Dataset Information

Gestational valproate alters BOLD activation in response to complex social and primary sensory stimuli.

ABSTRACT: Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V(1a) antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light) to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V(1a) receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V(1a) antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V(1a) neurotransmission.

SUBMITTER: Felix-Ortiz AC

PROVIDER: S-EPMC3355108 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Gestational valproate alters BOLD activation in response to complex social and primary sensory stimuli.

Felix-Ortiz Ada C AC Febo Marcelo M

PloS one 20120517 5

Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and behavior abnormalities. ...[more]

PMID: 22615973

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Project description:Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI). However, conventional fMRI analysis based on statistical parametric mapping (SPM) and the general linear model (GLM) is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA), have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past, this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbor (NN), Gaussian Naïve Bayes (GNB), and (regularized) Linear Discriminant Analysis (LDA) in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie. Results show that LDA regularized by principal component analysis (PCA) achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2 s apart during a 300 s movie (chance level 0.7% = 2 s/300 s). The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these results, the combination of naturalistic movie stimuli and classification analysis in fMRI experiments may prove to be a sensitive tool for the assessment of changes in natural cognitive processes under experimental manipulation.

Dataset Information

Gestational valproate alters BOLD activation in response to complex social and primary sensory stimuli.

Publications

Gestational valproate alters BOLD activation in response to complex social and primary sensory stimuli.

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