Modulating auditory attention and stimulus evaluation in the medial prefrontal cortex: A translational tone approach oddball paradigm in rats.

The three-class auditory oddball paradigm is used to study sensory processing, attention, and decision-making. In this paradigm, a rare behaviorally relevant target is presented among frequent behaviorally irrelevant standard and rare distractor tones. The Tone Approach Paradigm (TAP) was designed as a variation of this paradigm in which task difficulty increases as the target and distractor frequencies sequentially approach the frequency of the standard tone to investigate neurocognitive aspects of processing behaviorally relevant auditory stimuli under challenging hearing conditions in rats. Male Sprague-Dawley rats (n = 10) were trained to respond to target (5000 Hz), while ignoring distractor (1500 Hz) and standard tones (3000 Hz) in baseline (BSL) condition. After training, electrodes were implanted in the medial prefrontal cortex (mPFC) for local field potential recording during behavioral testing. Starting from BSL, the frequency differences between target and distractor to standard tones in the TAP sessions were reduced by 500 Hz per session. Hit ratios for targets declined with increasing difficulty of TAP sessions (p < 0.05). Cumulative distributions of reaction times shifted from a sigmoidal profile with stimulus-locked behavior to a more linear profile, suggesting less temporally clustered responding. Event-related potential amplitudes increased at low and moderate TAP difficulty, indicating higher processing effort, but decreased at the highest difficulty, suggesting impaired processing. Our findings show that manipulating task difficulty via frequency changes directly affects behavior and neural processing within the mPFC. TAP provides a translational framework for investigating neurophysiological mechanisms of attention and stimulus evaluation, with relevance for models of attention-related dysfunction.