INHIBITION OF VOLUNTARY MOVEMENT: AN OVERVIEW

CUADERNOS HISPANOAMERICANOS DE PSICOLOGÍA, Vol. 10 No. 1, 67-74 INHIBITION OF VOLUNTARY MOVEMENT: AN OVERVIEW Mauricio Bonilla Carreño 1 Universidad El Bosque Recibido: Agosto 25 de 2009. Aceptado: Octubre 12 de 2009. Resumen Este artículo revisa el concepto de inhibición de respuesta, los dos paradigmas importantes para su estudio y la diferencia entre estos dos paradigmas. Se describe también el modelo de carrera de caballos y el algoritmo de rastreo, dos elementos necesarios para el funcionamiento correcto del paradigma Stop. Se hace también una revisión somera sobre la investigación del tema de la inhibición de respuestas abiertas con las técnicas de potenciales corticales evocados (PRADS) y la resonancia magnética funcional (fmri) Palabras clave: Inhibición de respuesta, paradigma Stop, Potenciales Relacionados con Eventos, Resonancia Magnética. Abstract This article reviews the concept of overt response inhibition, the two important paradigms for studying it and the difference between these paradigms. It is also described the horse-race model and the staircase-tracking algorithm, two necessary elements for the correct functioning of the stop signal task paradigm. It is also reviewed the research on inhibition of overt responses by Event Related Potentials (ERP) and functional Magnetic Resonance Techniques (fmri) Key words: Response inhibition, Stop paradigm, Event Related Potentials, Magnetic Resonance. 1 Docente de la Facultad de Psicología de la Universidad El Bosque. Correo electrónico: bonillamauricio@unbosque.edu.co Cuadernos Hispanoamericanos de Psicología 67

Mauricio Bonilla Carreño Recently, there has been a growing interest within cognitive neuroscience in inhibitory processes, their related neural systems and their role in cognition (Kok, 1999). Inhibition is one of the core executive functions; important to adjust the behaviour and crucial for the maintenance and control of cognitive and motor events (Ramautar, Kok y Ridderinkhof, 2006). It is the last of the high order functions in developing but is the first one that deteriorates with age (Jonkman, 2006; Johnstone et al., 2006). Inhibition is a broad concept. It is the ability to actively suppress, withhold, delay or interrupt ongoing or planned actions in response to sudden changes in the environment and with our own drives. Without this ability we would be unable to avoid the execution of inappropriate responses (Dimoska, Johnstone y Barry, 2006; Filipovic, Jahanshahi y Rothwell, 2000; Johnstone et al., 2005; Ramautar et al., 2005; van den Wildenberg y van der Molen, 2004). Inhibition of motor responses is a concealed operation. It becomes manifest only through the absence of expected behaviour. (Band y van Boxtel, 1999). It is well known that patients with prefrontal brain disorders can have difficulty with inhibitory control and manifest behavioural impulsivity (Li Ray, Krystal y Mathalon, 2005). Different experimental paradigms have served to perform research on inhibition, to account for operational outcomes like increases in reaction time or amount of errors in high interference conditions (Kok, 1999). The two most recently paradigms to investigate inhibition are the GoNogo paradigm and the Stop paradigm. In the go/nogo paradigm, two equate stimuli (e.g. letter X and Y) are presented to subjects in random order. Subjects are asked to respond to one stimulus (e.g. X) with a button press and to withhold their response to the other stimulus (Y) (Kok, 1999). The stop-signal task is an even more direct task for measuring inhibitory control. Subjects have to be prepared to withdraw a response on each trial. An example of a stop task in a visual version could be the following: subjects are presented with a series of trials that begin with either letter A or letter B. Subjects perform a two-choice reaction time, responding to A with one button and to B with a second button. In 25% of the cases a stop signal (e.g. a letter S) is presented after A or B by a variable interval (eg. 200-600 ms.) instructing the subject not to execute the response. (Band, van der Molen y Logan, 2003; Ramautar et al., 2005; Schmajuk et al., 2006; van den Wildenberg y van der Molen, 2004). According to Brunia (2003) the essential difference between the two paradigms is that in the Go/No-Go task the instruction not to go is given before any action is undertaken, while in the Stop task the instruction not to go is given after a Go command has been issued. In the later case some of the underlying processes to the response have been already started. An advantage of the stop task is that it contains a greater inhibitory pressure on responserelated processes than the go/no-go task because it involves the withdrawal of a motor response that has been already triggered by the reaction signal (Kok et al., 2004). The horse-race model outlines the factors mediating inhibitory performance. According to this model, there is a set of processes comprising the go race and a set of processes comprising the inhibition response. If the go response finishes the race before the inhibition response, the go response is executed. If the inhibition response manages to stop the go response prior to its execution, the outcome is a successful stop (Band et al., 2003; Dimoska et al., 2006). A way to achieve successful response inhibition in about 50% of the cases is using a staircasetracking algorithm. This algorithm adjusts the interval between go signal and stop signal in a certain trial, depending upon the results of the previous trial. If the response in the previous trial is inhibited correctly, the interval in the next trial is made longer. If in the previous trial the subject made an incorrect response, the interval between 68 Cuadernos Hispanoamericanos de Psicología

INHIBITION OF VOLUNTARY MOVEMENT: AN OVERVIEW go signal and stop signal in the next trial is shorter. This continuous adaptation of the stop signal delay to the performance of the subject results in a distribution of these delays around the median of the go distribution (Brunia, 2003). Response execution has been studied in go trials using and index of behavioural performance such as reaction time, but it is difficult to study response inhibition in NoGo trials because of the absence of actual behavioural performance. Event-related potentials (ERPs) obtained by time-locked averaging electroencephalography (EEG) have been used to investigate neural processes which take place in the nervous central system. These psychophysiological measures in combination with behavioural measures can be useful to obtain detailed information of the point in time when the brain detects the stop-signal and decides to stop ongoing actions (Kok,1999; Nakata et al., 2005) When ERPs are elicited by NoGo trials, and they are compared with ERPs elicited by Go trials, a frontocentral negative wave at Fz peaking around 200-400 ms appears a NoGo-N2 component (Bekker, Kenemans y Verbaten, 2005) and less consistently a positive shift with maximum at Fz and Cz with latency of 300-500 ms. has been reported (Falkenstein, Hoormann y Hohnsbein, 1999). The evidence for a relationship of the Nogo-N2 to inhibition has come from various studies. Several researchers have studied the event-related brain potentials (ERPs) during a Go/NoGo task to elucidate the electrophysiological bases of executive and inhibitory control of responses. They found that the N2 component was consistenly observed in NoGo trials but was variable in Go trials. Besides, its source was located in the right lateral orbifrontal cortex. The NoGo-P3 component had larger amplitude and longer latency. Moreover it is more anteriorly located than Go-P3. (Bekker et al., 2005; Bokura, Yamaguchi y Kobayashi, 2001; Johnstone et al., 2006; Jonkman, 2006; Lavric, Pizzagalli y Forstmeier, 2004; Nakata et al, 2005). Schmajuk et al., 2006; Kok et al., 2004) examined how response inhibition is reflected in components of event-related potentials. They used the stop-signal paradigm to manipulate response inhibition processes. They found differences in latencies as well in amplitude between successful (SST) and unsuccessful stop-signal (USST) N2/P3 components. The authors concluded that processes underlying successful and unsuccessful stopping were not equivalent. The amplitude enhancements of N2/P3 occurred at slightly but significantly longer latencies at USST than SST and with greater amplitude for successful than failed inhibitions. These authors suggest that stop-signals on failed stop trials provide performance feedback to the subject regarding the inappropriateness of the go response, which leads an enhancement of N2. (Band y van Boxtel, 1999; Ramautar et al., 2005; van Boxtel et al., 2001) also found that stopping to a no/go signal was associated with a negative frontal potential, the N200. When their subjects performed a standard visual two-choice task in which visual stop signals and NoGo signals were presented on a small proportion of the trials. These authors suggest that the N200 can be interpreted as the reflection of a central inhibit signal. As the inhibit signal is raised, activity of the motor system is attenuated and the relevant motor output is cancelled. Ramautar et al. (2005) studied the effects of frequency occurrence of stop signals in the stopsignal paradigm. They found that presenting stop signals less frequently resulted in faster reaction times to the go stimulus and a lower probability of inhibition. N2 and P3 components of stop signals were observed to be larger and of longer latency when stop signals occurred less frequently. The amplitude enhancement of these N2 and P3 components were more pronounced for unsuccessful than for successful stop-signals trials. The authors concluded that their findings suggest that N2 reflected a greater significance of failed inhibitions after Cuadernos Hispanoamericanos de Psicología 69

Mauricio Bonilla Carreño a low probability stop signals while P3 reflected continued processing of the erroneous response after response execution. The issue of inhibition has also been addressed with fmri. Various authors wanted to elucidate the distinct roles played by different cortical structures in aspects of behavioural control with a Go/ NoGo task. Their results suggest a triple neuroanatomical dissociation of executive functions: right dorsolateral, prefrontal and right inferior parietal cortex were correlated to response inhibition and the cingulate to difficult inhibitions, error related processing and posterior performance adjustment. Left dorsolateral prefrontal cortex was activated when subjects adjusted their ongoing behaviour in response to an error. The authors reasoned that inferior frontal cortex may be specifically related to motor response inhibition, while dorsolateral, medial prefrontal and parietal cortices are possibly mediating more general metamotor executive functions such as motor attention, conflict monitoring and response selection, necessary for inhibition task performance (Bokura, Yamaguchi y Kobayashi, 2001; Fuster, 2000; Garavan Ross y Stein, 1999; Garavan, Ross, Murphy, Roche y Stein, 2002; Liddle, Kiehl y Smith, 2001; Rubia et al., 2001; Rubia, Smith, Brammer y Taylor, 2003; Ramautar et al., 2005; Ridderinkhof, van den Wildenberg, Segalowitz y Carter, 2004). Kelly et al. (2004) examined how changing tasks demands, directly affecting preparatory time, have an impact on the inhibitory network. The authors compared functional activations associated with correct withholds required during the fast presentation stream of stimuli to stops required during the slow presentation stream. The authors observed a functional dissociation of activation among conditions. In the slow stop condition there was a right anterior prefrontal cortical activation, and left inferior parietal cortex. In the fast stop condition, there was an increase in areas of the dorsolateral prefrontal cortex, the dorsal striatum and less robustly the insula and fusiform gyrus. The authors argue that without preparation, more widespread activation in the inhibitory network, which also includes the striatum and insula, was necessary in order to ensure successful inhibition of the response to the Nogo stimulus. According to the authors, these data suggest that corticostriatal circuits are involved in the implementation of inhibitory control under conditions of reduced preparation. Wager et al. (2005) wondered if the same brain mechanisms mentioned above are recruited when one has to inhibit a motor response with different forms of inhibition. The authors presented three tasks that shared the common requirement for response inhibition; one was a stimulus response compatibility task, the second was a Go/Nogo task, and the third was a flanker task. They found a set of commonly activated brain regions in three interference tasks. The regions include bilateral insula/frontal operculum, caudate, lateral prefrontal cortices, anterior cingulated and right premotor and parietal cortices. A subset of these structures, mostly consistently the insula, was correlated with poorer behavioural performance in each task. Besides the structures commonly associated to unsuccessful stopping in a stop signal tasks, bilateral insula was found to be particularly sensitive to detection of an unexpected stop signal or in processing of the erroneous response when inhibition failed (Ramautar et al., 2005) The data showed above with fmri techniques on neuroanatomical loci of inhibition and error monitoring are in part in accordance with the research of the effects of focal frontal lesions on response inhibition. For example, Picton et al. (2006) examined the performance of 38 normal subjects and 43 patients with focal lesions of the frontal lobes on a simple go-nogo task. Patients with lesions to the superior medial parts of the frontal lobes (left superior portion of Brodman 6 area) had an increased number of false alarms and lesions to the right ventrolateral prefrontal cortex. Besides, they increased the variability of the response perhaps 70 Cuadernos Hispanoamericanos de Psicología

INHIBITION OF VOLUNTARY MOVEMENT: AN OVERVIEW by disrupting monitoring performance. Also, patients with lesions to the right anterior cingulated were slower and more variable in their reaction time. Although almost all the research reports on the neuroanatomy of inhibition point to the right inferior prefrontal cortex, authors as Aron, Robbins y Poldrack (2004) believe that this region also implicates other functions such as category learning, visomotor conditional learning, memory retrieval and memory encoding. In sum, the right hemisphere parietal/prefrontal circuit and the cingulated cortex seem to be strongly involved in separate response inhibition and error detection processes. Also, they can be generators of the NoGo-N2/NoGo-P3 components. In studies with ERP, researchers have studied two components in relation to response inhibition: the N2 generated in NoGo and Stop conditions. The second ERP component is P3, the frontal P3 amplitude is larger in the Nogo or Stop than in Go condition. The three dimensional source localization analysis with lowresolution electromagnetic tomography (LORETA) showed that a neural activity occurred in the right frontal lobe during NoGo or Stop trials, than in go trials. P3 in the Go condition is maximal at centroparietal sites whereas in the NoGo or Stop conditions P3 was maximal at frontocentral sites. However, the NoGo-N2 has been explained in terms of the conflict monitoring hypothesis (Bekker et al., 2005; Donkers y van Boxtel, 2004), which states that it reflects the detection of response conflict occurring when two or more responses tendencies are simultaneously active. The location of the dipole-modelled source of N2 in the case of conflict is found in the anterior cingulated cortex (ACC). However, in a Go/Nogo study with somatosensory stimuli reported by Nakata et al. (2005) the authors manipulated inhibitory strengthen by asking the subjects to apply three different levels of response force in the Go trials. They confirmed a positive relationship between muscle force and inhibitory process. Their results showed that the amplitudes of the nogo-n140 component increased with increasing muscle force. The authors showed that a stronger response in the Go trials was accompanied by a stronger inhibition and a larger Nogo-N2 in the Nogo trials. Bokura et al. (2001), using the LORETA technique of ERP source localisation, attributed right lateral orbitofrontal and cingulated generators to the NoGo-N2 while left lateral orbitofrontal sources were found for the NoGo-P3. They conclude that both hemispheres and both the N2 and P3, were basic for the response inhibition process. Following Falkensteins (2006) reasoning, it seems that at least two different processes are reflected in the Nogo- N2. These two processes might be organised in a sequential manner; conflict might precede inhibition. When the individual finds a conflict between a two stimuli choice (ie. a blank and a red arrow), then commits an error when responding instead of inhibiting because here errors in speeded response tasks are premature, impulsive responses executed while stimulus analysis is still incomplete. Stimulus evaluation can continue leading to activation of correct response. Then, he or she learns the sequence and then is able to inhibit. Could a network of distributed sources, each probably contributing to the Nogo-N2, be considered if each single source subserves a specific function, such as inhibition or conflict detection? As seen, the functional significance of the Nogo- N2 is still in debate, although most of the studies aim to relate N2 with inhibition. More studies are needed to clarify the real nature of N2 component and how the inhibition process is affected by the type of stop signal. On the other hand, research on inhibition has focused on analyzing the N2-P3 components, but there are scarce studies on LRP and inhibition. It is important to clarify if the LRP is sensible to the response inhibition in stop tasks. It is also interesting to dilucidate if ERPs linked to inhibition of response are showed in a similar way in real or imagined execution of movement and if the modality of stop signals affects the ERPs obtained. Cuadernos Hispanoamericanos de Psicología 71

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