Decoding a Perceptual Decision Process across Cortex Adrián Hernández, Verónica Nácher, Rogelio Luna, Antonio Zainos, Luis Lemus, Manuel Alvarez, Yuriria Vázquez, Liliana Camarillo, Ranulfo Romo  Neuron  Volume 66, Issue 2, Pages 300-314 (April 2010) DOI: 10.1016/j.neuron.2010.03.031 Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 1 Discrimination Task (A) Sequence of events during discrimination trials. The mechanical probe is lowered, indenting the glabrous skin of one digit of the restrained hand (pd); the monkey places its free hand on an immovable key (kd); the probe oscillates vertically, at the base stimulus frequency (f1); after a fixed delay (3 s), a second mechanical vibration is delivered at the comparison frequency (f2); after another fixed delay (3 s) between the end of f2 and probe up (pu), the monkey releases the key (ku) and presses either a lateral or a medial push-button (pb) to indicate whether the comparison frequency was higher or lower than the base, respectively. (B) Stimulus set used during recordings. Each box indicates a base/comparison frequency stimulus pair. The number inside the box indicates overall percentage of correct trials for that (f1, f2) stimulus pair, except when the stimulus pair was identical (22 Hz; we plotted the number of times that animal pressed the lateral push button). (C) Psychophysical performance when f1 was maintained fixed at 22 Hz and f2 was variable (red curve), and when f2 was fixed at 22 Hz and f1 was variable (green curve). D.L. is the discrimination threshold in Hz. (D) Top view of the monkey brain and the cortical areas recorded during perceptual discrimination (orange spots). Recordings were made in primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) contralateral to the stimulated hand (left hemisphere) and in primary motor cortex (M1) contralateral to the responding hand/arm (right hemisphere). Recordings were made contralateral and ipsilateral to the stimulated fingertip in prefrontal cortex (PFC), ventral premotor cortex (VPC), medial premotor cortex (MPC), and dorsal premotor cortex (DPC). Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 2 Responses of a MPC Neuron during the Discrimination Task and Control Tests (A) Raster plots of responses during the discrimination task. This neuron responded with an f1 negative monotonic fashion to the increasing stimulus frequency f1 during the delay period between f1 and f2 and during the early delay period between the end of f2 and the beginning of the decision motor report (pu). Each row of ticks is a trial, and each tick is an action potential. Trials were delivered in random order (10 trials per stimulus pair). Labels at left indicate f1:f2 stimulus pairs. Black indicates f2 > f1; gray indicates f2 < f1. (B) Firing rate modulation (mean ± SEM) as a function of f1 or f2. (C) Resulting coefficient values for f1 (a1, green) and f2 (a2, red) for panels in (B). (D) Coefficients values as functions of time. Green and red traces correspond to a1 and a2, respectively. Filled circles indicate significant values. Black circles indicate points at which a1 and a2 were significant and of different magnitudes, but had opposite signs; these are partially differential (c) responses. Blue circles indicate points at which a1 and a2 were significant and of similar magnitude but had opposite signs; these are fully differential (d) or categorical responses. (E) Responses of the same neuron when the same set of stimuli (A) was delivered to the fingertip, but discrimination was restricted, just by removing the key and the interrupt target switches. Thus, in this condition the animal remained alert—by rewarding with drops of liquid at different times—but was no longer using the stimuli to indicate discrimination with the free hand/arm. Under this test condition, the neuron does not encode information about the stimuli. (F) Choice probability indices as function of time during the discrimination task. Filled circles are significant values that deviated from 0.5 (green for f1 values; black for c values; and blue for d values of D). (G) Choice probability index for the same neuron tested in the light instruction task. Under this condition, the choice probability indices were calculated by comparing the response distributions for lateral versus medial push button presses. Arm movements in this situation were identical to those in the vibrotactile discrimination task but were cued by visual stimuli. Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 3 Responses of a M1 Neuron during the Discrimination Task and Control Tests (A) Raster plots of responses during the discrimination task. This neuron responded with a negative monotonic fashion to the increasing f2 stimulus frequency during the delay period between the end of f2 and the beginning of the decision motor report (pu). Each row of ticks is a trial, and each tick is an action potential. Trials were delivered in random order (10 trials per stimulus pair). Labels at left indicate f1:f2 stimulus pairs. Black indicates f2 > f1; gray indicates f2 < f1. (B) Firing rate modulation (mean ± SEM) as a function of f1 or f2. (C) Resulting coefficient values for f1 (a1, green) and f2 (a2, red) for panels in (B). (D) Coefficients values as functions of time. Green and red traces correspond to a1 and a2, respectively. Red filled circles indicate significant f2 values. (E) Responses of the neuron when the same set of stimuli (panel A) was delivered to the fingertip, but discrimination was restricted, just by removing the key and the interrupt target switches. Thus, in this condition the animal remained alert—by rewarding with drops of liquid at different times—but was no longer using the stimuli to indicate discrimination with the free hand/arm. Under this test condition, the neuron does not encode information about f2, as shown in (D). (F) Choice probability indices as function of time. Filled circles are significant values that deviated from 0.5 for responses of (D). (G) Choice probability index for the same neuron tested in the light instruction task. Because in this test condition animals did not show incorrect responses, the choice probability index was calculated by comparing the response distributions for lateral versus medial push button presses. Arm movements in this situation were identical to those in the vibrotactile discrimination task, but were cued by visual stimuli. See also Figure S1. Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 4 Population Coefficient Values across Cortical Areas during the Different Components of the Discrimination Task Each point represents one neuron with at least one coefficient significantly different from zero. We analyzed five periods: f1 (500 ms), delay between f1 and f2 (3000 ms), f2 (500 ms), delay between the end of f2 and pu (3000 ms), and during a period posterior to pu (1000 ms). For each neuron, we identified a 200 ms bin with the highest modulation during each period. n = number of neurons. Green and red circles correspond respectively to neurons with significant a1 coefficients only or a2 coefficients only. Black circles correspond to neurons with both significant a1 and a2 coefficients of opposite signs but of significantly different magnitudes; these are partially differential responses (c). Blue circles correspond to neurons with both significant a1 and a2 coefficients, but of opposite signs and statistically equal magnitude; these are fully differential or categorical responses encoding f2 − f1 (d). S1, primary somatosensory cortex; S2, secondary somatosensory cortex; VPC, ventral premotor cortex; PFC, prefrontal cortex; MPC, medial premotor cortex; DPC, dorsal premotor cortex; M1, primary motor cortex. Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 5 Cortical Population Dynamics during the Discrimination Task (A) Percentage of neurons with significant coefficients as a function of time. Green and red traces correspond to a1 and a2 coefficients, respectively. Black traces indicate percentage of neurons with a1 and a2 coefficients of opposite sign but of different magnitudes. These neurons combine differential response with a sensory component. Blue traces indicate percentage of neurons with coefficients a1 and a2 of opposite sign but similar magnitude; these produce a differential signal. (B) Percentage of neurons that responded during passive stimulation. All these neurons are part of the populations studied in (A). S1, primary somatosensory cortex; S2, secondary somatosensory cortex; VPC, ventral premotor cortex; PFC, prefrontal cortex; MPC, medial premotor cortex; DPC, dorsal premotor cortex; M1, primary motor cortex. n = number of neurons. Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 6 Box Plots Illustrate Response Latency Distributions for f1 (Green), f2 (Red), Comparison (c, Black), and Differential (d, Blue) across Cortical Areas These boxes have lines at the lower quartile, median, and upper quartile values. The whiskers are lines extending from each end of the boxes to show the extent of the rest of the data. A comparative analysis (Wilcoxon rank-sum test; Siegel and Castellan, 1988) of the response latencies between the cortical areas showed that the f1 and f2 began earlier in S1 (p < 0.01) than in S2, PFC, VPC, MPC, DPC, and M1 (f1 was not present in M1). The response latencies for f1 and f2 in S2 (p < 0.01) began earlier than PFC, VPC, MPC, DPC, and M1. The response latencies for f1 and f2 began earlier in PFC and VPC (p < 0.01) than in MPC, DPC and M1. We found no differences in the response latencies for f1 and f2 between MPC, DPC, and M1 (p > 0.01). All f1 and f2 response latencies in all these cortical areas began earlier (p < 0.01) than the comparison (c) and differential responses (d). We found no statistical differences (p > 0.01) between the comparison and differential responses across the cortical areas. L, left hemisphere (contralateral to the stimulated hand); R, right hemisphere (ipsilateral to the stimulated hand). Recordings in primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) were made contralateral to the stimulated hand (left hemisphere) and in primary motor cortex (M1) contralateral to the responding hand/arm (right hemisphere). Recordings were made bilaterally in prefrontal cortex (PFC), ventral premotor cortex (VPC), medial premotor cortex (MPC), and dorsal premotor cortex (DPC). Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 7 Correlation between Neuronal Responses of Diverse Cortical Areas and Behavioral Choice (A) Percentage of neurons that had significant choice probability indices as a function of time. Green trace: neurons that encoded information about f1; red trace: neurons that carried information about f2; black trace: partially differential neurons that carried information about f1 and f2 (c); blue trace: fully differential neurons that carried information specifically about f2 − f1 only (d). See also Figure S2. (B) Percentage of the neurons in (A) that showed significant choice probability indices during the visual control task. In this test, animals had to follow a visual cue to produce the motor choice response. S1, primary somatosensory cortex; S2, secondary somatosensory cortex; PFC, prefrontal cortex; VPC, ventral premotor cortex; MPC, medial premotor cortex; DPC, dorsal premotor cortex; M1, primary motor cortex. n = number of neurons. Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 8 Neuronal Correlates of Bias Behavior (A) Distribution of coefficients a1/a2 ratios (312 experiments in four animals), obtained from linear regression analysis to the behavioral data. The histogram shows that coefficient a2 has a stronger weight than coefficient a1. (B) Bin distribution ratios for coefficients a1/a2 for neurons from medial premotor cortex (MPC) that showed coefficients a1 and a2 significantly different from zero and from each other. For each MPC neuron, we estimated the ratio between weights a1/a2 in a sliding window of 200 ms moving in steps of 20 ms, beginning during the onset of the comparison period and ending during the probe up that triggers the decision report. All these neurons showed the properties described in B and illustrated in Figures 4 and 5 (black dots and traces, respectively). This panel shows that coefficient a2 was more often higher than coefficient a1, and consequently there are more bins to the left relative to 1. (C) Distribution of bin ratios for behavioral bias/neuron bias. For each neuron of each cortical area, the resulting value a1/a2 of each cortical neuron was compared against the behavioral value a1/a2 obtained simultaneously in the same experiment. Data from primary somatosensory cortex (S1) are not shown, since there are no neurons that show the properties described in (B). DPC, dorsal premotor cortex; PFC, prefrontal cortex; M1, primary motor cortex; S2, secondary somatosensory cortex; VPC, ventral premotor cortex; μ, geometric mean (vertical line in each histogram). Gray bars in the histograms show percentage of bins close to 1 (arbitrary range, 1 ± 0.22). A value of 1 means close correspondence between neuronal activity and behavioral report. Neuron 2010 66, 300-314DOI: (10.1016/j.neuron.2010.03.031) Copyright © 2010 Elsevier Inc. Terms and Conditions