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Background: Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry., Methods: Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images., Results: Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate., Conclusions: These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.

This study of 31 college students employed the startle eye-blink modification (SEM) technique to index both early and later stages of attentional processing during a memory-load version of the Continuous Performance Test (CPT). Participants viewed a series of digits and pressed a button after the digit 7 of each 3-7 sequence. A startling noise burst was presented either 120 or 1,200 ms following three preselected prepulses: target (3), nontarget (non-3 and non-7 digits), or target plus distractor (3 and simultaneous tone distractor). Greater startle inhibition occurred 120 ms following target and target-plus-distractor prepulses compared with nontargets, indicating early selective attention. No difference was observed between SEM during target and target-plus-distractor prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the three prepulse types produced nondifferential inhibition, suggesting that modality-specific selective attention occurs in anticipation of the presentation of the next CPT prepulse. These findings indicate that SEM distinguishes between different early selective attention and later anticipatory attention subprocesses underlying the CPT.

Attentional modulation of the startle reflex was studied in 16 unmedicated schizophrenia patients and 15 control individuals during the 18F-2-deoxyglucose uptake period for positron emission tomography. In a task involving attended, ignored, and novel tones that served as prepulses, control individuals showed greater prepulse inhibition (PPI) at 120 ms and greater prepulse facilitation at 4,500 ms during attended than during ignored prepulses; the amount of PPI and facilitation during novel prepulses was intermediate. In contrast, patients failed to show differential PPI at 120 ms and tended to show greater facilitation at 4,500 ms during novel prepulses. For control individuals, greater PPI was associated with higher relative metabolic activity rates in prefrontal (Brodmann Areas 8, 9, and 10 bilaterally) and lower in visual cortex. Patients showed this relationship only for Area 10 on the left. Patients also had low metabolism in superior, middle, and inferior prefrontal cortex. Consistent with animal models, our results demonstrate the importance of the functional integrity of prefrontal cortex to PPI modulation.

Attentional modulation of startle eyeblink was studied in college students putatively at risk for psychosis and in normal controls. At-risk subjects had extreme scores on scales for either anhedonia or perceptual aberration-magical thinking (per-mags). Subjects were presented with to-be-attended and to-be-ignored tones; white noise startle probes were presented at lead intervals of 60, 120, 240, or 2,000 ms following the onset of attended and ignored tones and during intertone intervals. Controls showed greater inhibition of startle blink at 120 ms and greater facilitation at 2,000 ms during to-be-attended than to-be-ignored tone, demonstrating attentional modulation of prepulse inhibition and facilitation. Both at-risk groups showed normal overall levels of early inhibition and late facilitation. However, per-mags failed to show attentional modulation of either inhibition at 120 ms or facilitation at 2,000 ms; anhedonics showed no modulation of inhibition and modulation of facilitation was delayed in development. The results for the per-mags are strikingly similar to those observed in schizophrenic patients and suggest that these deficits index a trait-linked vulnerability to disorders in the schizophrenic spectrum.

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.