A neural mechanism of response bias Johan Lauwereyns Laboratory of Sensorimotor Research National Eye Institute, NIH

Yoriko TakikawaJuntendo Univ. Reiko KawagoeJuntendo Univ. Masashi KoizumiTamagawa Univ. Shunsuke KobayashiTamagawa Univ. Masamichi SakagamiTamagawa Univ. Brian CoeATR Hiro NakaharaRIKEN Katsumi WatanabeNIH Okihide HikosakaNIH

Goal-oriented behavior: Seeking salt (Curt Richter)

A Neural Mechanism of Reward-oriented Response Bias in the Basal Ganglia How does the brain incorporate reward value in the process of response selection?

A Neural Mechanism of Reward-oriented Response Bias in the Basal Ganglia How does the brain incorporate reward value in the process of response selection? Anticipatory bias toward reward in the activity of monkey caudate neurons

A Neural Mechanism of Reward-oriented Response Bias in the Basal Ganglia How does the brain incorporate reward value in the process of response selection? Anticipatory bias toward reward in the activity of monkey caudate neurons Studied using visually and memory-guided saccade tasks with asymmetrical reward schedule

Biased Saccade Task (BST)

Saccade-related brain areas (macaque monkey) FEF: frontal eye field SEF: supplementary eye field LIP: area LIP of parietal cortex CD: caudate nucleus SNr: substantia nigra pars reticulata SC: superior colliculus Clbm: cerebellum SG: brainstem saccade generators

DA neuron responds to Reward & Reward Predictor

Inputs to Striatal Medium Spiny Neuron Smith & Bolam (1990)

Medium Spiny Neuron in Striatum Preston, Bishop & Kitai (1980)

Single unit recording from Caudate Nucleus

L-CD neuron: R-reward Reward

L-CD neuron: RL-reward Reward

L-CD neuron: RLR-reward Reward

L-CD neuron: All Reward

Population activity of CD neurons (with contra-bias, n=25)

Motivational control of Eye Movements by the Basal Ganglia How does the selective anticipatory activity in caudate relate to saccade parameters?

Motivational control of Eye Movements by the Basal Ganglia How does the selective anticipatory activity in caudate relate to saccade parameters? Basic association between neuronal activity and response latency

Motivational control of Eye Movements by the Basal Ganglia How does the selective anticipatory activity in caudate relate to saccade parameters? Basic association between neuronal activity and response latency. But what’s the relationship for a given combination of saccade and reward direction?

Median-split analysis Divide the data in two groups of trials for each combination of saccade and reward direction

Median-split analysis Divide the data in two groups of trials for each combination of saccade and reward direction High-activity trials, with pretarget activity above the median for that condition Low-activity trials, with pretarget activity below the median for that condition

Discussion The data for contra-bias neurons provide evidence in favor of the hypothesis of selective preparation

Discussion The data for contra-bias neurons provide evidence in favor of the hypothesis of selective preparation High pretarget activity leads to short latency for saccades in the contralateral direction

Discussion The data for contra-bias neurons provide evidence in favor of the hypothesis of selective preparation High pretarget activity leads to short latency for saccades in the contralateral direction What about the data for ipsi-bias neurons?

Discussion (continued) The data for ipsi-bias neurons are a mirror-image of the data for contra-bias neurons

Discussion (continued) The data for ipsi-bias neurons are a mirror-image of the data for contra-bias neurons High pretarget activity of ipsi-bias neurons leads to long latency for unrewarded saccades in the contralateral direction

Discussion (continued) The data for ipsi-bias neurons are a mirror-image of the data for contra-bias neurons High pretarget activity of ipsi-bias neurons leads to long latency for unrewarded saccades in the contralateral direction Activity of these neurons disrupts contralateral saccades (“negative motivation”)

Summary The entire pattern of data suggests that the caudate anticipatory bias influences contralateral saccade latency

Summary The entire pattern of data suggests that the caudate anticipatory bias influences contralateral saccade latency Contra-bias neurons facilitate contralateral saccades, Ipsi-bias neurons disrupt contralateral saccades

Summary The entire pattern of data suggests that the caudate anticipatory bias influences contralateral saccade latency Contra-bias neurons facilitate contralateral saccades, Ipsi-bias neurons disrupt contralateral saccades These two type of neurons may reflect the physiology of the direct and indirect pathway in the basal ganglia

Neural Circuit of the Basal Ganglia

CD SNr SC CD SNr SC Direct pathway: Contra-bias neurons

CD SNr SC CD SNr SC GPe STN GPe STN Indirect pathway: Ipsi-bias neurons

Experiment 2 The data so far show an effect of selective response preparation on the basis of reward value

Experiment 2 The data so far show an effect of selective response preparation on the basis of reward value But could this merely reflect a more general type of spatially selective response preparation?

Experiment 2 The data so far show an effect of selective response preparation on the basis of reward value But could this merely reflect a more general type of spatially selective response preparation? Test with a “cognitive bias task”…

Cognitive Bias Task (delayed position matching)

CD activity in Cognitive & Motivational Tasks Cognitive Bias Motivational Bias

Cognitive Bias Most CD neurons show higher Motivational Bias than Cognitive Bias

Experiment 3 We’ve provided evidence for an effect of spatially selective reward-oriented response preparation

Experiment 3 We’ve provided evidence for an effect of spatially selective reward-oriented response preparation But is the reward-oriented bias really related to motor preparation or is it involved in more abstract or perceptual decision making?

Experiment 3 We’ve provided evidence for an effect of spatially selective reward-oriented response preparation But is the reward-oriented bias really related to motor preparation or is it involved in more abstract or perceptual decision making? Test with a memory-guided eye movement task with color-based reward association…

Discussion (Exp. 3) Color-reward associations do lead to significant effects in both behavior and caudate activity

Discussion (Exp. 3) Color-reward associations do lead to significant effects in both behavior and caudate activity The anticipatory activity is aimed at the visual onset, not the start of the eye movement

Discussion (Exp. 3) Color-reward associations do lead to significant effects in both behavior and caudate activity The anticipatory activity is aimed at the visual onset, not the start of the eye movement If this is indeed a ‘perceptual’ process, then how does the bias affect the neuronal activity to the visual target?

Discussion (Exp. 3; continued) Strong pre-cue activity leads to general increase, not improved discriminability

Discussion (Exp. 3; continued) Strong pre-cue activity leads to general increase, not improved discriminability Different from cortical mechanisms of visual attention: here additive, not multiplicative scaling

Discussion (Exp. 3; continued) Strong pre-cue activity leads to general increase, not improved discriminability Different from cortical mechanisms of visual attention: here additive, not multiplicative scaling Analogous to a shift of decision criterion?

Conclusion Anticipatory activity in caudate nucleus is influenced by the context of stimulus-reward mapping

Conclusion Anticipatory activity in caudate nucleus is influenced by the context of stimulus-reward mapping This activity can create a spatially selective bias that prioritizes an action with high reward value

Conclusion Anticipatory activity in caudate nucleus is influenced by the context of stimulus-reward mapping This activity can create a spatially selective bias that prioritizes an action with high reward value The bias also affects visual processing; Does this bias incorporate reward value in the process of perceptual decision making?

Future directions Motivational control of visual processing in humans:

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity –Systematic comparison with ‘visual attention’

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity –Systematic comparison with ‘visual attention’ –Modeling (LATER, ROC)

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity –Systematic comparison with ‘visual attention’ –Modeling (LATER, ROC) –Parkinsonian patients

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity –Systematic comparison with ‘visual attention’ –Modeling (LATER, ROC) –Parkinsonian patients –Feedback to monkey studies (design, analysis, modeling)

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity –Systematic comparison with ‘visual attention’ –Modeling (LATER, ROC) –Parkinsonian patients –Feedback to monkey studies (design, analysis, modeling) Pharmacological study of motivational control:

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity –Systematic comparison with ‘visual attention’ –Modeling (LATER, ROC) –Parkinsonian patients –Feedback to monkey studies (design, analysis, modeling) Pharmacological study of motivational control: –Create a rat model of the Biased Response Task

Future directions Motivational control of visual processing in humans: –Response bias, decision bias, perceptual sensitivity –Systematic comparison with ‘visual attention’ –Modeling (LATER, ROC) –Parkinsonian patients –Feedback to monkey studies (design, analysis, modeling) Pharmacological study of motivational control: –Create a rat model of the Biased Response Task –Study the neurochemical make-up of this system