Functional dissociation of pre-SMA and SMA-proper in temporal processing

Abstract

The ability to assess temporal structure is crucial in order to adapt to an ever-changing environment. Increasing evidence suggests that the supplementary motor area (SMA) is involved in both sensory and sensorimotor processing of temporal structure. However, it is not entirely clear whether the structural differentiation of the SMA translates into functional specialization, and how the SMA relates to other systems that engage in temporal processing, namely the cerebellum and cortico-striatal circuits. Anatomically, the SMA comprises at least two subareas, the rostral pre-SMA and the caudal SMA-proper. Each displays a characteristic pattern of connections to motor and non-motor structures. Crucially, these connections establish a potential hub among cerebellar and cortico-striatal systems, possibly forming a dedicated subcortico-cortical temporal processing network. To further explore the functional role of each SMA subarea, we performed a meta-analysis of functional neuroimaging studies by contrasting activations according to whether they linked with either sensory, sensorimotor, sequential, non-sequential, explicit, non-explicit, subsecond, or suprasecond temporal processing. This procedure yielded a set of functional differences, which mirror the rostro-caudal anatomical dimension. Activations associated with sensory, non-sequential, and suprasecond temporal processing tend to locate to the rostral SMA, while the opposite is true for the caudal SMA. These findings confirm a functional dissociation of pre-SMA and SMA-proper in temporal processing.

Introduction

The functional concept of classical motor structures, including the cerebellum, the basal ganglia, and the supplementary motor area (SMA), has changed substantially to consider their participation in non-motor, presumably more cognitive, processes (Strick et al., 2009). One such process that has been attributed to the cerebellum, the basal ganglia, and the SMA alike, is temporal processing, i.e. the mechanisms that underlie the encoding, decoding, and evaluation of temporal structure (for a recent review see Coull et al., 2011).

The SMA is a part of Brodmann area 6 in the medial frontal lobe that is associated with the programming, the generation, and the control of action sequences (Goldberg, 1985, Tanji, 1996). Early on, it has been demonstrated that these rather complex functions incorporate a number of temporal characteristics, e.g. the slowing of actions, rhythmic movements, as well as speech motor behavior comprising rhythmic, repetitive, stereotypic, and sustained vocalizations, (Brickner, 1939, Penfield, 1950). More recent neuroanatomical accounts further report structural differences and suggest a dissociation of the SMA along the “VAC line” (a vertical line intersecting the anterior comissure) into the more rostral pre-SMA and the more caudal SMA-proper (Lehéricy et al., 2004, Matsuzaka et al., 1992, Picard and Strick, 2001). Correspondingly, “SMA” is used as a generic term, while “pre-SMA” and “SMA-proper” are used as subordinate terms. Remarkably sparse connections between these subareas and specific connections to prefrontal areas and to the non-motor part of the cerebellar dentate nucleus in the case of the pre-SMA, as well as connections to primary motor cortex and to the motor part of the dentate in the case of the SMA-proper, further substantiate the proposed structural heterogeneity of this area (Akkal et al., 2007, Dum and Strick, 2003, Johansen-Berg et al., 2004, Strick et al., 2009). This development towards a more detailed structural description of the SMA is paralleled by an increasingly detailed dissociation within the functional domain (Nachev et al., 2008). For example, considering motor behavior, the pre-SMA engages in the initiation and updating of non-automatized, internally generated movements, as opposed to the SMA-proper, which plays a role in externally generated movements (Kennerley et al., 2004, Passingham et al., 2009). Furthermore, in speech production, activations due to lexical selection, linear sequence encoding, and the control of motor output group along a rostro-caudal gradient from pre-SMA to SMA-proper (Alario et al., 2006). Sequentially organized behavior, as in the above examples, depends in part on coherent temporal order and may therefore exploit to some extent the temporal coding and temporal processing capacity of the pre-SMA and SMA-proper as integral parts of a dedicated temporal processing network (Macar et al., 2002, Mita et al., 2009). Moreover, the ability to code temporal relations may be necessary in order to establish a temporal link between actions and effects, a function which relies on the pre-SMA (Moore et al., 2010).

Research on temporal processing develops along a number of fundamental dichotomies (Coull and Nobre, 2008), perhaps most importantly the distinction of intrinsic and dedicated models of temporal processing (Ivry and Schlerf, 2008). Intrinsic models assume that temporal processing is inherent to neural dynamics, whereas dedicated models refer to some specialized neural architecture, e.g. the cerebellum or cortico-striatal circuits (Buhusi and Meck, 2005). More specifically, the cerebellum is associated with event-based, automatic temporal processing in the millisecond range, whereas cortico-striatal circuits engage in attention-dependent temporal processing in the hundreds-of-milliseconds-to-minutes range (Ivry and Schlerf, 2008, Meck et al., 2008, Spencer et al., 2003). This structural dissociation of temporal processing systems in the milliseconds, or subsecond range, as opposed to the suprasecond range, is somewhat independent of the so-called “psychological”, “subjective”, or “phenomenal” present, which typically considers a window of 2–3 s (Fraisse, 1984, Pöppel, 2004). Crucially, while these dedicated temporal processing systems may work in parallel, they have been modeled relatively independent of each other. Yet, the SMA connects to both systems, and it has been associated with the “tagging” of temporal attributes and the online timing of stimulus durations (Coull et al., 2011, Pastor et al., 2006). These characteristics make the SMA not only a prime neural substrate of a temporal accumulator (Casini and Vidal, 2011), they also introduce an anatomical basis for interactions between different temporal processing systems across a wide range of durations (Allman and Meck, 2011). Principally, the temporal processing function pertains to both, the pre-SMA and the SMA-proper, and is not restricted to motor behavior. Both SMA subareas instead participate in a wide range of temporal processing tasks, including also sensory temporal processing (Lewis and Miall, 2003a, Lewis and Miall, 2003b, Macar et al., 2002). In line with this proposal, a recent meta-analysis of temporal processing studies reports consistent activation likelihood for the bilateral SMA across different temporal ranges and tasks, albeit without explicitly dissociating between its subareas (Wiener et al., 2010). However, pre-SMA and SMA-proper have been implicated in different aspects of temporal processing (Macar et al., 2006), e.g. attentional allocation to time in the sensory domain, and skillful control of time in the sensorimotor domain, engage pre-SMA and SMA-proper, respectively (Coull et al., 2004, Macar et al., 2006). In order to further specify the role of pre-SMA and SMA-proper in temporal processing, we thus used the contrast between sensory and sensorimotor temporal processing as a starting point to identify functional differences that may mirror the anatomical dissociation of SMA subareas by means of a meta-analysis of functional neuroimaging studies.

On the one hand, meta-analyses have a number of limitations, mainly due to a need in simplification and generalization. On the other hand, they provide the opportunity to identify commonalities across different studies, as well as trends beyond the scope of individual studies. Furthermore, it is important to note that the focus on SMA function constitutes a fundamental constraint in itself, as studies that do not report activation of the SMA were not considered. However, this procedure is justified to the extent that the right inferior frontal gyrus and the bilateral SMA are in fact the only regions of the brain that are consistently activated across different temporal ranges and task requirements (Wiener et al., 2010). Thus, given the crucial role of the SMA in temporal processing, formally addressing the functional dissociation of pre-SMA and SMA-proper deems necessary in order to refine speculations about the neural basis of temporal processing. In line with the proposal of the SMA as a hub within a dedicated, integrative subcortico-cortical temporal processing network, we expected to find dissociable clusters of fMRI peak activations for sensory and sensorimotor processing of temporal structure along a rostro-caudal axis propagating from the pre-SMA to the SMA-proper. Besides this primary contrast, we used the same set of studies to explore additional domain-general factors that also do not pertain to a specific task or modality by comparing sequential and non-sequential, explicit and non-explicit, as well as subsecond and (mixed-) suprasecond temporal processing in secondary contrasts. These secondary contrasts were included in order to address some of the issues associated with dedicated temporal processing, i.e. the recruitment of different mechanisms based on temporal range or with attention being explicitly directed towards temporal structure.