Chronic exposure to psychostimulants such as amphetamine (AMPH) can induce long-term disruptions in cognition via actions on prefrontal cortex dopamine. Previous work has shown that two types of executive functions, set shifting and working memory (WM), are disrupted by AMPH sensitization and that these cognitive domains are impaired in schizophrenics and stimulant abusers. We assessed the effects of AMPH sensitization on behavioural flexibility using a cross-maze set shifting task and a WM task using the delayed spatial win-shift (SWSh) task in Long Evans (LE) and Sprague Dawley (SD) rats. Rats were exposed to an AMPH sensitization regimen (15 AMPH or saline injections: 1-5 mg/kg every 2nd day, increasing the dose by 1 mg every 3rd injections) following habituation on the mazes. In experiment 1, LE and SD rats were initially trained on a visual cue discrimination. During the set shift, rats were required to shift from the previously acquired visual-cue-based strategy to a response strategy (e.g.; always turn left, ignore the visual cue). For the reversal, rats were trained to reverse their turn direction. AMPH treatment did not impair learning of the initial cue discrimination in either strain. However, AMPH treated rats learned the response discrimination faster than controls during the set shift and AMPH treated LE rats were faster than controls to reach acquisition criterion during the response reversal. AMPH treatment neither impaired nor improved reversal learning in SD rats. In experiment 2, rats were tested on the SWSh task in which spatial information acquired during a training phase was used 30 minutes later during the testing phase in order to retrieve food pellets on the maze. In this task, AMPH treated rats were faster to re-attain criterion than control rats. Correlational analysis further revealed that AMPH sensitized rats that required more days to reach criterion before AMPH treatment (i.e. slow learners) tended to make more errors during re-acquisition of the memory task. Viewed collectively, these results suggest that chronic AMPH treatment can enhance behavioural flexibility and WM assessed in this manner. However, repeated AMPH exposure may have exacerbated pre-existing cognitive deficits in slow learning rats.

Chronic exposure to psychostimulants such as amphetamine (AMPH) can induce long-term disruptions in cognition via actions on prefrontal cortex dopamine. Previous work has shown that two types of executive functions, set shifting and working memory (WM), are disrupted by AMPH sensitization and that these cognitive domains are impaired in schizophrenics and stimulant abusers. We assessed the effects of AMPH sensitization on behavioural flexibility using a cross-maze set shifting task and a WM task using the delayed spatial win-shift (SWSh) task in Long Evans (LE) and Sprague Dawley (SD) rats. Rats were exposed to an AMPH sensitization regimen (15 AMPH or saline injections: 1-5 mg/kg every 2nd day, increasing the dose by 1 mg every 3rd injections) following habituation on the mazes. In experiment 1, LE and SD rats were initially trained on a visual cue discrimination. During the set shift, rats were required to shift from the previously acquired visual-cue-based strategy to a response strategy (e.g.; always turn left, ignore the visual cue). For the reversal, rats were trained to reverse their turn direction. AMPH treatment did not impair learning of the initial cue discrimination in either strain. However, AMPH treated rats learned the response discrimination faster than controls during the set shift and AMPH treated LE rats were faster than controls to reach acquisition criterion during the response reversal. AMPH treatment neither impaired nor improved reversal learning in SD rats. In experiment 2, rats were tested on the SWSh task in which spatial information acquired during a training phase was used 30 minutes later during the testing phase in order to retrieve food pellets on the maze. In this task, AMPH treated rats were faster to re-attain criterion than control rats. Correlational analysis further revealed that AMPH sensitized rats that required more days to reach criterion before AMPH treatment (i.e. slow learners) tended to make more errors during re-acquisition of the memory task. Viewed collectively, these results suggest that chronic AMPH treatment can enhance behavioural flexibility and WM assessed in this manner. However, repeated AMPH exposure may have exacerbated pre-existing cognitive deficits in slow learning rats.

Chronic exposure to psychostimulants such as amphetamine (AMPH) can induce long-term disruptions in cognition via actions on prefrontal cortex dopamine. Previous work has shown that two types of executive functions, set shifting and working memory (WM), are disrupted by AMPH sensitization and that these cognitive domains are impaired in schizophrenics and stimulant abusers. We assessed the effects of AMPH sensitization on behavioural flexibility using a cross-maze set shifting task and a WM task using the delayed spatial win-shift (SWSh) task in Long Evans (LE) and Sprague Dawley (SD) rats. Rats were exposed to an AMPH sensitization regimen (15 AMPH or saline injections: 1-5 mg/kg every 2nd day, increasing the dose by 1 mg every 3rd injections) following habituation on the mazes. In experiment 1, LE and SD rats were initially trained on a visual cue discrimination. During the set shift, rats were required to shift from the previously acquired visual-cue-based strategy to a response strategy (e.g.; always turn left, ignore the visual cue). For the reversal, rats were trained to reverse their turn direction. AMPH treatment did not impair learning of the initial cue discrimination in either strain. However, AMPH treated rats learned the response discrimination faster than controls during the set shift and AMPH treated LE rats were faster than controls to reach acquisition criterion during the response reversal. AMPH treatment neither impaired nor improved reversal learning in SD rats. In experiment 2, rats were tested on the SWSh task in which spatial information acquired during a training phase was used 30 minutes later during the testing phase in order to retrieve food pellets on the maze. In this task, AMPH treated rats were faster to re-attain criterion than control rats. Correlational analysis further revealed that AMPH sensitized rats that required more days to reach criterion before AMPH treatment (i.e. slow learners) tended to make more errors during re-acquisition of the memory task. Viewed collectively, these results suggest that chronic AMPH treatment can enhance behavioural flexibility and WM assessed in this manner. However, repeated AMPH exposure may have exacerbated pre-existing cognitive deficits in slow learning rats. / Medicine, Faculty of / Graduate

The nature and assessment of executive function are areas of active research. Many current assessments of executive function are complex, have limited reliability and validity, and suffer from task impurity, meaning other cognitive processes may indirectly influence task performance. Additionally, measures may be culture, language, or education bound limiting their use in certain populations (Miyake, Emerson, & Friedman, 2000; Miyake, Friedman, et al., 2000; Strauss, Sherman, & Spreen, 2006; Stuss, 2007). The purpose of this project was to develop a novel set of executive function measures to address issues with current clinical measures. The new measures 1) can be used in an ERP environment, 2) use the same stimulus set to address task impurity and 3) use simpler cognitive operations of inhibition, set-shifting, and updating, identified in previous research by Miyake et al., (2000). Twenty-nine undergraduate participants at the University of South Florida were administered currently used clinical measures of executive function theorized to engage in inhibition, set-shifting, and updating and the set of the novel tasks. ERP data was collected during the administration of the novel tasks. Behaviorally, conditions theorized to engage executive function resulted in slower response reaction time than control conditions. Additionally, behavioral results indicated that performance on novel tasks were differentially related to different clinical EF tasks. ERP differences were observed between both Go/No-Go conditions (inhibition) and among N-back conditions (updating). Results suggest the novel executive function tasks are tapping into different cognitive processes and may be a viable tool for studying executive function in the future.

Yes / Phencyclidine (PCP), used to mimic certain aspects of schizophrenia, induces sexually dimorphic, cognitive deficits in rats. In this study, the effects of sub-chronic PCP on expression of brain-derived neurotrophic factor (BDNF), a neurotrophic factor implicated in the pathogenesis of schizophrenia, have been evaluated in male and female rats. Male and female hooded-Lister rats received vehicle or PCP (n = 8 per group; 2 mg/kg i.p. twice daily for 7 days) and were tested in the attentional set shifting task prior to being sacrificed (6 weeks post-treatment). Levels of BDNF mRNA were measured in specific brain regions using in situ hybridisation. Male rats were less sensitive to PCP-induced deficits in the extra-dimensional shift stage of the attentional set shifting task compared to female rats. Quantitative analysis of brain regions demonstrated reduced BDNF levels in the medial prefrontal cortex (p < 0.05), motor cortex (p < 0.01), orbital cortex (p < 0.01), olfactory bulb (p < 0.05), retrosplenial cortex (p < 0.001), frontal cortex (p < 0.01), parietal cortex (p < 0.01), CA1 (p < 0.05) and polymorphic layer of dentate gyrus (p < 0.05) of the hippocampus and the central (p < 0.01), lateral (p < 0.05) and basolateral (p < 0.05) regions of the amygdaloid nucleus in female PCP-treated rats compared with controls. In contrast, BDNF was significantly reduced only in the orbital cortex and central amygdaloid region of male rats (p < 0.05). Results suggest that blockade of NMDA receptors by sub-chronic PCP administration has a long-lasting down-regulatory effect on BDNF mRNA expression in the female rat brain which may underlie some of the behavioural deficits observed post PCP administration.

The present study examined the claim that neuropsychological deficits in set-shifting and emotional decision making are present in eating disordered patients, and to what extent these deficits relate to specific aspects of disordered eating. Sixteen eating disordered patients and 38 controls were given a battery of neuropsychological measures, as well as questionnaires measuring disordered eating. Compared to controls, patients demonstrated poorer performance on tasks of set-shifting, but not decision making, psychomotor speed, working memory, or IQ. Across groups, poor set-shifting was correlated with food-, shape-, and weight concerns, and restricting, whereas poor decision making was correlated to restricting. The study demonstrates that set-shifting deficits are present in eating disordered patients, and that specific relations exist between cognitive performance in different domains and disordered eating.

Executive functions are important cognitive processes critical for survival. Damage to the prefrontal cortex impairs executive functions, such as working memory, decision making and set-shifting. Interestingly, patients diagnosed with different psychiatric disorders are also impaired in executive functions, especially in the set-shift domain, often measured by the Wisconsin Card Sorting Task (WCST). Set-shifting is an essential cognitive process, in that it allows the individual to suppress non-reinforcing strategies and engage in new rewarding strategies. To date, little is known about the etiology of executive dysfunction in psychiatric disorders. However, some epidemiological and serological experiments have shown strong correlations between prenatal infection and the increased risk to develop psychiatric disorders in the adult offspring. One study found that schizophrenic patients pre-exposed to a prenatal infection perseverated more during the WCST, than non-pre-exposed patients. Despite these findings, there are still numerous limitations (e.g., ethical concerns) when conducting these studies. Thus, animal models are important and can further elucidate the etiology of executive dysfunctions in psychiatric disorders. Prenatal infection animal models have consistently shown that inflammation during gestation in rodents induces behavioural, anatomical and cognitive changes in the adult offspring similar to psychiatric patients. However, no studies have investigated the effects of prenatal infection on set-shifting in the adult offspring. Therefore, the present thesis examined whether prenatal treatment with PolyI:C (a viral mimetic) during middle/late gestation of the rat would induce cognitive inflexibilities (i.e., set-shifting and reversal learning in an operant based task analogous to the WCST) in the adult male and female offspring. The results showed PolyI:C male offspring perseverated during the set-shift but had fewer regressive errors during the reversal learning day. PolyI:C treated female offspring were not impaired during any of the test days; however, females were slower to respond to the lever and required more training when compared the male rats. Taken together, these results give support for prenatal infection in inducing cognitive inflexibility, by potentially altering the PFC in the adult offspring. MS-based thesis: Zhang, Y., Cazakoff, B. N., Thai, C. A., & Howland, J. G. (2011). Prenatal exposure to a viral mimetic alters behavioural flexibility in male, but not female, rats. Neuropharmacology, [epub ahead of print]. doi:10.1016/j.neuropharm.2011.02.022

The present study examined the claim that neuropsychological deficits in set-shifting and emotional decision making are present in eating disordered patients, and to what extent these deficits relate to specific aspects of disordered eating. Sixteen eating disordered patients and 38 controls were given a battery of neuropsychological measures, as well as questionnaires measuring disordered eating. Compared to controls, patients demonstrated poorer performance on tasks of set-shifting, but not decision making, psychomotor speed, working memory, or IQ. Across groups, poor set-shifting was correlated with food-, shape-, and weight concerns, and restricting, whereas poor decision making was correlated to restricting. The study demonstrates that set-shifting deficits are present in eating disordered patients, and that specific relations exist between cognitive performance in different domains and disordered eating.

Executive functions are important cognitive processes critical for survival. Damage to the prefrontal cortex impairs executive functions, such as working memory, decision making and set-shifting. Interestingly, patients diagnosed with different psychiatric disorders are also impaired in executive functions, especially in the set-shift domain, often measured by the Wisconsin Card Sorting Task (WCST). Set-shifting is an essential cognitive process, in that it allows the individual to suppress non-reinforcing strategies and engage in new rewarding strategies. To date, little is known about the etiology of executive dysfunction in psychiatric disorders. However, some epidemiological and serological experiments have shown strong correlations between prenatal infection and the increased risk to develop psychiatric disorders in the adult offspring. One study found that schizophrenic patients pre-exposed to a prenatal infection perseverated more during the WCST, than non-pre-exposed patients. Despite these findings, there are still numerous limitations (e.g., ethical concerns) when conducting these studies. Thus, animal models are important and can further elucidate the etiology of executive dysfunctions in psychiatric disorders. Prenatal infection animal models have consistently shown that inflammation during gestation in rodents induces behavioural, anatomical and cognitive changes in the adult offspring similar to psychiatric patients. However, no studies have investigated the effects of prenatal infection on set-shifting in the adult offspring. Therefore, the present thesis examined whether prenatal treatment with PolyI:C (a viral mimetic) during middle/late gestation of the rat would induce cognitive inflexibilities (i.e., set-shifting and reversal learning in an operant based task analogous to the WCST) in the adult male and female offspring. The results showed PolyI:C male offspring perseverated during the set-shift but had fewer regressive errors during the reversal learning day. PolyI:C treated female offspring were not impaired during any of the test days; however, females were slower to respond to the lever and required more training when compared the male rats. Taken together, these results give support for prenatal infection in inducing cognitive inflexibility, by potentially altering the PFC in the adult offspring. MS-based thesis: Zhang, Y., Cazakoff, B. N., Thai, C. A., & Howland, J. G. (2011). Prenatal exposure to a viral mimetic alters behavioural flexibility in male, but not female, rats. Neuropharmacology, [epub ahead of print]. doi:10.1016/j.neuropharm.2011.02.022

Deficits in cognitive control are associated with problems disengaging from ruminative thought, a significant risk factor for depression. Cognitive control refers to higher order cognitive processes used for goal-directed behavior, including emotion regulation. The current study examined associations between the switching component of cognitive control and rumination and tested the effects of two interventions used to improve cognitive control and thereby decrease ruminative thought. Undergraduate participants completed self-report measures to assess symptoms and an internal shift task to assess shifting ability. Participants completed a mood and rumination induction and were randomly assigned to one session of the Attention Training Technique (ATT), (n = 69), mindfulness meditation (n = 70), or an attention filler control task (n = 72). Switching deficits and rumination were not associated. The ATT moved participants’ focus of attention externally, and this outward shift in attention predicted lower state rumination. Decentering, however, was not impacted by attention training or mindfulness. Focus of attention did not impact mood recovery despite significant improvement in sad mood across all conditions. Overall, one session of attention training and mindfulness appears to have an impact on sad mood, but this effect is not superior to a simple distraction task. More than one session may be necessary to observe substantial benefits from the ATT or mindfulness. Implications and future research are discussed.