Here, we show that conditioned excitatory and inhibitory neural gain modulations in the human visual cortex were greatest around 100 ms after stimulus onset for acquired fear relevant and irrelevant stimuli, respectively. This was reflected by corresponding evoked gamma band power modulations between 18.9 Hz and 71 Hz in lower tiers of the visual cortex. Thereby, oscillatory neuromagnetic gamma band activity not only increased for the CS + during the acquisition phase of the CS-US association, but also decreased for the CS-. Critically, both, CS + and CS- related evoked gamma powers returned to pre-conditioning levels during extinction. Our findings not only replicate previous observations of excitatory and inhibitory short-term plasticity changes in the visual cortex by learning, but significantly extent these reports by demonstrating that these changes occur very fast within the first 180 ms peaking at around 100 ms after stimulus onset at early stages of the visual cortex. Our findings are in line with the observation that evoked short latency gamma power changes in the visual cortex represent very early visual processing stages14,15. In contrast, we did not find any gamma power modulations for induced gamma band responses (see supplementary information).
Early stages of visual processing could not be directly assessed by previous studies that showed opposing neural gain modulations in the visual cortex by learning, because these studies utilized steady state responses that reflect visual cortex activity across several seconds before US appearance5,6,10. However, Keil et al.21 also reported gamma band increases between 60 ms and 90 ms after CS + onset during fear conditioning of visual gratings paralleling our results. In line with our study, Keil and collaborators21 also observed the biggest learning induced gamma band modulations during the second acquisition block indicating increased neural gain for the fear relevant stimulus as a result of ongoing learning. However, these authors did not report inhibitory effects on gamma power for the CS-. This might be due to the utilization of unpleasant pictures as US. Here, we used a 90 dB SPL noise that may be more aversive and therefore probably induced more differential effects with respect to opposing neural gain modulations of the CS + and CS- in the visual cortex.
Conditioned inhibition of the gamma band response for the fear irrelevant CS- as observed here accords with animal studies in the auditory domain that showed similar opposing activity changes for the CS + and CS- in the amygdala, thalamus and auditory cortex22–24. At the cortical level these processes have been associated with frequency tuning shifts of neurons in the auditory system. Further, Headley and Weinberger17 have shown that neurons that code the tone frequency of the CS + exert gamma frequency boosts associated with increased phase-locking of single spike trains to gamma cycles. In contrast, neurons that code frequencies far from the CS + decreased in phase-locking of spike occurrence. In line with our observation of increased CS + gamma power and diminished CS- gamma band activity the opposing phase-locking patterns reported by Headley and Weinberger17 may represent a mechanism of a sharpened representation and down-stream processing of behaviorally relevant stimuli in comparison to irrelevant ones. Importantly, increased CS + gamma band oscillations after learning predicted the strength of associative memory and receptive field plasticity underscoring the behavioral relevance of these processes16.
Critically, Galuske, Munk, and Singer7 observed a similar mechanism in the cat’s visual cortex showing that cholinergic driven increased gamma band activity predicted changes of orientation preference in neural populations. The spatial extension of conditioned orientation domains was not only associated with increased gamma band responses to a conditioned orientation but also with a decrease of signal strength for the orthogonal orientation paralleling the opposing gamma power modulations in our study. It is likely that these processes are driven by disinhibition and inhibition of sensory cortex circuits modulated by cholinergic input from the basal forebrain during CS-US association learning8.
Interestingly, conditioned excitation and inhibition of gamma power changes in the visual cortex for the CS + and CS-, respectively, cannot only be explained by neurobiological informed models, but also formalized by classic learning theories25. The early Rescorla-Wagner model of how associative strength develops during the CS-US association learning and results in excitatory responses for the CS + also emphasizes the acquisition of conditioned inhibitory properties of the CS-26–28. Thereby, the final associative strength λ between the CS + and US must be ideally reach 1. This λ is approached during trial-by-trial learning that follows a decreasing linear function of the difference between the accumulative associative strength V and this predetermined λ value: ΔV = Φ(λ - V), whereby Φ stands for US intensity. In contrast, the final associative strength for the CS- must be ideally 0. However, as both, the CS- and the CS+, are always presented together with the background and experimental context, this context is also reinforced during CS + presentation and gains some associative strength with respect to the US. Now, when the CS- is presented together with the context, the final accumulative associative strength V for the CS- must be negative in order to counteract the conditioned excitatory context. This is how the CS- converts itself into a conditioned inhibitor as the Rescorla-Wagner model assumes that association learning encompasses stimulus combinations28.
Taken together, both, classic learning theory and neurobiological models of cholinergic driven plasticity changes in early sensory cortex can explain our observation of opposing gamma band power modulations in early visual cortex during fear conditioning of visual stimuli. Thereby, increased macroscopic neuromagnetic gamma band responses for the fear relevant sinus grating of a certain orientation may reflect shifts of preferred orientation selectivity of visual cortex neurons towards the fear relevant orientation7. This increased recruitment of neurons preferably firing for the fear conditioned orientation probably is accompanied by increased gamma power as measured at a macroscopic level. This process would also lead to a reduction of gamma power for the orthogonal oriented sinus gratings that are fear irrelevant. Importantly, this results in a sharpened sensorial representation of the CS + as neural activity is not only increased for the fear relevant but also decreased for the fear irrelevant CS-. Critically, we show that conditioned excitatory and inhibitory neural gain control for fear relevant and irrelevant stimuli, respectively, occurs very fast after stimulus onset in early visual cortex.