The effect of neuroleptic medication on prepulse inhibition in schizophrenia patients: current status and future issues.

RATIONALE: Prepulse inhibition (PPI) of the startle reflex is a powerful tool for investigating sensorimotor gating in both animals and humans. Evidence of impaired PPI in patients with schizophrenia suggests that PPI performance might serve as a promising model to investigate the neurobiological mechanisms of this disorder. Animal data show that experimentally induced PPI deficits can be removed by the administration of antipsychotic agents. Recent clinical studies suggest that neuroleptic medication is capable of improving deficient PPI performance in schizophrenia patients as well. OBJECTIVES: The present paper reviews the published data on PPI performance in schizophrenia patients, focussing on medication effects. Using a modified meta-analytic approach, the consistency of PPI deficits in schizophrenia patients across studies is explored. In particular, methodological issues of defining PPI deficits and assessing PPI improvements are considered. METHOD: Literature search produced 12 original studies that investigated PPI performance in schizophrenia patients using comparable experimental conditions. Percentage change scores were calculated to compare the actual amount of PPI observed in schizophrenia patients and healthy controls across studies. RESULTS: Results revealed that the amount of PPI in medicated schizophrenia patients was fairly consistent across all studies. For medicated schizophrenia patients, the amount of PPI varied between 30% and 65% for the critical lead intervals. Moreover, medicated patients showed around 20% less PPI than healthy controls. Whether these group differences were statistically significant depended on the composition of the control group that showed large variability across studies. CONCLUSIONS: To delineate the effects of neuroleptic medication on PPI performance more precisely, future research should not further rely on between-group comparisons. Rather, future clinical research should take advantage of longitudinal designs to disentangle state-dependent medication effects from more stable, trait-linked factors that contribute to PPI deficits in schizophrenia.

Affective picture processing: the late positive potential is modulated by motivational relevance.

Recent studies have shown that the late positive component of the event-related-potential (ERP) is enhanced for emotional pictures, presented in an oddball paradigm, evaluated as distant from an established affective context. In other research, with context-free, random presentation, affectively intense pictures (pleasant and unpleasant) prompted similar enhanced ERP late positivity (compared with the neutral picture response). In an effort to reconcile interpretations of the late positive potential (LPP), ERPs to randomly ordered pictures were assessed, but using the faster presentation rate, brief exposure (1.5 s), and distinct sequences of six pictures, as in studies using an oddball based on evaluative distance. Again, results showed larger LPPs to pleasant and unpleasant pictures, compared with neutral pictures. Furthermore, affective pictures of high arousal elicited larger LPPs than less affectively intense pictures. The data support the view that late positivity to affective pictures is modulated both by their intrinsic motivational significance and the evaluative context of picture presentation.

Brain potentials in affective picture processing: covariation with autonomic arousal and affective report.

Emotionally arousing picture stimuli evoked scalp-recorded event-related potentials. A late, slow positive voltage change was observed, which was significantly larger for affective than neutral stimuli. This positive shift began 200-300 ms after picture onset, reached its maximum amplitude approximately 1 s after picture onset, and was sustained for most of a 6-s picture presentation period. The positive increase was not related to local probability of content type, but was accentuated for pictures that prompted increased autonomic responses and reports of greater affective arousal (e.g. erotic or violent content). These results suggest that the late positive wave indicates a selective processing of emotional stimuli, reflecting the activation of motivational systems in the brain.

Probing affective pictures: attended startle and tone probes.

Reflexive eyeblinks to a startle probe vary with the pleasantness of affective pictures, whereas the corresponding P300 varies with emotional arousal. The impact of attention to the probe on these effects was examined by varying task and probe type. Probes were either nonstartling tones or startling noises presented during affective picture viewing. Half the participants performed a task requiring attention to the probes; the other participants were told to ignore the probes. Blinks to the startle probe varied with picture pleasantness for both task and nontask conditions. In contrast, P300 magnitudes for both startle and tone probes were reduced during emotionally arousing pictures, irrespective of pleasantness, in task and nontask conditions. Further, attending to the startle probe prompted an augmentation of N100 during unpleasant pictures. The data suggest that affective modulation of probe responses reflects obligatory processes in picture perception.

Probe P3 and blinks: two measures of affective startle modulation.

Two concurrent measures of the evoked startle response, the elicited blink reflex and the event-related potential, were measured while individuals viewed pictures that varied in pleasure and arousal. Replicating previous findings, the blink response was modulated by picture pleasantness, with larger reflexes elicited in the context of viewing unpleasant versus pleasant pictures. However, the probe P3 was primarily modulated by picture arousal, with smaller P3 responses elicited when viewing affective (pleasant or unpleasant) than when viewing neutral pictures. Both modulatory effects were sustained for probes presented in a subsequent picture imagery period. These data suggest that two measurable responses to the same startle probe are differentially modified by emotional context, with blink magnitude varying with pleasure and probe P3 varying with stimulus arousal.

Neurophysiological differences between perception and imagery.

The present study was designed to examine brain activity underlying mental imagery is conceptualized as behavior guided by internal representation only, the activity of the prefrontal lobes was assumed to be a measure of differentiation of imagery from perception. Twenty-one subjects were requested to observe and imagine a swinging pendulum and to touch and imagine a coshball in separate trials. The EEG was recorded from 15 standard electrode sites and analyzed with (1) traditional alpha power and (2) an estimation of dimensional complexity (a measure derived from nonlinear dynamics). Both EEG measures revealed expected object-related differences during perception as well as during imagery. The visual pendulum showed relative to the tactile coshball increased dimensional complexity and less alpha power at parietal and frontal sites. However, only the EEG dimension supported the main hypothesis: Imagery resulted in increased prefrontal dimensional complexity in comparison to perception independent of the modality of the image. In contrast, for alpha power the difference between imagery and perception was due to stimulus modality.

Positive shifts of event-related potentials: a state of cortical disfacilitation as reflected by the startle reflex probe.

Cortical positivity as measured by slow event-related potentials is assumed to represent a decreased excitability of cortical networks and suppression of their behavioral-cognitive output. The blink reflex probe is a commonly used defensive electromyographic response whose amplitude was shown to be modulated by emotional and attentional orientation. It was used here as an indicator of cortico-subcortical excitation. In study 1, 33 healthy subjects took part in a continuous performance test (CPT). Event-related potentials were recorded from 15 standard scalp locations. Acoustic startling noise bursts were delivered during conditions that required either performance of prepared motor responses (Go), inhibition of prepared motor responses (NoGo), or had no motor significance (Irrelevant condition). During the NoGo condition, EEG surface potentials showed a widespread P300-like positivity with a central maximum. Startle responses were inhibited during the NoGo condition as compared to the Irrelevant condition. In study 2 (21 subjects) the same format was used, except that the startle reflex was elicited visually. Startle reflexes again showed smaller magnitude during the NoGo condition, which evoked larger positivity at central sites in comparison to the Irrelevant condition. The relationship between positivity in the EEG and inhibited startle responses is in line with the hypothesis that positive EEG shifts reflect a state of cortical disfacilitation.