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.

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.

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.

Neuron classification based on temporal firing patterns by the dynamical analysis with changing time resolution (DCT) method.

Spike train data of many neurons can be obtained by multirecording techniques; however, the data make it difficult to estimate the connective structure in a large network. Neuron classification should be helpful in that regard, assuming that multiple neurons having similar connections with other neurons show a similar temporal firing pattern. We propose a novel method for classifying neurons based on temporal firing patterns of spike train data called the dynamical analysis with changing time resolution (DCT) method. The DCT method can evaluate temporal firing patterns by a simple algorithm with few arbitrary factors and automatically classify neurons by similarity of temporal firing patterns. In the DCT method, temporal firing patterns were objectively evaluated by analyzing their dependence on temporal resolution. We confirmed the effectiveness of the DCT method using actual spike train data.

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.

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.