Previous working memory studies using auditory stimuli at both encoding and retrieval show amplitude decreases in event-related potentials (N100 and late positive wave, LPW) at retrieval as a function of memory load. This study tested if these effects are associated with phonological or semantic coding by presenting visual stimuli at encoding and auditory stimuli at retrieval. We hypothesized that event-related potentials associated with phonological but not semantic coding would be affected by modality differences at encoding and retrieval. Memory sets having one, three, or five visual digits were followed by auditory probes that subjects classified as present or absent from the set. Reaction time increased and LPW amplitudes decreased with increases in memory load, but there were no significant effects of memory load on N100 amplitude. Results suggest that with respect to brain activity that covaries with memory load, probe N100 amplitude is associated with phonological coding and LPW amplitude is associated with semantic coding.

It is established that recall of an item from a list of sequentially presented items is sensitive to the item's position in the memorized list. However, little is known about the brain mechanisms that mediate these serial position effects. Studies of working memory retrieval using event-related potentials report amplitude reductions during retrieval (auditory cortical N100, neocortical late positive wave [LPW]) as memory load increases. We tested the hypothesis that N100 and LPW amplitudes to probes are also affected by serial position. Event-related potentials were recorded from subjects performing an auditory working memory task. A set of one or five digits was memorized, then subjects classified a probe digit as either present or absent from the memory set. A control task was also given. Amplitudes of the N100 and LPW were reduced in the 5-item versus the 1-item set. In the 5-item set N100 amplitude was significantly larger for the initial (1st) serial position, relative to Positions 2-5, while linear increases in LPW amplitude were seen across serial positions (5th > 1st position). A control task without memorization showed no N100 or LPW amplitude changes with set size or serial position. The findings reveal that the N100 and LPW are influenced differently by serial position during working memory retrieval: N100 shows a primacy effect and LPW demonstrates a recency effect. The results suggest that primacy and recency effects may be mediated by different brain regions at different times during memory retrieval.

Objective

To define brain activity and behavioral changes in mild cognitive impairment (MCI), an isolated memory deficit in the elderly that is a major risk factor for Alzheimer's disease.

Methods

Brain potentials and reaction time were examined in elderly controls (n=12) and MCI (n=15) using a target detection paradigm. Subjects listened to a sequence of tones and responded to high-pitched target tones (P=0.20) that were randomly mixed with low-pitched tones (P=0.80). Measures were a pre-stimulus readiness potential (RP), post-stimulus potentials (P50, N100, P200, N200, P300), and reaction time.

Results

Accuracy was equivalent between groups, but there was a trend for longer reaction times in MCI (P=0.08). Two potentials differed between groups: (1) P50 amplitude and latency were significantly increased in MCI, and (2) P300 latency was significantly longer in MCI. Results from two MCI subjects that converted to Alzheimer's disease are also discussed.

Conclusions

Brain potentials in MCI subjects during target detection have certain features similar to healthy aging (RP, N100, P200, N200), and other features similar to Alzheimer's disease (delayed P300 latency, slower reaction time). P50 differences in MCI may reflect pathophysiological changes in the modulation of auditory cortex by association cortical regions having neuropathological changes in early Alzheimer's disease.

Apolipoprotein E (ApoE) status and gender are risk factors for the development of Alzheimer's disease. Alzheimer's disease is more prevalent in female relative to male carriers of the ApoE epsilon 4 gene. We examined cortical sensory (P50, N100) and cognitive (P300) potentials in an auditory target detection task in females as a function of ApoE genotype (ApoE epsilon 4 carriers, ApoE epsilon 4 non-carriers) to define the incidence of abnormalities prior to the clinical expression of cognitive impairments. Both neuropsychological test scores and sensory cortical potentials did not differ between the two ApoE groups. In contrast, cognitive P300 potentials were significantly decreased in amplitude and delayed in latency for ApoE epsilon 4 carriers compared to non-carriers. Four out of the 10 ApoE epsilon 4 carriers had abnormally (>2S.D.) delayed P300 latency compared to one out of 20 non-carriers. Abnormal cognitive processes reflected by P300 latency delays are expressed at significantly higher incidence in normal older females who are carriers of the epsilon 4 allele than in non-carriers of this allele.

Mild cognitive impairment (MCI) patients have a high risk of converting to Alzheimer's disease. The most common diagnostic subtypes of MCI have an episodic memory disorder (amnestic MCI) occurring either alone [single domain (SD)] or with other cognitive impairments [multiple domain (MD)]. Previous studies report increased amplitudes of auditory cortical potentials in MCI, but their relationships to MCI subtypes and clinical outcomes were not defined. We studied subjects with amnestic MCI (n = 41: 28 SD, 13 MD), Alzheimer's disease (n = 14), and both younger (n = 22) and age-matched older controls (n = 44). Baseline auditory sensory (P50, N100) and cognitive potentials (P300) were recorded during an auditory discrimination task. MCI patients were followed for up to 5 years, and outcomes were classified as (i) continued diagnosis of MCI (MCI-stable, n = 16), (ii) probable Alzheimer's disease (MCI-convert, n = 18), or other outcomes (n = 7). Auditory potentials were analysed as a function of MCI diagnosis and outcomes, and compared with young, older controls, and mild Alzheimer's disease subjects. P50 amplitude increased with normal ageing, and had additional increases in MCI as a function of both initial diagnosis (MD > than SD) and outcome (MCI-convert > MCI-stable). P300 latency increased with normal ageing, and had additional increases in MCI but did not differ among outcomes. We conclude that auditory cortical sensory potentials differ among amnestic MCI subtypes and outcomes occurring up to 5 years later.

Although aging is accompanied by neurobiological changes and increased susceptibility to many neurological disorders, little is known about neurophysiological changes that start in old age. Here, neurophysiological changes during old age were assessed by recording brain potentials associated with motor preparation and stimulus expectancy (contingent negative variation, CNV) in young-old (60-69), oldest-old (85-98), and young (17-23) subjects. Individual trials began by a button press, followed 2.5 s later by either a low or high pitch tone. In the "motor" condition subjects responded following high pitch tones (P=0.20); in the "non-motor" condition subjects did not respond. Motor condition CNV amplitudes in the oldest old were more positive than the young and young-old groups, which were similar. In the non-motor condition, the young-old and oldest-old had similar CNV amplitudes that were positive in polarity, and were significantly different from young subjects. Motor potentials before button presses that started the trials were comparable among groups. Results show that neural activity associated with motor preparation and stimulus expectancy changes during advanced age, and that group differences can be modulated by task requirements.

Amnestic mild cognitive impairment (MCI) is an isolated episodic memory disorder that has a high likelihood of progressing to Alzheimer's disease. Auditory sensory cortical responses (P50, N100) have been shown to be increased in amplitude in MCI compared to older controls. We tested whether (1) cortical potentials to other sensory modalities (somatosensory and visual) were also affected in MCI and (2) cholinesterase inhibitors (ChEIs), one of the therapies used in this disorder, modulated sensory cortical potentials in MCI. Somatosensory cortical potentials to median nerve stimulation and visual cortical potentials to reversing checkerboard stimulation were recorded from 15 older controls and 15 amnestic MCI subjects (single domain). Results were analyzed as a function of diagnosis (Control, MCI) and ChEIs treatment (Treated MCI, Untreated MCI). Somatosensory and visual potentials did not differ significantly in amplitude in MCI subjects compared to controls. When ChEIs use was considered, somatosensory potentials (N20, P50) but not visual potentials (N70, P100, N150) were of larger amplitude in untreated MCI subjects compared to treated MCI subjects. Three individual MCI subjects showed increased N20 amplitude while off ChEIs compared to while on ChEIs. An enhancement of N20 somatosensory cortical activity occurs in amnestic single-domain MCI and is sensitive to modulation by ChEIs.

Objective

To determine if aging is associated with differences in attentional regulation using behavioral and event-related potential (ERP) measures.

Methods

Younger (n=13;M=20 years) and older (n=12;M=76 years) subjects performed an auditory cued attention task. Verbal cues correctly (valid) or incorrectly (invalid) predicted the ear receiving a target tone 1.5 s later, or were uninformative (neutral). Targets were either 'high' (2000 Hz) or 'low' (1000 Hz) pitch monaural tones. Subjects pressed one of 4 buttons to indicate target ear and pitch. ERPs following cues and targets (P50, N100, P200, slow waves), and negative slow potentials (CNV) between cues and targets were assessed.

Results

Cue information had significant effects on reaction time for both groups (validvalid) but not older subjects. Target slow waves were also affected by cue information (invalid>valid), and the difference was larger and lasted longer in older subjects. Slow waves following cues were significantly larger in older subjects, but the subsequent CNV amplitudes were comparable among groups.

Conclusions

When performing a cued attention task, age differences are present in transient ERPs following cues and targets.

Significance

Age differences in ERPs associated with attentional regulation support the hypothesis that attentional changes contribute to cognitive aging.

Progressive declines in memory function accompany normal aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Neuropathological studies suggest that damage to neurons providing connections between cortical areas may contribute to memory impairments in AD. Because AD develops slowly, similar neuropathological changes, to a lesser degree, may be present in MCI and some asymptomatic elderly subjects. In this study we tested the hypothesis that corticocortical interactions between sensory regions are impaired in aging, MCI, and AD, as compared with young subjects. When sensory cortical evoked potentials are elicited by pairs of stimuli the amplitudes of potentials to the second stimulus are attenuated. Corticocortical interactions were assessed by presenting stimulus pairs in different modalities (auditory/visual). There were significant group differences in the degree that a visual stimulus attenuated subsequent auditory potentials (young > healthy elderly > MCI > AD). Control experiments indicated equivalent amplitude reductions for all groups to the second stimulus for stimulus pairs having the same modality. These findings are compatible with progressive declines in corticocortical processing in aging, MCI, and AD.

Amnestic mild cognitive impairment (MCI) is a selective episodic memory deficit that often indicates early Alzheimer's disease. Episodic memory function in MCI is typically defined by deficits in free recall, but can also be tested using recognition procedures. To assess both recall and recognition in MCI, MCI (n = 21) and older comparison (n = 30) groups completed the USC-Repeatable Episodic Memory Test. Subjects memorized two verbally presented 15-item lists. One list was used for three free recall trials, immediately followed by yes/no recognition. The second list was used for three-alternative forced-choice recognition. Relative to the comparison group, MCI had significantly fewer hits and more false alarms in yes/no recognition, and were less accurate in forced-choice recognition. Signal detection analysis showed that group differences were not due to response bias. Discriminant function analysis showed that yes/no recognition was a better predictor of group membership than free recall or forced-choice measures. MCI subjects recalled fewer items than comparison subjects, with no group differences in repetitions, intrusions, serial position effects, or measures of recall strategy (subjective organization, recall consistency). Performance deficits on free recall and recognition in MCI suggest a combination of both tests may be useful for defining episodic memory impairment associated with MCI and early Alzheimer's disease.