Autonomic abnormalities in schizophrenia. State or trait indicators?

BACKGROUND: Tonic electrodermal measures have been widely used to index autonomic abnormalities in schizophrenia, whereas phasic electrodermal nonresponsiveness has been frequently used to index attentional orienting abnormalities. The primary objective of the present study was to assess whether these electrodermal abnormalities are episode indicators or vulnerability indicators. METHODS: Twenty patients with a recent first episode of schizophrenia were tested during symptomatically remitted states and psychotic states. Twenty demographically matched normal controls were tested at two comparable intervals. Testing for stability of abnormalities across remitted and psychotic states allowed us to determine whether tonic and phasic electrodermal measures qualify as episode indicators or vulnerability indicators. RESULTS: Tonic electrodermal activity was abnormally elevated only during the psychotic state, which indicates that it is an episode indicator in schizophrenia. Phasic hyporesponsiveness relative to levels of general activation was present in both the remitted and the psychotic states, most strikingly during the psychotic state, and the proportion of patients who were electrodermally nonresponsive tended to be abnormally high during the remission test. CONCLUSION: Tonic electrodermal hyperarousal appears to be a state-sensitive episode indicator, whereas phasic electrodermal hyporesponsiveness to innocuous stimuli relative to activation level appears to be a mediating vulnerability factor.

Ontogeny of selective attention effects on event-related potentials in attention-deficit hyperactivity disorder and normal boys.

A longitudinal study of young attention-deficit hyperactivity disorder (ADHD) boys has found clear evidence for developmental abnormalities in event-related potential (ERP) waves that reflect cognitive processes associated with selective attentional tasks. Boys alternated attention to auditory or visual modalities in a train of stimuli, in an attempt to detect target stimuli in the attended modality. Results suggest that ADHD boys' attentional difficulties are due to insufficient facilitation of responses to the attended stimuli and not to an inability to block ignored stimuli. Abnormalities in ERPs reflecting cognitive processes associated with both interchannel selection mechanisms (processing negativity) and intrachannel selection mechanisms (P3b) were found. The degree of abnormality in the P3b responses to target stimuli in ADHD boys (lower than normal boys) was found to increase with age. It is suggested that the abnormally low P36 response to attended target stimuli found in ADHD boys may be due in part to insufficient LC noradrenergic activity normally triggered by attended task-relevant or novel stimuli.

A cross-sectional and longitudinal study of age effects of electrophysiological measures in hyperactive and normal children.

Longitudinal and cross-sectional event-related potential, EEG power spectral, and skin conductance level data were obtained from 138 hyperactive and 60 normal boys. A age-by-diagnosis interaction was found for several measures in the cross-sectional data and for all three types of measures in the longitudinal data. These findings emphasize the importance of age in electrophysiological studies of young children and strongly suggest an abnormal maturational process in hyperactive children.

A prospective study of delinquency in 110 adolescent boys with attention deficit disorder and 88 normal adolescent boys.

The authors studied official arrests from childhood through adolescence in two groups of boys; one group (N = 110) was diagnosed in childhood as suffering from attention deficit disorder (ADD), and the second group (N = 88) consisted of normal control adolescents. Rates of single and multiple serious offenses and of institutionalization for delinquency were significantly higher in the ADD subjects. These findings suggest a strong relationship between childhood ADD and later arrests for delinquent behavior.

Allocation of cognitive processing capacity during human autonomic classical conditioning.

In each of two experiments, allocation of cognitive processing capacity was measured in college-student subjects during autonomic discrimination classical conditioning. A 7.0-sec delay paradigm was used to establish classically conditioned responses to a reinforced visual conditioned stimulus (CS+). Electrodermal responses were the primary measures of autonomic classical conditioning. Allocation of processing capacity was measured by monitoring performance on a secondary reaction-time (RT) task. The auditory secondary-task RT signal was presented before, and 300, 500, 3500, 6500, and 7500 msec following CS onset. The RT signal was also presented following properly and improperly cued shock unconditioned stimuli (UCSs). Significant discrimination classical conditioning was obtained in both experiments. Comparison with control subjects who did not receive the RT signals indicated that the presence of the RT signals did not interfere with the development of classical conditioning. Four principal findings were obtained with the secondary-task RT measure. First, RTs to signals presented during CS+ were consistently slower than RTs to signals presented during CS-. This finding indicates that greater capacity allocation occurred during CS+ than CS- and is consistent with recent cognitive interpretations of classical conditioning. Second, the largest capacity allocation (i.e., slowing of RTs) occurred 300 msec following CS+ onset. This finding is consistent with the notion that subjects are actively processing the signal properties of the CS+ at 300 msec following CS+ onset. Third, presentation of the UCS when improperly cued (following CS-) significantly increased capacity allocation, whereas presentation of the same UCS when properly cued (following CS+) did not affect capacity allocation. These findings indicate that subjects were actively prepared for the UCS following CS+ but not following CS- and that a surprising UCS elicits greater capacity allocation than does an expected UCS. Fourth, large electrodermal responders to the CSs exhibited patterns of capacity allocation during the CSs, particularly during the CS+, different from those of small electrodermal responders. In particular, they exhibited significantly longer RTs at 300 msec after CS+ onset than did the small responders, followed by a shortening of RT at 500 msec relative to the small responders. This finding suggests that large electrodermal responders devote greater processing capacity to significant environmental stimuli than do small responders and that their processing may begin and be completed more rapidly. All in all, the data indicate the complexity of the cognitive processes that occur during human classical conditioning and the usefulness of the secondary-task technique in integrating conditioning theories and psychophysiology with cognitive psychology.

Electrodermal anomalies in recent-onset schizophrenia: relationships to symptoms and prognosis.

Electrodermal activity was measured in recent-onset schizophrenic patients (n = 98) and matched normal control subjects (n = 40) as part of an ongoing longitudinal study. Results at the initial inpatient test were generally consistent with the current consensus in the literature. A large subgroup of the patients was found to be nonresponsive with the phasic skin conductance orienting response measure, whereas the remaining subgroup of patients was found to be electrodermally tonically hyperaroused. Heightened electrodermal activity at the inpatient test was associated with a number of symptoms in male patients and with poor recovery from the acute schizophrenic episode. Followup tests conducted when the patients were in states of remission and psychotic relapse revealed that tonic electrodermal arousal measures qualify as state-sensitive episode indicators, whereas phasic nonresponding may qualify as an atypical vulnerability indicator. Moreover, preliminary data from three patients suggest that increases in tonic electrodermal arousal may temporally precede psychotic relapses. The principal findings are consistent with a vulnerability/stress model that posits that electrodermal hyperarousal is part of a transient intermediate state that may lead to a psychotic episode in a vulnerable individual.

Concurrent and predictive electrodermal correlates of symptomatology in recent-onset schizophrenic patients.

Electrodermal activity and symptomatology were interrelated in a group of 56 male and 13 female recent-onset schizophrenic patients. Electrodermal activity was indexed by the frequency of nonspecific skin conductances responses and the number of trials to habituation of the skin conductance orienting response. Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS) on two separate test occasions. The first test occasion was during the inpatient period when psychotic symptoms were prevalent and medications were variable. The second test occasion was several months later during an outpatient period when symptoms were stabilized and medications held constant. Electrodermal activity was positively and significantly related to a number of symptoms in male patients, most reliably the BPRS factors Activation and Hostility/Suspiciousness. These relationships were most consistent during the outpatient period. Of particular theoretical interest, greater electrodermal activity during the inpatient period was associated with greater outpatient psychopathology. The results suggest that heightened inpatient electrodermal activity is predictive of poor short-term symptomatic recovery in recent-onset, acute, male schizophrenic patients.

Attention and schizophrenia: impaired modulation of the startle reflex.

The startle reflex (SR) elicited by abrupt stimuli can be modified by attention to nonstartling stimuli that shortly precede the startle-eliciting stimulus. The present study of 15 recent-onset, relatively asymptomatic schizophrenic outpatients and 14 demographically matched normal control subjects demonstrated that attentional modulation of SR is impaired in schizophrenic patients. Specifically, the control group exhibited greater startle eye-blink modification following to-be-attended prestimuli than following to-be-ignored prestimuli, whereas the patients failed to show the attentional modulation effect. These results suggest traitlike attentional deficits in schizophrenia because the patients were relatively asymptomatic. The measurement of attentional modulation of SR may provide a nonverbal, reflexive, state-independent marker of the vulnerability to schizophrenia.

Autonomic orienting and the allocation of processing resources in schizophrenia patients and putatively at-risk individuals.

The differential allocation of attentional resources to attended and ignored stimuli was examined by measuring skin conductance orienting responses and secondary reaction time in relatively asymptomatic schizophrenia outpatients, demographically matched normal controls, college students putatively at risk for psychosis, and a college student control group. At-risk participants were those with extreme scores on scales for either anhedonia or perceptual aberration-magical ideation (per-mags). Compared to control groups, the patients and per-mags showed secondary reaction time results suggesting a delay in the differential allocation of attentional resources. This deficit was observed particularly in patients and matched controls with few or no skin conductance orienting responses, suggesting that impaired autonomic orienting is related to underlying cognitive-attentional vulnerability factors.

Lateral asymmetries in electrodermal responses to nonattended stimuli: a reply to Walker and Ceci.

Walker and Ceci (1983) pose a number of interesting and potentially important criticisms and alternative explanations regarding the laterality finding and hypothesis of Dawson and Schell (1982). The present evaluation finds each of the criticisms and alternative explanations to be inadequate. We then distinguish between two alternative interpretations of the Dawson and Schell hypothesis, one based on inherent functional properties of the two hemispheres and the other based on the notion that each hemisphere is a partially independent pool of processing resources. Walker and Ceci's fundamental objection seems to apply only to the first interpretation.

Electrodermal responses to attended and nonattended significant stimuli during dichotic listening.

Some investigators have found that words previously associated with shock elicit electrodermal responses (EDRs) when presented in the nonattended channel of a dichotic listening task. The present experiment tested for this phenomenon while closely monitoring for shifts in attention to the nonattended channel. College student volunteers verbally shadowed a series of unrelated words presented to the attended channel while words made significant by previous association with shock (and semantically related words) were occasionally presented to the nonattended channel. Three principal findings were obtained. Fist, when EDRs were averaged across all trials and across all subjects, it was found that EDRs were elicited by the significant words presented in the nonattended channel. Second, for the subgroup of subjects that had the significant words presented to the right ear (activating the left cerebral hemisphere), it was found that EDRs were elicited by the significant words presented to the left ear (activating the right cerebral hemisphere), it was found that EDRs were elicited by the significant word seven on trials on which there were no apparent shifts in attention. The results of this study indicate the importance of closely controlling and monitoring for shifts in attention and suggest the potential importance of cerebral laterality in mediating EDRs to stimuli presented in a nonatttended channel.

Restrained and nonrestrained eaters' orienting responses to food and nonfood odors.

Dietary restraint was assessed by Stunkard and Messick's (1985) three-factor eating questionnaire, using the restraint subfactor score only in normal-weight college students (n = 41). The subjects were than assessed for skin conductance orienting responses (ORs) to food and nonfood odors when hungry and sated (after a standard breakfast and after an overnight fast). Subjects also rated their hunger and each odorant for pleasantness on separate 7-point scales. Results indicated that restrained eaters oriented less to odors than did nonrestrained subjects. Food deprivation did not differentially affect the ORs in restrained and nonrestrained eaters. The ORs, however, tended to be decreased in all of subjects who had had breakfast. Finally, nonrestrained subjects rated food and nonfood odors approximately equal in pleasantness, while the restrained eaters rated food odors as more pleasant than the nonfood odors. These results suggest that restrained eaters must certainly process odor stimuli related to foods, but also suggests that orienting to these salient (informative) cues is restricted. Perhaps in defense of the diet, restrained eaters learn methods/responses (cognitive strategies, instructional sets) to block orienting to food related cues such as odors.

Awareness of the CS-UCS contingency and classical conditioning of skin conductance responses with olfactory CSs.

The possibility of demonstrating acquisition of classically conditioned responses without awareness of the conditioned stimulus-unconditioned stimulus (CS-UCS) contingency using olfactory stimuli with 58 college student subjects was tested. A classical discrimination delay conditioning paradigm was employed, with electric shock as the UCS and two pleasant odors (perfumes) as the conditioned stimuli (CS+ and CS-). Trial-by-trial measures of skin conductance conditioned responses served as dependent variables. A masking task in the form of an olfactory memory task was employed for the purpose of delaying the onset of awareness of the conditioning contingency. Awareness of the conditioning contingency was assessed by a concurrent and a post hoc measure, and subjects who satisfied both criteria were considered aware of the CS-UCS contingency. Conditioning was observed only in the aware subjects, and only after the onset of awareness of the CS+-UCS contingency. Respiratory activity, measured as a check against possible artifacts, had no effect on the SCR measures. It was concluded that the awareness of the CS-UCS contingency is necessary for acquisition of discriminative conditioned responses in humans, regardless of the sensory modality in which CSs are presented. Sex differences in skin conductance measures and performance on the olfactory memory task were observed.

Modification of the acoustic startle-reflex eyeblink: a tool for investigating early and late attentional processes.

The present experiment examined the sensitivity of short and long lead interval startle eyeblink modification to attentional processing. Eighteen college student subjects were presented with a series of intermixed high and low pitched tones and instructed to attend to tones of one pitch and to ignore tones of the other pitch. The majority of the attended and ignored tones served as prepulses for an eyeblink-eliciting burst of white noise presented at lead intervals of 60, 120, 240 and 2000 ms following prepulse onset. Results indicate that both attended and ignored prepulses produce significant startle eyeblink modification: significant blink inhibition at the 60, 120 and 240 ms short lead intervals, and blink facilitation at the 2000 ms long lead interval. In addition, compared with the ignored prepulse, the attended prepulse produced significantly greater blink inhibition at the 120 ms lead interval as well as significantly greater blink facilitation at the 2000 ms lead interval. These results suggest that both short and long lead interval startle eyeblink modification measures may be useful tools for future investigations of the early and later stages of attentional processing.

The psychological significance of human startle eyeblink modification: a review.

The human startle eyeblink reflex is reliably modified by both cognitive and emotional processes. This review provides a comprehensive survey of the current literature on human startle modification and its psychological significance. Issues raised for short lead interval startle inhibition include its interpretation as a measure of protection of processing, sensorimotor gating and early attentional processing. For long lead interval effects, interpretations related to attentional and emotional processing are discussed. Also reviewed are clinical applications to information processing dysfunctions in the schizophrenia spectrum disorders, and to emotional processing disorders. Finally, an integrative summary that incorporates most of the cognitive findings is presented and directions for future research are identified regarding both cognitive and emotional modification of startle.

Autonomic classical conditioning as a function of awareness of stimulus contingencies.

Two groups of 32 college students were presented compound CSs (lights and tones presented simultaneously) during a classical conditioning paradigm. By means of a masking task and verbal instructions, a partially informed group was made aware of only the visual CS's contingency with the UCS, while a fully informed group was made aware of both the visual and auditory contingencies. Autonomic indices of conditioning (electrodermal responses, heart rate, and digital pulse volume) were later measured to the individual component CSs and to various compound CSs. It was found that: (1) the partially informed group exhibited conditioning exclusively to the visual CS+ and to compounds which included the visual CS+, while (2) the fully informed group exhibited conditioning to both visual and auditory CS+s. The results confirm the importance of awareness in human autonomic discrimination classical conditioning. It is suggested that human autonomic conditioning may be usefully conceptualized as an information processing task with the autonomic indices of conditioning reflecting central cognitive processes.

Startle reactivity and PTSD symptoms in a community sample of women.

Exaggerated startle and PTSD symptoms have been investigated primarily in relation to acute or Type I stressors. The present study examined PTSD symptoms and startle eyeblink response in relation to chronic or Type II stressors. Type II stressors were operationally defined as high levels of childhood corporal punishment and high levels of current partner aggression. This study recruited a sample of 52 women from a metropolitan community and administered several questionnaires assessing experience of corporal punishment in childhood, current intimate partner aggression and level of PTSD symptoms. Following questionnaires, women were presented with eight auditory startle probes (white noise). Results showed that both childhood corporal punishment and intimate partner aggression were associated with women's PTSD symptom scores. However, only PTSD symptom scores were associated with reduced startle. Results are discussed in light of Type I and Type II stressors, and recent suggestions in the PTSD literature that a subgroup of individuals may experience physiological suppression rather than heightened physiological reactivity.

On the clinical and cognitive meaning of impaired sensorimotor gating in schizophrenia.

Schizophrenia patients have been shown to have a defective sensorimotor gating process as indexed by impaired prepulse inhibition of the startle eyeblink reflex. Moreover, we have previously reported that schizophrenia patients have dysfunctional attentional modulation of prepulse inhibition. The present experiment combined our previous sample of 14 schizophrenia outpatients and 12 demographically matched control subjects with a new sample of 10 outpatients and 6 control subjects. All participants performed a tone-length judgement task that involved attending to one pitch of tone (the attended prepulse) and ignoring another pitch of tone (the ignored prepulse). During this task the acoustic startle eyeblink reflex was electromyographically recorded from the orbicularis oculi muscle. The results replicated the finding of impaired attentional modulation of prepulse inhibition in the new sample of schizophrenia outpatients compared to demographically matched control subjects. Specifically, the new control group exhibited greater startle modification during the attended prepulse, whereas the new patient group failed to show this differential effect. In addition, impaired prepulse inhibition following the attended prepulse was significantly correlated with heightened delusions, conceptual disorganization, and suspiciousness as measured with the expanded Brief Psychiatric Rating Scale. These correlations were significant with prepulse inhibition to the attended prepulse but not with prepulse inhibition to the ignored prepulse. Impaired prepulse inhibition was not correlated with negative symptoms. All in all, the results support the hypothesis that impaired attentional modulation of startle prepulse inhibition reflects basic neurocognitive processes related to thought disorder in schizophrenia.

Diagnostic utility of autonomic measures for major depressive disorders.

The diagnostic utility (sensitivity, specificity, and overall efficiency) of autonomic nervous system measures in distinguishing hospitalized patients with unipolar depression from age-matched normal controls is reported. Tonic resting skin conductance level (SCL), tonic resting heart rate level (HRL), and the phasic skin conductance and heart rate responses (SCRs and HRRs) to task-related stimuli were used. The overall efficiency of SCL of 70% was generally consistent with previous research. The other measures yielded greater efficiency: 80% for SCR, 90% for HRL, and 83% for HRR. The possible role of autonomic measures in the diagnosis of major depressive episodes is discussed.

Attentional modulation of short- and long-lead-interval modification of the acoustic startle eyeblink response: comparing auditory and visual prestimuli.

Studies in our laboratory have shown that modification of startle by lead stimuli with short- and long-lead-intervals is modulated by stimulus significance. The significant stimulus in a tone duration judgement task generates enhanced short-lead-interval startle inhibition as well as pronounced long-lead-interval startle facilitation. The present study was designed to compare tones with simple visual stimuli as lead stimuli in a counterbalanced within-subjects design (Experiment I) or between-subjects design (Experiment II). The results show that auditory compared to visual lead stimuli generate more short-lead-interval inhibition but comparable amounts of long-lead-interval startle facilitation, which was significantly enhanced on to-be-attended trials independent of sensory modality. The attentional manipulation did not yield short-lead-interval effects in Experiment I, but previously reported attention effects were replicated in Experiment II. The results suggest early modality effects on startle modification, reflected by the differing levels of inhibition. Late effects of both modality and attention, however, seem to reflect a sensory modality independent process in startle modification.