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A framework for investigating information processing in cortico-thalamocortical (cortico-TC) networks is presented, that in part can be used to model and interpret individual changes in electroencephalographic spectra and event-related potentials such as those from the Brain Resource International Database. Scientific work covering neurophysiology, TC firing modes, and TC models are explored in the framework to explain how the brain might process complex information in a multistage process. It is proposed that the thalamus and the cortico-TC system have unique ionic properties and transmission delays (in humans), which are suited to the function of taking "snapshots" or samples of complex environmental stimuli, rather than continuous data streams. This leads to careful and sequential coordination of stimulus and response processes, and increases the probability of information transfer and the resulting information complexity in higher cortical regions. Given the scope of this framework, the multidimensional and standardized Brain Resource International Database provides a pertinent set of measures for both testing hypotheses generated from the model, and for fitting the model to experimental data to investigate mechanisms underlying information processing.

Using a standardized database of EEG data, recorded during the habituation and oddball paradigms, changes in the auditory event-related potential (ERP) are demonstrated on the time scale of seconds and minutes. Based on previous research and a mathematical model of neural activity, neural mechanisms that could account for these changes are proposed. When the stimulus tones are not relevant to a task, N100 magnitude decreases substantially for the first repetition of a stimulus pattern and increases in response to a variant tone. It is argued these short-term changes are consistent with the hypothesis that there is a refractory period in the neural elements underlying the ERP. In the oddball paradigm, when the stimulus tones are task-relevant, the magnitudes of both N100 and P200 for backgrounds decrease over the entire six-minute recording session. It is argued that these changes are mediated by a decreasing arousal level, and consistent with this, a subject's electrodermal activity (EDA) is shown to reduce over the recording session. By fitting ERPs generated by a biophysical model of neural activity, it is shown that the changes in the background ERPs over the recording session can be reproduced by changing the strength of connections between populations of cortical neurons. For ERPs elicited by infrequent stimuli, there is no corresponding trend in the magnitudes of N100 or P300 components. The effects of stimuli serial order on ERPs are also assessed, showing that the N100 for background ERPs and the N100 and P300 for target ERPs increases as the probability, and expectancy, of receiving a task relevant stimulus increases. Cortical neuromodulation by acetylcholine (ACh) is proposed as a candidate mechanism to mediate the ERP changes associated with attention and arousal.

Evidence supporting the concept of a role of central cholinergic mechanisms in learning and memory processes has mainly been obtained from (i) psychopharmacological investigations; (ii) correlations between deficits in cognitive functions and either pathological or experimentally-induced decrease in cholinergic markers in defined cholinergic pathways; (iii) attenuation of these deficits by drugs that directly (i.e., cholinergic agonists) or indirectly (through trans-synaptic regulation of cholinergic neurones) improve cholinergic transmission, and by cholinergic-rich grafts. Even though there is no question that systemic administration of cholinergic antagonists can produce deleterious effects on performance of a large spectrum of learning and memory tasks, any attempt at a unitary formulation of central cholinergic function using this data base seems difficult. However, the presently available data suggest globally that the ascending cholinergic neurones of the basal forebrain complex play an important role in modulating the activity of certain limbic and cortical structures that have been independently shown to subserve cognitive processes involved in different forms of memory. Recent experiments have emphasized the need to take into account the multiple trans-synaptic interactions between cholinergic neurones and other neuromodulatory systems, as well as to directly study the temporal dynamics of changes in the activity of cholinergic neurones occuring at different stages or resulting from different types of learning and memory testing. Together with neurophysiological investigations, results from these recent experiments will undoubtely contribute to a better and more integrated understanding of the role of central cholinergic synapses in memory processes; moreover they offer some promise in developing pharmacological strategies aimed at counteracting cholinergic hypofunction and thereby at ameliorating the memory deficits observed in normal aging and senile dementia. However, tacit acceptance of this current paradigm inevitably leads to such a ramification of the initial “integrative” causal scheme (i.e.,: acetylcholine → memory) that one may wonder if a full understanding of cholinergic involvement in learning and memory processes may be achieved in this manner.

Classical conditioning rapidly produces enduring frequency-specific modification of receptive fields (RF) in the auditory cortex (ACx) which favor the processing of the frequency of the conditioned stimulus (CS). Responses to the CS are increased whereas responses to the pre-training best frequency (BF) and other frequencies are decreased; tuning is often completely shifted so that the frequency of the CS becomes the BF. Such plasticity is observed both for single tone and for two-tone discrimination training. CS-specific RF plasticity may be reversed by extinction training. Sensitization training produces only general increases in responsiveness. Habituation produces frequency-specific decreased responses in the RF. Tuning shifts similar to those produced by conditioning can be produced by iontophoretic application of muscarinic agonists or cholinesterase antagonists to the ACx and pairing one tone with application of ACh to the auditory cortex produces receptive field plasticity which is specific to the frequency of the paired tone. Dual medial geniculate (MG) input to the auditory cortex consists of a frequency-specific non-plastic nucleus (MGv) and a broadly-tuned plastic nucleus (MGm). A preliminary model of receptive field plasticity and behavioral learning is presented. It links MGv and MGm influences on auditory cortex with cholinergic neuromodulation, and makes several predictions, some of which have recently been supported.