used questionnaires and have rarely investigated sensory processing in Typical Development (TD) alongside Autism Spec...

Background: Autistic individuals exhibit atypical patterns of sensory processing that are known to be related to quality of life, but which are also highly heterogeneous. Previous investigations of this heterogeneity have ordinarily used questionnaires and have rarely investigated sensory processing in Typical Development (TD) alongside Autism Spec...

Individuals with autism spectrum disorder (ASD) demonstrate impairments in non-verbal communication, including gesturing and imitation deficits. Reduced sensitivity to biological motion (BM) in ASD may impair processing of dynamic social cues like gestures, which in turn may impede encoding and subsequent performance of these actions. Using both an...

Objective: Selective serotonin reuptake inhibitors like sertraline have been shown in observational studies and anecdotal reports to improve language development in young children with fragile X syndrome (FXS). A previous controlled trial of sertraline in young children with FXS found significant improvement in expressive language development as me...

Background: Metformin is a drug commonly used in individuals with type 2 diabetes, obesity, and impaired glucose tolerance. It has a strong safety profile in both children and adults. Studies utilizing the Drosophila model and knock out mouse model of fragile X syndrome (FXS) have found metformin to rescue memory, social novelty deficits, and neur...

Ventricular enlargement (VE) is commonly observed in aging and fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. VE may generate a mechanical force causing structural deformation. In this longitudinal study, we examined the relationships between VE and structural changes in the corpus callosum (CC) and pu...

Fragile X syndrome (FXS) is a genetic disorder caused by a trinucleotide CGG expansion within the FMR1 gene located on the X chromosome. Children with FXS have been shown to be impaired in dynamic visual attention processing. A key component of dynamic processing is orienting—a perceptual ability that requires disengagement and engagement of attent...

Autism spectrum disorder (ASD), characterized by impairments in social communication and repetitive behaviors, often includes altered responses to sensory inputs as part of its phenotype. The neurobiological basis for altered sensory processing is not well understood. The UC Davis Medical Investigation of Neurodevelopmental Disorders Institute Auti...

Background Nucleotide repeat expansions are among the most common inherited cause of neurodegeneration and neurological disorders. Fragile X-Tremor/ Ataxia syndrome (FXTAS) is caused by 55-200 CGG expansions in the 5' untranslated region of FMR1 gene. Premutation disorders are associated with increased level of FMR1 mRNA and the proposed molecular...

Approximately 30–40% of male and 8–16% of female carriers of the Fragile X premutation will develop a neurodegenerative movement disorder characterized by intentional tremor, gait ataxia, autonomic dysfunction, cognitive decline, and Parkinsonism during their lifetime. At the molecular level, premutation carriers have increased expression levels of...

Here we report five cases of male FMR1 premutation carriers who present without clinical symptoms of the fragile X-associated tremor/ataxia syndrome (FXTAS), but who on MRI demonstrate white matter hyperintensities in the middle cerebellar peduncles (MCP sign) and other brain regions, a rare finding. MCP sign is the major radiological feature of FX...

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a severe neurodegenerative movement disorder affecting over 40% of male and 16% of female FMR1 premutation carriers over the age of 50. However, there is a lack of prognostic biomarkers to aid early diagnosis and treatment planning. Therefore, this study aimed to assess the utility of the Magne...

Understanding another’s actions, including what they are doing and why they are doing it, can be difficult for individuals with autism spectrum disorder (ASD). This understanding is supported by the action observation (AON) and mentalizing (MZN) networks, as well as the superior temporal sulcus. We examined these areas in children with ASD and typi...

Background: Fragile X premutation carriers are at increased risk for fragile X-associated tremor ataxia syndrome (FXTAS), but to date we know little about prediction of onset and rate of progression and even less about treatment of this neurodegenerative disease. Thus, the longitudinal study of carriers, and the identification of potential biomark...

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting approximately 45% of male and 16% of female carriers of the FMR1 premutation over the age of 50 years. Currently, no effective treatment is available. We performed an open-label intervention study to assess whether allopregnanolone, a neurostero...

Background: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. FXS is caused by a silencing of the FMR1 gene that results in a loss or absence of the gene's protein product, fragile X mental retardation protein. The phenotype of FXS is consistently associated with heightened anxiety, although no previous study h...

This study examines attentional biases in the presence of angry, happy and neutral faces using a modified eye tracking version of the dot probe task (DPT). Participants were 111 young children between 9 and 48 months. Children passively viewed an affective attention bias task that consisted of a face pairing (neutral paired with either neutral, ang...

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55e200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We...

The prevalence of the fragile X premutation (55–200 CGG repeats) among the general population is relatively high, but there remains a lack of clear understanding of the links between molecular biomarkers and clinical outcomes. In this study we investigated the correlations between molecular measures (CGG repeat size, FMR1 mRNA, FMRP expression leve...

This study examines how social cues facilitate learning by manipulating the familiarity of a social cue. Participants were forty-nine infants between 12–18 months. Infants were taught a novel label for a novel object under two pre-recorded gaze conditions—one in which the caregiver was seen gazing at a novel object while a verbal label was played,...

In this chapter, we review the neuroimaging findings associated with fragile X-associated tremor/ataxia syndrome (FXTAS). We review what is currently known about radiological signs of the disorder including both white matter lesions and mild to severe cortical loss. We also review findings on the integrity of white matter tracts in the brain (using...

Several studies have demonstrated increased rates of anxiety and depressive disorders among female carriers of the fragile X premutation. However, the majority of these studies focused on mothers of children with fragile X syndrome, who experience higher rates of parenting stress that may contribute to the emergence of these disorders. The present...

Objective: Observational studies and anecdotal reports suggest that sertraline, a selective serotonin reuptake inhibitor, may improve language development in young children with fragile X syndrome (FXS). Methods: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled...

Objective: Clinical observations and a limited number of research studies provide evidence that the fragile X premutation may confer risk for autism, executive dysfunction, and psychopathology. The link to autism spectrum symptoms and social cognition deficits with the premutation remains uncertain, and thus was the focus of the present investigat...

Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large seg...

The investigation of the ability to perceive, recognize, and judge upon social intentions, such as communicative intentions, on the basis of body motion is a growing research area. Cross-cultural differences in ability to perceive and interpret biological motion, however, have been poorly investigated so far. Progress in this domain strongly depend...

Previous research has shown that infants can learn from social cues. But is a social cue more effective at directing learning than a non-social cue? This study investigated whether 9-month-old infants (N = 55) could learn a visual statistical regularity in the presence of a distracting visual sequence when attention was directed by either a social...

Carriers of the fragile X premutation allele (fXPCs) have an expanded CGG trinucleotide repeat size within the FMR1 gene and are at increased risk of developing fragile x-associated tremor/ataxia syndrome (FXTAS). Previous research has shown that male fXPCs with FXTAS exhibit cognitive decline, predominantly in executive functions such as inhibitor...

Social impairments in individuals with autism spectrum disorders (ASD) may be in part due to difficulty perceiving and recognizing the actions of others. Evidence from imitation studies, which involves both observation and execution of an action, suggests differences, in individuals with ASD, between the ability to imitate goal-directed actions inv...

Background Fragile X premutation carriers (fXPCs) have an expansion of 55–200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (fragile X-associated tremor/ataxia syndrome (FXTAS)) often accompanied by cognitive decline. Several broad domains are implicated as core systems of dysfunction in fXPC...

Fragile X premutation carriers (fXPC) are characterized by 55-200 CGG trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X-Associated Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted f...

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting a subset of carriers of the FMR1 (fragile X mental retardation 1) premutation. Penetrance and expression appear to be significantly higher in males than females. Although the most obvious aspect of the phenotype is the movement disorder that...

Background Fragile X syndrome (FXS) results from a trinucleotide repeat expansion (full mutation >200 cytosine-guanine-guanine (CGG) repeats) in the FMR1 gene, leading to a reduction or absence of the gene’s protein product, fragile X mental retardation protein (FMRP), ultimately causing cognitive and behavioral impairments that are characteristic...

Objective: Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate eleva...

Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Large expansions of the CGG repeat (> 200 repeats) consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55 to 200 of CGG repeats) are often...

Approximately 40% of males with the fragile X premutation develop fragile X-associated tremor/ataxia syndrome after age 50. Although the thalamus and basal ganglia play a crucial role in movement disorders, their involvement in fragile X premutation carriers has not been systematically investigated. The current study characterized structural abnorm...

Importance: Individuals with the fragile X premutation express expanded CGG repeats (repeats 55-200) in the FMR1 gene and elevated FMR1 messenger RNA (mRNA) levels, both of which may underlie the occurrence of the late-onset neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Because the core feature of FXTAS is motor i...

Objective: Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Previous open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Method: Randomized, double-blind, placebo-controlle...

Background Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and non-idiopathic autism. Individuals with FXS present with a behavioral phenotype of specific and selective deficits in an array of cognitive skills. Disruption of number processing and arithmetic abilities in higher-functioning adults and female ado...

Background A previous study reported enhanced psychomotor speed, and subtle but significant cognitive impairments, modulated by age and by mutations in the fragile X mental retardation 1 (FMR1) gene in adult female fragile X premutation carriers (fXPCs). Because male carriers, unlike females, do not have a second, unaffected FMR1 allele, male fXPCs...

Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and...