Intermittent, chronically delivered electrical stimulation of the vagus nerve (VNS) is an FDA-approved procedure for the treatment of refractory complex/partial epilepsy in humans. Stimulation of the vagus has also been shown to enhance memory storage processes in laboratory rats and human subjects. Recent evidence suggests that some of these effects of VNS may be due to the activation of neurons in the nucleus locus coeruleus resulting in the release of norepinephrine (NE) throughout the neuraxis. Because antagonism of NE systems has been shown to delay recovery of function following brain damage, it is possible that enhanced release of NE in the CNS may facilitate recovery of function. To evaluate this hypothesis the lateral fluid percussion injury (LFP) model of traumatic brain injury was used and a variety of motor and cognitive behavioral tests were employed to assess recovery in pre-trained stimulated, control, and sham-injured laboratory rats. Two hours following moderate LFP, vagus nerve stimulation (30.0-sec trains of 0.5 mA, 20.0 Hz, biphasic pulses) was initiated. Stimulation continued in each animal's home cage at 30-min intervals for a period of 14 days, with the exception of brief periods when the animals were disconnected for behavioral assessments. Motor behaviors were evaluated every other day following LFP and tests included beam walk, locomotor placing, and skilled forelimb reaching. In each measure an enhanced rate of recovery and /or level of final performance was observed in the VNS-LFP animals compared to nonstimulated LFP controls. Behavior in the Morris water maze was assessed on days 11-14 following injury. Stimulated LFP animals showed significantly shorter latencies to find the hidden platform than did controls. Despite these behavioral effects, neurohistological examination did not reveal significant differences in lesion extent, density of fluorojade positive neurons, reactive astrocytes or numbers of spared neurons in the CA3 subarea of the hippocampus, at least at the one time point studied 15 days post-injury. These results support the idea that vagus nerve stimulation enhances the neural plasticity that underlies recovery of function following brain damage and provides indirect support for the hypothesis that enhanced NE release may mediate the effect. Importantly, since VNS facilitated both the rate of recovery and the extent of motor and cognitive recovery, these findings suggest that electrical stimulation of the vagus nerve may prove to be an effective non-pharmacological treatment for traumatic brain injury.

A relationship between brain responses at birth and later emerging language and reading skills have been shown, but questions remain whether changes in brain responses after birth continue to predict the mastery of language-related skills such as reading development. To determine whether developmental changes in the brain-based perceptual skills are systematically related to differences in wordlevel reading proficiency at age 8 years, brain event-related potentials (ERPs) to speech and nonspeech stimuli were recorded annually at the ages of 1 through 8 years in a sample of 109 typically developing children. Two measures of wordlevel reading (one that requires decoding of real words and one of pseudowords) were administered at age 8 years. Growth curve analysis, using the hierarchical linear models, related reading performance (average versus low) to the longitudinal maturation in the ERP waveform peak and latencies. Maturational changes (e.g., slope, acceleration, and cubic growth) in N1 amplitude from ages 1 to 4 were related to proficiency in decoding pseudoword stimuli only, with children who were less proficient in decoding pseudowords evidencing more steeply negative declines in amplitude with age, particularly at the frontal and parietal recording sites in response to both speech and nonspeech stimuli. In contrast, proficiency in decoding real words was related to developmental changes in N2 amplitudes from ages 4 to 8 only at the parietal recording site, and only in response to nonspeech stimuli. The early development of biologically based differences in the perception and processing of auditory information contributes to later group differences in reading proficiencies at school age.

Development of reading skills was examined in 4-year-old children from low-income homes attending a prekindergarten program. Fall to spring gains in letter identification were examined and compared with skills in phonological processing, rhyme detection, and environmental print, and with performance on a screening tool (Get Ready to Read). It was anticipated that participants might show slow skill development. However, the identification of a large group of children (n = 30) who made little or no gains in letter identification compared to their classmates (n = 27), whose gains averaged 7 letters, was not anticipated. Fall to spring gains in letter identification correlated with phonological processing, rhyme detection, environmental print, and Get Ready to Read! scores. Age and general cognitive skills influenced performance on some tasks. More knowledge of the characteristics of children who show the most variations in skill development may lead to insights on using classroom curriculum to focus on skill development.

This paper focuses on methods useful for identifying differences in the development of language reading abilities in children that rely on measures of brain responses and behavioral assessments. Findings from longitudinal and cross-sectional studies using brain and behavior measures are described, along with findings from research designed to influence changes in brain and behavioral responses through training. The findings show differences in event-related potentials (ERP) responses recorded at birth that are related to a child's later performance on language and reading tasks. Such findings point to a strong biological influence on the development of language and reading skills. However, other findings show that the influence of biological factors on brain processing can be modified through learning. In fact, several studies show that even brief periods of stimulation and opportunities for learning can produce changes in the brain's ERP repsonses. Such findings suggest that new approaches to evaluating the effectiveness of interventions might change the rate and likelihood of developmental changes.

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