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The Journal of Neuroscience, December 1, 1999, 19(23):10451-10460
Trial-to-Trial Variability and State-Dependent Modulation of
Auditory-Evoked Responses in Cortex
Michael A.
Kisley and
George L.
Gerstein
Department of Neuroscience, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104-6074
Recent experimental work has provided evidence that trial-to-trial
variability of sensory-evoked responses in cortex can be explained as a
linear superposition of random ongoing background activity and a
stationary response. While studying single trial variability and
state-dependent modulation of evoked responses in auditory cortex of
ketamine/xylazine-anesthetized rats, we have observed an apparent
violation of this model.
Local field potential and unit spike trains were recorded and analyzed
during different anesthesia depths deep, medium, and light which were
defined by the pattern of ongoing cortical activity. Estimation of
single trial evoked response was achieved by considering whole
waveforms, rather than just one or two peak values from each wave.
Principal components analysis was used to quantitatively classify
waveforms on the basis of their time courses (i.e., shapes).
We found that not only average response but also response variability
is modulated by depth of anesthesia. Trial-to-trial variability is
highest under medium levels of anesthesia, during which ongoing
cortical activity exhibits rhythmic population bursting activity. By
triggering the occurrence of stimuli from the spontaneously occurring
burst events, we show that the observed variability can be accounted
for by the background activity. In particular, the ongoing activity was
found to modulate both amplitude and shape (including latency) of
evoked local field potentials and evoked unit activity in a manner not
predicted by linear superposition of background activity and a
stereotyped evoked response. This breakdown of the linear model is
likely attributable to rapid transitions between different levels of
thalamocortical excitability (e.g., spike-wave discharges), although
brain "state" is relatively fixed.
Key words:
variability; modulation; local field potential; principal
components analysis; anesthesia; ketamine; xylazine; auditory cortex; spike-wave discharge; high-voltage spindle
Copyright © 1999 Society for Neuroscience 0270-6474/99/192310451-10$05.00/0
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