Electrophysiological correlates of categorization: P300 amplitude as index of target similarity.

Two experiments examined event-related potentials (ERPs) and behavioral correlates of categorizing stimuli varying in perceptual similarity to targets. Participants performed a target-detection task in which non-target stimuli varied in target similarity but occurred with equivalent probability. The stimuli were variations of a schematic human face comprised of eight distinct features: two eyes, two eyebrows, one nose, one mouth, and two ears. Non-target stimuli that were perceptually similar to targets produced larger P300-like neurophysiological responses than did other non-target stimuli. These effects emerged whether participants' target was relatively complex (eight features) or quite simple (zero features). Accordingly, the presence of many constituent elements of a test stimulus does not appear necessary to trigger increases in categorical processing of non-targets that are similar to a target. The data further suggest that the P300 amplitude may be used as a good index of perceptual similarity between target and non-target stimuli.

Does process-specific slowing account for cognitive deficits in Lyme disease?

Although several studies have suggested that cognitive slowing is a symptom in Lyme disease, it is not clear whether this slowing is general or relates to specific cognitive tasks. This study examined cognitive speed in 25 Lyme disease patients using a mental arithmetic task. These patients showed significant impairments when initiating the cognitive processes involved in counting, but performed as well as healthy participants (n = 23) when the number of counting increments increased. Lyme patients also performed a speeded perceptual-motor matching task as well as healthy participants. Lyme-related initiation speed deficits were significantly correlated with performance on standardized neuropsychological tests, including the Trail Making Test and the Digit Symbol Test, but not with self-reported depression. These results suggest that the cognitive deficits seen on speeded tasks are process specific in the Lyme patient group, and are not the result of generalized slowing.

Comparison of endogenous event-related potentials in attend and non-attend conditions: latency changes with normal aging.

OBJECTIVE: Endogenous event-related potential (ERP) components have been observed under both attend and non-attend conditions, but it appears that at least some of the attend and non-attend components are functionally and topographically distinct. Also, under active task conditions, motivational and attentional variations may modulate the amplitude of the ERP. These various effects of attention on the ERP can complicate comparisons of the ERPs of normal subjects with the ERPs of clinical subjects, who may have reduced attentional capabilities. The experiment reported here sought to develop a non-task paradigm that reliably produces the same ERP components typically seen under task conditions. METHODS: Using rare auditory stimuli that were discrepant from the frequent stimuli both in frequency and intensity, stimuli were presented under non-attend instructions and under instruction to count the rare stimuli. The ERPs in these two conditions were compared with ERPs in a standard oddball paradigm which used stimulus parameters comparable to those of most previous experiments on ERPs in aging. Fifty subjects, ranging in age from 20 to 77, participated. RESULTS: The ERPs to the DISCREPANT oddball stimuli under non-task conditions were similar in scalp distribution to the ERPs to the same stimuli in the ATTEND condition and to the ERPs in the STANDARD/ATTEND condition. Furthermore, there were no significant differences in the age-related increase in ERP latencies among the DISCREPANT/IGNORE, the DISCREPANT/ATTEND, and the STANDARD/ATTEND conditions. CONCLUSION: The results indicate that increases in ERP latencies with aging can be assessed in the absence of task requirements, and that the paradigm described here may prove useful in investigating cognitive processing speed in clinical populations.

Cognitive processing speed in Lyme disease.

OBJECTIVE: The goal of this study was to more precisely define the nature of the cognitive processing deficits in the patients with Lyme disease. BACKGROUND: Lyme disease has been associated with cognitive disturbances. METHOD: Sixteen patients who met the Centers for Disease Control's case definition for Lyme disease and 15 age- and education-matched control subjects completed two computerized assessments. The first was a matching procedure that assessed perceptual/motor speed. The second task was an alphabet-arithmetic (AA) test that measured the speed of mental arithmetic. On the matching task, subjects judged as true or false simple identity equations (e.g., B + 0 = B). On the AA task, subjects indicated the veracity of equations of the same form as those of the matching task but which required mental arithmetic (e.g., A + 3 = D). The use of this paradigm permits sensory or motor slowing to be distinguished from slowed cognitive processing speed. Also, the tests do not involve automated or overlearned responses. RESULTS: Lyme disease patients and healthy controls did not differ in perceptual/motor speed. However, Lyme disease patients' response times were significantly longer than those of healthy controls during the AA task, demonstrating specific impairments in mental activation speed. CONCLUSIONS: These results suggest that Lyme disease patients show specific deficits when initiating a cognitive process. These impairments are independent of sensory, perceptual, or motor deficits.

Event-related potentials to inspiratory flow-resistive loads in young adults: stimulus magnitude effects.

Event-related potentials were recorded to brief presentations of four levels of inspiratory flow-resistive loads in young adults. We labeled the loads according to the level of resistance they provided subjectively: sub-threshold (0.34 cmH2O/l per s), near-threshold (4.01 cmH2O/l per s), intermediate (10.4cmH2O/l per s), and near-occlusion (57.5 cmH2O/l per s). No discernible ERPs were elicited by the undetected, sub-threshold stimulus but late components of the ERP (P2, N2, and P3) were observed to each of the three larger stimuli. They were related, in part, to behavioral judgments obtained during the stimulus periods. Both the latency and amplitude of the ERP components varied systematically as a function of stimulus magnitude, in a manner comparable to that observed in ERP paradigms using auditory and visual stimuli. Thus, the data show that event-related potentials to breathing are sensitive to physiologic effects of resistive loads present at the onset of inspiration. Respiratory ERPs may be used to infer sensory and perceptual responses to increases in airflow resistance and, accordingly, may relate to the perception of airflow obstruction in patient populations.

Many-valued logic and event-related potentials.

In previous experiments on event-related potentials (ERPs) during linguistic judgments, the subjects' decisions have been categorical (e.g., true vs false). In this experiment, more realistic variations in truth value and subject certainty were used. Thirty-eight naive undergraduates read a story about a fictional murder. ERPs were recorded as the subjects rated the strength of their beliefs about statements relating to suspects in the crime. Because no subject was sure which of the suspects was guilty of committing the crime, binary (true-false) category judgments were inappropriate. Three components of the ERP waveforms were affected by the experimental manipulations. An early positive component was largest to sentences concerning the suspect considered most likely to have committed the crime. A subsequent broad posterior positivity (LPC) also showed significant sentence-type differences, but it was larger to sentences considered probable--whether they were true or false--than to more ambiguous sentences. A third ERP component (N400) was negative at midline electrode sites and peaked at approximately 420 ms. Subjects' truth-value judgments had no effect on the N400. N400 was, however, affected by the subject's task. It was more negative when subjects made graded judgments about truth value than when they made binary true-false judgments. Overall, naturalistic judgments of sentence validity produced a variety of brain responses that reflected different aspects of linguistic decision making.

Phonological processing and the role of strategy in silent reading: behavioral and electrophysiological evidence.

To examine the contribution of phonological processing in silent reading, 51 native English speakers made decisions about targets presented either in word pairs or in sentences. The target words were homophonically (plain-plane), orthographically (plane-place), or semantically (plane-jet) related. N200 was enhanced only to homophonic targets, suggesting the use of phonological information in silent reading. Memory load did not affect the N200 amplitude. N400 was enhanced to all semantically incongruent words and was larger in the word pair condition. Reaction times were influenced by both experimental condition and target relationships; homophonic stimuli elicited the fastest RTs in the word pair condition and the slowest RTs in the sentence condition, suggesting the use of different strategies. Thus, ERP components and behavioral responses registered different aspects of language processing.

Auditory evoked potentials in multiple sclerosis: correlation with magnetic resonance imaging.

The present study addresses issues regarding the location of neural sources (i.e. generators) of human auditory evoked potentials (AEPs), and the pattern of neural conduction in the auditory pathway. AEPs were recorded from fifteen patients with multiple sclerosis (MS) and compared to normals. The recordings included auditory brainstem responses (ABRs), mid-latency responses (MLRs), and long-latency responses (LLRs). AEP latency abnormalities were related to the locus of demyelinating lesions, as determined by magnetic resonance imaging (MRI) scans. The data demonstrated several anatomical patterns relating abnormal ABR wave intervals and abnormal MRI signals. From these patterns specific loci for ABR neural sources in the brainstem might be postulated. In addition, the earlier the ABR waves, the more unilateral the abnormalities appeared, suggesting bilateral sources for later waves. The MLRs were highly correlated with ABR wave V and were associated with greater abnormality in MRI signals in midbrain and forebrain regions. In general, patients with abnormal LLRs also had widespread AEP and MRI abnormalities, supporting a multiple source approach for the N1 wave of the LLRs. The observation that LLRs were only abnormal in the presence of bilateral ABR abnormalities suggests a cross wiring which would serve as a compensatory mechanism for unilateral disturbances. The AEP data showed dissociation between early and late wave abnormalities, thus supporting parallel channels for neural conduction in the central auditory system. Such a model calls for some degree of independence of AEP generators along the auditory pathway.

ECT and non-memory cognition: a review.

The literature on the effects of electroconvulsive therapy (ECT) on non-memory cognitive functions is reviewed. It is concluded that with early methods of ECT administration (sine wave, high dose), these effects are larger than those of depression. They are less pronounced, and usually do not exceed the effects of depression, when modern methods of ECT administration (brief pulse, moderate or low dose) are used. Following ECT, these functions progressively improve. At one week to seven months after ECT, performance is better than before ECT, probably because of the alleviation of both the effects of depression and of ECT. The time course to full recovery of the non-memory effects resembles that of the recovery of amnesic effects, although the latter are more pronounced. With bilateral ECT, as with right unilateral ECT, there is evidence that right hemisphere effects are more pronounced. The results of this review argue that clinicians should take the non-memory cognitive effects of ECT into account, and patients should be informed of their existence before they sign consent for ECT.

Construct validity in the Trail Making Test: what makes Part B harder?

The Trail Making Test (TMT) is primarily a test of motor speed and visual attention. In Trail Making, Part A, the subject's task is to quickly draw lines on a page connecting 25 consecutive numbers. In Part B, the subject must draw the lines alternating between numbers and letters. To determine what makes Part B harder than Part A, variations of the standard Trail Making Test were assessed. Forty college students (20 male, 20 female) were given four forms of the Trail Making Test. The results show that Trail Making, Part B with just numbers took longer to complete than the standard Part A with numbers. Part B is 56 cm longer and has more visually interfering stimuli than Part A. These results indicate that Part B is more difficult than Part A not only because it is a more difficult cognitive task, but also because of its increased demands in motor speed and visual search.

Event-related potentials to airway occlusion in young and old subjects.

Event-related potentials (ERPs) were recorded to both inspiratory and expiratory airway occlusion in young (21-28 years) and old (55-67 years) subjects under both attend and ignore conditions. Early and late components of the ERP (N1, P2, N2, P3) were observed to both types of occlusions in both conditions. Variations in these components were consistent in both direction and degree with those observed in oddball tasks employing exteroceptive stimuli. ERPs for breathing may serve to clarify sensory attributes of respiratory stimuli in humans and to identify central processing abnormalities in patient populations.

Psychophysical measures of central auditory dysfunction in multiple sclerosis: neurophysiological and neuroanatomical correlates.

Central auditory function was assessed in 15 patients with multiple sclerosis (MS) to determine whether the demyelinating lesions resulted in disruption of temporal processing. Auditory evoked potential (AEP) recordings included all three latency regions: Auditory brain stem responses (ABRs), midlatency responses (MLRs), and long-latency responses (LLRs). Two psychophysical tasks thought to involve temporal processing were used: a monaural-processing task (gap-detection) and a binaural-processing task (masking level difference; MLD). Further, AEP abnormalities and psychophysical performance deficits were related to lesion location, based on magnetic resonance imaging (MRI) scans. Reduced MLDs were seen in six MS subjects. Abnormal MLDs were always accompanied by abnormal ABRs and MLRs, and compared to subjects with normal MLDs, the subjects with abnormal MLDs were more likely to have bilateral abnormalities in the AEPs. Further, MLR indices of abnormal binaural interaction appeared to be specifically related to the psychophysical measure of binaural processing. The MRI data of these patients indicated widespread involvement of the auditory pathway. MS subjects with abnormal MRI signals restricted to levels caudal to the lateral lemniscus did not have abnormal MLDs. Gap-detection thresholds were more resistant to the effects of the demyelinating lesions; only two subjects had abnormal gap-detection thresholds. These subjects had extensive AEP abnormalities (bilaterally, in all three latency regions). The gap-detection thresholds were most specifically related to abnormalities of the LLRs. In addition, the subjects with elevated gap-detection thresholds were the only ones with a prolonged interval between the ABRs and MLRs. Thus, efficient neural conduction between the upper brain stem and auditory cortex appears to be crucial for normal monaural temporal processing. The results indicate that demyelinating lesions can cause deficits in temporal processing in the central auditory pathway. However, auditory temporal processing is not a unitary phenomenon since abnormalities at different levels of the auditory system disrupt different types of temporal processing. Finally, abnormal psychophysical performance was not seen in all subjects with AEP and MRI evidence of involvement of the auditory pathway; rather, these psychophysical measures appeared to be sensitive to disruption only in specific portions of the auditory system.

Auditory event-related potentials and brain dysfunction in sleep apnea.

Auditory event-related potentials (ERPs) were recorded from 14 subjects with obstructive sleep apnea (OSA) before and after treatment with nasal continuous positive airway pressure (nCPAP). After 2 nights of treatment, there was dramatic improvement in the sleep patterns of the OSA patients, improvements in measures of apnea severity and oxygenation, and decrease in daytime sleepiness. The results of neuropsychological tests of a broad range of cognitive functions failed to confirm the patients' subjective reports of improvement in psychological functioning after treatment. The latencies of the N2 and P3 components were significantly prolonged prior to treatment, and there was a trend towards smaller N2 and P3 amplitude in the apneic subjects. The latency of P3 (but not N2) changed with treatment, decreasing almost to normative values. The results suggest that ERPs may be useful in documenting neural dysfunction in patients with OSA, in evaluating treatment efficacy, and possibly in determining the causes of the daytime symptoms of OSA.

Evoked potential changes and neuropsychological performance in Parkinson's disease.

Auditory brainstem responses (ABRs) and long latency exogenous and endogenous auditory evoked potentials (EPs) were investigated in 16 patients with Parkinson's disease and 11 control subjects. Parkinson's disease patients were impaired on mental status testing. While ABRs and the N1 component of the auditory EP were of normal latency in Parkinson patients, the endogenous components, N2 and P3, were prolonged. Prolongation of P3 latency in Parkinson's disease correlated with mental status decline, but not with severity of motoric disturbance. Thirteen PD patients also received neuropsychological evaluation. P3 latency was correlated with tests requiring learning or mental manipulation of information, but not with measures of verbal performance, immediate memory, or depression. P3 latency prolongation appears to have a selective relationship to intellectual changes in PD, and may be most sensitive to deficits requiring significant cognitive effort.

The relation of P3b to prior events and future behavior.

A prediction paradigm was used to explore the relationship of the amplitude of the scalp-recorded event-related potential to the sequence of preceding signals and to preceding and subsequent behavior. P3b was found to be the only component which related systematically to prior sequence of signals. The CNV, P300E and Slow Wave were not affected by signal sequence. The P3b findings were the same for the emitted and evoked P3b, thus ruling out a sensory interpretation of the effect of signal sequence on P3b amplitude. Furthermore, it was found that signal sequence interacts with the subject's predictions in determining P3b amplitude. For signal discontinuations, P3b was large in amplitude regardless of what had been predicted. However, for signal continuations, P3b was small when continuations had been predicted, but large when discontinuations had been predicted. Finally, we found that for both correctly and incorrectly predicted signal continuations, larger P3bs were more likely than smaller P3bs to be followed by a prediction that the signal for the next trial would be different.

Central transmission time differences in the auditory brainstem response as a function of sex, age, and ear of stimulation.

Averaged auditory brainstem responses (ABRs) to monaural clicks were recorded from twenty-nine men and women and twenty children. Differences in the wave I to wave V transmission time, and wave I to wave III transmission time as a function of ear of stimulation and reference, sex, size and age were investigated. The wave I-V transmission time was shorter for the women compared to the men. Individual wave latencies were compared and the transmission time difference was found to be due to small, incremental differences between successive waves rather than to one particular wave component. Size differences, as measured by nasion-inion length and subject height, did not correlate to the transmission time difference and did not appear to contribute to the sex difference. An ear of stimulation difference was found in the women's group. The sex difference in transmission time was seen in the children's data, but the difference was not significant. Thus, sex differences, age differences, and ear of reference differences are seen in ABR transmission times.

Brain generators of evoked potentials: the late (endogenous) components.

Locating the synapses which generate endogenous potential components recorded at the scalp would permit some aspects of the neural activity directly underlying cognition to be probed non-invasively. Knowing which synapses are functioning abnormally in certain neurological and psychiatric diseases may suggest rational treatment strategies aimed at local brain regions. Although it is not possible to localize the generating synapses using scalp topography, large potentials can be recorded in the hippocampal formation during the same task conditions which evoke scalp endogenous potentials. Phase-reversal of these hippocampal potentials over short distances, accompanied by changes in simultaneously recorded unit-activity, indicates that they are generated locally. Demonstration that they volume-conduct to the scalp would, however, require observation of lesion effects, and recordings from other candidate structures, as well as a realistic model for propagation.

Endogenous potentials generated in the human hippocampal formation and amygdala by infrequent events.

Infrequent, attended, auditory and visual stimuli evoke large potentials in the human limbic system in tasks that usually evoke endogenous potentials at the scalp. The limbic potentials reverse polarity over small distances and correlate with unit discharges recorded by the same electrodes, indicating that they are locally generated.