Reiko Kawagoe

Expectation of reward modulates cognitive signals in the basal ganglia

Action is controlled by both motivation and cognition. The basal ganglia may be the site where these kinds of information meet. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual and memory responses of caudate neurons are modulated by expectation of reward so profoundly that a neurons preferred direction often changed with the change in the rewarded direction. The subsequent saccade to the target was earlier and faster for the rewarded direction. Our results indicate that the caudate contributes to the determination of oculomotor outputs by connecting motivational values (for example, expectation of reward) to visual information.

Influence of skin blood flow on near-infrared spectroscopy signals measured on the forehead during a verbal fluency task.

Brain activity during a verbal fluency task (VFT) has been the target of many functional imaging studies. Most studies using near-infrared spectroscopy (NIRS) have reported major activation in the frontal pole, but those using PET or fMRI have not. This led us to hypothesize that changes in the NIRS signals measured in the forehead during VFT were due to changes in skin blood flow. To test this hypothesis, we measured NIRS signals and the Doppler tissue blood flow signals in the foreheads of 50 participants. The measurements were performed while each participant produced words during two 60-s periods with an interval of 100 s. In addition to a conventional optode separation distance of 30 mm (FAR channels), we used a short distance--5mm (NEAR channels)--to measure NIRS signals that originated exclusively from surface tissues. The oxygenated hemoglobin (oxyHb) concentration in the FAR and NEAR channels, as well as the Doppler blood flow signal, increased in a similar manner during the two periods of word production; the signal increase in the first period was twice as high as that in the second period. Accordingly, the mean changes in oxyHb concentration in the FAR channels were correlated closely with the changes in the NEAR channels (R(2) = 0.91) and with the integrated Doppler skin blood flow signal (R(2) = 0.94). Furthermore, task-related NIRS responses disappeared when we blocked skin blood flows by pressing a small area that covered a pair of optodes. Additionally, changes in the FAR channel signals were correlated closely with the magnitude of pulsatile waves in the Doppler signal (R(2) = 0.92), but these signals were not highly correlated with the pulse rate (R(2) = 0.43). These results suggest that a major part of the task-related changes in the oxyHb concentration in the forehead is due to task-related changes in the skin blood flow, which is under different autonomic control than heart rate.

Dopamine Neurons Can Represent Context-Dependent Prediction Error

Midbrain dopamine (DA) neurons are thought to encode reward prediction error. Reward prediction can be improved if any relevant context is taken into account. We found that monkey DA neurons can encode a context-dependent prediction error. In the first noncontextual task, a light stimulus was randomly followed by reward, with a fixed equal probability. The response of DA neurons was positively correlated with the number of preceding unrewarded trials and could be simulated by a conventional temporal difference (TD) model. In the second contextual task, a reward-indicating light stimulus was presented with the probability that, while fixed overall, was incremented as a function of the number of preceding unrewarded trials. The DA neuronal response then was negatively correlated with this number. This history effect corresponded to the prediction error based on the conditional probability of reward and could be simulated only by implementing the relevant context into the TD model.

Modulation of saccadic eye movements by predicted reward outcome

Abstract. Reward is a primary goal of behavior and is crucial for survival of animals. To explore the mechanisms underlying such reward-oriented behavior, we devised a memory-guided saccade task in which only one fixed direction out of four was rewarded, which was called the one-direction-rewarded task (1DR). As the rewarded direction was changed in four blocks, saccades in a given direction were rewarded in one block (constituting reward-oriented behavior), but non-rewarded in the other blocks (non-reward-oriented behavior). As a control, an all-directions-rewarded task (ADR) was used. Using these tasks, we found that the parameters of saccades changed depending on whether or not the saccade was followed by reward. (1) The mean saccadic peak velocity was higher and the mean saccade latency was shorter in the rewarded condition than in the non-rewarded condition. (2) The mean saccade amplitude showed no difference in two out of three monkeys. (3) The variations of saccadic velocity, latency and amplitude were smaller in the rewarded condition. (4) Within a block of 1DR, the saccade velocity remained high in the rewarded condition, but decreased gradually in the non-rewarded condition; it decreased only slightly in ADR. The saccade latency showed the opposite pattern of change, but less clearly. (5) The saccades in the non-rewarded condition tended to have slower velocities and longer latencies in the trials shortly after a rewarded trial. (6) The ratio of error trials was much higher in the non-rewarded condition than the rewarded condition. (7) The errors, which were due to premature or incorrect saccades, showed unique spatiotemporal patterns that would reflect the competition between the cognitive and motivational processes. These results provide important constraints to the neuronal mechanism underlying reward-oriented behavior because it must satisfy these rules.

Feature-Based Anticipation of Cues that Predict Reward in Monkey Caudate Nucleus

A subset of caudate neurons fires before cues that instruct the monkey what he should do. To test the hypothesis that the anticipatory activity of such neurons depends on the context of stimulus-reward mapping, we examined their activity while the monkeys performed a memory-guided saccade task in which either the position or the color of a cue indicated presence or absence of reward. Some neurons showed anticipatory activity only when a particular position was associated with reward, while others fired selectively for color-reward associations. The functional segregation suggests that caudate neurons participate in feature-based anticipation of visual information that predicts reward. This neuronal code influences the general activity level in response to visual features without improving the quality of visual discrimination.

Functional differences between macaque prefrontal cortex and caudate nucleus during eye movements with and without reward

The prefrontal cortex and the basal ganglia form mutually connected networks and are thought to play essential roles together in guiding goal-directed behaviors. Yet, these structures seem to have independent pathways to motor outputs as well, suggesting differential contributions to goal-directed behaviors. We hypothesized that the prefrontal cortex guides actions to a direction required by external demands and the basal ganglia guide actions to an internally motivated direction. To test this hypothesis, we used a task in which monkeys were required to make a memory-guided saccade to a direction indicated by a visual cue while only one direction was associated with reward. We observed a functional dissociation between the lateral prefrontal cortex (LPFC), which commonly represented the cue direction, and the caudate nucleus (CD), which commonly represented the reward-associated direction. Furthermore, cue-directed and reward-directed signals were integrated differently in the two areas; when the cue direction and the reward direction were opposite, LPFC neurons maintained tuning to the cue direction, whereas CD neurons lost the tuning. Different types of spatial tuning in the two brain areas may contribute to different types of goal-directed behavior.

Presaccadic omnidirectional burst activity in the basal interstitial nucleus in the monkey cerebellum

Abstract We recorded saccade-related neurons in the vicinity of the dentate nucleus of the cerebellum in two monkeys trained to perform visually guided saccades and memory-guided saccades. Among 76 saccade-related neurons, 38 showed presaccadic bursts in all directions. More than 80% of such burst neurons were located in the area ventral to, not inside, the dentate nucleus, which corresponded to the basal interstitial nucleus (BIN as previously described). We found that the activity of the BIN neurons was correlated with saccade duration but not with saccade amplitude or velocity. Thus, when tested with visually guided saccades, the burst started about 16 ms before saccade onset and ended about 33 ms before saccade offset, regardless of saccade amplitude. The characteristic timing of the BIN cell activity was maintained for different types of saccades (visually guided, memory-guided and spontaneous saccades), which had different dynamics. Although the number of spikes in a burst for each neuron was linearly correlated with saccade amplitude for a given type of saccade, the slope varied depending on the type of saccade. Peak burst frequency was uncorrelated with saccadic peak velocity. In contrast, burst duration was highly correlated with saccade duration regardless of the type of saccade. These results suggest that BIN neurons may carry information to determine the timing of saccades.

Differences in the Pulsatile Component of the Skin Hemodynamic Response to Verbal Fluency Tasks in the Forehead and the Fingertip.

Several studies have claimed that hemodynamic signals measured by near-infrared spectroscopy (NIRS) on the forehead exhibit different patterns during a verbal fluency task (VFT) in various psychiatric disorders, whereas many studies have noted that NIRS signals can reflect task-related changes in skin blood flow. If such a task-related skin hemodynamic response is also observed in the fingertip, a simpler biomarker may be developed. Furthermore, determining the difference in the response pattern may provide physiological insights into the condition. We found that the magnitude of the pulsatile component in skin hemodynamic signals increased on the forehead (p < 0.001 for N = 50, p = 0.073 for N = 8) but decreased on the fingertip (p < 0.001, N = 8) during the VFT, whereas the rate in both areas increased (p < 0.02, N = 8). We also did not find a repetition effect in both the rate and the magnitude on the fingertip, whereas the effect was present in the magnitude (p < 0.02, N = 8) but not in the rate on the forehead. These results suggest that the skin vasomotor system in the forehead could have a different vessel mechanism to psychological tasks compared to the fingertip.

L-Glutamic acid as an excitatory transmitter at the crayfish neuromuscular junction.

Abstract 1. Release of glutamate and aspartate from the crayfish muscle was measured by mass fragmentography. 2. Nerve stimulation significantly increased glutamate efflux, but the change in aspartate efflux was very small and not significant. 3. Black widow spider venom (BWSV) increased the frequency of miniature EPSPs and the efflux of glutamate. 4. These results provide further evidence for the glutamate-transmitter hypothesis.

Dopaminergic neurons show visual responses in highly motivated condition

A series of lesion experiments (Gilbert et al. 1991; Patterson et al. 1992) have suggested that the memory trace of passive avoidance task could relocate from hyperstriatum vent&e (IMHV: analogue of mammalian associate cortex) to lobus parolfactorius (LPO: avian homologue of caudate-putamen) within an hour or so after the training. Here arises a simple question: what aspects of neuronal activities remain unchanged through the course of relocation, and how? Responses of LPO neurons in slice preparations showed concomitant modulations of converging excitatory synaptic inputs; LTP in dorsal EPSPs (issued from local intemeurons) and LTD in ventral EPSPs (presumably due to projection neurons from archistriatum). The concomitant LTP/LTD occurred only when synchronized theta-tetani (3 pulses at SO Hz, 300 trains applied at 200 ms intervals) were applied to both inputs with exogenous dopamine (100 l.tM) in the bath perfusate. Similar tetanic stimulations, if given with a 100 ms lag in an anti-phase fashion to both inputs, failed to induce both of the LTP and the LTD. Pretreatment of slices with Dl antagonist SCH-23390 (3 pM) also blocked the LTP, while sparing the LTD. Whole cell recording of EPSCs revealed that theta-tetanus applied to the dorsai inputs, if accompanied by exogenous dopamine and post-synaptic depolarization to -45 or -30 mV, induced the LTP in half of the neurons examined. These results lead us to hypothesize that; synaptic drive issued from IMHV via archistriatum (ventral EPSPs) could instruct the local synapses (dorsal EPSPs) in LPO, so that only those local synaptic drives with strictly the same temporal patterns are selectively potentiated at the expense of the instructor’s depression,