Objective

To examine the affects of aging on auditory cortical activity during a short-term memory task.

Methods

Young and elderly subjects performed a working memory task using acoustically presented digits while evoked potential components (N100, P200) generated by auditory cortex were recorded. Reaction time and N100/P200 amplitudes and latency were analyzed as a function of memory load.

Results

N100 amplitude to probes decreased as a function of memory load in young subjects, but increased as a function of memory load in the elderly. Young subjects also exhibited changes in N100 latency during memorization of list items, a result not found in elderly subjects.

Conclusions

We conclude that normal aging is associated with a qualitatively different pattern of N100 responses during memory retrieval, and a static N100 response during encoding. The findings suggest that aging is accompanied by functional reorganization of the neural network that supports retrieval in auditory working memory.

Objectives

To examine evoked potentials and behavior as a function of stimulus sequence in an auditory target detection paradigm in Alzheimer's disease (AD).

Methods

Evoked potentials and reaction times were collected from 12 healthy elderly controls and 10 patients with mild AD. Subjects pressed a response button to high-pitched target tones (P=0.20) that were randomly intermixed with low-pitched frequent tones. We measured pre-stimulus readiness potential (RP), event-related potentials (P50, N100, P200, N200 and P300), and reaction time as a function of the stimulus sequence.

Results

AD subjects performed at comparable levels of accuracy as controls, but had significantly increased reaction times. Grand averaged potentials in AD showed a significant reduction of the amplitude of the RP, and an increase of P300 latency. Both controls and AD showed speeding of reaction time, increases in RP amplitude, and decreases in P300 latency as a function of the number of frequents preceding the target. Sequential changes of other components (P200 and N200) were found in controls but not AD.

Conclusions

AD patients have systematic changes of both RT and certain of the evoked potential components as a function of stimulus sequence. Moment-by-moment changes in target expectancy are largely preserved in AD, even though overall performance and evoked potential measures of expectancy (RP) and stimulus classification (P300 latency) are abnormal.

Objective: To examine the utility of multivariate measure< of event-related brnin polo!ntials and rcac1ion 1irne (RT) 10 accurately cla"-ing the detection of a rnre torgct stimulu' have found group difference> in RT and brnin potentials (P300 and readinC"-< poten1ial. n.- RP) he1wecn AD and cld.,rly cnn1rol>. However. the«: individual measures do 1101 have 1he requisite "'nsi1ivi1y or specifici1y 10 be useful for defining an individual a' having AD. The purpose of 1he present experiment was to determine of u multivariate approach usine RT. RP. and P300 would improve' ..cn,i1ivi1y and "pccificity. Mctluxk We srudicd healthy ~omrols (n • IX: M age 69.7 -+- 7.7). und AD patient< (n - I l ; M age 72.0 + 9.0: Mini-mental >tatu> ~ 23.3 ~ 2.9). Heahhy <·ontrols were >ereened using a bauery of neuropll>. In the targc1 detectiun task subjec1> listened to a hz: n - 240) and target (2000 h1: n 60) tones were presented in a random 10 quiclly pr"-"' a button when a target ""s presented. Bchaviorul measure\ were r~al:llOn tim~ and acl"uracy. EEG ~a~ l'Ontiouously recorded from 7 sites using >tandard technique>. E\-oked pmential> to target and frequent lune.< were averaged off-line. Linear discriminant analysi\ was used to predict group 111embe!1'hip (AD or cnntrol) for each >ubject on the ba .01 ). RP ampli1ude (p > .02). and PJ(l() la1ency (p < .0 I J between controls and AD. Median 1->eorcs for AD relative to control' were 1.-l (RT) . ·I.I (RP) . and 1.6 (P300 latency). Discriminant analysis showed 81.8 q. sensitivity (correctly cla.,,,ifoed AD) and IOO<;r specificity (correctly classified controls). Conclu~ ions: We identified 'ignific:mt difference< hctween healthy control> and i\D pancnts on three meolllurcs U>ing a ta.,k that 1s easy 10 perform. The comhince of RT. RP, and P300 latency was capable of distingui.•hing mild AD patienL< from age-matched subject~ wi1h a high degree of accuracy. The method may hlingubhing normal aging from early AD.

Objectives

To examine reaction times and event-related potentials (ERPs) in an auditory cued attention task varying motor requirements, cue validity, and cue location.

Methods

Subjects (n=13) listened to cue-target stimulus pairs. Verbal cues (monaural, binaural) indicated the ear to receive a target tone 1.5s later. Cues correctly (valid) or incorrectly (invalid) predicted target ear, or were uninformative (neutral). In separate conditions subjects either responded by pressing one of two buttons, or did not respond to targets. ERPs for cues and targets (P50, N100, P200, late slow wave), and negative slow potentials between cues and targets were assessed.

Results

Target reaction times for valid cues were significantly shorter than for invalid cues, with intermediate values for neutral cues. When no motor response was required larger ERPs were seen to both cues and targets. Negative slow potentials had larger amplitudes before target presentation when subjects responded to targets; and were larger following neutral, vs. valid/invalid, cues. ERPs (N100, P200) to invalidly cued targets were significantly larger and a subsequent late slow wave was more positive, relative to validly cued targets.

Conclusions

Expectancy for targets begins shortly after cue presentation, and is affected by both motor requirements and the information content of the cue. ERP amplitudes to targets are modulated by the correspondence between cue information and actual target location.

Objective

Mild cognitive impairment (MCI) is a selective episodic memory deficit in the elderly with a high risk of Alzheimer's disease. The amplitudes of a long-latency auditory evoked potential (P50) are larger in MCI compared to age-matched controls. We tested whether increased P50 amplitudes in MCI were accompanied by changes of middle-latency potentials occurring around 50 ms and/or auditory brain-stem potentials.

Methods

Auditory evoked potentials were recorded from age-matched controls (n = 16) and MCI (n = 17) in a passive listening paradigm at two stimulus presentation rates (2/s, 1/1.5 s). A subset of subjects also received stimuli at a rate of 1/3 s.

Results

Relative to controls, MCI subjects had larger long-latency P50 amplitudes at all stimulus rates. Significant group differences in N100 amplitude were dependent on stimulus rate. Amplitudes of the middle-latency components (Pa, Nb, P1 peaking at approximately 30, 40, and 50 ms, respectively) did not differ between groups, but a slow wave between 30 and 49 ms on which the middle-latency components arose was significantly increased in MCI. ABR Wave V latency and amplitude did not differ significantly between groups.

Conclusions

The increase of long-latency P50 amplitudes in MCI reflects changes of a middle-latency slow wave, but not of transient middle-latency components. There was no evidence of group difference at the brain-stem level.

Significance

Increased slow wave occurring as early as 50 ms may reflect neurophysiological consequences of neuropathology in MCI.

Objective

To define changes in cortical function in persons inheriting familial Alzheimer disease (FAD) mutations before the onset of cognitive decline.

Methods

Twenty-six subjects with a family history of FAD were divided into 2 subgroups according to genotype (FAD mutation carriers, n = 15; FAD noncarriers, n = 11). Subjects were given standardized tests of cognitive function and the Clinical Dementia Rating scale (CDR). Sensory (P50, N100, P200) and cognitive (N200, P300) event-related potentials were recorded during an auditory discrimination task. Amplitudes and latencies of cortical potentials were compared among FAD mutation carriers and noncarriers.

Results

FAD mutation carriers and noncarriers did not significantly differ in age or on measures of cognitive function, but FAD carriers had a greater incidence of 0.5 CDR scores (1/10 noncarriers, 5/15 carriers). Relative to noncarriers, FAD mutation carriers had significantly longer latencies of the N100, P200, N200, and P300 components, and smaller slow wave amplitudes. Subanalyses of subjects having CDR scores of 0.0 also showed latency increases in FAD mutation carriers.

Conclusions

Auditory sensory and cognitive cortical potentials in persons with familial Alzheimer disease (FAD) mutations are abnormal approximately 10 years before dementia will be manifest. Longer event-related potential latencies suggest slowing of cortical information processing in FAD mutation carriers.