Ken-ichi Oshio

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.

Geometrical structure of the neuronal network of Caenorhabditis elegans

The neuronal network of the soil nematode Caenorhabditis elegans (C. elegans), which is a good prototype for biological studies, is investigated. Here, the neuronal network is simplified as a graph. We use three indicators to characterize the graph; vertex degree, generalized eccentricity (GE), and complete subgraphs. The graph has the central part and the strong clustering structure. We present a simple model, which shows that the neuronal network has a high-dimensional geometrical structure.

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.

Magnetically evoked EMGs in rats

Abstract 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.

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.

Possible functions of prefrontal cortical neurons in duration discrimination.

The physical duration of a stimulus can be held invariant in different sensory modalities, such as vision and audition. The prefrontal cortex (PFC) is a region for convergence of inputs that originate in distinct sensory areas, and is considered an area of cross-modal association (Fuster et al., 2000). Assuming that the PFC participates in duration discrimination, such cross-modal integration appears crucial in support of an “amodal” clock used to time intervals in the seconds-to-minutes range (Meck and Church, 1982; Cordes et al., 2007). Indeed, brain-imaging studies have demonstrated that the PFC contributes to duration discrimination (for a review, see Meck et al., 2008). However, the actual roles of PFC neurons remain unclear. Although single-unit recording is effective in terms of elucidating the functional roles of each area, only a few investigations have been made of PFC neurons in interval-timing tasks in primates (for a rodent homolog of the role of PFC neurons in timing see Matell et al., 2003, 2011). Here, we review recent results of single-unit recording from monkey PFC neurons, discuss their possible functions, and then comment on future directions. We recorded single-unit activity while monkeys were performing a duration discrimination task in a series of studies (Oshio et al., 2006, 2008). In the task, red and blue cues were presented consecutively on a computer monitor for different durations ranging from 0.2 to 2.0 s, and the monkeys were then required to choose which color cue had lasted longer. Each cue was followed by a delay period of 1.0 s. The first cue, first delay, second cue, and second delay are referred to as C1, D1, C2 and D2, respectively. First, we found that PFC neurons showed significantly different activity during either the D1 or D2 period when comparing activity in C1-longer (LS) and C2-longer (SL) trials (Oshio et al., 2006). As for the D1 activity, the result indicates that the PFC neurons responded as if they encoded the duration category (e.g., “long” or “short”) of the C1 cue as early as the D1 period. Taken together with the correlated D2 activity, our findings suggest that PFC neurons not only encode duration category, but also implement strategic processes such as the representation of trial type (LS or SL) and the retention of cue information. Next, we analyzed neurons that were responsive during the C1 period, and found that phasic (transient) activity was the most common mode of activity (Oshio et al., 2008). Peak time of this phasic activity was broadly distributed with a delay of approximately 0.8 s after cue onset. Such phasic activity following a constant delay after cue onset might serve as a mechanism to filter or separate the current trials cue duration from the peak time in activity. The most frequent peak time was close to the time separating cue durations into “long” and “short” categories. As a consequence, the activity of this peak time might have played a role in filtering or selecting the appropriate response for the duration discrimination. Outputs of this temporal filtering, as a function of the phasic activity, would have been represented as the categorical response in the D1 period. Recently, two other research groups have successfully recorded single-unit activity in the monkey PFC during an interval-timing task, and found neuronal activities with various temporal profiles, including phasic, tonic, ramping, and so on, during cue and/or delay periods. As a consequence, it was proposed that PFC neurons may play a variety of roles in temporal processing, including the monitoring of cue duration and memory encoding (Sakurai et al., 2004; Genovesio et al., 2009 – see also Matell et al., 2011). There is considerable agreement among the above-mentioned studies that PFC neurons represent the absolute cue duration as well as other types of temporal information during ensuing delay periods. Scalar timing theory postulates three stages of temporal processes in duration discrimination: clock, memory, and comparison (Gibbon et al., 1984). The reported delay period activity suggests that PFC neurons contribute to the memory stage. This is reasonable, because PFC activity is well-known to support working memory function (e.g., Miller et al., 1996). Slight differences in PFC activity across various experiments have been attributed to differences in behavioral tasks, i.e., differences in the strategy that monkeys use to solve the task, etc. This also seems reasonable given that the PFC is considered to also serve strategic function. Moreover, subjects may actually adopt different strategies based on the nature of the timing task. The exact strategies taken by subjects can be inferred from behavioral data to some extent, but neuronal data may be more informative in this case and should be taken into consideration when analyzing the behavioral data. There is controversy over whether the internal clock is modality-specific or modality-independent and centralized or distributed (see Buhusi and Meck, 2005; Bueti and Walsh, 2009). The PFC, an area of cross-modal association, is a candidate for a centralized, amodal timing mechanism. Experiments with timing tasks using unimodal and bimodal sensory stimuli, including vision and audition, should be carried out to clarify whether the PFC serves as a centralized clock or not. In addition, neuroimaging studies have revealed that other brain areas also participate in timing tasks, for example, the basal ganglia, the parietal cortex, the cerebellum, and the supplementary motor area (Buhusi and Meck, 2005). However, the contributions of these areas to duration discrimination are much less understood than the PFC. The PFC has anatomical connections with all of these areas, and is known to cooperate with those areas in cognitive and motor functions (Fuster, 2008). Therefore, further elucidation of the roles of the PFC would be helpful to uncover their contributions to timing and time perception. In summary, the PFC is a key area to determine the functional and neural mechanisms of interval timing. More extensive research on the properties of PFC neurons is required in order to construct and test neurophysiological models of interval timing (see Matell and Meck, 2004; Lustig et al., 2005; Karmarkar and Buonomano, 2007).

Motor evoked potentials in rats with congenital hydrocephalus

Abstract 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.

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

Abstract. 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.

Prefrontal neurons contribute to temporal filtering in duration discrimination

A salient stimulus (a red target among green distractors) can automatically attract our attention. To examine neural representation of visual saliency, we trained monkeys to perform a visual search task in which a singleton target was different from distractors in color. We manipulated the degree of visual saliency of the target by independently changing “target-distractor color contrast” and “stimulusbackground luminance contrast”. For the estimation of the degree of visual saliency, we used saccade latency. Both contrasts can modulate saccade latency (when one of the contrasts larger, saccade latency became shorter). We found that these two contrasts differentially modulated neuronal activity in the posterior parietal cortex (PPC). Target-distractor color contrast modulated the late-period activity, whereas stimulus-background luminance contrast modulated the early-period activity. Thus,these results suggest that visual saliency derived from the different types of stimulus contrast is represented with different temporal dynamics in the activity of PPC neurons.

Cue-period activity of monkey prefrontal neurons during a duration-discrimination task

The prefrontal cortex (PFC) is one of areas involved in time perception; however, roles of this area remains unclear. We recorded single neuronal activity from the PFC of two monkeys while they performed a durationdiscrimination task. In the task, two visual cues (squares in blue or red) in different durations were presented consecutively followed by delay periods and the subjects then chose one of the cues presented longer in duration. We focused analysis on the first cue (C1) activity, because the neuronal activity of the second cue period (C2) may carry temporal information of both the C1 and C2. We found that prefrontal neurons showed activity that was related to temporal processing. For instance, a group of neurons exhibited phasic responses after constant intervals from the C1 onset. Our results suggest that the PFC contributes to compare current C1 durations with template duration that is learned after repeated trials, due to sort the C1s into possibly long or short cues in the present task.