Neuronal activity in the monkey prefrontal cortex during a duration discrimination task with visual and auditory cues.

To investigate neuronal processing involved in the integration of auditory and visual signals for time perception, we examined neuronal activity in prefrontal cortex (PFC) of macaque monkeys during a duration discrimination task with auditory and visual cues. In the task, two cues were consecutively presented for different durations between 0.2 and 1.8 s. Each cue was either auditory or visual and was followed by a delay period. After the second delay, subjects indicated whether the first or the second cue was longer. Cue- and delay-responsive neurons were found in PFC. Cue-responsive neurons mostly responded to either the auditory or the visual cue, and to either the first or the second cue. The neurons responsive to the first delay showed activity that changed depending on the first cue duration and were mostly sensitive to cue modality. The neurons responsive to the second delay exhibited activity that represented which cue, the first or second cue, was presented longer. Nearly half of this activity representing order-based duration was sensitive to cue modality. These results suggest that temporal information with visual and auditory signals was separately processed in PFC in the early stage of duration discrimination and integrated for the final decision.

Locomotor kinematics and EMG activity during quadrupedal versus bipedal gait in the Japanese macaque.

Several qualitative features distinguish bipedal from quadrupedal locomotion in mammals. In this study we show quantitative differences between quadrupedal and bipedal gait in the Japanese monkey in terms of gait patterns, trunk/hindlimb kinematics, and electromyographic (EMG) activity, obtained from 3 macaques during treadmill walking. We predicted that as a consequence of an almost upright body axis, bipedal gait would show properties consistent with temporal and spatial optimization countering higher trunk/hindlimb loads and a less stable center of mass (CoM). A comparatively larger step width, an ~9% longer duty cycle, and ~20% increased relative duration of the double-support phase were all in line with such a strategy. Bipedal joint kinematics showed the strongest differences in proximal, and least in distal, hindlimb joint excursions compared with quadrupedal gait. Hindlimb joint coordination (cyclograms) revealed more periods of single-joint rotations during bipedal gait and predominance of proximal joints during single support. The CoM described a symmetrical, quasi-sinusoidal left/right path during bipedal gait, with an alternating shift toward the weight-supporting limb during stance. Trunk/hindlimb EMG activity was nonuniformally increased during bipedal gait, most prominently in proximal antigravity muscles during stance (up to 10-fold). Non-antigravity hindlimb EMG showed altered temporal profiles during liftoff or touchdown. Muscle coactivation was more, but muscle synergies less, frequent during bipedal gait. Together, these results show that behavioral and EMG properties of bipedal vs. quadrupedal gait are quantitatively distinct and suggest that the neural control of bipedal primate locomotion underwent specific adaptations to generate these particular behavioral features to counteract increased load and instability. NEW & NOTEWORTHY Bipedal locomotion imposes particular biomechanical constraints on motor control. In a within-species comparative study, we investigated joint kinematics and electromyographic characteristics of bipedal vs. quadrupedal treadmill locomotion in Japanese macaques. Because these features represent (to a large extent) emergent properties of the underlying neural control, they provide a comparative, behavioral, and neurophysiological framework for understanding the neural system dedicated to bipedal locomotion in this nonhuman primate, which constitutes a critical animal model for human bipedalism.

Effects of pulsed magnetic stimulation on isolated crayfish heart.

Cardiac muscular contraction of the neurogenic heart that could be excited by pulsed magnetic stimulation (PMS) was investigated using preparation of the isolated crayfish heart. When a figure-eight magnetic coil was set over the isolated heart, cardiac contraction induced by a single PMS was not observed. Cardiac arrest occurred immediately after repetitive PMS and persisted for dozens of seconds depending on the number of stimuli. We concluded that PMS caused neuronal modulation in the neuronal network in the cardiac ganglion.

Neuronal representation of duration discrimination in the monkey striatum.

Functional imaging and lesion studies in humans and animals suggest that the basal ganglia are crucial for temporal information processing. To elucidate neuronal mechanisms of interval timing in the basal ganglia, we recorded single-unit activity from the striatum of two monkeys while they performed a visual duration discrimination task. In the task, blue and red cues of different durations (0.2-2.0 sec) were successively presented. Each of the two cues was followed by a 1.0 sec delay period. The animals were instructed to choose the longer presented colored stimulus after the second delay period. A total of 498 phasically active neurons were recorded from the striatum, and 269 neurons were defined as task related. Two types of neuronal activity were distinguished during the delay periods. First, the activity gradually changed depending on the duration of the cue presented just before. This activity may represent the signal duration for later comparison between two cue durations. The activity during the second cue period also represented duration of the first cue. Second, the activity changed differently depending on whether the first or second cue was presented longer. This activity may represent discrimination results after the comparison between the two cue durations. These findings support the assumption that striatal neurons represent timing information of sensory signals for duration discrimination.

Functional properties of parietal hand manipulation-related neurons and mirror neurons responding to vision of own hand action.

Parietofrontal pathways play an important role in visually guided motor control. In this pathway, hand manipulation-related neurons in the inferior parietal lobule represent 3-D properties of an object and motor patterns to grasp it. Furthermore, mirror neurons show visual responses that are concerned with the actions of others and motor-related activity during execution of the same grasping action. Because both of these categories of neurons integrate visual and motor signals, these neurons may play a role in motor control based on visual feedback signals. The aim of this study was to investigate whether these neurons in inferior parietal lobule including the anterior intraparietal area and PFG of macaques represent visual images of the monkey's own hand during a self-generated grasping action. We recorded 235 neurons related to hand manipulation tasks. Of these, 54 responded to video clips of the monkey's own hand action, the same as visual feedback during that action or clips of the experimenter's hand action in a lateral view. Of these 54 neurons, 25 responded to video clips of the monkey's own hand, even without an image of the target object. We designated these 25 neurons as "hand-type." Thirty-three of 54 neurons that were defined as mirror neurons showed visual responses to the experimenter's action and motor responses. Thirteen of these mirror neurons were classified as hand-type. These results suggest that activity of hand manipulation-related and mirror neurons in anterior intraparietal/PFG plays a fundamental role in monitoring one's own body state based on visual feedback.

Influence of background complexity on visual sensitivity and binocular summation using patterns with and without noise.

PURPOSE: To investigate how background complexity influences visual sensitivity and binocular summation. METHODS: Using two noise backgrounds (noise-sparse and noise-dense) and two corresponding noise-free backgrounds with the same luminance for each noise background, monocular and binocular thresholds were measured in six visually normal subjects (average age, 27.3 ± 1.1 years). The noise-sparse and noise-dense backgrounds respectively had 312 and 936 white-light dots projected on them-the same size white-light dots (0.431° of visual angle) as those that were used for the white-spot target in the threshold measurement. The target was tested at the fovea and at 3° intervals on the 45°, 135°, 225°, and 315° meridians. A total of 25 locations were tested. RESULTS: The monocular threshold for the noise-dense background was higher than that for its corresponding noise-free background, with significant differences seen at 15° and 18° (P < 0.01). No significant differences in the binocular threshold were seen, either between the noise-dense and its corresponding backgrounds or between the noise-sparse and its corresponding backgrounds. The binocular summation ratios for both noise backgrounds were significantly higher than the ratios for the noise-free backgrounds, and the difference increased with eccentricity, with significances seen at 15° and 18° (P < 0.01). CONCLUSIONS: Only the monocular threshold increases with background complexity. The binocular summation increases with background complexity in the periphery. When the background becomes more complex and the monocular visual processing reaches its limit, binocular interaction functions efficiently.

Influence of target size and eccentricity on binocular summation of reaction time in kinetic perimetry.

To assess how target size and eccentricity affect binocular summation (BS) of reaction time (RT) at suprathreshold level, we measured RT using targets of 0.108° and 0.216° at four eccentricities (0°, 5°, 15°, 25°) in six normal volunteers. The difference between the monocular/binocular RT differentials for both sizes significantly increased in the periphery (P<0.05). The smaller target required significantly longer monocular RT at 25° (P<0.01) and generated greater neural summation than the larger target (P<0.01). This suggests that when monocular function has reached its limit in visual processing in the periphery, BS increases, facilitates visual processing, and shortens binocular RT.

Shared mapping of own and others' bodies in visuotactile bimodal area of monkey parietal cortex.

Parietal cortex contributes to body representations by integrating visual and somatosensory inputs. Because mirror neurons in ventral premotor and parietal cortices represent visual images of others' actions on the intrinsic motor representation of the self, this matching system may play important roles in recognizing actions performed by others. However, where and how the brain represents others' bodies and correlates self and other body representations remain unclear. We expected that a population of visuotactile neurons in simian parietal cortex would represent not only own but others' body parts. We first searched for parietal visuotactile bimodal neurons in the ventral intraparietal area and area 7b of monkeys, and then examined the activity of these neurons while monkeys were observing visual or tactile stimuli placed on the experimenter's body parts. Some bimodal neurons with receptive fields (RFs) anchored on the monkey's body exhibited visual responses matched to corresponding body parts of the experimenter, and visual RFs near that body part existed in the peripersonal space within approximately 30 cm from the body surface. These findings suggest that the brain could use self representation as a reference for perception of others' body parts in parietal cortex. These neurons may contribute to spatial matching between the bodies of the self and others in both action recognition and imitation.

Temporal filtering by prefrontal neurons in duration discrimination.

Neural imaging studies have revealed that the prefrontal cortex (PFC) participates in time perception. However, actual functional roles remain unclear. We trained two monkeys to perform a duration-discrimination task, in which two visual cues were presented consecutively for different durations ranging from 0.2 to 2.0 s. The subjects were required to choose the longer cue. We recorded single-neuron activity from the PFC while the subjects were performing the task. Responsive neurons for the first cue period were extracted and classified through a cluster analysis of firing rate curves. The neuronal activity was categorized as phasic, ramping and sustained patterns. Among them, the phasic activity was the most prevailing. Peak time of the phasic activity was broadly distributed about 0.8 s after cue onset, leading to a natural assumption that the phasic activity was related to cognitive processes. The phasic activity with constant delay after cue onset might function to filter current cue duration with the peak time. The broad distribution of the peak time would indicate that various filtering durations had been prepared for estimating C1 duration. The most frequent peak time was close to the time separating cue durations into long and short. The activity with this peak time might have had a role of filtering in attempted duration discrimination. Our results suggest that the PFC contributes to duration discrimination with temporal filtering in the cue period.

Striatal neurons encoded temporal information in duration discrimination task.

To clarify the roles of the basal ganglia in time perception, single-unit activity was recorded from both sides of the striatum of a monkey performing a duration discrimination task. In the task, two visual cues were presented successively in different durations (0.2 approximately 1.6 s). Each cue presentation was followed by a 1-s delay period. The subject was instructed to choose a longer presented cue after the second delay period. There were two types of trials for sequence of cue duration, the long-short (LS) trials in which the first cue (C1) was longer than the second cue (C2) and the short-long (SL) trials in which the C1 was shorter than the C2. Striatal neurons phasically responded during the first delay (D1) and second delay (D2) periods. Responses during the D1 period changed depending on C1 duration. Activity of populations of D1-response neurons correlated with C1 duration positively or negatively. Responses during the D2 period differed between the LS and SL trials. Activity of population of D2-response neurons also changed depending on C2 duration. But the dependence on C2 duration was affected by the trial type, that is, whether the C2 was longer or shorter compared to the C1. These findings suggest that striatal neurons could encode cue durations with monotonically changing responses in the D1 period and discrimination results between the two cue durations in the D2 period.

Delay period activity of monkey prefrontal neurones during duration-discrimination task.

Evidence from brain imaging studies has indicated involvement of the prefrontal cortex (PFC) in time perception; however, the role of this area remains unclear. To address this issue, we recorded single neuronal activity from the PFC of two monkeys while they performed a duration-discrimination task. In the task, two visual cues (a blue or red square) were presented consecutively followed by delay periods and subjects then chose the cue presented for the longer duration. Durations of both cues, order of cue duration [long-short (LS) or short-long (SL)] and order of cue colour (blue-red or red-blue) were randomized on a trial-by-trial basis. We found that subjects responded differently between LS and SL trials and that most prefrontal neurones showed significantly different activity during either the first or the second delay period when comparing activity in LS and SL trials. The present result offers new insights into neural mechanisms of time perception. It appears that, during the delay periods, the PFC contributes to implement a strategic process in temporal processing associated with a trial type (LS or SL) such as representation of the trial type, retention of cue information and anticipation of the forthcoming cue.

Phosphate metabolites in muscular contraction caused by magnetic stimulation.

The metabolism of high energy phosphates during muscular contraction due to direct electrical stimulation, indirect stimulation via nerve excitation, and magnetic stimulation was studied in isolated muscles (frog sartorius muscles) by (31)P nuclear magnetic resonance ((31)P-NMR). Twitch amplitudes elicited by each stimulus were measured alternatively at 3 mm displacement loading and 5 g weight. Both the creatine/inorganic phosphate (PCr/Pi) and pH changes were more marked in direct electrical stimulation than in magnetic stimulation. The muscular contraction caused by magnetic stimulation showed less fatigue than that caused by direct electrical muscular stimulation.

Motor evoked potentials in rats with congenital hydrocephalus.

Motor evoked potential (MEP) by focal transcranial magnetic stimulation was used to test the functional integrity of the motor cortex in congenital hydrocephalic rats. Magnetic MEPs, using a figure-eight coil above the head, were recorded in the tibialis anterior muscle. The latency of transcranial magnetic MEP was 3.4 msec in nonhydrocephalic rats. In the hydrocephalic rats, the MEP had a lower threshold than in nonhydrocephalic rats, and showed two peaks. Latencies of early and late peaks were 3.9 msec and from 5.4 msec to 10.0 msec, respectively. Our findings suggest that hydrocephalus in rats is associated with changes in pyramidal cell excitability in the motor cortical area, probably induced by the fluctuations in cortical excitability and synaptic interaction in hydrocephalic rats.

Thalamocortical and intracortical connections of monkey cingulate motor areas.

Although there has been an increasing interest in motor functions of the cingulate motor areas, data concerning their input organization are still limited. To address this issue, the patterns of thalamic and cortical inputs to the rostral (CMAr), dorsal (CMAd), and ventral (CMAv) cingulate motor areas were investigated in the macaque monkey. Tracer injections were made into identified forelimb representations of these areas, and the distributions of retrogradely labeled neurons were analyzed in the thalamus and the frontal cortex. The cells of origin of thalamocortical projections to the CMAr were located mainly in the parvicellular division of the ventroanterior nucleus and the oral division of the ventrolateral nucleus (VLo). On the other hand, the thalamocortical neurons to the CMAd/CMAv were distributed predominantly in the VLo and the oral division of the ventroposterolateral nucleus-the caudal division of the ventrolateral nucleus. Additionally, many neurons in the intralaminar nuclear group were seen to project to the cingulate motor areas. Except for their well-developed interconnections, the corticocortical projections to the CMAr and CMAd/CMAv were also distinctively preferential. Major inputs to the CMAr arose from the presupplementary motor area and the dorsal premotor cortex, whereas inputs to the CMAd/CMAv originated not only from these areas but also from the supplementary motor area and the primary motor cortex. The present results indicate that the CMAr and the caudal cingulate motor area (involving both the CMAd and the CMAv) are characterized by distinct patterns of thalamocortical and intracortical connections, reflecting their functional differences.

Magnetically evoked EMGs in rats.

Magnetic stimulation of the brain and spinal cord was carried out in rats to record electromyogram (EMGs) from the gastrocnemius. A figure-eight coil was set over the middle of the dorsum, and shifted from the cervical vertebrae to the sacrum. The motor evoked potentials (MEPs) with 4.8 msec latency by transcranial magnetic stimulation and the descending wave with 4.7 msec latency by C3-C4 stimulation were recorded. In evoked EMGs by magnetic stimulation over T9-T10, L4-L5, S2-S3 and Ca2-Ca3 spinal cord levels, the causes of these two evoked components with short (1.5 msec) and long (4.1 msec) latencies were estimated to be the eddy current generated from the rostral to the caudal portion of the spinal cord. With the increase in magnetic stimuli, the relative sizes and disappearance of H- and M-like responses were comparable with the ordinary M- and H-responses in electrically evoked EMGs. The magnetic stimulation of the spinal cord activated the sciatic nerve at their vertebral exit, because the latencies of the H- and M-responses were constant despite the changing stimulus sites. Although magnetic stimulation with the figure-eight coil can be focused on the target, it is necessary to take into consideration the influence of the eddy current flowing in the body.

The relationship between MI and SMA afferents and cerebellar and pallidal efferents in the macaque monkey.

The purpose of the present study was to determine the interrelationship between the thalamic afferents arising from the cerebellum (Cb) and the internal segment of the globus pallidus (GPi) with the neurons projecting to the primary motor cortex (MI) and to the supplementary motor area (SMA). We combined fluorescent retrograde tracers with a double anterograde labeling technique. Multiple injections of a combination of Diamidino Yellow and Fast Blue were made into either the MI or SMA hand/arm representation as determined by intracortical microstimulation. In the same animal, biotinylated dextran amine was injected into the GPi and horseradish peroxidase conjugated to wheat germ agglutinin was injected into the contralateral cerebellar nuclei. The results revealed that the cerebellar and pallidal thalamic territories are largely separate. The ventral anterior nucleus (VA) and the ventral lateral nucleus pars oralis (VLo) contained a greater density of pallidal labeling while a greater density of cerebellar label was observed more caudally in the ventral posterior lateral nucleus pars oralis (VPLo) as well as in nucleus X (X). Moreover, we observed that the greatest coincidence of retrograde cell labeling was within the pallidal thalamic territory following the SMA injections and within the cerebellar thalamic territory following the MI injections. However, interdigitating foci of pallidal and cerebellar label were also observed particularly in the ventral lateral nucleus pars oralis (VLo) and the ventral lateral nucleus pars caudalis (VLc). In both VLo and VLc, we additionally observed coincidence between the cerebellar labeling and SMA projection neurons as well as between pallidal labeling and MI projection neurons. These data suggest that while MI primarily receives inputs originating from Cb and SMA primarily receives inputs originating from GPi, it also appears that MI and SMA receive secondary afferents arising from GPi and Cb, respectively.

Effects of morphine on two types of nucleus raphe dorsalis neurons in awake cats.

Forty-nine neurons recorded within the nucleus raphe dorsalis (NRD) in awake cats were classified into 2 groups: 29 regularly firing (clock-like) and 20 irregularly firing (non-clock-like) neurons. Hardly any of the clock-like neurons were influenced either by noxious stimulation (0.1 ml of 5% formalin, s.c.) or by a single dose (1 mg/kg, i.p.) or cumulative doses (0.25, 0.5, 1 mg/kg) of morphine. In contrast, about half the non-clock-like neurons were activated both by noxious stimulation and by administration of morphine. Morphine-induced activation of non-clock-like neurons was dose-related and reversed by naloxone (0.2 mg/kg, i.p.). These findings suggest that clock-like neurons in the NRD are not involved in morphine analgesia. Non-clock-like neurons, however, may play a role in the mediation of such analgesia.