Psychiatric disorders

Psychiatric illnesses including schizophrenia, major depressive disorder (MDD), bipolar disorder (BD), post-traumatic stress disorder (PTSD), panic disorder, and alcohol use disorders are common and leading causes of global disability. Conventionally, diagnosis and treatment of these disorders has relied solely on clinicical observation of symptoms and inference of underlying neural dysfunction. Recently, however, technological advances have allowed for direct measurement of brain functioning in these disorders, and there has been increased interest in the exploration of sensory processing deficits involved. In this context, MMN is regarded as a ‘breakthrough biomarker’ for advancing the understanding and treatment of psychiatric illness. As MMN is among the most widely studied translational biomarkers and has already undergone extensive psychometric validation (e.g. reliability, suitability for use as a repeated measure, sensitivity to pharmacologica and non-pharmacological interventions), it is widely used for development of new treatments for brain disorders.

Aging

This chapter shows that MMN and its magnetoencephalographic (MEG) equivalent MMNm are sensitive indices of aging-related perceptual and cognitive decline. Importantly, the age-related neural changes are associated with a decrease of general brain plasticity, i.e. that of the ability of the brain to form and maintain sensory-memory traces, a necessary basis for veridical perception and appropriate cognitive brain function. MMN/MMNm to change in stimulus duration is particularly affected by aging, suggesting the increased vulnerability of temporal processing to brain aging and accounting, for instance, for a large part of speech-perception difficulties of the aged beyond the age-related peripheral hearing loss.

The development of MMN

The brain can detect sound changes very early on, even prenatally. Both positively and negatively displaced responses to deviant stimuli have been found in infancy, with the majority of studies reporting, however, positive mismatch responses (MMR) in infants within the first few months of life. Besides neural development, stimulation parameters may influence polarity. The positively displaced MMR develops towards the adult-like MMN between the ages of 3 and 9 months, there being a wide inter-individual variation in this development. From school age onwards, sound changes elicit MMNs with negative polarities fairly systematically. The MMN peak latency becomes shorter with development, similar to other event-related potential components, which is consistent with the development of myelination. MMN/MMR studies have illuminated auditory abilities and learning mechanisms in infants, suggesting, for example, that the infant brain can extract information on the regularities of sound input and foetuses can form long-lasting memory traces.

Concluding discussion

This chapter looks at potential common underlying factors linking MMN/MMNm deficiency to the broad range of heterogeneous clinical conditions outlined in the book. Several promising clinical applications of MMN/MMNm are summarized, including the prediction of conversion to psychosis among clinically at-risk individuals, the prediction of the recovery of consciousness and cognitive capabilities in patients in a comatose or persistent vegetative state, the early detection of perceptual deficits in developmental brain disorders, and the early identification of the presence of Mild Cognitive Impairment (MCI). Furthermore, the evaluation of the cognitive decline occurring in different brain disorders, as well as the prediction of cognitive recovery after the occurrence of a stroke or other brain injury, and the objective monitoring of age-related cognitive brain change and potential countermeasures to slow down this age-related cognitive decline are discussed.

How to record and analyse MMN

This chapter will introduce and discuss different experimental paradigms that can be used for eliciting MMN. The classical paradigm for this purpose is the auditory oddball paradigm with repetitive ‘standard’ stimuli interspersed with infrequent deviant stimuli which elicit MMN reflecting change detection. Subsequently, more informative multi-deviant paradigms were developed that provide profiles of auditory-discrimination accuracy including different auditory stimulus dimensions, such as sound frequency, duration, and locus of origin. These paradigms are sensitive to various forms of training, thereby reflecting brain plasticity, and they are selectively affected in different cognitive brain disorders.

The mismatch negativity (MMN): An introduction

In this chapter, the mismatch negativity (MMN) event-related brain potential is introduced. MMN is an automatic response to any sound change generated primarily in auditory and frontal cortices, reflecting auditory change detection and discrimination accuracy. Analogous responses have also been found in other sensory modalities. MMN can, for example, index improvement of sound discrimination as a function of learning or recovery. Consistent with this, MMN appears to index general brain plasticity, essential for learning and memory, and to reflect different cognitive brain disorders. It is elicited irrespective of the direction of attention, being, therefore, a feasible tool for investigating even inattentive participants, such as sleeping infants or comatose patients.

Neurological disorders

The MMN amplitude is decreased and/or peak latency prolonged in a large number of different neurological disorders, such as neurodegenerative diseases, brain lesions, cochlear lesions, chronic pain, or tinnitus. This is to a great extent due to a decreased brain plasticity affecting the formation of memory traces for different sensory stimuli essential for different cognitive operations of the brain. Furthermore, MMN can serve as a measure of recovery or neural reorganization in different neurological disorders. For example, the recovery from aphasic symptoms after stroke was associated with the enhancement of MMN. MMN has also been useful in determining neural plastic changes of the auditory system associated with cochlear implantation.

Developmental disorders

Developmental brain disorders, such as developmental dyslexia, specific language impairment (SLI), autism spectrum of disorders (ASD), and oral clefts, include perceptual-cognitive deficits of language, audition, attention, and memory. It is important to detect these dysfunctions in early childhood in order to determine how the development of perception and cognition differs from the typical course and to design interventions supporting development. The MMN, being elicited from the foetal stage onwards, is a promising tool for this purpose. It has illuminated low-level perceptual-cognitive dysfunctions in these disorders and shows promise as an early neural marker of future language-related dysfunction.