Localized and global representation of prior value, sensory evidence, and choice in male mouse cerebral cortex.

Adaptive behavior requires integrating prior knowledge of action outcomes and sensory evidence for making decisions while maintaining prior knowledge for future actions. As outcome- and sensory-based decisions are often tested separately, it is unclear how these processes are integrated in the brain. In a tone frequency discrimination task with two sound durations and asymmetric reward blocks, we found that neurons in the medial prefrontal cortex of male mice represented the additive combination of prior reward expectations and choices. The sensory inputs and choices were selectively decoded from the auditory cortex irrespective of reward priors and the secondary motor cortex, respectively, suggesting localized computations of task variables are required within single trials. In contrast, all the recorded regions represented prior values that needed to be maintained across trials. We propose localized and global computations of task variables in different time scales in the cerebral cortex.

Oddball-irrelevant visual stimuli cross-modally attenuate auditory mismatch negativity in rats.

OBJECTIVE: To elaborate the recent theory of prediction models of the brain in light of actual neural activities, it is important to investigate the cross-modal interactions in the context of prediction construction. To this end, in this study, we assessed whether cross-modal disturbances would result in the attenuation of mismatch negativity in anesthetized animal models. METHODS: A surface electrode array recorded neural activities from the visual and auditory cortices of rats under isoflurane anesthesia, during an auditory oddball paradigm over the course of three audiovisual sequences. In the audiovisual sequences, the visual stimuli were simultaneously presented with the first, second, or third standard before the deviants. RESULTS: The interrupting visual stimuli decrease the amplitude of mismatch negativity in the auditory and visual cortices. In addition, the correlation coefficients between the amplitude of middle-latency potential for the interrupting visual stimuli and the amplitude of mismatch negativity to the following auditory deviant stimuli were smaller when the visual stimuli were presented alongside the third standards from the deviants. CONCLUSION: Such attenuation in mismatch negativity has been often associated with a top-down mechanism and the present anesthesia selectively attenuates top-down transmission. Taken together, our study's findings indicate that the cross-modal disturbances on prediction and deviation detection may also be mediated by bottom-up mechanisms, as well as previously reported top-down mechanisms.

Auditory, Visual, and Cross-Modal Mismatch Negativities in the Rat Auditory and Visual Cortices.

When the brain tries to acquire an elaborate model of the world, multisensory integration should contribute to building predictions based on the various pieces of information, and deviance detection should repeatedly update these predictions by detecting "errors" from the actual sensory inputs. Accumulating evidence such as a hierarchical organization of the deviance-detection system indicates that the deviance-detection system can be interpreted in the predictive coding framework. Herein, we targeted mismatch negativity (MMN) as a type of prediction-error signal and investigated the relationship between multisensory integration and MMN. In particular, we studied whether and how cross-modal information processing affected MMN in rodents. We designed a new surface microelectrode array and simultaneously recorded visual and auditory evoked potentials from the visual and auditory cortices of rats under anesthesia. Then, we mapped MMNs for five types of deviant stimuli: single-modal deviants in (i) the visual oddball and (ii) auditory oddball paradigms, eliciting single-modal MMN; (iii) congruent audio-visual deviants, (iv) incongruent visual deviants, and (v) incongruent auditory deviants in the audio-visual oddball paradigm, eliciting cross-modal MMN. First, we demonstrated that visual MMN exhibited deviance detection properties and that the first-generation focus of visual MMN was localized in the visual cortex, as previously reported in human studies. Second, a comparison of MMN amplitudes revealed a non-linear relationship between single-modal and cross-modal MMNs. Moreover, congruent audio-visual MMN exhibited characteristics of both visual and auditory MMNs-its latency was similar to that of auditory MMN, whereas local blockage of N-methyl-D-aspartic acid receptors in the visual cortex diminished it as well as visual MMN. These results indicate that cross-modal information processing affects MMN without involving strong top-down effects, such as those of prior knowledge and attention. The present study is the first electrophysiological evidence of cross-modal MMN in animal models, and future studies on the neural mechanisms combining multisensory integration and deviance detection are expected to provide electrophysiological evidence to confirm the links between MMN and predictive coding theory.

Information flow in the rat thalamo-cortical system: spontaneous vs. stimulus-evoked activities.

The interaction between the thalamus and sensory cortex plays critical roles in sensory processing. Previous studies have revealed pathway-specific synaptic properties of thalamo-cortical connections. However, few studies to date have investigated how each pathway routes moment-to-moment information. Here, we simultaneously recorded neural activity in the auditory thalamus (or ventral division of the medial geniculate body; MGv) and primary auditory cortex (A1) with a laminar resolution in anesthetized rats. Transfer entropy (TE) was used as an information theoretic measure to operationalize "information flow". Our analyses confirmed that communication between the thalamus and cortex was strengthened during presentation of auditory stimuli. In the resting state, thalamo-cortical communications almost disappeared, whereas intracortical communications were strengthened. The predominant source of information was the MGv at the onset of stimulus presentation and layer 5 during spontaneous activity. In turn, MGv was the major recipient of information from layer 6. TE suggested that a small but significant population of MGv-to-A1 pairs was "information-bearing," whereas A1-to-MGv pairs typically exhibiting small effects played modulatory roles. These results highlight the capability of TE analyses to unlock novel avenues for bridging the gap between well-established anatomical knowledge of canonical microcircuits and physiological correlates via the concept of dynamic information flow.

Prepulse inhibition predicts subjective hearing in rats.

Auditory studies in animals benefit from quick and accurate audiometry. The auditory brainstem response (ABR) and prepulse inhibition (PPI) have been widely used for hearing assessment in animals, but how well these assessments predict subjective audiometry still remains unclear. Human studies suggest that subjective audiometry is consistent with the ABR-based audiogram, not with the PPI-based audiogram, likely due to top-down processing in the cortex that inhibits PPI. Here, we challenged this view in Wistar rats, as rodents exhibit less complexity of cortical activities and thereby less influence of the cerebral cortex on PPI compared to humans. To test our hypothesis, we investigated whether subjective audiometry correlates with ABR- or PPI-based audiograms across the range of audible frequencies in Wistar rats. The subjective audiogram was obtained through pure-tone audiometry based on operant conditioning. Our results demonstrated that both the ABR-based and PPI-based audiograms significantly correlated to the subjective audiogram. We also found that ASR strength was information-rich, and adequate interpolation of this data offered accurate audiometry. Thus, unlike in humans, PPI could be used to predict subjective audibility in rats.