Continuous-processing related ERPS in adult schizophrenia: continuity with childhood onset schizophrenia.

BACKGROUND: Previous work with schizophrenic children disclosed deficits on two continuous performance tests (CPTs) and ERP indices of reduced attentional resource allocation. METHODS: The two CPTs were administered to adult schizophrenics and matched control subjects. The simple CPT required only that the subject respond whenever the target digit was displayed. The complex version required a response whenever any digit was displayed on two successive trials. Event-related potentials (ERPs) were recorded during task performance. RESULTS: Schizophrenics had fewer hits on both CPT versions, showed a greater drop in performance from the simple to the complex CPT, and took longer to respond than controls. The processing negativity (Np) showed a greater amplitude increase from nontarget to target in normals than in schizophrenics, and the overlapping P2 component was more negative in normals. P3 latency was longer in schizophrenics, but P3 amplitude did not differ. CONCLUSIONS: Group performance and processing negativity effects replicated those from an earlier study of schizophrenic and normal children administered the same versions of the CPT, suggesting similar abnormalities in the allocation and modulation of information processing resources.

Event-related potential correlates of linguistic information processing in schizophrenics.

Event-related potentials (ERPs) were recorded from adult schizophrenics and age- and education-matched normal controls during performance of an idiom recognition task involving judgments of the meaningfulness of idiomatic, literal, and nonsense phrases. Schizophrenics produced more errors and had prolonged reaction times while attempting to correctly differentiate meaningful from meaningless phrases. An ERP correlate of that deficit was a larger than normal N400 to idioms and literals, with no difference in N400 amplitude to nonsense phrases. This result was interpreted as evidence that the influence of the linguistic context provided by the first word of two-word idiomatic and literal phrases is reduced in schizophrenia. Schizophrenics also showed reduced amplitude P300.

Continuous-processing--related event-related potentials in children with attention deficit hyperactivity disorder.

Visual information processing in children with attention deficit hyperactivity disorder (ADHD) was studied using event-related potentials recorded during two versions of the Continuous Performance Task (CPT). ADHD children made more errors, and had longer reaction times than normal children on both the single- and dual-target CPT. Event-related potential waveforms were normal in the ADHD children with reference to early processing stages, i.e., contingent negative variation, P1-N1 laterality, and processing negativities, suggesting that ADHD children did not differ in their level of preparedness or their ability to mobilize resources for target identification and categorization. With respect to later processing, P3 amplitude was reduced in the ADHD group, whereas P3 latency was longer than normal. ADHD children had a diminished late frontal negative component, suggestive of reduced involvement in postdecisional processing.

Children with a schizophrenic disorder: neurobehavioral studies.

This paper summarizes retrospective and cross-sectional neurobehavioral studies of schizophrenic children. Retrospective studies of schizophrenic children reveal that during early childhood, prior to the first onset of schizophrenic symptoms, most schizophrenic children showed delays in language acquisition and/or impairments and delays in visual-motor coordination. These impairments appear to be developmental delays rather than fixed neurobehavioral impairments, because cross-sectional studies conducted when the children are at least 10 years of age, after the first onset of psychosis, fail to detect the same deficits. The results of behavioral, cognitive/neuropsychological studies as well as the study of event-related potentials measured during performance of cognitive tasks suggests that schizophrenic children suffer from limitations in processing resources. It is argued that the developmental delays observed in schizophrenic children represent the greater time it takes them to automate certain skills. The delay in automation may reflect their limited information-processing capacity.

Reduced attention-related negative potentials in schizophrenic adults.

Event-related potentials were recorded from outpatient adult schizophrenics receiving maintenance doses of neuroleptics and from normal control subjects during performance of a reaction time task and a complex visual discrimination task, the Span of Apprehension. Difference potentials were computed to isolate endogenous activity associated with the processing demands of the Span task. Schizophrenics produce significantly less early endogenous negative activity than do normal subjects. This processing-related negativity reflects pattern matching activity to an attentional trace during the serial scan of the visual icon. We previously reported an identical reduction in processing-related negativity in childhood-onset schizophrenia, suggesting that this deficit is age independent. Both frontal contingent negative variation and an early frontal P3 were larger in the schizophrenics than in normal subjects, suggesting an inappropriate mobilization of nonspecific attentional resources. A later posterior P3 was significantly smaller in schizophrenics than in normal subjects.

Continuous-processing related ERPS in schizophrenic and normal children.

The continuous performance task (CPT) has proven to be sensitive to schizophrenic impairments. Multichannel event-related potential (ERP) data were recorded from schizophrenic and normal children during performance of easy and hard versions of the CPT. Schizophrenics produced fewer hits, more false alarms, and prolonged reaction times. Poor performance in schizophrenics was associated with four ERP abnormalities: (1) Schizophrenics did not exhibit the normal increase in amplitude of an early-onset, processing-related negativity from nontarget to target stimuli, suggesting a failure to appropriately allocate attentional resources to discriminative processing. (2) Although P3 amplitude to targets was not significantly smaller in schizophrenic children, the distribution of P3 amplitude between target and nontarget responses in the easy and hard versions of the CPT was abnormal, suggesting that schizophrenics differed in the strategic allocation of resources in later stages of CPT processing. (3) In all task conditions schizophrenics showed a parietal negative component with a latency of 400 msec seen in younger, but not older normal children, suggestive of maturational lag. (4) ERP data demonstrated absence of right-lateralized P1/N1 amplitude in schizophrenic children. Taken together these data indicate that at several stages of information processing, schizophrenics are deficient in the control and strategic allocation of processing resources.

Information-processing deficits across childhood- and adult-onset schizophrenia.

Event-related potentials were recorded for childhood- and adult-onset schizophrenia subjects performing the span of apprehension (Span) task, which is sensitive to vulnerability factors in schizophrenia. Subjects responded to the onset of the Span arrays in a reaction time condition and then responded differentially to the presence of one of two target letters in the Span condition. While neither the childhood- nor the adult-onset group exhibited abnormalities in preparatory contingent negative variation activity, both groups produced significantly less endogenous negative activity between 100 and 300 ms after Span stimulus onset than age-matched normals. This endogenous negative activity reflects attentional effort associated with serial search and stimulus identification. These results support the position that schizophrenia subjects are impaired in their ability to allocate adequate attentional resources for processing Span stimuli. Moreover, the similarity of this information-processing deficit in the two groups suggests that childhood- and adult-onset schizophrenia lie on a continuum in this regard.

Event-related potentials in high-functioning adult autistics: linguistic and nonlinguistic visual information processing tasks.

Event-related potentials (ERPs) were recorded from high-functioning adult autistics and age- and IQ-matched normal controls during performance of two non-linguistic information processing tasks, the Continuous Performance Task (CPT) and Span of Apprehension (SPAN), and an Idiom Recognition Task (IRT) involving idiomatic, literal and nonsense phrases. The autistics exhibited behavioral deficits only when attempting to identify idiomatic phrases. The ERP correlate of that deficit was greatly reduced N400 to idioms. In addition, autistics produced larger N1 amplitudes in all tasks, and larger P3s in the IRT and CPT.

Reduced attention-related negative potentials in schizophrenic children.

ERPs were recorded from normal and schizophrenic children during performance of a reaction time task (RT) followed by a complex visual discrimination, the span of apprehension task (Span), sensitive to vulnerability factors in schizophrenia. Subjects responded rapidly to the onset of the visual arrays in the RT condition and differentially to the presence of 1 of 2 target letters in the Span condition. The EEG was recorded at 19 scalp sites and ERPs included activity 1 sec before through 1 sec after Span array onset. Difference potentials (Span-RT) were computed to remove unvarying exogenous activity, thus isolating endogenous activity associated with the processing demands of the Span task. When RT and Span task ERPs are compared, schizophrenic children produced a significantly smaller than normal increment in endogenous negative activity. This endogenous negativity differed in its topography and time course from the exogenous components (P1, N1 and P2), and most likely reflects attentional effort associated with serial search, pattern recognition and stimulus identification. We believe that the current results support the position that schizophrenics are impaired in their ability to allocate adequate attentional resources for the processing of the Span stimuli. It is important to note that this deficit is apparent quite early in discriminative processing.

Midlatency auditory evoked responses: differential effects of a cholinergic agonist and antagonist.

The effects of a cholinergic antagonist (scopolamine) and agonist (physostigmine) on the auditory middle latency evoked responses (MLRs) were studied in 7 normal male volunteers. Scalp recordings were made from a central (Cz) electrode referenced to linked ear lobes on one channel and to a non-cephalic, sternovertebral reference on a second channel. Three components were statistically analyzed for changes in latency and amplitude: Pa, with peak positivity in the 25-40 msec latency range, Nb, with peak negativity 40-50 msec, and P1, with peak positivity 50-65 msec. Control recordings included responses to click rates of 1, 5, 8 and 10/sec; as has been previously reported, P1 showed a marked decrease and disappeared at the faster rates of stimulation whereas Pa showed no change in amplitude. Intravenous injections of scopolamine resulted in a rapid and complete disappearance of P1 and a slight increase in Pa; concurrently, the subjects reported feeling drowsy but were awake with eyes open through the recordings. Subsequent injections of physostigmine resulted in a rapid reversal of the scopolamine effects so that the subjects became alert, Pa decreased, and P1 reappeared and increased to control amplitudes. Rapid click rates caused P1 to diminish, as in the control period, indicating a common P1 recovery cycle in both the control and physostigmine conditions. These data are discussed in terms of the hypothesis that the P1 generator system is comprised of a cholinergic brain-stem-thalamic component of the ascending reticular activating system.

PET and P300 relationships in early Alzheimer's disease.

The P300 (P3) wave of the auditory brain event-related potential was investigated in patients with probable Alzheimer's disease to determine whether P300 latency discriminated these patients from controls and whether prolonged P300 latency correlated with rates of brain glucose metabolism as measured by Positron Emission Tomography. P300 latency was prolonged by more than 1.5 standard deviations from age expectancy in 14 of 18 patients, but none of 17 controls. In these subjects P300 latency was shown to be inversely correlated with relative metabolic rates of parietal and, to a lesser extent, temporal and frontal association areas, but not with subcortical areas.

Event-related potential correlates of impaired attention in schizophrenic children.

Electrophysiological correlates of focused attention were studied in 13 schizophrenic and 19 age- and gender-matched children. Subjects performed a version of the Continuous Performance Task (CPT) in which a target was designated as any digit from 0 through 9 occurring on two successive stimulus presentations. Signal digits were surrounded by distractor digits which varied in position, value, and number. Event-related potentials (ERPs) elicited by each stimulus of a target pair were recorded from midline and homologous parietal, temporal, and occipital electrode placements. Schizophrenic children made significantly more errors of omission and commission than normal children. The amplitude and time course of the intertrial CNV was the same for both groups. There was a circumscribed amplitude asymmetry, left smaller than right, for the P1/N1 and P2 measures which was greater in normal than in schizophrenic children. The P3 component was significantly larger to the second stimulus of the target pair than to the first for both groups, and larger for the normal than the schizophrenic children to both stimuli.

Longitudinal P300 latency changes in Alzheimer's disease.

A longitudinal study of the changes in latency of the P300 (P3) wave of the auditory event-related brain potential was undertaken in a group of 18 thoroughly screened and diagnosed possible and probable Alzheimer's disease (pAD) patients and 15 normal controls. On initial recording, P3 latency was significantly prolonged in the pAD group by more than 1.5 standard deviations (40 msec) beyond the normal group. Over the course of the next 3 years, the rate of increase in P3 latency was significantly greater for the patient group than for the controls. The rate of change in P3 latency may reflect accelerated senescence in Alzheimer's disease. Development of the auditory P300 as a marker of neurobiological processes in aging and dementia is discussed.

Intracellular analysis of the innervation of a crayfish sensory interneuron by regenerating afferents.

Mechanoreceptors of the crayfish tail fan have peripheral somata and send their axons to the last (sixth) abdominal ganglion via five bilateral pairs of nerve roots (R1-R5). Comparisons were made between normal crayfish and regenerate preparations in which R4 had been cut and directed back to an extensively denervated sixth abdominal ganglion; 8 to 15 weeks postoperatively, an identified target interneuron (A) in this ganglion was impaled, and its response to water currents, electrical excitation of R4, and stimulation of individual sensory hairs supplying axons to R4 was studied along with several other properties of the pre- and post-synaptic neurons. Normal levels of excitability in A to R4 stimulation were achieved within six weeks as judged by extracellular criteria. Subsequent intracellular analysis revealed that few differences exist between regenerated and normal inputs: probability of (re-) connection, unitary EPSP amplitude and time course distributions, resting membrane potentials, and critical firing levels were comparable in the two groups; input impedance, however, may have been lower in regenerates. Compound electrically elicited EPSPs were similar in amplitude, rise time, and half amplitude width, but differed slightly in latency to onset (regenerates greater than normals). This was accounted for by differences in conduction time to the ganglion in regenerates, and central delay estimates suggest that connections in both groups are monosynaptic. The body root (R1) providing input to A that remained intact in the regenerate preparations increased in efficacy; over 12 postoperative weeks the response of A to R1 activation by water drops steadily increased and at 12 weeks unitary increments to ascending electrical stimulation of R1 were significantly larger than in normals. The response to giant interneuron activation demonstrated that recurrent inhibitory inputs were normal in regenerates. In addition, synaptic depression, normally responsible for behavioral habituation in this system, was comparable across groups. Further, protection from habituation was observed in both normals and regenerates if R4 stimulation was preceded by giant interneuron activation, thus indicating that normal presynaptic inhibitory inputs to the regenerated afferent terminals have also successfully regenerated.(ABSTRACT TRUNCATED AT 400 WORDS)

Event-related potential concomitants of information processing dysfunction in schizophrenic children.

ERPs were recorded from 10 schizophrenic and 13 normal children during the performance of the Span of Apprehension task (Span). This task involves the discrimination of a randomly placed target letter among distractors, and it has been shown to discriminate between normal and schizophrenic individuals. The EEG was recorded at 7 scalp loci, and ERPs were averaged over a 1500 msec interval initiated by a warning tone which preceded the visual Span stimuli by 500 msec. Stimulus arrays were grouped into 4 levels of difficulty. The data from both subject groups were combined in a single principal components analysis (separate PCAs exhibited few differences between groups) generating 8 rotated factors which were readily interpreted in terms of conventional ERP components. Factor scores for the two groups were examined using Analysis of Variance. The schizophrenic children produced a small CNV which was slow to develop and resolve as well as diminished amplitudes for the N1, P3 and slow wave components. This suggests that these children are impaired in their ability to regulate processes involved in the mobilization and direction of attention and the discrimination of target stimuli. Significantly, the schizophrenic children did not show progressive increases in N1 and SW amplitudes in response to increases in information processing demand (array difficulty) as was the case in the normal children. ERP components of the schizophrenic children were most aberrant at frontal leads, but midline and lateralized deficits were also seen at vertex and posterior recording sites.