Premovement activity in the mesocortical system links peak force but not initiation of force generation under incentive motivation.

Motivation facilitates motor performance; however, the neural substrates of the psychological effects on motor performance remain unclear. We conducted a functional magnetic resonance imaging experiment while human subjects performed a ready-set-go task with monetary incentives. Although subjects were only motivated to respond quickly, increasing the incentives improved not only reaction time but also peak grip force. However, the trial-by-trial correlation between reaction time and peak grip force was weak. Extensive areas in the mesocortical system, including the ventral midbrain (VM) and cortical motor-related areas, exhibited motivation-dependent activity in the premovement "Ready" period when the anticipated monetary reward was displayed. This premovement activity in the mesocortical system correlated only with subsequent peak grip force, whereas the activity in motor-related areas alone was associated with subsequent reaction time and peak grip force. These findings suggest that the mesocortical system linking the VM and motor-related regions plays a role in controlling the peak of force generation indirectly associated with incentives but not the initiation of force generation.

The dorsal premotor cortex encodes the step-by-step planning processes for goal-directed motor behavior in humans.

The dorsal premotor cortex (PMd) plays an essential role in visually guided goal-directed motor behavior. Although there are several planning processes for achieving goal-directed behavior, the separate neural processes are largely unknown. Here, we created a new visuo-goal task to investigate the step-by-step planning processes for visuomotor and visuo-goal behavior in humans. Using functional magnetic resonance imaging, we found activation in different portions of the bilateral PMd during each processing step. In particular, the activated area for rule-based visuomotor and visuo-goal mapping was located at the ventrorostral portion of the bilateral PMd, that for action plan specification was at the dorsocaudal portion of the left PMd, that for transformation was at the rostral portion of the left PMd, and that for action preparation was at the caudal portion of the bilateral PMd. Thus, the left PMd was involved throughout all of the processes, but the right PMd was involved only in rule-based visuomotor and visuo-goal mapping and action preparation. The locations related to each process were generally spatially separated from each other, but they overlapped partially. These findings revealed that there are functional subregions in the bilateral PMd in humans and these subregions form a functional gradient to achieve goal-directed behavior.

Cerebellar outputs contribute to spontaneous and movement-related activity in the motor cortex of monkeys.

Cerebellar outputs originate from the dentate nucleus (DN), project to the primary motor cortex (M1) via the motor thalamus, control M1 activity, and play an essential role in coordinated movements. However, it is unclear when and how the cerebellar outputs contribute to M1 activity. To address this question, we examined the response of M1 neurons to electrical stimulation of the DN and M1 activity during performance of arm-reaching tasks. Based on response patterns to DN stimulation, M1 neurons were classified into facilitation-, suppression-, and no-response-types. During tasks, not only facilitation- and suppression-type M1 neurons, but also no response-type M1 neurons increased or decreased their firing rates in relation to arm reaching movements. However, the firing rates of facilitation- and suppression-type neurons were higher than those of no-response-type neurons during both inter-trial intervals and arm reaching movements. These results imply that cerebellar outputs contribute to both spontaneous and movement-related activity in the M1, which help to maintain muscle tones and execute coordinated movements, although other inputs also contribute to movement-related activity. Pharmacological inactivation of the DN supports this notion, in that DN inactivation reduced both spontaneous firing rates and movement-related activity in the M1.

[Cortical Areas for Controlling Voluntary Movements].

The primary motor cortex is located in Brodmann area 4 at the most posterior part of the frontal lobe. The primary motor cortex corresponds to an output stage of motor signals, sending motor commands to the brain stem and spinal cord. Brodmann area 6 is rostral to Brodmann area 4, where multiple higher-order motor areas are located. The premotor area, which is located in the lateral part, is involved in planning and executing action based on sensory signals. The premotor area contributes to the reaching for and grasping of an object to achieve a behavioral goal. The supplementary motor area, which occupies the mesial aspect, is involved in planning and executing actions based on internalized or memorized signals. The supplementary motor area plays a central role in bimanual movements, organizing multiple movements, and switching from a routine to a controlled behavior. Thus, Brodmann areas 4 and 6 are considered as central motor areas in the cerebral cortex, in which the idea of an action is transformed to an actual movement in a variety of contexts.

Visuomotor signals for reaching movements in the rostro-dorsal sector of the monkey thalamic reticular nucleus.

The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. This unique connectivity suggests that the TRN plays a pivotal role in regulating information flow through the thalamus. Here, we analyzed the roles of TRN neurons in visually guided reaching movements. We first used retrograde transneuronal labeling with rabies virus, and showed that the rostro-dorsal sector of the TRN (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a visuomotor task. We found that neurons in the TRNrd and PMv showed visual-, set-, and movement-related activity modulation. These results indicate that the TRNrd, as well as the PMv, is involved in the reception of visual signals and in the preparation and execution of reaching movements. The fraction of neurons that were non-selective for the location of visual signals or the direction of reaching movements was greater in the TRNrd than in the PMv. Furthermore, the fraction of neurons whose activity increased from the baseline was greater in the TRNrd than in the PMv. The timing of activity modulation of visual-related and movement-related neurons was similar in TRNrd and PMv neurons. Overall, our data suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs that are predominantly devoid of spatial selectivity, and that these signals modulate how these nuclei engage in both sensory processing and motor output during visually guided reaching behavior.

Rostrocaudal functional gradient among the pre-dorsal premotor cortex, dorsal premotor cortex and primary motor cortex in goal-directed motor behaviour.

The dorsal premotor cortex residing in the dorsolateral aspect of area 6 is a rostrocaudally elongated area that is rostral to the primary motor cortex (M1) and caudal to the prefrontal cortex. This region, which is subdivided into rostral [pre-dorsal premotor cortex (pre-PMd)] and caudal [dorsal premotor cortex proper (PMd)] components, probably plays a central role in planning and executing actions to achieve a behavioural goal. In the present study, we investigated the functional specializations of the pre-PMd, PMd, and M1, because the synthesis of the specific functions performed by each area is considered to be essential. Neurons were recorded while monkeys performed a conditional visuo-goal task designed to include separate processes for determining a behavioural goal (reaching towards a right or left potential target) on the basis of visual object instructions, specifying actions (direction of reaching) to be performed on the basis of the goal, and preparing and executing the action. Neurons in the pre-PMd and PMd retrieved and maintained behavioural goals without encoding the visual features of the visual object instructions, and subsequently specified the actions by multiplexing the goals with the locations of the targets. Furthermore, PMd and M1 neurons played a major role in representing the action during movement preparation and execution, whereas the contribution of the pre-PMd progressively decreased as the time of the actual execution of the movement approached. These findings revealed that the multiple processing stages necessary for the realization of an action to accomplish a goal were implemented in an area-specific manner across a functional gradient from the pre-PMd to M1 that included the PMd as an intermediary.

Area- and band-specific representations of hand movements by local field potentials in caudal cingulate motor area and supplementary motor area of monkeys.

The caudal cingulate motor area (CMAc) and the supplementary motor area (SMA) play important roles in movement execution. The present study examined the neural mechanisms underlying these roles by investigating local field potentials (LFPs) from these areas while monkeys pressed buttons with either their left or right hand. During hand movement, power increases in the high-gamma (80-120 Hz) and theta (3-8 Hz) bands and a power decrease in the beta (12-30 Hz) band were observed in both the CMAc and SMA. High-gamma and beta activity in the SMA predominantly represented contralateral hand movements, whereas activity in the CMAc preferentially represented movement of either hand. Theta activity in both brain regions most frequently reflected movement of either hand, but a contralateral hand bias was more evident in the SMA than in the CMAc. An analysis of the relationships of the laterality representations between the high-gamma and theta bands at each recording site revealed that, irrespective of the hand preference for the theta band, the high-gamma band in the SMA preferentially represented contralateral hand movement, whereas the high-gamma band in the CMAc represented movement of either hand. These findings suggest that the input-output relationships for ipsilateral and contralateral hand movements in the CMAc and SMA differ in terms of their functionality. The CMAc may transform the input signals representing general aspects of movement into commands to perform movements with either hand, whereas the SMA may transform the input signals into commands to perform movement with the contralateral hand.

Distinct neuronal organizations of the caudal cingulate motor area and supplementary motor area in monkeys for ipsilateral and contralateral hand movements.

The caudal cingulate motor area (CMAc) and the supplementary motor area (SMA) play important roles in movement execution. The present study aimed to characterize the functional organization of these regions during movement by investigating laterality representations in the CMAc and SMA of monkeys via an examination of neuronal activity during a button press movement with either the right or left hand. Three types of movement-related neuronal activity were observed: 1) with only the contralateral hand, 2) with only the ipsilateral hand, and 3) with either hand. Neurons in the CMAc represented contralateral and ipsilateral hand movements to the same degree, whereas neuronal representations in the SMA were biased toward contralateral hand movement. Furthermore, recording neuronal activities using a linear-array multicontact electrode with 24 contacts spaced 150 µm apart allowed us to analyze the spatial distribution of neurons exhibiting particular hand preferences at the submillimeter scale. The CMAc and SMA displayed distinct microarchitectural organizations. The contralateral, ipsilateral, and bilateral CMAc neurons were distributed homogeneously, whereas SMA neurons exhibiting identical hand preferences tended to cluster. These findings indicate that the CMAc, which is functionally organized in a less structured manner than the SMA is, controls contralateral and ipsilateral hand movements in a counterbalanced fashion, whereas the SMA, which is more structured, preferentially controls contralateral hand movements.

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.

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.

[Neural mechanisms underlying the integration of perception and action].

The hallmark of higher-order brain functions is the ability to integrate and associate diverse sets of information in a flexible manner. Thus, fundamental knowledge about the mechanisms underlying of information in the brain can be obtained by examining the neural mechanisms involved in the generation of an appropriate motor command based on perceived sensory signals. In this review article, we have focused on the involvement of the neuronal networks centered at the lateral aspect of the frontal cortex in the process of motor selection and motor planning based on visual signals. We have initially discussed the role of the lateral prefrontal cortex in integrating multiple sets of visual signals to select a reach target and the participation of the premotor cortex in retrieving and integrating diverse sets of motor information, such as where should one reach out or which arm is to be used. Next, based on the results of the studies on ideomotor apraxia, we have hypothesized that there are at least 2 distinct levels of neural representation (virtual level and physical level). We have reviewed the evidence supporting the operation of 2 distinct classes of neuronal activities corresponding to these 2 levels. In conclusion, we propose that the frontal cortex initially processes information across sensory and motor domains at the virtual level to generate information about a forthcoming motor action (virtual action plan) and that this information is subsequently transformed into a motor command, such as muscle activity or movement direction, for an actual body movement at the physical level (physical motor plan). This proposed framework may be useful for explaining the diverse clinical conditions caused by brain lesions as well as for clarifying the neural mechanisms underlying the integration of perception and action.

[On somatotopical organization of cortical motor areas].

Early studies on cortical motor areas have been centered on their somatotopical organization: a reasonable direction of research from the standpoint of skeletomotor control of limb and body movements. On the primary motor cortex, anatomical and physiological studies revealed aspects of somatotopical organization in progressively finer scales. Earlier studies were directed at elucidating the fine-grain modular organization of the primary motor cortex. Later studies, however, emphasized the diversity of output organization in individual part of the cortex, even at a single-cell level. At present, there is no convincing evidence for the existence of microstructures representing any form of unitary function. As for nonprimary motor areas, the existence of somatotopical organization has been inferred based on anatomical studies and on studies utilizing microstimulation. In the supplementary motor area, the body-part representation is broadly organized rostrocaudally in the order of face, forelimb and hindlimb areas, although with an extensive overlap of each area. In contrast, somatotopy is not apparent in the presupplemenetary motor area; effector-independent control of motor behavior seems to be dominant in this area. In the premotor cortex, motor acts involving the hindlimb appears to be much less represented than actions involving hand-arm and face. Overall, in considering the workings of nonprimary areas, aspects of motor behavior involving sensorial guidance, action-selection, or visuomotor association appear to be of primary importance rather than the determination of body parts to be used.

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.

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.

Sex differences in the relationship between cortisol levels and the Empathy and Systemizing Quotients in humans.

OBJECTIVE: Little is known regarding the relationship between cortisol (a stress hormone) levels and psychological cognitive styles. Baron-Cohen proposed two fundamental cognitive styles, which are measured by the Empathy Quotient (EQ) and the Systemizng Quotient (SQ). Previous studies have examined the influences of prenatal testosterone exposure on EQ and SQ scores. This study aimed to examine the relationships between morning cortisol levels and EQ and SQ scores, and the 'brain types' which were determined by two quotients in both sexes. These relationships are potentially important in the developmental psychopathology of autism and neuroeconomics of empathy. METHODS: We assessed morning cortisol levels with LC/MS (liquid chromatography-mass spectrometry) and ESQ in healthy male and female university students. CONCLUSIONS: Results indicate clear sex differences between brain types: i.e. E-type males and S-type females (participants with atypical cognitive styles) have significantly higher cortisol levels than S-type males and E-type females (participants with typical cognitive styles). Implications for the role of sex in social adaptation of autistic patients are discussed.

[A case of chrome asthma induced by exposure to the stone cutter dust].

The case of a forty-six year old, male patient with asthma caused by exposure to dust containing chrome is presented. When the patient was nineteen years old, he started working as a stonemason in a factory. He cut and ground stone with a stone-cutter to make statues and tombstones. Three years after staring to work, contact dermatitis was observed on his arms and hands. Within six years of work, he suffered from chronic coughing. After eight years, he experienced bronchial asthma attacks with wheezing and dyspnea. He had been exposed to dust for eight years before developing asthma. The symptoms increased gradually. He fell into severe asthma attacks causing unconsciousness and dyspnea. Several common therapies were not effective. The characteristics of his clinical course and occupational history suggested that the asthma must be caused by exposure to dust containing metal generated in the factory. Skin Patch Tests (SPT) were performed for cobalt, copper, iron, chrome, tin, and manganese salt. The result of the SPT indicated a strong positive result for potassium dichromate and positive for chromium sulfate, but did not show any indications in the control or for other metallic salt. Fluorescent X-ray analysis detected that chrome was present in the powder dust under the stone-cutter machine. However, the fluorescent X-ray analysis did not detect chrome in the stone materials. It was suggested that chrome must be contained in the metal dust generated from the steel cutter used to cut off and grind the stone. The metal component in the used cutter edge and the unused cutter edge were analyzed with electro-probe microanalyzer (EPMA). The result revealed that chrome was contained in the used, dull cutter edge and not in the new sharp cutter edge. Thus, the patient had been exposed to the dust containing chrome generated from part of the stainless steel of cutter. He had sensitized to chrome and this had caused the occupational chrome-asthma.

Cortisol levels and prospective and retrospective memory in humans.

OBJECTIVES: The aim of this study was to examine (i) the influence of cortisol on both prospective and retrospective memory performance and (ii) the role of emotional valence in both types of memory. METHODS: Thirty-four male students participated in a memory task, which measured both prospective and retrospective memory performance. Baseline salivary cortisol levels were assessed. RESULTS: Spearman's rank order correlation analysis showed a significant positive correlation between salivary cortisol levels and retrospective memory performance for neutral words. Cortisol levels were not significantly correlated with prospective memory performance for either negative nor neutral words. CONCLUSIONS: The present results indicate chronic cortisol levels are positively associated with retrospective memory at relatively low concentration ranges, but not prospective memory, in healthy young men. Implications for evaluating the beneficial effects of low-dose cortisol treatment on posttraumatic stress disorder is discussed.