Old dog, new tricks: the attentional set-shifting test as a novel cognitive behavioral task after controlled cortical...

Cognitive impairment associated with prefrontal cortical dysfunction is a major component of disability in traumatic brain injury (TBI) survivors. Specifically, deficits of cognitive flexibility and attentional set-shifting are present across all levels of injury severity. Though alterations in spatial learning have been extensively described in experimental models of TBI, studies investigating more complex cognitive deficits are relatively scarce. Hence, the aim of this preclinical study was to expand on this important issue by evaluating the effect of three injury levels on executive function and behavioral flexibility performance as assessed using an attentional set-shifting test (AST). Isoflurane-anesthetized male rats received a controlled cortical impact (CCI) injury (2.6, 2.8, and 3.0 mm cortical depth at 4 m/sec) or sham injury, whereas an additional group had no surgical manipulation (naïve). Four weeks postsurgery, rats were tested on the AST, which involved a series of discriminative tasks of increasing difficulty, such as simple and compound discriminations, stimulus reversals, and intra- and extradimensional (ED) shifts. TBI produced accompanying impact depth-dependent increases in cortical lesion volumes, with the 3.0-mm cortical depth group displaying significantly larger injury volumes than the 2.6-mm group (p=0.05). Further, injury severity-induced deficits in ED set-shifting and stimulus reversals, as well as increases in total response error rates and total set loss errors, were observed. These novel findings demonstrate executive function and behavioral flexibility deficits in our animal model of CCI injury and provide the impetus to integrate the AST in the standard neurotrauma behavioral battery to further evaluate cognitive dysfunction after TBI. Ongoing experiments in our laboratory are assessing AST performance after pharmacological and rehabilitative therapies post-TBI, as well as elucidating possible mechanisms underlying the observed neuropsychological deficits.