Mismatch negativity

New perspectives in cognitive1,2 and clinical3,4 neuroscience have been opened up with the recent discovery of mismatch negativity (MMN),5 an auditory event-related brain potential (ERP) elicited by infrequent deviant sounds occurring in a sequence of repeated tones.1 The MMN appears as a negative displacement on the ERP to deviant sounds relative to that to standard sounds, with a peak latency between 100 and 200 ms from stimulus onset. MMN is generated in the supratemporal auditory cortex,6 apparently as the output of an automatic stimulus change-detector system, which compares each new auditory input with a neural trace of the previous standard stimuli developed and maintained in the auditory sensory (echoic) memory.7–9 The use of MMN for sensory memory evaluation purposes is based on studies which, in healthy adult subjects, have shown that MMN is no longer elicited when the interval between the stimuli delivered to the subject exceeds a certain limit,10–12 for instance about 10 s,13 reflecting the decay of the sensory memory trace.1,9 The auditory sensory memory trace duration indexed by MMN seems to be age-related, as it is shorter in elderly people.14 Decay of the memory trace might also be faster in patients with Alzheimer’s disease than in normal subjects.15 The clinical and pathophysiological relevance of MMN-related sensory memory studies is also confirmed by the selective suppression of MMN by MK-801,16 a blocker of the NMDA receptors to glutamate, which are involved in long-term potentiation and in synaptic processes of memory and learning.17 In studies of sensory memory duration using the conventional paradigm to obtain the MMN, both standard and deviant stimuli are presented at a constant inter-stimulus interval (ISI), which coincides with the duration of the memory probe interval (MPI) under examination.10,12,13,15 Thus, if various long ISIs need to be tested, as is the case when obtaining an ISI-MMN amplitude function, sessions can last up to several hours, involving various daily sessions over several days.13 The major disadvantages arising from the excessive duration of this test are a considerable outlay in time required for apparatus and personnel,13 boredom and fatigue of the subjects under study, which can affect the quality of the signal recorded,1,18 and potential difficulties in recording with children and patients who do not easily tolerate long sessions without moving. For these reasons, a reduction in the length of auditory sensory memory testing based on MMN recordings is highly desirable. We here propose a new, faster paradigm for eliciting the MMN based on a development of the logic underlying MMN theory1. According to this theory, the purpose of repeating the information conveyed by standard tones in a paradigm for eliciting MMN is that of mutual interaction for developing a Cognitive Neuroscience