Pergamon 0031-9384(94)00393-9 Physiology & Behavior,Vol. 57, No. 5, pp. 927-935, 1995 Copyright © 1995 ElsevierScienceLtd Printed in the USA. All rights reserved 0031-9384/95 $9.50 + .00 Habituation of Auditory N100 Correlates With Amygdaloid Volumes and Frontal Functions in Age-Associated Memory Impairment H. S. SOININEN, *~ J. KARHU,~" J. PARTANEN,~" A. P~KKONEN,~" V. JOUSM,~KI,'I" T. I-IANNINEN,* M. HALLIKAINEN,* K. PARTANEN,:~ M. P. LAAKSO,* K. KOIVISTO* AND P. J. RIEKKINEN, SR.*§ Departments of*Neurology, tClinical Neurophysiology and ~Clinical Radiology, University Hospital of Kuopio, and §A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, SF-70211 Kuopio, Finland Received 27 September 1994 SOININEN, H..~I, J. KARHU, J. PARTANEN, A. P~KKONEN, V. JOUSM)~KI, T. H,~NNINEN, M. HALLIKAINEN, K. PARTANEN, M. P. LAAKSO, K. KOIVISTO AND P. J. RIEKKINEN, SR. Habituation of auditory MOO correlates with amygdaloid volmnesandfrontalfunctions in age-associated memoryimpairment. PHYSIOL BEHAV 57(5) 927-935, 1995.-- We studied the habituation of auditory NI00 responses in subjects with age-associated memory impairment (AAMI) and in healthy age-matched volunteers. The findings were correlated with volumes of the amygdala, hippocampus, and frontal lobe measured by magnetic resonance imaging (MRI), as well as with subjects' performance on tests assessing frontal lobe functions and memory. Habituation of N100 did not differ across AAMI subjects and controls. However, in AAMI subjects there was a significant correlation between habituation of NI00 and volumes of the amygdala; the more reduced habituation, the smaller volume. In addition, decline in habituation of N 100 correlated with impaired performance on a visual memory test (Heaton Visual Retention Test; r = 0.77; p < 0.001) and impairment on tests assessing frontal functions (Verbal Fluency, Trail Making Test, and Stroop). Habituation of N 100 was not related to age or sex. To our knowledge this is the first study to demonstrate a relationship between habituation of evoked responses, MRI volumetric measures, and performance on psychometric tests. The results suggest that impaired memory and frontal lobe functions in AAMI subjects may be associated with poor habituation of N100. Since habituation reflects focusing tff attention to relevant features of stimuli, impairment of this mechanism and subsequent defective memory trace formation may contribute to the observed deficits on memory tests. Aging Alzhaimer's disease Amygdala Arousal Auditory evoked potential Frontal lobe Magnetic resonance imaging Memory NI00 AUDITORY evoked potentials reflect activation in the auditory afferent pathways and :in the corresponding cortical receiving areas. The brain stem and middle-latency auditory evoked poten- tials at 1-50 ms are modulated primarily by the physical prop- erties of the stimuli, whereas the later peaks are modified by endogenous factors such as alertness, attention, and the mean- ingfulness of the stimuli (46,47), Several neural generators con- tribute to auditory N100 deflection (41), which follows the onset of any tone by about 103 ms. Both electrical and neuromagnetic recordings imply main sources in the auditory cortex in the upper bank of the Sylvian fissure (23,64), and possibly also in frontal cortical areas (41). Endogenous neural processes cause event- related potential (ERPs) overlapping with the N100 deflection, when the different tones are attended (25), and even when a de- viant tone is not perceived (mismatch negativity, 40,46). Attended deviant stimuli elicit late ERP components, N2 and P3 or P300 (about 300 ms after the stimulus onset), as well. Particularly P300, which presumably primarily reflects the en- dogenous processing of stimuli, has been studied in various cog- nitive disorders such as Alzheimer's disease (22). Even though many dementia patients have delayed latency and show a de- creased amplitude of P300, there is a considerable overlap be- tween dementia patients and normal elderly individuals. Further- more, the latency of P300 is strongly age-dependent. Thus, there are limitations in the usefulness of P300 in clinical diagnostics (45). The several neural generators, such as the hippocampus, have been suggested for P300. N 100 declines in amplitude after repeated auditory stimula- tion: a short-term reduction to the asymptotic level can be ob- served after the second to fourth stimulus in a train of tones (52), and long-term reduction develops mostly within the first half- hour of stimulation (53). The behavior of auditory N100 fulfills many of the classic criteria by Thompson and Spencer (62) for a response habituation: the decrease in amplitude is most pro- Requests for reprints should be addressed to H. S. Soininen, Department of Neurology, University of Kuopio, P.O. Box 1627, SF-70 211 Kuopio, Finland. 927