ABSTRACT
Neuropsychological studies in electrical injury patients have reported deficits in attention, learning, and working memory, but the neural substrates of these deficits remain poorly characterized. In this study we sought to examine whether electrical injury subjects demonstrate abnormal patterns of brain activation during working memory and procedural learning tasks. Fourteen electrical injury subjects and fifteen demographically matched healthy control subjects performed a spatial working memory paradigm and a procedural learning paradigm during functional MRI studies. For the spatial working memory task, electrical injury patients exhibited significantly greater activation in the middle frontal gyrus and motor and posterior cingulate cortices. Increased activation in EI subjects also was observed on a visually-guided saccade task in several sensorimotor regions, including the frontal and parietal eye fields and striatum. On the procedural learning task, electrical injury patients exhibited significantly less activation in the middle frontal gyrus, anterior cingulate cortex, and frontal eye fields than controls. This is the first study to document task-dependent, system-level cortical and subcortical dysfunction in individuals who had experienced an electrical shock trauma.
Subject(s)
Brain/physiopathology , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Electric Injuries/complications , Adult , Brain/anatomy & histology , Brain Mapping , Cognition Disorders/diagnosis , Corpus Striatum/anatomy & histology , Corpus Striatum/physiopathology , Disability Evaluation , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/physiopathology , Gyrus Cinguli/anatomy & histology , Gyrus Cinguli/physiopathology , Humans , Learning Disabilities/diagnosis , Learning Disabilities/etiology , Learning Disabilities/physiopathology , Magnetic Resonance Imaging , Male , Memory Disorders/diagnosis , Memory Disorders/etiology , Memory Disorders/physiopathology , Middle Aged , Motor Cortex/anatomy & histology , Motor Cortex/physiopathology , Nerve Net/anatomy & histology , Nerve Net/physiopathology , Neuropsychological Tests , Ocular Motility Disorders/diagnosis , Ocular Motility Disorders/etiology , Ocular Motility Disorders/physiopathology , Parietal Lobe/anatomy & histology , Parietal Lobe/physiopathology , Psychomotor Performance/physiologyABSTRACT
RATIONALE: Two rat auditory evoked potential (AEP) components P13 and N40 are suggested as analogues to the human P50, which has abnormal suppression properties in schizophrenia. However, P50 likely reflects neural activity from several different brain areas. Studies examining each of these components in the rat model have proposed circuitry that involves alpha2 norepinephrine (NE) receptors, and different disruption effects are predicted depending on whether effects are presynaptic or postsynaptic. OBJECTIVES: The aim of this paper is to test differential effects of NE antagonism on disruption of normal P13 and N40 expression. MATERIALS AND METHODS: AEPs were recorded simultaneously in alert, freely moving rats using the alpha2 antagonist yohimbine. Amplitudes of P13 and N40 elicited by 500-ms interstimulus interval click pairs were measured after administration of a placebo and three doses of the yohimbine. RESULTS: A high dose of yohimbine yielded smaller P13 amplitudes to both clicks, consistent with presynaptic action. However, a moderate yohimbine dose yielded increased P13 amplitudes to both clicks. For N40, a moderate dose of yohimbine yielded increased amplitudes to the second stimulus, and a high dose restored normal suppression, which is consistent with previously reported findings. CONCLUSIONS: This study demonstrated that noradrenergic activity differentially affects P13 and N40 components. As P13 and N40 are each models of human P50, these findings highlight the complex circuitry that likely underlies P50. An appreciation for these complexities is critical for understanding the mechanisms of the P50 suppression deficit in schizophrenia, which may be influenced by both trait and state factors.
