Analysis of event-related potential (ERP) data includes several steps to ensure that ERPs meet an appropriate level of signal quality. One such step, subject exclusion, rejects subject data if ERP waveforms fail to meet an appropriate level of signal quality. Subject exclusion is an important quality control step in the ERP analysis pipeline as it ensures that statistical inference is based only upon those subjects exhibiting clear evoked brain responses. This critical quality control step is most often performed simply through visual inspection of subject-level ERPs by investigators. Such an approach is qualitative, subjective, and susceptible to investigator bias, as there are no standards as to what constitutes an ERP of sufficient signal quality. Here, we describe a standardized and objective method for quantifying waveform quality in individual subjects and establishing criteria for subject exclusion. The approach uses bootstrap resampling of ERP waveforms (from a pool of all available trials) to compute a signal-to-noise ratio confidence interval (SNR-CI) for individual subject waveforms. The lower bound of this SNR-CI (SNRLB) yields an effective and objective measure of signal quality as it ensures that ERP waveforms statistically exceed a desired signal-to-noise criterion. SNRLB provides a quantifiable metric of individual subject ERP quality and eliminates the need for subjective evaluation of waveform quality by the investigator. We detail the SNR-CI methodology, establish the efficacy of employing this approach with Monte Carlo simulations, and demonstrate its utility in practice when applied to ERP datasets.
Early-life administration of risperidone, the most widely used antipsychotic drug in children, leads to persistently elevated locomotor activity in adult rats. This study determined if and when elevated locomotor activity emerges during developmental risperidone administration. Developing and adult rats were given daily injections of risperidone (1.0 and 3.0 mg/kg) or vehicle for four weeks beginning at postnatal day (PND) 14 and 74, respectively. Starting with the first injection and every seven days thereafter, locomotor activity was measured immediately after the injection and 20 minutes prior to the next day’s injection. Activity was also recorded one week after the final injection. Risperidone profoundly decreased locomotor activity in developing and adult rats immediately after injection. Within 24 h after their first injection, adult rats administered risperidone demonstrated greater activity levels. In contrast, developing rats did not demonstrate compensatory hyperactivity until the beginning of the fourth week of risperidone administration. One week after the final risperidone injection, there was no evidence of hyperactivity in the adult rats maintained on risperidone, but developing rats administered risperidone, especially females, exhibited greater activity levels relative to vehicle-administered controls. In comparison to adult rats, the emergence of compensatory hyperactivity during long-term APD administration is delayed in developing rats but persists after treatment cessation.
Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0 mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at one-hour post-injection. At 23 hours post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at one hour post-injection. At 23 hours post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development.
Neuroimaging and patient work over the past decade have indicated that, following retinal deafferentation, the human visual cortex undergoes a large-scale and enduring reorganization of its topography such that the classical retinotopic organization of deafferented visual cortex remaps to represent non-classical regions of visual space. Such long-term visual reorganization is proposed to occur through changes in the functional balance of deafferented visual circuits that engage more lasting changes through activity-dependent neuroplasticity. Here, we investigated the short-term changes in functional balance (short-term plasticity; homeostatic plasticity) that occur within deafferented human visual cortices. We recorded electroencephalogram (EEG) while observers were conditioned for 6 s with a simulated retinal scotoma (artificial scotoma) positioned 8.0° in the periphery. Visual evoked potentials (VEPs) evoked by the onset of sinusoidal visual probes that varied in their tilt were used to examine changes in cortical excitability within and around cortical representations of the simulated scotoma. Psychophysical orientation functions obtained from discrimination of visual probe tilt were used to examine alterations in the stimulus selectivity within the scotoma representations. Consistent with a mechanism of homeostatic disinhibition, an early extrastriate component of the VEP (the early phase P1) exhibited increased amplitude following the condition with a simulated scotoma relative to a stimulus-matched control condition. This increased visual cortical response was associated with a reduction in the slope of the psychophysical orientation function, suggesting a broader tuning of neural populations within scotoma representations. Together, these findings support a mechanism of disinhibition in promoting visual plasticity and topographical reorganization.
Introduction: Research participation during undergraduate years has a powerful influence on career selection and attitudes toward scientific research. Most undergraduate research programs in academic health centers are oriented toward basic research or address a particular disease focus or research discipline. Undergraduate research programs that expose students to clinical and translational research may alter student perceptions about research and influence career selection. Methods: We developed an undergraduate summer research curriculum, anchored upon a clinical and translational research study developed to address a common unmet needs in neonatal nurseries (e.g., assessment of neonatal opioid withdrawal syndrome). Program topics reflected the cross-disciplinary expertise that contributed to the development of this “bedside to bench” study, including opioid addiction, vulnerable populations, research ethics, statistics, data collection and management, assay development, analytical laboratory analysis, and pharmacokinetics. The curriculum was delivered through three offerings over 12 months, using Zoom video-conferencing due to restrictions imposed by the COVID-19 pandemic. Results: Nine students participated in the program. Two-thirds reported the course enhanced their understanding of clinical and translational research. Over three-quarters reported the curriculum topics were very good or excellent. In open-ended questions, students reported that the cross-disciplinary nature of the curriculum was the strongest aspect of the program. Conclusion: The curriculum could be readily adapted by other Clinical and Translational Science Award programs seeking to provide clinical and translational research-oriented programs to undergraduate students. Application of cross-disciplinary research approaches to a specific clinical and translational research question provides students with relevant examples of translational research and translational science.
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