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Jared W Young - One of the best experts on this subject based on the ideXlab platform.
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Amphetamine improves rat 5-choice Continuous Performance Test (5C-CPT) irrespective of concurrent low-dose haloperidol treatment
Psychopharmacology, 2020Co-Authors: Jared W Young, Benjamin Z. Roberts, Michelle Breier, Neal R. SwerdlowAbstract:Rationale Cognitive dysfunction mediates functional impairment in patients with schizophrenia, necessitating the timely development of pro-cognitive therapeutics. An important initial step in this process is to establish what, if any, pro-cognitive agents and associated mechanisms can be identified using cross-species translational paradigms. For example, attentional deficits—a core feature of schizophrenia—can be measured across species using the 5-choice Continuous Performance Test (5C-CPT). The psychostimulant, amphetamine, improves human and rodent 5C-CPT Performance. Objective Here, we Tested whether amphetamine would similarly improve 5C-CPT Performance in the presence of dopamine D2 receptor blockade, since pro-cognitive treatments in schizophrenia would virtually always be used in conjunction with D2 receptor antagonists. Methods We established the dose-response effects of amphetamine (0, 0.1, 0.3, or 1.0 mg/kg) and haloperidol (0, 3.2, 10, or 32 μg/kg) on 5C-CPT Performance in Long Evans rats, and then Tested an amphetamine (0.3 mg/kg) × haloperidol (10 μg/kg) interaction; the low dose was chosen because higher doses exerted deleterious non-specific effects on Performance. Results Amphetamine improved 5C-CPT Performance in poorly performing rats by increasing target detection, independent of haloperidol pretreatment. Conclusions The pro-attentional effects of amphetamine were most likely mediated by dopamine release at D1-family receptors, since they persisted in the presence of acute D2 blockade. Alternative explanations for these findings are also discussed, as are their potential implications for future pro-cognitive therapeutics in schizophrenia.
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amphetamine improves rat 5 choice Continuous Performance Test 5c cpt irrespective of concurrent low dose haloperidol treatment
Psychopharmacology, 2020Co-Authors: Jared W Young, Benjamin Z. Roberts, Michelle R Breier, Neal R. SwerdlowAbstract:Cognitive dysfunction mediates functional impairment in patients with schizophrenia, necessitating the timely development of pro-cognitive therapeutics. An important initial step in this process is to establish what, if any, pro-cognitive agents and associated mechanisms can be identified using cross-species translational paradigms. For example, attentional deficits—a core feature of schizophrenia—can be measured across species using the 5-choice Continuous Performance Test (5C-CPT). The psychostimulant, amphetamine, improves human and rodent 5C-CPT Performance. Here, we Tested whether amphetamine would similarly improve 5C-CPT Performance in the presence of dopamine D2 receptor blockade, since pro-cognitive treatments in schizophrenia would virtually always be used in conjunction with D2 receptor antagonists. We established the dose-response effects of amphetamine (0, 0.1, 0.3, or 1.0 mg/kg) and haloperidol (0, 3.2, 10, or 32 μg/kg) on 5C-CPT Performance in Long Evans rats, and then Tested an amphetamine (0.3 mg/kg) × haloperidol (10 μg/kg) interaction; the low dose was chosen because higher doses exerted deleterious non-specific effects on Performance. Amphetamine improved 5C-CPT Performance in poorly performing rats by increasing target detection, independent of haloperidol pretreatment. The pro-attentional effects of amphetamine were most likely mediated by dopamine release at D1-family receptors, since they persisted in the presence of acute D2 blockade. Alternative explanations for these findings are also discussed, as are their potential implications for future pro-cognitive therapeutics in schizophrenia.
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amphetamine improves mouse and human attention in the 5 choice Continuous Performance Test
Neuropharmacology, 2018Co-Authors: David A Macqueen, Jared W Young, Mark A Geyer, Arpi Minassian, Johnny A Kenton, William Perry, Jonathan L BrigmanAbstract:Abstract Non-medical use of prescription stimulants amongst college students is common, with claims of cognitive and academic benefits. The mechanism, magnitude, and pervasiveness of the cognitive enhancing effects of stimulants in healthy adults remain poorly understood however. The present study determined the effects of dextroamphetamine (D-amp) on the 5-choice Continuous Performance Test (5C-CPT) of attention in healthy young adult humans and mice. A mixed gender sample received placebo (n = 29), 10 (n = 17) or 20 mg D-amp (n = 25) in a double-blind fashion before 5C-CPT Testing. In addition, male C57BL/6J mice were trained on a touchscreen adaptation of the 5C-CPT and Tested after receiving saline or D-amp (0.1, 0.3, 1.0 mg/kg; n = 8/dose). In humans, D-amp significantly improved 5C-CPT Performance. Both doses improved signal detection driven by increased hit rate (reduced omissions). Both doses also improved response accuracy and reduced hit reaction time (HRT) variability. In mice, similar effects (improved signal detection, hit rate, and response accuracy) were observed at the moderate dose (0.3 mg/kg). In contrast to human participants however, no effect on HRT variability was detected in mice, with no effect on HRT in either species. Human 5C-CPT Performance was consistent with prior studies and consistent with alternative CPT paradigms. The Performance of C57BL/6J mice on the touchscreen 5C-CPT mirrored Performance of this strain on 5-hole operant chambers. Importantly, comparable facilitation of attention with D-amp was observed in both species. The 5C-CPT provides a cross-species paradigm by which the cognitive enhancing properties of stimulants and the neural underpinnings of attention can be assessed.
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differences in the Performance of nk1r knockout and wildtype mice in the 5 choice Continuous Performance Test
Behavioural Brain Research, 2016Co-Authors: Ashley J Porter, Jared W Young, Katharine Pillidge, Clare S StanfordAbstract:Mice lacking functional NK1 (substance P-preferring) receptors typically display excessive inattentiveness (omission errors) and impulsivity (premature responses) when compared with wildtypes in the 5-Choice Serial Reaction-Time Test (5-CSRTT). These abnormal behaviours are analogous to those seen in humans suffering from Attention Deficit Hyperactivity Disorder (ADHD). Here we used the 5-Choice Continuous‑Performance Test (5C-CPT) to ascertain whether NK1R−/− mice also display excessive false alarms (an inappropriate response to a ‘no-go’ signal), which is another form of impulsive behaviour. NK1R−/− mice completed more trials than wildtypes, confirming their ability to learn and carry out the task. At the start of Stage 1 of training, but not subsequently, they also scored more premature responses than wildtypes. When the mice were Tested for the first time, neither false alarms nor premature responses was higher in NK1R−/− mice than wildtypes but, as in the 5-CSRTT, the latter behaviour was strongly dependent on time of day. NK1R−/− mice expressed excessive perseveration during all stages of the 5C-CPT. This behaviour is thought to reflect compulsive checking, which is common in ADHD patients. These findings point to differences in the 5-CSRTT and 5C-CPT protocols that could be important for distinguishing why the cognitive Performance and response control of NK1R−/− mice differs from their wildtypes. The results further lead to the prediction that ADHD patients with polymorphism of the TACR1 gene (the human equivalent of Nk1r) would express more perseveration, but not false alarms, in Continuous Performance Tests when compared with other groups of subjects.
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Sleep deprivation impairs Performance in the 5-choice Continuous Performance Test: Similarities between humans and mice
Behavioural brain research, 2013Co-Authors: Jordy Van Enkhuizen, Mark A Geyer, Dean T. Acheson, Victoria B. Risbrough, Sean P.a. Drummond, Jared W YoungAbstract:Abstract Several groups undergo extended periods without sleep due to working conditions or mental illness. Such sleep deprivation (SD) can deleteriously affect attentional processes and disrupt work and family functioning. Understanding the biological underpinnings of SD effects may assist in developing sleep therapies and cognitive enhancers. Utilizing cross-species Tests of attentional processing in humans and rodents would aid in mechanistic studies examining SD-induced inattention. We assessed the effects of 36 h of: (1) Total SD (TSD) in healthy male and female humans ( n = 50); and (2) REM SD (RSD) in male C57BL/6 mice ( n = 26) on Performance in the cross-species 5-choice Continuous Performance Test (5C-CPT). The 5C-CPT includes target trials on which subjects were required to respond and non-target trials on which subjects were required to inhibit from responding. TSD-induced effects on human psychomotor vigilance Test (PVT) were also examined. Effects of SD were also examined on mice split into good and poor Performance groups based on pre-deprivation scores. In the human 5C-CPT, TSD decreased hit rate and vigilance with trend-level effects on accuracy. In the PVT, TSD slowed response times and increased lapses. In the mouse 5C-CPT, RSD reduced accuracy and hit rate with trend-level effects on vigilance, primarily in good performers. In conclusion, SD induced impaired 5C-CPT Performance in both humans and mice and validates the 5C-CPT as a cross-species translational task. The 5C-CPT can be used to examine mechanisms underlying SD-induced deficits in vigilance and assist in Testing putative cognitive enhancers.
Keith H Nuechterlein - One of the best experts on this subject based on the ideXlab platform.
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probing attentional dysfunctions in schizophrenia startle modification during a Continuous Performance Test
Psychophysiology, 2008Co-Authors: Erin A Hazlett, Michael E Dawson, Anne M Schell, Keith H NuechterleinAbstract:Startle eyeblink modification was measured in 20 relatively asymptomatic medicated schizophrenia outpatients and 18 matched controls in order to Test for deficits in early and later stages of attentional processing during a memory-load version of the Continuous Performance Test. Participants viewed a series of digits and pressed a button after the digit 7 of each 3-7 sequence. On some trials, a startling noise burst was presented either 120 or 1200 ms following cues that a response might be needed soon (the digit 3) and also following noncues. Controls showed greater startle inhibition at 120 ms following cue than noncue prepulses, whereas patients showed equal inhibition to both, suggesting a deficiency in allocation of controlled attentional resources in early stages of processing. The patients, however, did show large startle inhibition at 120 ms when a distracting stimulus accompanied the task-relevant cue, unlike the controls, who ignored the distracting stimulus. In contrast, both groups showed equal startle inhibition 1200 ms following cue and noncue prepulses, indicating that later modality-specific attention processes are not impaired in patients during this paradigm. Both groups also showed equal inhibition at 120 ms during passively attended prepulses, suggesting that automatic attentional processes were not impaired in these patients.
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attentional stages of information processing during a Continuous Performance Test a startle modification analysis
Psychophysiology, 2001Co-Authors: Erin A Hazlett, Michael E Dawson, Anne M Schell, Keith H NuechterleinAbstract:This study of 31 college students employed the startle eye-blink modification (SEM) technique to index both early and later stages of attentional processing during a memory-load version of the Continuous Performance Test (CPT). Participants viewed a series of digits and pressed a button after the digit 7 of each 3-7 sequence. A startling noise burst was presented either 120 or 1,200 ms following three preselected prepulses: target (3), nontarget (non-3 and non-7 digits), or target plus distractor (3 and simultaneous tone distractor). Greater startle inhibition occurred 120 ms following target and target-plus-distractor prepulses compared with nontargets, indicating early selective attention. No difference was observed between SEM during target and target-plus-distractor prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the three prepulse types produced nondifferential inhibition, suggesting that modality-specific selective attention occurs in anticipation of the presentation of the next CPT prepulse. These findings indicate that SEM distinguishes between different early selective attention and later anticipatory attention subprocesses underlying the CPT.
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glucose metabolic correlates of Continuous Performance Test Performance in adults with a history of infantile autism schizophrenics and controls
Schizophrenia Research, 1995Co-Authors: Benjamin V Siegel, Keith H Nuechterlein, Lennart Abel, Monte S. BuchsbaumAbstract:Twenty-five schizophrenic patients, fourteen adults with a history of infantile autism, and twenty normal controls performed a Test of sustained attention, the degraded stimulus Continuous Performance Test (CPT), during the 35 minute 18-fluoro-2-deoxyglucose uptake period preceding positron emission tomographic (PET) scan acquisition. This is the first analysis comparing correlations between glucose metabolic rate (GMR) for selected regions and CPT Performance. CPT Performance differed in controls and schizophrenics, but autistics did not differ from either group. In controls and schizophrenic patients, task Performance correlated with GMR in medial superior frontal gyrus and lateral inferior temporal gyrus, suggesting that activation of those regions is important in the normal Performance of the task and that damage to those regions, which also showed low GMR in schizophrenics, contributes to the attentional dysfunction in schizophrenia. Also, schizophrenics showed negative correlations of task Performance with anterior cingulate activity suggesting that overactivity of that region, which is involved in mental effort and whose GMR was low in our larger study of schizophrenia, impairs task Performance in schizophrenics. Autistic patients showed negative correlations of medial frontal cortical GMR with attentional Performance, suggesting that neuronal inefficiency in that region may contribute to poor Performance.
Maitane Caballeropuntiverio - One of the best experts on this subject based on the ideXlab platform.
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adhd medication and the inverted u shaped curve a pharmacological study in female mice performing the rodent Continuous Performance Test rcpt
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2020Co-Authors: Linda Lerdrup, Maitane Caballeropuntiverio, L Arvastson, Susana Aznar, Jesper T. AndreasenAbstract:Abstract Background The rodent Continuous Performance Test (rCPT) is an analogue of human CPTs where mice have to discriminate between target and non-target stimuli. The rCPT offers a readout of attentional Performance and impulsive behaviour. This study aimed to determine if female C57BL/6 J mice could be trained in the rCPT since previously published rCPT studies have only used male mice and to study whether the effects of methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (AMPH) on attention and impulsivity depend on baseline (reference) levels of Performance. Methods 48 female mice underwent rCPT training. Effects of MPH (1, 2, and 3 mg/kg), ATX (1, 3, and 5 mg/kg) and AMPH (0.3, 0.6, and 1 mg/kg) were assessed in a variable stimulus duration probe. Drugs were administered intraperitoneally and sequentially Tested following a Latin-square design. Data were analysed using a repeated measurements mixed effect model and reference-dependent effects were studied. Results ATX and AMPH improved Performance as seen by increases in discriminability. These improvements were a result of a decreased false-alarm rate. AMPH showed a reference-dependent effect, improving the task Performance of low-performing mice and decreasing the Performance of high-performing mice. MPH also showed this reference-dependent effects, albeit to a lesser extent. ATX and AMPH decreased premature responses and increased response criterion, but no reference-dependent effects were observed for these parameters. Conclusion This study presents a novel method to analyse baseline-dependent effects. It shows that the rCPT can be successfully used in pharmacological studies in female mice and demonstrates that the effect of ADHD medication is in line with the inverted U-shape theory of Performance-arousal relationship.
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effect of adhd medication in male c57bl 6j mice performing the rodent Continuous Performance Test
Psychopharmacology, 2019Co-Authors: Linda Lerdrup, M. Grupe, C. W. Larsen, A. G. Dietz, Maitane Caballeropuntiverio, Jesper T. AndreasenAbstract:Rationale The rodent Continuous Performance Test (rCPT) is a novel rodent paradigm to assess attention and impulsivity that resembles the human CPT. This task measures the rodents’ ability to discriminate between target and non-target stimuli. The effect of attention-deficit/hyperactivity disorder (ADHD) medication on rCPT Performance in mice remains to be fully characterized.
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effect of adhd medication in male c57bl 6j mice performing the rodent Continuous Performance Test
Psychopharmacology, 2019Co-Authors: Linda Lerdrup, M. Grupe, C. W. Larsen, A. G. Dietz, Maitane Caballeropuntiverio, Jesper T. AndreasenAbstract:The rodent Continuous Performance Test (rCPT) is a novel rodent paradigm to assess attention and impulsivity that resembles the human CPT. This task measures the rodents’ ability to discriminate between target and non-target stimuli. The effect of attention-deficit/hyperactivity disorder (ADHD) medication on rCPT Performance in mice remains to be fully characterized. To investigate the predictive validity of the mouse rCPT by studying the effects of ADHD medication methylphenidate, atomoxetine, amphetamine, guanfacine, and modafinil in four behavioral subgroups based on Performance and impulsivity levels. Two cohorts of male C57BL/6J mice were used, and the effect of treatment was Tested in a variable stimulus duration probe. Performance and impulsive subgroups were made based on discriminability and percentage premature responses, respectively. Methylphenidate, atomoxetine, and amphetamine improved Performance in the low-performing animals, with no effect in the high-performers. These improvements were a result of increased hit rate and/or decreased false-alarm rate. Furthermore, these drugs decreased percentage premature responses in the high-impulsive group. Methylphenidate, guanfacine, and modafinil increased premature responses in the low-impulsive group. Modafinil impaired Performance in the high-performers by increasing false-alarm rate. The effect of ADHD treatment was dependent on baseline, as seen by increases in Performance for the low-performers and decreases in impulsivity for the high-impulsive animals. These results agree with clinical data and may support the inverted U-shaped arousal-Performance theory. The rCPT combined with behavioral separation into subgroups has high predictive validity, and our study is a step forward towards establishing the clinical translatability of the rCPT.
Erin A Hazlett - One of the best experts on this subject based on the ideXlab platform.
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probing attentional dysfunctions in schizophrenia startle modification during a Continuous Performance Test
Psychophysiology, 2008Co-Authors: Erin A Hazlett, Michael E Dawson, Anne M Schell, Keith H NuechterleinAbstract:Startle eyeblink modification was measured in 20 relatively asymptomatic medicated schizophrenia outpatients and 18 matched controls in order to Test for deficits in early and later stages of attentional processing during a memory-load version of the Continuous Performance Test. Participants viewed a series of digits and pressed a button after the digit 7 of each 3-7 sequence. On some trials, a startling noise burst was presented either 120 or 1200 ms following cues that a response might be needed soon (the digit 3) and also following noncues. Controls showed greater startle inhibition at 120 ms following cue than noncue prepulses, whereas patients showed equal inhibition to both, suggesting a deficiency in allocation of controlled attentional resources in early stages of processing. The patients, however, did show large startle inhibition at 120 ms when a distracting stimulus accompanied the task-relevant cue, unlike the controls, who ignored the distracting stimulus. In contrast, both groups showed equal startle inhibition 1200 ms following cue and noncue prepulses, indicating that later modality-specific attention processes are not impaired in patients during this paradigm. Both groups also showed equal inhibition at 120 ms during passively attended prepulses, suggesting that automatic attentional processes were not impaired in these patients.
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attentional stages of information processing during a Continuous Performance Test a startle modification analysis
Psychophysiology, 2001Co-Authors: Erin A Hazlett, Michael E Dawson, Anne M Schell, Keith H NuechterleinAbstract:This study of 31 college students employed the startle eye-blink modification (SEM) technique to index both early and later stages of attentional processing during a memory-load version of the Continuous Performance Test (CPT). Participants viewed a series of digits and pressed a button after the digit 7 of each 3-7 sequence. A startling noise burst was presented either 120 or 1,200 ms following three preselected prepulses: target (3), nontarget (non-3 and non-7 digits), or target plus distractor (3 and simultaneous tone distractor). Greater startle inhibition occurred 120 ms following target and target-plus-distractor prepulses compared with nontargets, indicating early selective attention. No difference was observed between SEM during target and target-plus-distractor prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the three prepulse types produced nondifferential inhibition, suggesting that modality-specific selective attention occurs in anticipation of the presentation of the next CPT prepulse. These findings indicate that SEM distinguishes between different early selective attention and later anticipatory attention subprocesses underlying the CPT.
Lauren M Scimeca - One of the best experts on this subject based on the ideXlab platform.
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examining conners Continuous Performance Test 3 cpt 3 embedded Performance validity indicators in an adult clinical sample referred for adhd evaluation
Developmental Neuropsychology, 2021Co-Authors: Lauren M Scimeca, Lindsey Holbrook, Tasha Rhoads, Brian M Cerny, Kyle J Jennette, Zachary J ReschAbstract:This study evaluated multiple previously-identified Continuous Performance Test-Third Edition (CPT-3) scores as embedded validity indicators (EVIs) among 201 adults undergoing neuropsychological evaluation for Attention-Deficit/Hyperactivity Disorder (ADHD) divided into valid (n = 169) and invalid (n = 32) groups based on seven criterion measures. Although 6/10 CPT-3 scores accurately detected invalidity, only two reached minimally acceptable classification accuracy of ≥0.70. The remaining four had unacceptably low accuracy (AUCs = 0.62-0.69) with 0.19-0.41 sensitivity at ≥0.90 specificity. Composite scores did not provide better classification accuracy than individual CPT-3 scores. In sum, CPT-3 individual and composite scores generally are not accurate PVTs among adults undergoing clinical evaluation for ADHD.