PHYSIOLOGICAL INTEGRATION OF THE DECLARATIVE MEMORY SYSTEM

Despite extensive experimental investigations of human amnesia, the basic nature of this vivid syndrome remains surrounded by controversy. The dynamics of amnesia, the rapid, selective and long-lasting plasticity of hippocampal synapses, and the connections between the hippocampal formation and association neocortex. all suggest that amnesia may result from damage to the medial temporal site where the recent declarative memory trace is temporarily laid down. Alternatively, amnesics' preserved capacity for procedural learning on indirect memory tests suggests that their deficit may rather be in intentional, sustained and directed (i.e., active) encoding/retrieval processes. It has been difficult to distinguish between these possibilities because amnesics are most impaired on direct memory tasks that involve both a new integrative trace and active processes. It is possible that different amnesics may have a relatively greater defect either in the memory trace, or in active memory processes, or both, and these differences could correspond to differences in their anatomical lesions. Specifically, hippocampal formation lesions may disrupt all recent declarative memory traces, whereas brainstem lesions could produce amnesia by impairing modulatory processes essential for encoding/retrieval or for storage. In this model, the different areas of association neocortex with bidirectional hippocampal connections would contribute specificity to encoding/retrieval, with posterior areas encoding the sensory/semantic aspects of events, and prefrontal cortex the ongoing context. Active modulatory processes arising in the brainstem would then function to integrate this extensive declarative memory system. The cognitive correlates and neural substrates of the evoked potentials recorded during declarative memory tasks suggest that they may embody such modulatory processes. Finally, since the prefrontal cortex and the medial temporal lobe appear to control the onset, intensity and duration of the ascending neuromodulation, lesions of these structures may impair aspects of both the trace and of the processes supporting declarative memory. In summary, a model is proposed in which the association neocortex (encoding/retrieval) and hippocampus (trace) are integrated by the brainstem (modulation) to produce the psychological properties of declarative memory.