The depth and complexity of the non-coding transcriptome in nervous system tissues provides a rich substrate for adenosine de-amination acting on RNA (ADAR). Non-coding RNAs (ncRNAs) serve diverse regulatory and computational functions, coupling signal flow from the environment to evolutionarily coded analog and digital information elements within the transcriptome. We present a perspective of ADARs interaction with the non-coding transcriptome as a computational matrix, enhancing the information processing power of the cell, adding flexibility, rapid response, and fine tuning to critical pathways. Dramatic increases in ADAR activity during stress response and inflammation result in powerful information processing events that change the functional state of the cell. This review examines the pathways and mechanisms of ADAR interaction with the non-coding transcriptome, and their functional consequences for information processing in nervous system tissues.