Detection of sounds is a fundamental function of the auditory system. While studies of auditory cortex have gained substantial insight into detection performance using animals performing operant conditioning tasks, previous subcortical studies have mostly taken place under anesthesia, in passively listening animals, or have not measured performance at threshold,. These limitations preclude direct comparisons between neuronal responses and behavior. To address this, we simultaneously measured auditory detection performance and single-unit activity in the inferior colliculus (IC) and cochlear nucleus (CN) in macaques. The spontaneous activity and response variability of CN neurons were higher than those observed for IC neurons. Signal detection theoretic methods revealed that the magnitude of responses of IC neurons provided more reliable estimates of psychometric threshold and slope compared to the responses of CN neurons. Correlations between spike count and behavioral response emerged 50-75 ms after sound onset for most IC neurons, but for fewer neurons in the CN. Electrical stimulation of the IC enhanced or degraded detection performance, depending on the response magnitude of the neurons being stimulated. These results highlight the differences between neurometric-psychometric correlations in CN and IC, and have important implications for how subcortical information could be decoded.

Adjuvant chemotherapy has been used for decades to treat cancer, and it is well known that disruptions in cognitive function and memory are common chemotherapeutic adverse effects. However, studies using neuropsychological metrics have also reported group differences in cognitive function and memory before or without chemotherapy, suggesting that complex factors obscure the true etiology of chemotherapy-induced cognitive dysfunction (CICD) in humans. Therefore, to better understand possible mechanisms of CICD, we explored the effects of CICD in rats through cognition testing using novel object recognition (NOR) and contextual fear conditioning (CFC), and through metabolic neuroimaging via [F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Cancer-naïve, female Sprague-Dawley rats were administered either saline (1 mL/kg) or doxorubicin (DOX) (1 mg/kg in a volume of 1 mL/kg) weekly for five weeks (total dose = 5 mg/kg), and underwent cognition testing and PET imaging immediately following the treatment regime and 30 days post treatment. We did not observe significant differences with CFC testing post-treatment for either group. However, the chemotherapy group exhibited significantly decreased performance in the NOR test and decreasedF-FDG uptake only in the prefrontal cortex 30 days post-treatment. These results suggest that long-term impairment within the prefrontal cortex is a plausible mechanism of CICD in this study, suggesting DOX-induced toxicity in the prefrontal cortex at the dose used.

The relationship between sound duration and detection threshold has long been thought to reflect temporal integration. Reports of species differences in this relationship are equivocal: some meta-analyses report no species differences, whereas others report substantial differences, particularly between humans and their close phylogenetic relatives, macaques. This renders translational work in macaques problematic. To reevaluate this difference, tone detection performance was measured in macaques using a go/no-go reaction time (RT) task at various tone durations and in the presence of broadband noise (BBN). Detection thresholds, RTs, and the dynamic range (DR) of the psychometric function decreased as the tone duration increased. The threshold by duration trends suggest macaques integrate at a similar rate to humans. The RT trends also resemble human data and are the first reported in animals. Whereas the BBN did not affect how the threshold or RT changed with the duration, it substantially reduced the DR at short durations. A probabilistic Poisson model replicated the effects of duration on threshold and DR and required integration from multiple simulated auditory nerve fibers to explain the performance at shorter durations. These data suggest that, contrary to previous studies, macaques are uniquely well-suited to model human temporal integration and form the baseline for future neurophysiological studies.

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