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We report a random-effects analysis of an event-related fMRI study (n = 28) of cerebral activity during the reading of sentences that ended with a word that was either congruent or incongruent with the previous sentence context. Event-related potential studies have shown that this task elicits a late negativity peaking around 400 ms poststimulus (N400) that is larger for incongruent than for congruent sentence endings. A direct comparison of the activation for incongruent words versus that for congruent words revealed significantly greater activation for incongruent words than congruent words in bilateral inferior frontal and inferio-medial temporal cortex, left lateral frontal cortex, left posterior fusiform gyrus, bilateral motor cortex, and supplementary motor area. These results are consistent with data from intracranial electrical recording studies of the N400 electrical potential. The results are discussed as they relate to the localization of the cerebral sites underlying semantic processing in general and the localization of the scalp recorded N400 event-related potential in particular.

Recent hemodynamic imaging studies have shown that processing of low probability task-relevant target stimuli (i.e., oddballs) and low probability task-irrelevant novel stimuli elicit widespread activity in diverse, spatially distributed cortical and subcortical systems. The nature of this distributed response supports the model that processing of salient and novel stimuli engages many brain regions regardless of whether said regions were necessary for task performance. However, these latter neuroimaging studies largely employed small sample sizes and fixed-effect analyses, limiting the characterization and inference of the results. The present study addressed these issues by collecting a large sample size (n = 100) and employed random effects statistical models. Analyses were also conducted to determine the inter-subject reliability of the hemodynamic response and the effects of gender and age on target detection and novelty processing. Group data demonstrated highly significant activation in all 34 specified regions of interest for target detection and all 24 specified regions of interest for processing of novel stimuli. Neither age nor gender systematically influenced the results. These data are discussed within the context of a model that proposes that the mammalian brain has evolved to adopt a strategy of engaging distributed neuronal systems when processing salient stimuli despite the low probability that many of these brain regions are required for successful task performance. This process may be termed 'adaptive reflexive processing.' The implications of these results for interpreting functional MRI studies are discussed.

Healthy subjects show increased activation in left temporal lobe regions in response to speech sounds compared to complex nonspeech sounds. Abnormal lateralization of speech-processing regions in the temporal lobes has been posited to be a cardinal feature of schizophrenia. Event-related fMRI was used to test the hypothesis that schizophrenic patients would show an abnormal pattern of hemispheric lateralization when detecting speech compared with complex nonspeech sounds in an auditory oddball target-detection task. We predicted that differential activation for speech in the vicinity of the superior temporal sulcus would be greater in schizophrenic patients than in healthy subjects in the right hemisphere, but less in patients than in healthy subjects in the left hemisphere. Fourteen patients with schizophrenia (selected from an outpatient population, 2 females, 12 males, mean age 35.1 years) and 29 healthy subjects (8 females, 21 males, mean age 29.3 years) were scanned while they performed an auditory oddball task in which the oddball stimuli were either speech sounds or complex nonspeech sounds. Compared to controls, individuals with schizophrenia showed greater differential activation between speech and nonspeech in right temporal cortex, left superior frontal cortex, and the left temporal-parietal junction. The magnitude of the difference in the left temporal parietal junction was significantly correlated with severity of disorganized thinking. This study supports the hypothesis that aberrant functional lateralization of speech processing is an underlying feature of schizophrenia and suggests the magnitude of the disturbance in speech-processing circuits may be associated with severity of disorganized thinking.

A recent theoretical account delineated the role of the anterior cingulate cortex (ACC) in cognitive control as the detection of conflict between competing information streams. Using functional magnetic resonance imaging, we examined the activity of this brain structure during different forms and degrees of conflict between the word and the color dimensions of Stroop stimuli. Overall, our results showed a dissociation between the degree of conflict and ACC activation. More specifically, although ACC activation was very extensive when print color interfered with word reading performance, the level of conflict, as measured by reaction time costs, was only moderate compared to other conditions. These results suggest that either the ACC is differentially sensitive to various types of conflict or its function should be extended to include other cognitive constructs, such as resolution of prior inhibition.

Schizophrenia is a diffuse brain disease that affects many facets of cognitive function. One of the most replicated findings in the neurobiology of schizophrenia is that the event-related potentials to auditory oddball stimuli are abnormal, suggesting abnormalities in attention and memory processes. Recently, we have used event-related fMRI to elucidate the abnormal neural architecture underlying target detection in chronic patients with schizophrenia. Compared with control participants, selective deficits were observed in the lateral frontal cortex, thalamus, superior temporal gyms, cingulate, and parietal lobes. Here we present the results of a similar study from a group of first-episode psychotic patients. Consistent with the results observed with chronic medicated patients, diffuse hemodynamic abnormalities were observed in the first episode patients in multiple cortical and subcortical sites. The first episode patients were also tested six weeks after treatment with atypical neuroleptics. Improvements in neural function, manifest as significantly larger hemodynamic responses to target stimuli, were observed in bilateral amygdala, hippocampus, dorsolateral prefrontal cortex, and supramarginal gyms and in the posterior cingulate. These data are consistent with the hypothesis that schizophrenia is characterized by a widespread pathological process affecting many cerebral areas. The data also suggest atypical neuroleptics improve neural function at diverse cerebral sites.

Introduction Psychopathy is a personality disorder characterised by disturbance in affective, interpersonal, and behavioural domains. Typically, it is the behavioural disturbances, including impulsivity, poor behavioural controls, and persistent contravention of societal norms, that brings the psychopath to the attention of society. The psychopaths’ behavioural disturbance has been conceptualized as arising from impaired response inhibition. Event-related potential research (Kiehl et al., 2000, Biological Psychiatry, 48) suggests that psychopathy is associated with abnormal neural activity during suppression of inappropriate responses. We used event-related fMRI to elucidate the neurobiological correlates of response inhibition during performance of a Go/NoGo task. Using this task in healthy controls Liddle et al. (2001, Human Brain Mapping, 12) demonstrated the importance of lateral frontal cortex in response inhibition. We hypothesised that psychopaths would show less activation in lateral frontal cortex during processing of NoGo stimuli than would healthy controls. Methods Fourteen psychopaths were recruited from a maximum-security prison and compared with fourteen healthy control participants selected from the general population. Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (PCL-R) (Hare, 1991). Groups were matched for age, parental socioeconomic status, and IQ. All participants were right-handed, native English speakers, without history of head injury or psychotic illness. Task procedures are as described in Liddle et al. (2001). The visual stimuli for the Go and NoGo trials were the letters ‘X’ and ‘A’ respectively, presented for a period of 250 msecs each. Each trial commenced with a descending count of asterisks in order to increase motor response preparation. Twenty-four Go and 24 NoGo trials were randomly presented in a single scanning session. Imaging was performed using a General Electric 1.5 T whole body system fitted with a Horizon echo-speed upgrade. Functional image volumes were collected with a gradient-echo sequence (TR/IE 2500/50 ms, flip angle 90”, FOV 24x24 cm, 64x64 matrix, 62.5 kHz bandwidth, 3.75x3.75 mm in plane resolution, 4 mm slice thickness, 29 slices). Functional images were realigned, normalised, and smoothed using Statistical Parametric Mapping (SPM99). Event-related responses to the Go and NoGo stimuli were modeled with a synthetic haemodynamic response function composed of two gamma functions and their temporal derivatives. To test the hypothesis of reduced activation in lateral frontal cortex in psychopaths, we tested for significant group differences in activation during NoGo trials within I0mm diameter spherical regions centred on the loci of activation in lateral frontal cortex reported by Liddle et al. (2001). Results No significant differences between groups in accuracy of performance were observed. In accordance with the hypothesis, psychopaths exhibited significantly less activation in lateral frontal cortex, bilaterally, than healthy controls during NoGo trials: xyz = -48 -4 52, Z=3.78; xyz = 36 0 36, Z=3.66. Discussion We have demonstrated that inhibiting a behavioural response is associated with less lateral frontal activation in psychopaths compared to healthy control subjects. This is consistent with previous electrophysiological findings. Kiehl et al. (2000) reported that psychopaths exhibited a reduced amplitude of the frontal negative potential (N275) during NoGo trials. Taken together, these findings indicate that the cerebral mechanism for response inhibition is impaired in psychopathy.