Dataset Information

Functional brain connectivity in a rodent seizure model of autistic-like behavior.

ABSTRACT:

Objective

There is increasing evidence that Autism Spectrum Disorder (ASD) is a disorder of functional connectivity with both human and rodent studies demonstrating alterations in connectivity. Here, we hypothesized that early-life seizures (ELS) in rats would interrupt normal brain connectivity and result in autistic-like behavior (ALB).

Methods

Following 50 seizures, adult rats were tested in the social interaction and social novelty tests and then underwent qualitative and quantitative intracranial electroencephalography (EEG) monitoring in the medial prefrontal cortex (PFC) and the hippocampal subfields, CA3 and CA1.

Results

Rats with ELS showed deficits in social interaction and novelty, and compared with control, rats had marked increases in coherence within the hippocampus (CA3-CA1) and between the hippocampus and PFC during the awake and sleep states indicating hyperconnectivity. In addition, sleep spindle density was significantly reduced in rats with ELS. There were no differences in voltage correlations and power spectral densities between the ELS and control rats in any bandwidths.

Conclusion

Taken together, these findings indicate that ELS can result in ALB and alter functional connectivity as measured by coherence and sleep spindle density. These findings implicate altered connectivity as a robust neural signature for ALB following ELS.

SUBMITTER: Mouchati PR

PROVIDER: S-EPMC7117868 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Functional brain connectivity in a rodent seizure model of autistic-like behavior.

Mouchati Philippe R PR Barry Jeremy M JM Holmes Gregory L GL

Epilepsy & behavior : E&B 20190424

<h4>Objective</h4>There is increasing evidence that Autism Spectrum Disorder (ASD) is a disorder of functional connectivity with both human and rodent studies demonstrating alterations in connectivity. Here, we hypothesized that early-life seizures (ELS) in rats would interrupt normal brain connectivity and result in autistic-like behavior (ALB).<h4>Methods</h4>Following 50 seizures, adult rats were tested in the social interaction and social novelty tests and then underwent qualitative and quan ...[more]

PMID: 31030078

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Project description:Functional connectivity mapping with resting-state magnetic resonance imaging (MRI) has become an immensely powerful technique that provides insight into both normal cognitive function and disruptions linked to neurological disorders. Traditionally, connectivity is mapped using data from an entire scan (minutes), but it is well known that cognitive processes occur on much shorter time scales (seconds). Recent studies have demonstrated that the correlation between the blood oxygenation level-dependent (BOLD) MRI signal from different areas varies over time, motivating a further exploration of these fluctuations in apparent connectivity. However, it has also been shown that similar changes in correlation can arise when the timing relationships between voxels are randomized (Handwerker et al., 2012 ). In this work, we show that functional connectivity in the anesthetized rat exhibits dynamic properties that are similar to those previously observed in awake humans (Chang and Glover, 2010 ) and anesthetized monkeys (Hutchison et al., 2012 ). Sliding window correlation between BOLD time courses obtained from bilateral cortical and subcortical regions of interest results in periods of variable positive and negative correlation for most pairs of areas except homologous areas in opposite hemispheres, which exhibit a primarily positive correlation. A comparison with sliding window correlation of randomly matched time courses suggests that with the exception of homologous areas and sensorimotor connections, the dynamics cannot be distinguished from random fluctuations in correlation over time, supporting the idea that some of these dynamic patterns may be due to inherent properties of the signal rather than variations in neural coherence. Within the pairs of areas where the dynamics are most different from those of randomly matched time courses, ten common patterns of connectivity are identified, and their occurrence as a function of time is plotted for all animals. The observation of time-varying correlation in the rodent model will facilitate the future multimodal experiments needed to determine whether the changes in apparent connectivity are linked to underlying neural variability.

Dataset Information

Functional brain connectivity in a rodent seizure model of autistic-like behavior.

Objective

Methods

Results

Conclusion

Publications

Functional brain connectivity in a rodent seizure model of autistic-like behavior.

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