Multisynaptic projections from the ventrolateral prefrontal cortex to the dorsal premotor cortex in macaques – anatomical substrate for conditional visuomotor behavior

Lines of evidence indicate that both the ventrolateral prefrontal cortex (vlPFC) (areas 45/12) and dorsal premotor cortex (PMd) (rostral F2 in area 6) are crucially involved in conditional visuomotor behavior, in which it is required to determine an action based on an associated visual object. However, virtually no direct projections appear to exist between the vlPFC and PMd. In the present study, to elucidate possible multisynaptic networks linking the vlPFC to the PMd, we performed a series of neuroanatomical tract‐tracing experiments in macaque monkeys. First, we identified cortical areas that send projection fibers directly to the PMd by injecting Fast Blue into the PMd. Considerable retrograde labeling occurred in the dorsal prefrontal cortex (dPFC) (areas 46d/9/8B/8Ad), dorsomedial motor cortex (dmMC) (F7 and presupplementary motor area), rostral cingulate motor area, and ventral premotor cortex (F5 and area 44), whereas the vlPFC was virtually devoid of neuronal labeling. Second, we injected the rabies virus, a retrograde transneuronal tracer, into the PMd. At 3 days after the rabies injections, second‐order neurons were labeled in the vlPFC (mainly area 45), indicating that the vlPFC disynaptically projects to the PMd. Finally, to determine areas that connect the vlPFC to the PMd indirectly, we carried out an anterograde/retrograde dual‐labeling experiment in single monkeys. By examining the distribution of axon terminals labeled from the vlPFC and cell bodies labeled from the PMd, we found overlapping labels in the dPFC and dmMC. These results indicate that the vlPFC outflow is directed toward the PMd in a multisynaptic fashion through the dPFC and/or dmMC.     

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.     

Predicting and memorizing observed action: Differential premotor cortex involvement

Many studies have shown the involvement of the premotor cortex in action observation, recognizing this region as the neural marker of action simulation (i.e., internal modeling on the basis of the observer's own motor repertoire). So far, however, we have remained unaware of how action simulation differs from more general action representation in terms of premotor activation. The present fMRI experiment is the first to demonstrate how premotor structures contribute to action simulation as opposed to other action‐related cognitive tasks, such as maintaining action representations. Using similar stimuli, a prediction condition requiring internal simulation of transiently occluded actions was compared to three different action‐related control tasks differing solely in task instructions. Results showed right pre‐SMA activation as a correlate of maintaining action representations in general. Moreover, the prediction condition was most efficient in activating the left pre‐SMA and left PMd. These results suggest that the conjoint activation of the pre‐SMA and PMd reflects a core neural driver of action simulation. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Patterns of afferent input to the caudal and rostral areas of the dorsal premotor cortex (6DC and 6DR) in the marmoset monkey

Corticocortical projections to the caudal and rostral areas of dorsal premotor cortex (6DC and 6DR, also known as F2 and F7) were studied in the marmoset monkey. Both areas received their main thalamic inputs from the ventral anterior and ventral lateral complexes, and received dense projections from the medial premotor cortex. However, there were marked differences in their connections with other cortical areas. While 6DR received consistent inputs from prefrontal cortex, area 6DC received few such connections. Conversely, 6DC, but not 6DR, received major projections from the primary motor and somatosensory areas. Projections from the anterior cingulate cortex preferentially targeted 6DC, while the posterior cingulate and adjacent medial wall areas preferentially targeted 6DR. Projections from the medial parietal area PE to 6DC were particularly dense, while intraparietal areas (especially the putative homolog of LIP) were more strongly labeled after 6DR injections. Finally, 6DC and 6DR were distinct in terms of inputs from the ventral parietal cortex: projections to 6DR originated preferentially from caudal areas (PG and OPt), while 6DC received input primarily from rostral areas (PF and PFG). Differences in connections suggest that area 6DR includes rostral and caudal subdivisions, with the former also involved in oculomotor control. These results suggest that area 6DC is more directly involved in the preparation and execution of motor acts, while area 6DR integrates sensory and internally driven inputs for the planning of goal‐directed actions. They also provide strong evidence of a homologous organization of the dorsal premotor cortex in New and Old World monkeys. J. Comp. Neurol. 522:3683–3716, 2014. © 2014 Wiley Periodicals, Inc.     

Neurofilament protein distribution in the macaque monkey dorsolateral premotor cortex

Regional and laminar distribution patterns of neurofilament proteins in the dorsolateral premotor cortex (PMd) were studied with monoclonal antibody SMI-32 in five adult macaque monkeys and compared with the cytoarchitectonical features of the PMd. Our goal was to reveal whether the increasing functional diversity of the PMd which electrophysiological studies have unravelled over the last years is reflected on a structural level by differences in the neurochemical phenotype. Differences in size, shape and packing density of immunopositive layer III and V pyramidal cells define areas much more clearly than do differences in cytoarchitecture. The PMd can be subdivided into a rostral and a caudal part at a level slightly anterior to the genu of the arcuate sulcus. The extent of these two areas matches the two cytoarchitectonically defined areas F7 and F2, respectively. Within area F2, differences in layer V immunoreactive neurons define a dorsal (F2d) and a ventral (F2v) region. The border between areas F2d and F2v lies at the superior precentral dimple and cannot be detected cytoarchitectonically in Nissl-stained sections. Neurofilament proteins are involved in the stabilization of the cytoskeleton of the axon and have been correlated with axonal size and conduction velocity of nerve fibres. This regional variability in the neurochemical phenotype of layer V within the caudal PMd may reflect a differential organization of the descending output from this part of the premotor cortex. It might also be related to differences in the motor control of voluntary arm and leg movements.     

Transcallosal connection patterns of opposite dorsal premotor regions support a lateralized specialization for action and perception

Lateralization of higher brain functions requires that a dominant hemisphere collects relevant information from both sides. The right dorsal premotor cortex (PMd), particularly implicated in visuomotor transformations, was hypothesized to be optimally located to converge visuospatial information from both hemispheres for goal‐directed movement. This was assessed by probabilistic tractography and a novel analysis enabling group comparisons of whole‐brain connectivity distributions of the left and right PMd in standard space (16 human subjects). The resulting dominance of contralateral PMd connections was characterized by right PMd connections with left visual and parietal areas, indeed supporting a dominant role in visuomotor transformations, while the left PMd showed dominant contralateral connections with the frontal lobe. Ipsilateral right PMd connections were also stronger with posterior parietal regions, relative to the left PMd connections, while ipsilateral connections of the left PMd were stronger with, particularly, the anterior cingulate, the ventral premotor and anterior parietal cortex. The pattern of dominant right PMd connections thus points to a specific role in guiding perceptual information into the motor system, while the left PMd connections are consistent with action dominance based on a lead in motor intention and fine precision skills.     

Effects of long-term practice and task complexity in musicians and nonmusicians performing simple and complex motor tasks: implications for cortical motor organization

Motor practice induces plastic changes within the cortical motor system. Whereas rapidly evolving changes of cortical motor representations were the subject of a number of recent studies, effects of long-term practice on the motor system are so far poorly understood. In the present study pianists and nonmusicians were investigated using functional magnetic resonance imaging. Both groups performed simple and complex movement sequences on a keyboard with the right hand, the tasks requiring different levels of ordinal complexity. The aim of this study was to characterize motor representations related to sequence complexity and to long-term motor practice. In nonmusicians, complex motor sequences showed higher fMRI activations of the presupplementary motor area (pre-SMA) and the rostral part of the dorsal premotor cortex (PMd) compared to simple motor sequences, whereas musicians showed no differential activations. These results may reflect the higher level of visuomotor integration required in the complex task in nonmusicians, whereas in musicians this rostral premotor network was employed during both tasks. Comparison of subject groups revealed increased activation of a more caudal premotor network in nonmusicians comprising the caudal part of the PMd and the supplementary motor area. This supports recent results suggesting a specialization within PMd. Furthermore, we conclude that plasticity due to long-term practice mainly occurs in caudal motor areas directly related to motor execution. The slowly evolving changes in M1 during motor skill learning may extend to adjacent areas, leading to more effective motor representations in pianists.     

Contribution of writing to reading: Dissociation between cognitive and motor process in the left dorsal premotor cortex

Functional brain imaging studies reported activation of the left dorsal premotor cortex (PMd), that is, a main area in the writing network, in reading tasks. However, it remains unclear whether this area is causally relevant for written stimulus recognition or its activation simply results from a passive coactivation of reading and writing networks. Here, we used chronometric paired‐pulse transcranial magnetic stimulation (TMS) to address this issue by disrupting the activity of the PMd, the so‐called Exner's area, while participants performed a lexical decision task. Both words and pseudowords were presented in printed and handwritten characters. The latter was assumed to be closely associated with motor representations of handwriting gestures. We found that TMS over the PMd in relatively early time‐windows, i.e., between 60 and 160 ms after the stimulus onset, increased reaction times to pseudoword without affecting word recognition. Interestingly, this result pattern was found for both printed and handwritten characters, that is, regardless of whether the characters evoked motor representations of writing actions. Our result showed that under some circumstances the activation of the PMd does not simply result from passive association between reading and writing networks but has a functional role in the reading process. At least, at an early stage of written stimuli recognition, this role seems to depend on a common sublexical and serial process underlying writing and pseudoword reading rather than on an implicit evocation of writing actions during reading as typically assumed. Hum Brain Mapp 37:1531‐1543, 2016. © 2016 Wiley Periodicals, Inc.     

Uncovering a context-specific connectional fingerprint of human dorsal premotor cortex

Primate electrophysiological and lesion studies indicate a prominent role of the left dorsal premotor cortex (PMd) in action selection based on learned sensorimotor associations. Here we applied transcranial magnetic stimulation (TMS) to human left PMd at low or high intensity while right-handed individuals performed externally paced sequential key presses with their left hand. Movements were cued by abstract visual stimuli, and subjects either freely selected a key press or responded according to a prelearned visuomotor mapping rule. Continuous arterial spin labeling was interleaved with TMS to directly assess how stimulation of left PMd modulates task-related brain activity depending on the mode of movement selection. Relative to passive viewing, both tasks activated a frontoparietal motor network. Compared with low-intensity TMS, high-intensity TMS of left PMd was associated with an increase in activity in medial and right premotor areas without affecting task performance. Critically, this increase in task-related activity was only present when movement selection relied on arbitrary visuomotor associations but not during freely selected movements. Psychophysiological interaction analysis revealed a context-specific increase in functional coupling between the stimulated left PMd and remote right-hemispheric and mesial motor regions that was only present during arbitrary visuomotor mapping. Our TMS perturbation approach yielded causal evidence that the left PMd is implicated in mapping external cues onto the appropriate movement in humans. Furthermore, the data suggest that the left PMd may transiently form a functional network together with right-hemispheric and mesial motor regions to sustain visuomotor mapping performed with the left nondominant hand.     

Movement‐related activity during goal‐directed hand actions in the monkey ventrolateral prefrontal cortex

Grasping actions require the integration of two neural processes, one enabling the transformation of object properties into corresponding motor acts, and the other involved in planning and controlling action execution on the basis of contextual information. The first process relies on parieto‐premotor circuits, whereas the second is considered to be a prefrontal function. Up to now, the prefrontal cortex has been mainly investigated with conditional visuomotor tasks requiring a learned association between cues and behavioural output. To clarify the functional role of the prefrontal cortex in grasping actions, we recorded the activity of ventrolateral prefrontal (VLPF) neurons while monkeys (Macaca mulatta) performed tasks requiring reaching–grasping actions in different contextual conditions (in light and darkness, memory‐guided, and in the absence of abstract learned rules). The results showed that the VLPF cortex contains neurons that are active during action execution (movement‐related neurons). Some of them showed grip selectivity, and some also responded to object presentation. Most movement‐related neurons discharged during action execution both with and without visual feedback, and this discharge typically did not change when the action was performed with object mnemonic information and in the absence of abstract rules. The findings of this study indicate that a population of VLPF neurons play a role in controlling goal‐directed grasping actions in several contexts. This control is probably exerted within a wider network, involving parietal and premotor regions, where the role of VLPF movement‐related neurons would be that of activating, on the basis of contextual information, the representation of the motor goal of the intended action (taking possession of an object) during action planning and execution.     

The primary motor and premotor areas of the human cerebral cortex.

Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.     

Comparison of unilateral and bilateral complex finger tapping-related activation in premotor and primary motor cortex

Sixteen healthy right-handed subjects performed a complex finger-tapping task that broadly activates the motor and premotor regions, including primary motor (M1), ventral premotor (PMv), and dorsal premotor (PMd) cortex. This task was performed with the right hand only, left hand only and both hands simultaneously. Behavioral performance and the possibility of mirror movements were controlled through the use of MRI-compatible gloves to monitor finger movements. Using spatially normalized ROIs from the Human Motor Area Template (HMAT), comparisons were made of the spatial extent and location of activation in the left and right motor regions between all three tasks. During unilateral right and left hand tapping, ipsilateral precentral gyrus activation occurred in all subjects, mainly in the PMv and PMd. Ipsilateral M1 activation was less consistent and shifted anteriorly within M1, towards the border of M1 and premotor cortex. Regions of ipsilateral activation were also activated during contralateral and bilateral tasks. Overall, 83%/70%/58% of the ipsilaterally activated voxels in M1/PMd/PMv were also activated during contralateral and bilateral tapping. The mean percent signal change of spatially overlapping activated voxels was similar in PMv and PMd between all three tasks. However, the mean percent signal change of spatially overlapping M1 activation was significantly less during ipsilateral tapping compared with contra- or bilateral tapping. Results suggest that the ipsilateral fMRI activation in unilateral motor tasks may not be inhibitory in nature, but rather may reflect part of a bilateral network involved in the planning and/or execution of tapping in the ipsilateral hand.     

Anatomical and physiological definition of the motor cortex of the marmoset monkey

We used a combination of anatomical and physiological techniques to define the primary motor cortex (M1) of the marmoset monkey and its relationship to adjacent cortical fields. Area M1, defined as a region containing a representation of the entire body and showing the highest excitability to intracortical microstimulation, is architecturally heterogeneous: it encompasses both the caudal part of the densely myelinated "gigantopyramidal" cortex (field 4) and a lateral region, corresponding to the face representation, which is less myelinated and has smaller layer 5 pyramidal cells (field 4c). Rostral to M1 is a field that is strongly reminiscent of field 4 in terms of cyto- and myeloarchitecture but that in the marmoset is poorly responsive to microstimulation. Anatomical tracing experiments revealed that this rostral field is interconnected with visual areas of the posterior parietal cortex, whereas M1 itself has no such connections. For these reasons, we considered this field to be best described as part of the dorsal premotor cortex and adopted the designation 6Dc. Histological criteria were used to define other fields adjacent to M1, including medial and ventral subdivisions of the premotor cortex (fields 6M and 6V) and the rostral somatosensory field (area 3a), as well as a rostral subdivision of the dorsal premotor area (field 6Dr). These results suggest a basic plan underlying the histological organization of the caudal frontal cortex in different simian species, which has been elaborated during the evolution of larger species of primate by creation of further morphological and functional subdivisions.     

Architecture and frontal cortical connections of the premotor cortex (area 6) in the rhesus monkey

The premotor cortex (area 6) has several architectonic sectors that can be delineated on the basis of cytoarchitectonic and myeloarchitectonic features. Area 6 may be broadly subdivided into a dorsal and a ventral sector at the spur of the arcuate sulcus. Dorsal 6 lacks a granular layer IV, but ventral 6 has an emergent layer IV that separates laminae III and V. Dorsal 6 has a higher myelin content than ventral 6. Dorsal area 6 is further subdivided into a caudal and a rostral sector on the basis of the presence of large pyramidal cells in the caudal but not in the rostral sector. The rostral sector of area 6 can be subdivided into a medial region distinguished from a more laterally situated area by the presence of more compact and darkly stained cells in layers III and V. Ventral area 6 can be subdivided into an upper and lower division. The upper part has more prominent pyramidal cells in layers III and V, and a better developed outer Baillarger band and vertical plexus than the lower division. The efferent and afferent connections of area 6 were studied with anterograde and retrograde tracers. The frontal connections of dorsal area 6 are restricted to neighboring dorsal frontal regions. Only the caudal sector of dorsal area 6 is connected with the motor cortex. In contrast, ventral area 6 is not only connected with the prefrontal cortex, but also directly with the motor cortex, the parainsular gustatory area, and with somatosensory areas in the frontal operculum. The widespread connections of ventral area 6 may be related to the specialization of the head, neck, and face structures that are represented ventrally within the premotor cortex.     

Dissociating the role of prefrontal and premotor cortices in controlling inhibitory mechanisms during motor preparation

Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated in a timely manner. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution, whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation.     

Interhemispheric connections of the ventral premotor cortex in a new world primate

This study describes the pattern of interhemispheric connections of the ventral premotor cortex (PMv) distal forelimb representation (DFL) in squirrel monkeys. Our objectives were to describe qualitatively and quantitatively the connections of PMv with contralateral cortical areas. Intracortical microstimulation techniques (ICMS) guided the injection of the neuronal tract tracers biotinylated dextran amine or Fast blue into PMv DFL. We classified the interhemispheric connections of PMv into three groups. Major connections were found in the contralateral PMv and supplementary motor area (SMA). Intermediate interhemispheric connections were found in the rostral portion of the primary motor cortex, the frontal area immediately rostral and ventral to PMv (FR), cingulate motor areas (CMAs), and dorsal premotor cortex (PMd). Minor connections were found inconsistently across cases in the anterior operculum (AO), posterior operculum/inferior parietal cortex (PO/IP), and posterior parietal cortex (PP), areas that consistently show connections with PMv in the ipsilateral hemisphere. Within-case comparisons revealed that the percentage of PMv connections with contralateral SMA and PMd are higher than the percentage of PMv connections with these areas in the ipsilateral hemisphere; percentages of PMv connections with contralateral M1 rostral, FR, AO, and the primary somatosensory cortex are lower than percentages of PMv connections with these areas in the ipsilateral hemisphere. These studies increase our knowledge of the pattern of interhemispheric connection of PMv. They help to provide an anatomical foundation for understanding PMv's role in motor control of the hand and interhemispheric interactions that may underlie the coordination of bimanual movements.     

Comprehensive analysis of area‐specific and time‐dependent changes in gene expression in the motor cortex of macaque monkeys during recovery from spinal cord injury

The present study aimed to assess the molecular bases of cortical compensatory mechanisms following spinal cord injury in primates. To accomplish this, comprehensive changes in gene expression were investigated in the bilateral primary motor cortex (M1), dorsal premotor cortex (PMd), and ventral premotor cortex (PMv) after a unilateral lesion of the lateral corticospinal tract (l‐CST). At 2 weeks after the lesion, a large number of genes exhibited altered expression levels in the contralesional M1, which is directly linked to the lesioned l‐CST. Gene ontology and network analyses indicated that these changes in gene expression are involved in the atrophy and plasticity changes observed in neurons. Orchestrated gene expression changes were present when behavioral recovery was attained 3 months after the lesion, particularly among the bilateral premotor areas, and a large number of these genes are involved in plasticity. Moreover, several genes abundantly expressed in M1 of intact monkeys were upregulated in both the PMd and PMv after the l‐CST lesion. These area‐specific and time‐dependent changes in gene expression may underlie the molecular mechanisms of functional recovery following a lesion of the l‐CST.     

Dorsal premotor activity and connectivity relate to action selection performance after stroke

Compensatory activation in dorsal premotor cortex (PMd) during movement execution has often been reported after stroke. However, the role of PMd in the planning of skilled movement after stroke has not been well studied. The current study investigated the behavioral and neural response to the addition of action selection (AS) demands, a motor planning process that engages PMd in controls, to movement after stroke. Ten individuals with chronic, left hemisphere stroke and 16 age‐matched controls made a joystick movement with the right hand under two conditions. In the AS condition, participants moved right or left based on an abstract, visual rule; in the execution only condition, participants moved in the same direction on every trial. Despite a similar behavioral response to the AS condition (increase in reaction time), brain activation differed between the two groups: the control group showed increased activation in left inferior parietal lobule (IPL) while the stroke group showed increased activation in several right/contralesional regions including right IPL. Variability in behavioral performance between participants was significantly related to variability in brain activation. Individuals post‐stroke with relatively poorer AS task performance showed greater magnitude of activation in left PMd and dorsolateral prefrontal cortex (DLPFC), increased left primary motor cortex‐PMd connectivity, and decreased left PMd‐DLPFC connectivity. Changes in the premotor‐prefrontal component of the motor network during complex movement conditions may negatively impact the performance and learning of skilled movement and may be a prime target for rehabilitation protocols aimed at improving the function of residual brain circuits after stroke. Hum Brain Mapp 37:1816–1830, 2016. © 2016 Wiley Periodicals, Inc .     

One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence‐specific implicit learning

Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence‐specific learning. Thirty‐three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence‐specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence‐specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow‐up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation‐induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence‐specific learning of a visuomotor task and offer converging evidence for competing memory systems.     

Direct projections from the dorsal premotor cortex to the superior colliculus in the macaque (macaca mulatta)

The dorsal premotor cortex (PMd) is part of the cortical network for arm movements during reach‐related behavior. Here we investigate the neuronal projections from the PMd to the midbrain superior colliculus (SC), which also contains reach‐related neurons, to investigate how the SC integrates into a cortico‐subcortical network responsible for initiation and modulation of goal‐directed arm movements. By using anterograde transport of neuronal tracers, we found that the PMd projects most strongly to the deep layers of the lateral part of the SC and the underlying reticular formation corresponding to locations where reach‐related neurons have been recorded, and from where descending tectofugal projections arise. A somewhat weaker projection targets the intermediate layers of the SC. By contrast, terminals originating from prearcuate area 8 mainly project to the intermediate layers of the SC. Thus, this projection pattern strengthens the view that different compartments in the SC are involved in the control of gaze and in the control or modulation of reaching movements. The PMD–SC projection assists in the participation of the SC in the skeletomotor system and provides the PMd with a parallel path to elicit forelimb movements. J. Comp. Neurol. 523:2390–2408, 2015. © 2015 Wiley Periodicals, Inc.