Glutamatergic modulation of auditory cortex connectivity with attentional brain networks in unpredictable perceptual environment.

In a stable environment the brain can minimize processing required for sensory input by forming a predictive model of the surrounding world and suppressing neural response to predicted stimuli. Unpredicted stimuli lead to a prediction error signal propagation through the perceptual network, and resulting adjustment to the predictive model. The inter-regional plasticity which enables the model-building and model-adjustment is hypothesized to be mediated via glutamatergic receptors. While pharmacological challenge studies with glutamate receptor ligands have demonstrated impact on prediction-error indices, it is not clear how inter-individual differences in the glutamate system affect the prediction-error processing in non-medicated state. In the present study we examined 20 healthy young subjects with resting-state proton MRS spectroscopy to characterize glutamate + glutamine (rs-Glx) levels in their Heschl's gyrus (HG), and related this to HG functional connectivity during a roving auditory oddball protocol. No rs-Glx effects were found within the frontotemporal prediction-error network. Larger rs-Glx signal was related to stronger connectivity between HG and bilateral inferior parietal lobule during unpredictable auditory stimulation. We also found effects of rs-Glx on the coherence of default mode network and frontoparietal network during unpredictable auditory stimulation. Our results demonstrate the importance of Glx in modulating long-range connections and wider networks in the brain during perceptual inference.

Hierarchical modulation of auditory prediction error signaling is independent of attention.

The auditory system is tuned to detect rhythmic regularities in the environment which can occur on different timescales. Event-related potentials such as mismatch negativity (MMN) and P3b are thought to index local and global deviance, respectively. However, it is not clear how these hierarchical levels interact and to what extent attention modulates this interaction. In this EEG study with 17 healthy young adults, we used a hierarchical oddball paradigm with local (sequence-level) and global (block-level) violations in attended and unattended conditions. Amplitude of N2 and P3b were analyzed in a 2*2*2 factorial model (local status, global status, attention condition). We found a significant interaction between the local and global status on the N2 amplitude, while there was no significant three-way interaction with attention, together demonstrating that lower-level prediction error is modulated by detection of higher-order regularity but expressed independently of attention. By contrast, higher-level prediction error, indexed by P3b, was sensitive to global regularity violations if the auditory stream was attended. The results demonstrate the capacity of our auditory perception to preattentively resolve conflicts between different levels of predictive hierarchy even across longer time intervals as indexed by MMN modulation, while P3b represents a different, attention-dependent system.