1. The spatial extent of cortical synchronization: Modulation by internal and external factors Adrian M Bartlett, BA Cog. Sci. Perception & Plasticity Lab Psychology Graduate Program Neuroscience Graduate Diploma Program Centre for Vision Research York University

2. Outline Introduction: Distance and synchrony References Methods: Space constants – Definition – Estimation Linear correlation of local field potentials (Pearson’s r) Spike-triggered averaging of local field potentials (STAs) Results: Modulation of space constants – by Behavioural state (internal) – by Stimulus strength (external) Conclusions

3. Introduction: Distance and synchony Cortical synchronization is know to be strongly dependent on the distance between sites – Constrained by small-world architecture of neocortex – Synchronization falls off as a function of distance – Distance of synchronization inversely proportional to oscillation frequency

4. References Destexhe A, Contreras D, Steriade M (1999) Spatiotemporal analysis of local field potentials and unit discharges in cat cerebral cortex during natural wake and sleep states. J Neurosci 19:4595-4608 – ‘inside-out’ – awake & sleeping cats (within-subject comparisons) – linear array of 8 electrodes in supra-sylvian gyrus (SS) Areas 5-7, secondary visual area, receives inputs from LGN & Area 17/18 (cat V1/2) 0.8-1mm depth; 1mm distance 0.1mm diameter

5. Space constants: definition A single scalar number used to describe rate of change as a function of space/distance – For our purposes, how synchronization/correlation of neural activity decreases as a function of the spatial separation between recording sites – Typically describes the slope/a parameter of a linear or exponential function fitted to the data

6. Space constants: definition A single scalar number used to describe rate of change as a function of space/distance – Conventionally symbolized by τ (tau), which for exponentials describes the point at which the function has decayed ~63.2% to it’s asymptotic value τ 36.8% of max

7. Space constants: estimation Spatial correlations (Pearson’s r) – Linear correlation between voltage values for a given pair of LFP sites over time – Averaged across electrode pairs of a given distance (Destexhe et al., 1999)

8. Results: behavioural state Awake: correlations fall off rapidly with distance (small space constant) SWS: large space constant REM: similar to awake; small space constant

9. Results: behavioural state AWAKE: Transient, local correlations SWS: Sustained, distant correlations REM: Transient, local correlations

10. Results: behavioural state Summary: Lower space constants in SWS relative to REM & waking

11. Results: behavioural state Negative correlation between high & low frequency power Positive correlation of low frequency power and space constant

12. Space constants: estimation And now for another method to calculate space constants…

13. Space constants: estimation spike-triggered average LFP (STA) – Average LFP voltage traces in a small window around the time of every spike – same or different electrodes Time of action potentials

14. Space constants: estimation wave-triggered average unit activity (WTA) – Find local minima (negative potentials) in LFP – Use peak negativities as trigger to average firing rates Time of peak negativities

15. Space constants: estimation spike-triggered average LFP (STA) – STA’s calculate from spikes off the circled electrode

16. Space constants: estimation spike-triggered average LFP (STA) – Amplitude: size of initial negative deflection – Latency: time from spike occurance to peak amplitude – How do amplitude and latency of STA vary as a function of distance between two electrodes?

17. Results: behavioural state R: STA Averaged over all electrodes BOTTOM LINE: distal synchrony only during SWS (generally…)

18. Summary: behavioural state Dominant frequency band inversely covaries with space constant

19. Transition We saw the ‘inside-out’ approach – How behavioural state / level of arousal affects space constants Now, we will take an ‘outside-in’ approach – Do external stimuli change the degree of synchronization as a function of distance?

20. References Nauhaus I, Busse L, Carandini M, Ringach DL (2008) Stimulus contrast modulates functional connectivity in visual cortex. Nat Neurosci 12:70- 76. – ‘outside-in’ – Context: resolved conflicting reports of the strength of lateral connections in V1 – Anesthetized cats & monkeys – Rectangular 10x10 Utah array Area 18 (cat), V1 (monkey) 0.4mm distance 0.8-1mm depth Utah array being implanted in a human brain

21. Results: external factors STA calculated during spontaneous activity under anesthesia max min mid Far Near Same

22. Results: external factors Independent of distance, the similarity of orientation selectivity tuning curves also predicts the degree of coupling between LFP recording sites

23. Results: external factors STA-based space constants are reduced by visual stimulation max min mid

24. Results: external factors LFP correlations are overall lower and drop off faster with distance for stimulus-induced activity

25. Conclusions Behavioural state modulates the spatial extent of LFP synchrony – Large space constants & distal, sustained, low-frequency synchrony during SWS – Small space constants & local, transient, high frequency synchrony during REM and waking External stimuli de-correlate / desynchronize distal LFP synchrony – Large space constants and correlations during spontaneous activity under anesthesia – Reduction of space constants and correlations in a signal strength- dependent manner*

26. Results: exceptions Transient large- scale synchrony during REM & waking

27. Results: exceptions Transient local high-frequency oscillations during SWS

28. Results: exceptions Transient local high- frequency oscillations during SWS

29. Results: behavioural state L: WTA Averaged over 4 most distal electrodes R: STA Averaged over all electrodes BOTTOM LINE: distal synchrony only during SWS (generally…)

30. Results: external factors Results are consistent across sites max min mid Far Near Same

31. Results: external factors Results are consistent across different orders of mammals max min mid Far Near Same

32. Results: external factors STA-based space constants are reduced by visual stimulation max min mid

33. Results: external factors Space constants vary smoothly as a function of stimulus contrast. A weak signal leads to space constants between that seen for spontaneous and weak signals