Elsevier

NeuroImage

Volume 43, Issue 2, 1 November 2008, Pages 388-398
NeuroImage

Symbolic representations of action in the human cerebellum

https://doi.org/10.1016/j.neuroimage.2008.07.010Get rights and content

Abstract

Cerebellar cortical areas connected to the neocortical motor system process information important for the sensory guidance of action. Converging evidence also supports the view that cerebellar cortical areas connected with the prefrontal cortex process information similarly in the cognitive domain. Here, we test the hypothesis that the prefrontal-projecting zones in the human cerebellum process the abstract content of information embedded within sensory cues. Specifically, we use event-related fMRI to determine whether symbolic visual instructions activate the prefrontal-projecting zones of the cerebellum. On the basis of connectional anatomy, we predicted that such activity would be found in lobule HVIIA and adjacent vermal territories in the same lobule. Our experimental design enabled us to investigate activity time-locked specifically to instructions foraction that were either purely symbolic, or specified actions directly. Such activity was independent of action. Activity specifically time-locked to symbolic cues (compared with non-symbolic control cues) activated cerebellar cortical lobule HVIIA (Crus I and Crus II). Our results provide support for the view that prefrontal-projecting areas of the cerebellar cortex process information that is of a purely abstract nature.

Introduction

A wealth of anatomical data demonstrates that in non-human primates the heaviest connections with the cerebellum originate in the cortical motor system (Brodal, 1978a, Brodal, 1978b, Glickstein et al., 1985, Schmahmann et al., 2004). Evidence from several branches of experimental and theoretical neurobiology suggests that the cerebellum plays an important role in the sensory guidance of movement (Stein and Glickstein, 1992, Miall et al., 1993, Wolpert and Miall, 1996, Glickstein, 1998, Kawato and Wolpert, 1998). It has been argued that sensory guidance of the online control of movements is critical for the coordinated execution of actions, and it is well known that cerebellar lesions in humans and in non-human primates result in severe coordination deficits (Bastian and Thach, 1995, Bastian et al., 1996, Miall, 1998, Ramnani et al., 2001).

There is an increasing body of evidence suggesting that the cerebellum also plays an important role in higher cognitive function (Leiner et al., 1986, Leiner et al., 1993, Ivry and Baldo, 1992, Fiez, 1996, Schmahmann and Caplan, 2006). This view is supported not only by studies in clinical populations (Grafman et al., 1992, Tucker et al., 1996, Schmahmann and Sherman, 1998, Levisohn et al., 2000, Schmahmann, 2004, Ravizza et al., 2006), but also by neuroimaging evidence in healthy populations(Petersen et al., 1988, Kim et al., 1994, Allen et al., 1997, Chen and Desmond, 2005a). In the present study, we consider the contribution of cerebellar circuits to higher cognitive function in the context of their connections with the prefrontal cortex.

The anatomical relationships between the cerebellum and the cerebral cortex are becoming increasingly well established. Converging evidence suggests the existence of multiple independent cortico-cerebeller loops. Cerebral cortical outputs reach distinct zones of the cerebellar cortex via the pontine nuclei (Brodal, 1978a, Schmahmann and Pandya, 1997, Schmahmann et al., 2004), and these zones project back to the same areas of the cerebral cortex via the cerebellar nuclei and thalamus creating closed loops. Two distinct loops have been identified by Kelly and Strick (2003). In the ā€˜motor loopā€™, the primary motor cortex projects to cerebellar cortical lobules V, VI and HVIIB andHVIII, and projects back to the same regions of cortex via dorsal parts of the cerebellar dentate nucleus and the motor thalamus. In the ā€˜prefrontal loop', area 46 (Walker, 1940) of the prefrontal cortex projects to lobule HVIIA (principally Crus I and Crus II) via the pontine nuclei, and this area returns projections to the same areas of the prefrontal cortex via ventral parts of the cerebellar dentate nucleus andmediodorsal thalamus (Goldman-Rakic and Porrino, 1985, Barbas et al., 1991, Middleton and Strick, 2001, Kelly and Strick, 2003). Evidence suggests that the cortical and cerebellar components of the prefrontal loop have undergone a selective expansion in the human brain (Whiting and Barton, 2003). Connections from the prefrontal cortex to the ponto-cerebellar system have also expanded disproportionately relative to the inputs arising in the cortical motor areas (Ramnani et al., 2006). While the anatomical organization of these loops is becoming increasing clear, the nature of their functions remains elusive.

The information processed in the cerebral cortical components of these loops may shed light on the nature of information conveyed in these pathways. It has been argued that the functional organization of the lateral convexity of the frontal lobe follows a rostro-caudal gradient extending from the central sulcus posteriorly to the frontal pole anteriorly (Miller and Cohen, 2001, Ramnani and Owen, 2004, Petrides, 2005, Koechlin and Summerfield, 2007). The primary motor cortex (area 4; caudal part of the motor strip) contains neurons in which information is represented in terms of the physical parameters of motor control (Georgopoulos, 1991, Porter and Lemon, 1993). The premotor cortex, situated in the rostral part of the motor strip, contains neurons that exhibit preparatory set activity (Wise, 1985). It has been argued that information in area 46 of the prefrontal cortex (anterior to area 6) encodes abstract information related to action (Passingham, 1996), rules (Wallis et al., 2001) and the monitoring of information in working memory (Petrides, 1994). These areas are interconnected to form a hierarchically organized network in which executive control is achieved through a cascade of information from areas of the prefrontal cortex through to the primary motor cortex via the premotor system. It has been argued that representations are increasingly abstract at higher levels of this network. Hence, it is arguable that information processed in the cerebellar components of the prefrontal loop are likely to be of a more abstract nature than that in the motor loop (Ramnani, 2006). Here, we propose that the cerebellum has an additional role in the processing of symbolic information that is used to instruct action rather than information concerned directly with the parameters of movement. Specifically, we tested the hypothesis that cerebellar cortical lobule HVIIA (including Crus I and Crus II) and adjacent vermal areas in lobule VIIA that are reciprocally connected with the prefrontal cortex, will be activated specifically by the abstract content of information embedded within sensory cues that signal action.

The ability to acquire associations between symbolic instructions, actions and outcomes is a hallmark of the flexibility that is typical of primate cognition. We used a conditional motor task, in which subjects learn to arbitrarily associate symbolic visual instruction cues with actions. Importantly, there is no information inherently present in these cues that can specify the required action ā€” the ability of the cue to indicate which action is to be executed is learned through trial and error (Wise and Murray, 2000). The circuitry that underlies this form of learning in the frontal lobe is well characterized. Studies in humans and non-human primates have consistently implicated the dorsal areas of the premotor cortex (Petrides, 1982, Weinrich and Wise, 1982, Halsband and Passingham, 1985, Toni et al., 1999, Toni et al., 2001b). The prefrontal cortex has also been implicated, particularly in the early stages of learning when mappings are unfamiliar (Gaffan and Harrison, 1989). This form of learning depends on well defined cognitive operations that can be brought under stringent experimental control in studies that employ event-related fMRI (Ramnani and Miall, 2003, Ramnani and Miall, 2004).

Our study is concerned with localizing activity evoked by the purely cognitive process of translating symbolic information, rather than other trial components (e.g. responses and error feedback). Our event-related experimental design uses conditional motor trials to dissociate activity time-locked to the processing of symbolic information into action from the confounding effects of other forms of processing such as the generation of motor responses. Based on the connectional organization of the primate cerebellum with dorsal parts of the prefrontal cortex (Walker's area 46) we hypothesize that regions of the cerebellum connected with the prefrontal cortex (Crus I and Crus II; (Kelly and Strick, 2003) will be activated by the abstract content of symbolic cues that guide action (Ramnani, 2006).

Section snippets

Subjects

Subjects were fifteen neurologically normal, healthy right-handed participants (aged between 18 and 30; 10 female). Participants gave written informed consent and the study was approved by the Royal Holloway University of London Psychology Department Ethics Committee, and the study conformed to regulations set out in the CUBIC MRI Rules of Operations (http://www.pc.rhul.ac.uk/sites/cubic/).

Apparatus

Subjects lay supine in an MRI scanner with the fingers of the right hand positioned on a four-button

Reaction times

Reaction times (see Fig. 2) were analysed using a two way repeated measures analysis of variance (ANOVA). This revealed that subjectsā€™ reaction times were significantly reduced when they were able to prepare movements after Informative cues, compared with trials in which Uninformative cues were presented in which no specific responses could be prepared (Main effect of Factor 2; F(1,14)Ā =Ā 195.027; pĀ <Ā 0.001). There was no effect of cue type on reaction time (Main effect of Factor 1; F(1,14)Ā =Ā .578; pĀ >Ā 

Discussion

In this study, we have used a factorial design to investigate the role of the cerebellum in processing Informative or Uninformative instruction cues that were either Symbolic or Direct. These forms of information allow us to contrast effects of stimulus-response mappings that were entirely rule based and arbitrary, with those that inherently specified the required action. As hypothesised, prefrontal-projecting regions of cerebellum were specifically activated by symbolic, rule-based information

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