1. The auditory cortex mediates the perceptual effects of acoustic temporal expectation Santiago Jaramillo & Anthony M Zador Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA Nature Neuroscience, Published online 19 December 2010 1

2. Introduction Anticipation of an event can influence the speed of behavioral response as well as our perception of the event, but it is not known how these improvements in perception arise from changes in neuronal activity. 2

3. Introduction They developed a behavioral procedure in rats to study the neuronal mechanisms that underlie the perceptual consequences of temporal expectation. 1) assess changes in perception due to expectation 2) establish a causal link between neuronal activity and perception 3) quantify changes in sensory representation that result from temporal expectation 3

4. Introduction 4 Their results indicate that changes in neuronal representation as early as primary sensory cortex mediate the perceptual advantage conferred by temporal expectation.

5. Animal subjects 14 adult male rats were used for the experiment: 8 for behavioral analysis 5 for inactivation 3 implanted with tetrode microdrives for recording ( 2 of these included in behavioral analysis )

6. Behavioral task The task consisted of an auditory two-alternative choice procedure for freely moving rats. poking their nose into the center port a sequence of pure tones was presented a frequency-modulated target sound present move to left or right port to get water reward 6 A silent delay of random duraton (250-350ms) animal was required to stay in the center port Target carrier freq: 6KHz=left, 31KHz=right

7. 7 Behavioral task Fig. 1a

8. Behavioral task Sounds stopped once the subject left the center port. A maximum of 14 sounds (2.1 s) were presented on a trial. Valid trials: the animal stayed in the center port until the time of the target onset. Error trials: the animal tried to collect reward on the wrong side port after the presentation of the target. Ignored trials: the animal withdraw from the center port before the target present. 8

9. Behavioral task In the experiments described here, the frequency discrimination component was designed to be easy, so that errors were mainly due to failures of detection. They manipulated detection difficulty by varying target modulation depth (TMD), so that an unmodulated target (TMD = 0) was indistinguishable from a pure tone. 9

10. Behavioral task Temporal expectation was manipulated in blocks of trials. Expect-early block: 85% early targets and 15% late targets Expect-late block: 85% late targets and 15% early targets 10 Fig. 1b c

11. Result-1 11 Valid temporal expectation improved performance Fig. 2a Behavioral responses were faster on trials with expected targets. 2b Median reaction time for each rat (dots) on the easiest difficulty tested, and average across all eight rats for early targets that were expected (blue) or unexpected (green).

12. Result-1 12 Valid temporal expectation improved performance Fig. 2c Behavioral responses were more accurate on trials with expected targets. Example for one rat of the percentage of correct trials as a function of difficulty, varied here by the modulation depth of the target (TMD). 2d Modulation depth needed to achieve 75% correct trials for each rat (dots) and average across all eight rats (colored bars). **P < 0.01

13. Result-2 13 Inactivation of auditory cortex decreased performance Fig. 3a Bilateral reversible inactivation of auditory cortex (AC) was performed by applying the GABAA receptor agonist muscimol to the surface of the exposed dura mater. 3b Performance on expected early targets as a function of difficulty on interleaved inactivation (gray) and control (black) sessions. The plot shows mean ± s.e.m. for five rats.

14. Result-2 14 Inactivation of auditory cortex decreased performance Supplementary Fig. 5 Inactivation of auditory cortex completely impaired performance in some animals.

15. Result-3 15 Temporal expectation modulated neuronal activity Fig. 4a Responses of a single neuron to the same sequence of tones under two temporal expectation conditions: expecting an early (blue) or a late (red) target

16. Result-3 16 Temporal expectation modulated neuronal activity Fig. 4b The population of responsive neurons showed an enhancement in evoked activity, as indicated by the distribution of modulation indices

17. Result-3 17 Temporal expectation modulated neuronal activity Fig. 4c Evoked local field potential (mean ± s.e.m.) at one recording site. The onset of the early target is indicated by the blue triangle. 4d Modulation of local field potentials. Colors as in b.

18. Result-4 18 Modulation was specific to driven activity Supplementary Fig. 10: Frequency tuning was estimated by randomizing the frequency of the third tone. Spike raster of cell from Fig. 4a. Trials are grouped by the frequency of the third tone as indicated on the left. Trials in blue are from expect-early blocks, in red from expect-late.

19. They have a priori that, the modulation of the neuron activity might depend on the relationship between the neuron’s preferred frequency and the frequency of either the stimulus or the target.

20. Result-4 20 Modulation was specific to driven activity Fig. 5a Frequency tuning of a single cell, estimated from responses to the third tone in each expectation condition (Supplementary Fig. 10). 5b Average frequency tuning of 58 cells recorded with a third tone of random frequency.

21. Result-4 21 Modulation was specific to driven activity Supplementary Fig. 11: Modulation of response to tones did not depend on the relation between preferred and target frequencies. The figure shows the modulation index as a function of preferred frequency for each cell.

22. Result-4 22 Modulation was specific to driven activity Supplementary Fig. 13: Modulation of neuronal responses to target sounds. Change in evoked response to the target sound between expectation conditions (expected- unexpected) as a function of the mismatch between the preferred frequency of each cell and that of the target.

23. Result-4 23 Modulation was specific to driven activity Fig. 6a Frequency tuning of cell in Figure 5a as the time of the late target approaches. 6b Neuronal response to each cell’s preferred frequency (PF) as the time of the target approaches.

24. Result-5 24 Neuronal activity in AC predicted performance. Supplementary Fig. 2: Slow behavioral responses were associated with error trials.

25. Result-5 25 Neuronal activity in AC predicted performance Fig. 7a Average evoked LFP from a single electrode for trials with expected early targets grouped according to reaction time. Averages are taken over those trials with the 20% fastest (blue solid) or the 20% slowest (blue dashed) reaction times. 7b Evoked LFPs were larger on trials with faster behavioral responses. 7c Evoked spiking activity was higher on trials with faster behavioral responses.

26. Summary In their experiments, they described the influence of temporal expectation on behavioral responses as well as on neuronal signals related to sensory stimuli. And their analysis of correlations between response magnitude and performance in Fig.7 link neuronal activity to improvements in performance. 26

27. Summary Their results suggest that temporal expectation improves auditory perception by modulating the response properties of single cells at early cortical stages of processing 27

28. Thank you! 28