A stop-signal task for sheep: introduction and validation of a direct measure for the stop-signal reaction time

Franziska Knolle,Rita P Goncalves,Sebastian D Mcbride,James E Stewart,A Jennifer Morton

doi:10.1007/s10071-017-1085-7

Abstract

Huntington’s disease (HD) patients show reduced flexibility in inhibiting an already-started response. This can be quantified by the stop-signal task. The aim of this study was to develop and validate a sheep version of the stop-signal task that would be suitable for monitoring the progression of cognitive decline in a transgenic sheep model of HD. Using a semi-automated operant system, sheep were trained to perform in a two-choice discrimination task. In 22% of the trials, a stop-signal was presented. Upon the stop-signal presentation, the sheep had to inhibit their already-started response. The stopping behaviour was captured using an accelerometer mounted on the back of the sheep. This set-up provided a direct read-out of the individual stop-signal reaction time (SSRT). We also estimated the SSRT using the conventional approach of subtracting the stop-signal delay (i.e., time after which the stop-signal is presented) from the ranked reaction time during a trial without a stop-signal. We found that all sheep could inhibit an already-started response in 91% of the stop-trials. The directly measured SSRT (0.974 ± 0.04 s) was not significantly different from the estimated SSRT (0.938 ± 0.04 s). The sheep version of the stop-signal task adds to the repertoire of tests suitable for investigating both cognitive dysfunction and efficacy of therapeutic agents in sheep models of neurodegenerative disease such as HD, as well as neurological conditions such as attention deficit hyperactivity disorder.

Highlights

Huntington’s disease (HD) is associated with profound changes in cognitive abilities (e.g., Stout et al 2011; Papoutsi et al 2014; Bates et al 2015)
During Training Stage 3, the response inhibition was introduced using a short presentation of the stop-signal
Our findings show that sheep are able to inhibit an already-started response with a reaction time of about 1 s and successfully revised their selection behaviour after the stop-signal

Summary

Introduction

Huntington’s disease (HD) is associated with profound changes in cognitive abilities (e.g., Stout et al 2011; Papoutsi et al 2014; Bates et al 2015). Response inhibition is a crucial cognitive skill that allows successful and flexible interactions with a constantly changing environment, by interrupting an action that is no longer desired (Verbruggen and Logan 2008; Ridderinkhof et al 2004). This cognitive ability is affected in neurodegenerative disorders such as HD (Rao et al 2014; Wiecki et al 2016), and in Parkinson’s disease (e.g., Gauggel et al 2004) and Alzheimer’s disease (e.g., Zancada-Menendez et al 2013), as well as in a variety of other psychiatric and psychological conditions such as schizophrenia (e.g., Enticott et al 2008), obsessive–compulsive disorder (e.g., Menzies et al 2007), hyperactivity (e.g., Solanto et al 2001; Winstanley et al 2006), impulsivity (e.g., Logan et al 1997), alcoholism (e.g., Li et al 2009; Noel et al 2016), obesity (e.g., Nederkoorn et al 2007), and gambling (e.g., Brevers et al 2012; Lawrence et al 2009).

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