Biology subjects

Tervo-Clemmens, B.

Publications and source records attributed to Tervo-Clemmens, B..

23 records · Page 2Linked to original sources

bioRxiv2022

Changes in prefrontal GABA and glutamate through adolescence supports excitation/inhibition balance

Animal and human postmortem studies provide evidence for changes in gamma-aminobutyric acid (GABA) and glutamate in prefrontal cortex (PFC) during adolescence, suggesting shifts in excitation and inhibition balance consistent with critical period plasticity. However, how GABA and glutamate change through adolescence and how the balance of these inhibitory and excitatory neurotransmitters changes is not well understood in vivo in humans. High field (7 Tesla) Magnetic Resonance Spectroscopic Imaging was used to investigate age-related changes in the balance of GABA/creatine (Cr) and glutamate/Cr in multiple developmentally-relevant regions of PFC in 144 10 to 30-year-olds. Results indicated a homogenous pattern of age-related Glu/Cr decreases across PFC regions, while age-related changes in GABA/Cr were heterogenous, with a mix of stable and decreasing age effects. Importantly, balance between glutamate/Cr and GABA/Cr in areas of prefrontal cortex increased through adolescence, suggesting the presence of critical period plasticity in PFC at this significant time of development when adult trajectories are established.

neuroscience↗

bioRxiv2020

Towards Reproducible Brain-Wide Association Studies

Magnetic resonance imaging (MRI) continues to drive many important neuroscientific advances. However, progress in uncovering reproducible associations between individual differences in brain structure/function and behavioral phenotypes (e.g., cognition, mental health) may have been undermined by typical neuroimaging sample sizes (median N=25)1,2. Leveraging the Adolescent Brain Cognitive Development (ABCD) Study3 (N=11,878), we estimated the effect sizes and reproducibility of these brain-wide associations studies (BWAS) as a function of sample size. The very largest, replicable brain-wide associations for univariate and multivariate methods were r=0.14 and r=0.34, respectively. In smaller samples, typical for brain-wide association studies (BWAS), irreproducible, inflated effect sizes were ubiquitous, no matter the method (univariate, multivariate). Until sample sizes started to approach consortium-levels, BWAS were underpowered and statistical errors assured. Multiple factors contribute to replication failures4-6; here, we show that the pairing of small brain-behavioral phenotype effect sizes with sampling variability is a key element in wide-spread BWAS replication failure. Brain-behavioral phenotype associations stabilize and become more reproducible with sample sizes of N{gap}2,000. While investigator-initiated brain-behavior research continues to generate hypotheses and propel innovation, large consortia are needed to usher in a new era of reproducible human brain-wide association studies.

neuroscience↗

bioRxiv2020

Dopamine-related striatal neurophysiology is associated with specialization of frontostriatal reward circuitry through adolescence

Characterizing developmental changes in frontostriatal circuitry is critical to our understanding of adolescent development and can clarify neurobiological mechanisms underlying increased reward sensitivity and sensation seeking, and the emergence of psychopathology during this period. However, the role of striatal neurobiology in the development of frontostriatal circuitry through human adolescence remains largely unknown. We combine longitudinal MR-based assessments of striatal tissue-iron as a correlate of dopamine-related neurobiology with functional magnetic resonance imaging indices of resting-state and reward-state connectivity to investigate the contribution of dopaminergic processes to developmental changes in frontostriatal circuitry. Connectivity between the nucleus accumbens and ventral anterior cingulate, subgenual cingulate, and orbitofrontal cortices decreased through adolescence into adulthood. Nucleus accumbens tissue-iron mediated age-related changes and was associated with variability in connectivity. Our results provide evidence that developmental changes in dopamine-related striatal properties contribute to specialization of frontostriatal circuitry, potentially underlying changes in sensation seeking and reward sensitivity into adulthood.

neuroscience↗

bioRxiv2020

Developmental Influences on Symptom Expression in Antipsychotic-Naive First-Episode Psychosis

IntroductionThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression - how a persons age affects clinical presentation in first-episode psychosis - has not been thoroughly investigated. MethodUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naive individuals experiencing a first episode of psychosis (N=340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990-2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We also tested for age-associated effects on change in positive or negative symptom severity following baseline assessment, and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development. ResultsIn the cross-sectional and longitudinal data, perceptual positive symptoms significantly decreased with increasing age (F=7.0, p=0.0007; q=0.003) while non-perceptual positive symptoms increased with increasing age (F=4.1, p=0.01, q=0.02). These relationships remained significant when SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p>0.25). Finally, an association between severity of non-perceptual and perceptual symptoms developed with increasing age, with a significant association starting at age 18. ConclusionThese findings suggest that as cognitive maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced, reflecting influences of developmental processes on psychosis expression. Findings underscore how pathological brain-behavior relationships vary as a function of development.

neuroscience↗

bioRxiv2019

Neurocognitive development of inhibitory control and substance use vulnerability

Previous research indicates that risk for substance use is associated with poor inhibitory control. However, it remains unclear whether at risk youth use follow divergent patterns of inhibitory control development. As part of the longitudinal National Consortium on Adolescent Neurodevelopment and Alcohol (NCANDA) study, participants (N = 113, baseline age: 12-21) completed a rewarded antisaccade task during fMRI, with up to three time points. We examined whether substance use risk factors, including dimensional measures of psychopathology (externalizing, internalizing) and family history of substance use disorder, were associated with developmental differences in inhibitory control performance and BOLD activation at both the trial-level and within individual antisaccade epochs (cue, preparation, and response). Among substance use risk factors, only externalizing psychopathology predicted developmental differences in inhibitory control, where high externalizing predicted lower correct response rates and faster latencies were observed in early adolescence, but normalized by late adolescence. Neuroimaging results revealed high externalizing was associated with developmentally-stable hypo-activation in the left middle frontal gyrus (trial-level), but divergent developmental patterns of posterior parietal cortex activation (cue epoch). Developmental differences in inhibitory control associated with externalizing suggest early adolescence may be a unique period of substance use vulnerability via cognitive and phenotypic disinhibition.\n\nHighlightsO_LICharacterized inhibitory control development in adolescents at-risk for substance use.\nC_LIO_LIExternalizing psychopathology is associated with lower antisaccade correct response rate and faster latencies in early adolescence.\nC_LIO_LIExternalizing performance differences normalize by late adolescence.\nC_LIO_LIExternalizing is associated with prefrontal hypo-activation across development.\nC_LIO_LIExternalizing moderates age-related increases in posterior parietal cortex activity.\nC_LI

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