Dynamics and maintenance of categorical responses in primary auditory cortex during task engagement.

Grouping sets of sounds into relevant categories is an important cognitive ability that enables the association of stimuli with appropriate goal-directed behavioral responses. In perceptual tasks, the primary auditory cortex (A1) assumes a prominent role by concurrently encoding both sound sensory features and task-related variables. Here, we sought to explore the role of A1 in the initiation of sound categorization, shedding light on its involvement in this cognitive process. We trained ferrets to discriminate click trains of different rates in a Go/No-Go delayed categorization task and recorded neural activity during both active behavior and passive exposure to the same sounds. Purely categorical response components were extracted and analyzed separately from sensory responses to reveal their contributions to the overall population response throughout the trials. We found that categorical activity emerged during sound presentation in the population average and was present in both active behavioral and passive states. However, upon task engagement, categorical responses to the No-Go category became suppressed in the population code, leading to an asymmetrical representation of the Go stimuli relative to the No-Go sounds and pre-stimulus baseline. The population code underwent an abrupt change at stimulus offset, with sustained responses after the Go sounds during the delay period. Notably, the categorical responses observed during the stimulus period exhibited a significant correlation with those extracted from the delay epoch, suggesting an early involvement of A1 in stimulus categorization.

Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit.

Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. The small population of surviving patients suffer extensive brain damage that results in substantial morbidity. Mitochondrial dysfunction in most organs after CA has been implicated as a major source of injury. Metformin, a first-line treatment for diabetes, has shown promising results in the treatment for other diseases and is known to interact with the mitochondria. For the treatment of CA, prior studies have utilized metformin in a preconditioning manner such that animals are given metformin well before undergoing CA. As the timing of CA is quite difficult to predict, the present study, in a clinically relevant manner, sought to evaluate the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial-CA rat model. This is the first study to show that metformin treatment post-CA (a) improves 72 h survival and neurologic function, (b) protects mitochondrial function with a reduction in apoptotic brain injury without activating AMPK, and (c) potentiates earlier normalization of brain electrophysiologic activity. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA.