Yoshihisa Nakayama

Transformation of a Virtual Action Plan into a Motor Plan in the Premotor Cortex

Before preparing to initiate a forthcoming motion, we often acquire information about the future action without specifying actual motor parameters. The information for planning an action at this conceptual level can be provided with verbal commands or nonverbal signals even before the associated motor targets are visible. Under these conditions, the information signifying a virtual action plan must be transformed to information that can be used for constructing a motor plan to initiate specific movements. To determine whether the premotor cortex is involved in this process, we examined neuronal activity in the dorsal premotor cortex (PMd) of monkeys performing a behavioral task designed to isolate the behavioral stages of the acquisition of information for a future action and the construction of a motor plan. We trained the animals to receive a symbolic instruction (color and shape of an instruction cue) to determine whether to select the right or left of targets to reach, despite the physical absence of targets. Subsequently, two targets appeared on a screen at different locations. The animals then determined the correct target (left or right) based on the previous instruction and prepared to initiate a reaching movement to an actual target. The experimental design dissociated the selection of the right/left at an abstract level (action plan) from the physical motor plan. Here, we show that activity of individual PMd neurons initially reflects a virtual action plan transcending motor specifics, before these neurons contribute to a transformation process that leads to activity encoding a motor plan.

Distinct Information Representation and Processing for Goal-Directed Behavior in the Dorsolateral and Ventrolateral Prefrontal Cortex and the Dorsal Premotor Cortex

Although the lateral prefrontal cortex (lPFC) and dorsal premotor cortex (PMd) are thought to be involved in goal-directed behavior, the specific roles of each area still remain elusive. To characterize and compare neuronal activity in two sectors of the lPFC [dorsal (dlPFC) and ventral (vlPFC)] and the PMd, we designed a behavioral task for monkeys to explore the differences in their participation in four aspects of information processing: encoding of visual signals, behavioral goal retrieval, action specification, and maintenance of relevant information. We initially presented a visual object (an instruction cue) to instruct a behavioral goal (reaching to the right or left of potential targets). After a subsequent delay, a choice cue appeared at various locations on a screen, and the animals could specify an action to achieve the behavioral goal. We found that vlPFC neurons amply encoded object features of the instruction cues for behavioral goal retrieval and, subsequently, spatial locations of the choice cues for specifying the actions. By contrast, dlPFC and PMd neurons rarely encoded the object features, although they reflected the behavioral goals throughout the delay period. After the appearance of the choice cues, the PMd held information for action throughout the specification and preparation of reaching movements. Remarkably, lPFC neurons represented information for the behavioral goal continuously, even after the action specification as well as during its execution. These results indicate that area-specific representation and information processing at progressive stages of the perception–action transformation in these areas underlie goal-directed behavior.

Processing of Visual Signals for Direct Specification of Motor Targets and for Conceptual Representation of Action Targets in the Dorsal and Ventral Premotor Cortex

Previous reports have indicated that the premotor cortex (PM) uses visual information for either direct guidance of limb movements or indirect specification of action targets at a conceptual level. We explored how visual inputs signaling these two different categories of information are processed by PM neurons. Monkeys performed a delayed reaching task after receiving two different sets of visual instructions, one directly specifying the spatial location of a motor target (a direct spatial-target cue) and the other providing abstract information about the spatial location of a motor target by indicating whether to select the right or left target at a conceptual level (a symbolic action-selection cue). By comparing visual responses of PM neurons to the two sets of visual cues, we found that the conceptual action plan indicated by the symbolic action-selection cue was represented predominantly in dorsal PM (PMd) neurons with a longer latency (150 ms), whereas both PMd and ventral PM (PMv) neurons responded with a shorter latency (90 ms) when the motor target was directly specified with the direct spatial-target cue. We also found that excited, but not inhibited, responses of PM neurons to the direct spatial-target cue were biased toward contralateral preference. In contrast, responses to the symbolic action-selection cue were either excited or inhibited without laterality preference. Taken together, these results suggest that the PM constitutes a pair of distinct circuits for visually guided motor act; one circuit, linked more strongly with PMd, carries information for retrieving action instruction associated with a symbolic cue, and the other circuit, linked with PMd and PMv, carries information for directly specifying a visuospatial position of a reach target.

Involvement of the globus pallidus in behavioral goal determination and action specification.

Multiple loop circuits interconnect the basal ganglia and the frontal cortex, and each part of the cortico-basal ganglia loops plays an essential role in neuronal computational processes underlying motor behavior. To gain deeper insight into specific functions played by each component of the loops, we compared response properties of neurons in the globus pallidus (GP) with those in the dorsal premotor cortex (PMd) and the ventrolateral and dorsolateral prefrontal cortex (vlPFC and dlPFC) while monkeys performed a behavioral task designed to include separate processes for behavioral goal determination and action selection. Initially, visual signals instructed an abstract behavioral goal, and seconds later, a choice cue to select an action was presented. When the instruction cue appeared, GP neurons started to reflect visual features as early as vlPFC neurons. Subsequently, GP neurons began to reflect goals informed by the visual signals no later than neurons in the PMd, vlPFC, and dlPFC, indicating that the GP is involved in the early determination of behavioral goals. In contrast, action specification occurred later in the GP than in the cortical areas, and the GP was not as involved in the process by which a behavioral goal was transformed into an action. Furthermore, the length of time representing behavioral goal and action was shorter in the GP than in the PMd and dlPFC, indicating that the GP may play an important role in detecting individual behavioral events. These observations elucidate the involvement of the GP in goal-directed behavior.

Premotor cortex (PM) is involved in converting a concept for action into a motor plan

The cerebellar cortex is compartmentalized into more than 20 longitudinal stripes by the aldolase C (=zebrin) expression pattern, which is tightly correlated with the topography of the olivocortical climbing fiber projection. Here we labeled Purkinje cells in different aldolase C stripes of the cerebellar cortex with biotinylated dextran amine and analyzed their axonal trajectories to clarify the compartmentalization of the cerebellar nuclei in the rat. Each Purkinje cell axon had a relatively small termination area in the cerebellar nucleus, which were often elongated from the surface toward the hilus of the nucleus. The axonal projection seemed to be organized according to fine cortico-nuclear topography. Purkinje cells in the aldolase C-positive and negative stripes in the cortex projected to the caudoventral and rostrodorsal parts of the nuclei, respectively. These results supported that the aldolase C expression is tightly related with the functional cortico-nuclear organization.

Involvement of lateral prefrontal cortex (LPFC) in a concept-based action planning

study whether the DRN activity is involved in delay-based cost–benefit decisionmaking, we recorded single-neuronal activity in the DRN while a monkey performed a delayed-reward visually-guided saccade task. In the task, reward value (0.01 ml vs. 0.5 ml) was indicated by the location of saccade target (right vs. left), and after saccade, a reward was delivered with a 1600 ms delay. We found that about half (23/45) of DRN neurons exhibited sustained activity during the delay period ‘after’ saccade and before reward delivery, with either largeor small-reward preference. The same neurons often showed significantly less reward modulation if the delay (1600 ms) was introduced ‘before’ saccade in a memory-guided saccade task. These results suggest that the coding of the size of delayed reward is dependent on the task context such as the sequence in a task.

Involvement of subareas within the dorsal premotor area (PMd) in a conceptually demanding visuomotor task

The aim of this study was to identify the origin of multisynaptic inputs from the GPi to two sectors of the PMd. We injected rabies virus into the rostral (F2r) or caudal part (F2c) of the PMd in macaque monkeys. The virus was transported across synapses from postsynaptic to presynaptic neurons. After a 3-day postinjection period that allows for the second-order neuron labeling, the GPi contained labeled neurons. There was a difference in the distribution area of neuronal labeling between the two injection cases. After the F2r injection, labeled GPi neurons were found in the associative territory. By contrast, the F2c injection led to labeling of the motor territory. The present results revealed that F2r and F2c participate in the associative or motor loop, respectively, suggesting a distinct involvement of these regions in motor planning versus execution.