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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.

The current protocol can be used to examine selective attention. It has been used to acquire behavioral performance data in neurologically healthy normal control subjects and schizophrenic patients. A modified version, also described here, has been used to acquire functional neuroimaging data in normal subjects using positron emission tomography. Subject response accuracy and reaction times are recorded while subjects detect visual stimuli in either hemifield (left vs. right of a fixation point) or along the vertical meridian (above or below fixation). The lateralized presentation of stimuli permits the study of hemispheric specialization for selective attentional processes. Attentional load is manipulated by presenting larger-sized target stimuli alone (i.e., the letter 'O') or smaller-sized target stimuli surrounded by flanking letters. This protocol report includes a description of subject exclusion criteria, procedural details, relevant experimental conditions and variables, suggestions for data analysis, expected results, and a discussion of the protocol's significance for attentional research along with suggestions for future research.

A letter-identification task, previously demonstrated to show activation of the pulvinar nucleus of the thalamus with fluodeoxyglucose position emission tomography, was administered to 20 normal volunteers. The letter to be detected could appear alone as a big stimulus or as a small one stimulus surrounded by flanking letters. To test for a hemispheric specialization for filtering processes, the stimuli were displayed horizontally, either in the left or in the right hemifield, or vertically, either above or below the fixation point. In addition, to study the effect of cognitive processes on selective attention resources, we varied the feedback conditions, by delivering or not delivering a blue flash in cases of misses or mistakes. The results show a significant interaction between the type of stimulus (alone or surrounded by flankers) and the hemifield of presentation (left or right) only in the condition where the subjects were presented stimuli horizontally without any feedback. In this condition, reaction times (RTs) were shorter in the left hemifield than in the right hemifield for single stimuli, whereas for stimuli surrounded by flankers, the opposite pattern was observed, that is, shorter RT in the right hemifield than in the left one. The present findings suggest a hemispheric specialization for selective attention, in particular at the subcortical level.

Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography in 10 patients with schizotypal personality disorder (SPD) and nine age- and sex-matched normal volunteers. Subjects performed both the Wisconsin Card Sort Test (WCST) and a control task, the Symbol Matching Test (SMT). Four-way analyses of variance were performed to assess relative rCBF of the prefrontal cortex and of the medial temporal region. Normal volunteers showed more marked activation in the precentral gyrus, while SPD patients showed greater activation in the middle frontal gyrus. Relative flow in the left prefrontal cortex was correlated with better WCST performance in normal volunteers. SPD patients, however, showed no such correlations in the left prefrontal cortex, but demonstrated correlations of good and bad performance with CBF in the right middle and inferior frontal gyrus, respectively. Thus, at least some SPD patients demonstrate abnormal patterns of prefrontal activation, perhaps as a compensation for dysfunction in other regions.

Twenty-five schizophrenic patients, fourteen adults with a history of infantile autism, and twenty normal controls performed a test of sustained attention, the degraded stimulus continuous performance test (CPT), during the 35 minute 18-fluoro-2-deoxyglucose uptake period preceding positron emission tomographic (PET) scan acquisition. This is the first analysis comparing correlations between glucose metabolic rate (GMR) for selected regions and CPT performance. CPT performance differed in controls and schizophrenics, but autistics did not differ from either group. In controls and schizophrenic patients, task performance correlated with GMR in medial superior frontal gyrus and lateral inferior temporal gyrus, suggesting that activation of those regions is important in the normal performance of the task and that damage to those regions, which also showed low GMR in schizophrenics, contributes to the attentional dysfunction in schizophrenia. Also, schizophrenics showed negative correlations of task performance with anterior cingulate activity suggesting that overactivity of that region, which is involved in mental effort and whose GMR was low in our larger study of schizophrenia, impairs task performance in schizophrenics. Autistic patients showed negative correlations of medial frontal cortical GMR with attentional performance, suggesting that neuronal inefficiency in that region may contribute to poor performance.

Eighty-three patients with schizophrenia and 47 healthy controls received positron emission tomography (PET) with 18F-2-deoxyglucose uptake while they were executing the Continuous Performance Test (CPT). The entire cortex was divided into 16 regions of interest in each hemisphere, four in each lobe of the brain, and data from corresponding right and left hemispheric regions were averaged. Data from the schizophrenic patients were subjected to a factor analysis, which revealed five factors that explained 80% of the common variance. According to their content, the factors were identified and labelled 'parietal cortex and motor strip', 'associative areas', 'temporal cortex', 'hypofrontality' (which included midfrontal and occipital areas) and 'frontal cortex'. Hemispheric asymmetry was only confirmed for the temporal cortex. Factor weights obtained in the schizophrenic group were applied to the metabolic data of the healthy controls and factors scales computed. Schizophrenics were significantly more hypofrontal than the controls, with higher values on the 'parietal cortex and motor strip' factor and a trend towards higher values in the temporal cortex. A canonical discriminant analysis confirmed that the 'hypofrontality' and 'parietal cortex and motor strip' factors accurately separated the schizophrenic group from the healthy controls. Hemispheric asymmetry was only confirmed for the temporal lobe. Significantly higher factor scores for the left temporal lobe in schizophrenics than in normals were obtained when calculated for the right and left hemisphere separately. Taken together, our results confirm the importance of hypofrontality as a pattern of cortical metabolic rate and point to the potential importance of parietal and motor strip function in schizophrenia.

Sixteen high-functioning adults with a history of childhood autism and 26 normal control subjects underwent [18F]fluoro-2-deoxyglucose positron-emission tomography to assess regional cerebral glucose metabolic rate (GMR). Autistic patients had a left > right anterior rectal gyrus asymmetry, as opposed to the normal right > left asymmetry in that region. Patients also showed low GMR in the left posterior putamen and high GMR in the right posterior calcarine cortex. Brain regions with GMR > 3 SD from the normal mean were more prevalent in patients than in control subjects. This variable pattern of abnormal activity is consistent with heterogeneous neurophysiological etiology; group differences in striatum and cortex may represent a final common pathway.

Multiple studies have demonstrated prefrontal dysfunction among schizophrenics. The prefrontal cortex does not function in isolation, but instead relies on extensive connections with other brain areas. Functional relationships between cortical areas were assessed by calculating the coherences between different scalp electroencephalogram (EEG) signals recorded from 13 unmedicated male patients with schizophrenia and 9 normal male subjects. Alpha-band coherences linked to prefrontal areas in schizophrenic patients were about the same as those of normal controls when subjects were cognitively "at rest," but they were reduced for certain electrode pairs in the former group when performing the degraded-stimulus continuous performance test. Most of these findings were not accounted for by changes in alpha power, suggesting that "cortical circuits" extending beyond prefrontal areas may be disrupted in schizophrenia.

Positron emission tomographic scans were recorded from human subjects following an object-identification task, one version of which required attentional selection and the other version of which did not. In one experimental session, the attention-demanding displays were presented in the left visual field and the nonattention displays were presented in the right visual field. In a second session, the sides of the displays were reversed. Analysis of the scans indicated that, averaged across the 2 sessions, the pulvinar showed greater glucose uptake when it was contralateral to the display of the selective attention task than when it was contralateral to the display of the nonattention task. The pattern of the data indicated that the degree of the attention task effect on pulvinar glucose uptake may differ between the hemispheres. In view of known connections between the pulvinar and cortical areas that mediate object identification, the present finding suggests that the pulvinar operates interactively with these cortical structures when an identification process demands selective attention.

Twenty patients with major depressive disorder were studied with evoked potential (EP) topographic mapping after receiving placebo, imipramine, or amoxapine for 2 days in a random-assignment, double-blind design. Patients performed the Continuous Performance Test (CPT), a visual vigilance test. The stimuli were the digits 0-9, with 0 a target to be responded to with a button press. EPs were recorded from 32 channels and were averaged separately for detected and undetected targets and for false positives and correctly identified nontargets (no button press). Twenty-one normal controls were also tested. Amoxapine enhanced N120 amplitude in midline parietal and right parietal cortex where selective attention effects have been found to be greatest in studies of normal controls. Both amoxapine and imipramine enhanced differences in P200 between target and nontarget stimuli in comparison to placebo, with amoxapine differences again being greatest over midline parietal locations. CPT performance was significantly better on amoxapine than placebo.

15 patients with schizophrenia and nine normal volunteers had 32 channel topographic EEG recorded for spectral analysis during the uptake of 18-F-deoxyglucose (FDG) for positron emission tomography (PET). Both patients and controls performed the Continuous Performance Test, a visual vigilance task, during FDG uptake. EEG was also obtained during an initial pre-FDG resting period. Each EEG epoch was individually inspected for eye movement artifacts. Analysis confirmed increased delta activity in the frontal region of patients with schizophrenia in comparison to normal controls, and a significant correlation between increased frontal delta and relative reduction in frontal lobe metabolism among patients with schizophrenia. This finding of increased delta is consistent with PET, blood flow and topographic EEG studies of schizophrenia, suggesting reduced frontal activity.

Deficient sustained attention is a symptom of hyperactivity that can be improved by stimulant medication. Recently, amphetamine has been shown to increase detections during a vigilance task in both normal and hyperactive boys. The present study applied signal detection analysis to the vigilance performance of 15 hyperactive and 14 normal boys dsivided into two age groups (6-9 and 10-12). A computerized continuous performance test was administered under amphetamine and placebo. Overall group comparisons indicated that perceptual sensitivity or d' was higher for the normal boys and the older groups, and analysis of drug treatments showed that amphetamine significantly increased d'. Interactions between drugs and age groups demonstrated that amphetamine affected the younger boys to a significantly greater degree than the older children for both d' and response bias or beta. It is notable that the results were essentially parallel for both normal and hyperactive children.