Emerg Top Life Sci. 2022 Nov 21:ETLS20220009. doi: 10.1042/ETLS20220009. Online ahead of print.

ABSTRACT

Cognitive dysfunction, particularly attentional impairment, is a core feature of many psychiatric disorders, yet is inadequately addressed by current treatments. Development of targeted therapeutics for the remediation of attentional deficits requires knowledge of underlying neurocircuit, cellular, and molecular mechanisms that cannot be directly assayed in the clinic. This level of detail can only be acquired by testing animals in cross-species translatable attentional paradigms, in combination with preclinical neuroscience techniques. The 5-choice continuous performance test (5C-CPT) and rodent continuous performance test (rCPT) represent the current state of the art of preclinical assessment of the most commonly studied subtype of attention: sustained attention, or vigilance. These tasks present animals with continuous streams of target stimuli to which they must respond (attention), in addition to non-target stimuli from which they must withhold responses (behavioral inhibition). The 5C-CPT and rCPT utilize the same measures as gold-standard clinical continuous performance tests and predict clinical efficacy of known pro-attentional drugs. They also engage common brain regions across species, although efforts to definitively establish neurophysiological construct validity are ongoing. The validity of these tasks as translational vigilance assessments enables their use in characterizing the neuropathology underlying attentional deficits of animal models of psychiatric disease, and in determining therapeutic potential of drugs ahead of clinical testing. Here, we briefly review the development and validation of such tests of attentional functioning, as well as the data they have generated pertaining to inattention, disinhibition, and impulsivity in psychiatric disorders.

PMID:36408755 | DOI:10.1042/ETLS20220009