Peter F. Liddle

Comparing Functional (PET) Images: The Assessment of Significant Change

Statistical parametric maps (SPMs) are potentially powerful ways of localizing differences in regional cerebral activity. This potential is limited by uncertainties in assessing the significance of these maps. In this report, we describe an approach that may partially resolve this issue. A distinction is made between using SPMs as images of change significance and using them to identify foci of significant change. In the first case, the SPM can be reported nonselectively as a single mathematical object with its omnibus significance. Alternatively, the SPM constitutes a large number of repeated measures over the brain. To reject the null hypothesis, that no change has occurred at a specific location, a threshold adjustment must be made that accounts for the large number of comparisons made. This adjustment is shown to depend on the SPMs smoothness. Smoothness can be determined empirically and be used to calculate a threshold required to identify significant foci. The approach models the SPM as a stationary stochastic process. The theory and applications are illustrated using uniform phantom images and data from a verbal fluency activation study of four normal subjects.

A PET study of word finding

We have used PET in conjunction with psychological activations to identify cortical areas involved in the intrinsic activation of word representations. In four normal subjects intrinsic generation of a word (verbal fluency) was associated with an increase in left dorsolateral prefrontal cortical activity (BA 46) and a bilateral decrease in activity in auditory and superior temporal cortices. Conversely, when subjects made lexical decisions about words that were heard, there was an increase in superior temporal activity with no change in area 46. We suggest that the superior temporal regions are the site of stored word representations and that inhibitory modulation of these areas by the left prefrontal cortex is the basis of intrinsic word generation.

Error processing and the rostral anterior cingulate: An event‐related fMRI study

The anterior cingulate is believed to play a crucial role in the regulation of thought and action. Recent evidence suggests that the anterior cingulate may play a role in the detection of inappropriate responses. We used event-related functional magnetic resonance imaging techniques to examine the neural responses to appropriate (correct rejects and correct hits) and inappropriate (errors of commission) behavioral responses during a go/no-go task. Analyses of the inappropriate responses revealed extensive activation in the rostral anterior cingulate cortex and in the left lateral frontal cortex. These areas were not activated for correctly classified trials (correct rejects and correct hits). These data suggest that the rostral anterior cingulate and left lateral frontal cortex are integral components of the brains error checking system.

Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging

BACKGROUND Psychopathy is a complex personality disorder of unknown etiology. Central to the disorder are anomalies or difficulties in affective processing. METHODS Functional magnetic resonance imaging was used to elucidate the neurobiological correlates of these anomalies in criminal psychopaths during performance of an affective memory task. RESULTS Compared with criminal nonpsychopaths and noncriminal control participants, criminal psychopaths showed significantly less affect-related activity in the amygdala/hippocampal formation, parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate gyri. Psychopathic criminals also showed evidence of overactivation in the bilateral fronto-temporal cortex for processing affective stimuli. CONCLUSIONS These data suggest that the affective abnormalities so often observed in psychopathic offenders may be linked to deficient or weakened input from limbic structures.

Event-related fMRI study of response inhibition

Event‐related functional magnetic resonance imaging (erfMRI) was employed to measure the hemodynamic response during a Go/No‐go task in 16 healthy subjects. The task was designed so that Go and No‐go events were equally probable, allowing an unbiased comparison of cerebral activity during these two types of trials. In accordance with prediction, anterior cingulate was active during both the Go and No‐go trials, dorsolateral and ventrolateral prefrontal cortex was more active during the No‐go trials, while primary motor cortex, supplementary motor area, pre‐motor cortex and cerebellum were more active during Go trials. These findings are consistent with the hypothesis that the anterior cingulate cortex is principally engaged in making and monitoring of decisions, while dorsolateral and ventral lateral prefrontal sites play a specific role in response inhibition. Hum. Brain Mapping 12:100–109, 2001.

Schizophrenic syndromes, cognitive performance and neurological dysfunction

In a sample of chronic schizophrenic patients, a group of symptoms which included poverty of speech and lack of spontaneous movement was found to be associated with poor performance in tests of conceptual thinking, object naming and long-term memory, and also with cortical neurological signs. A second group of symptoms which included formal thought disorder and inappropriate affect was associated with poor performance in tests of concentration, immediate recall and word learning, and with cortical neurological signs. The findings suggest that these two syndromes are associated with dysfunction at two different sites within the frontal lobes. A third group of symptoms, comprising various delusions and hallucinations, was associated with poor figure-ground perception, and might reflect temporal lobe dysfunction.

Neural sources involved in auditory target detection and novelty processing: an event-related fMRI study.

We used event-related functional magnetic resonance imaging (erfMRI) techniques to examine the cerebral sites involved with target detection and novelty processing of auditory stimuli. Consistent with the results from a recent erfMRI study in the visual modality, target processing was associated with activation bilaterally in the anterior superior temporal gyrus, inferior and middle frontal gyrus, inferior and superior parietal lobules, anterior and posterior cingulate, thalamus, caudate, and the amygdala/hippocampal complex. Analyses of the novel stimuli revealed activation bilaterally in the inferior frontal gyrus, insula, inferior parietal lobule, and in the inferior, middle, and superior temporal gyri. These data suggest that the scalp recorded event-related potentials (e.g., N2 and P3) elicited during similar tasks reflect an ensemble of neural generators located in spatially remote cortical areas.

PLASTIC TRANSFORMATION OF PET IMAGES

A theory and technique are presented that allow nonlinear resampling of positron emission tomography data to remove nonlinear differences in brain shape. The resampling is determined empirically by a function relating the observed image and a desired template. The validity, reliability, and precision of the plastic transformation are compared with linear rescaling alone, within, and between subjects.

Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

The insular cortex is one of the brain regions that show consistent abnormalities in both structural and functional neuroimaging studies of schizophrenia. In healthy individuals, the insula has been implicated in a myriad of physiologic functions. The anterior cingulate cortex (ACC) and insula together constitute the salience network, an intrinsic large-scale network showing strong functional connectivity. Considering the insula as a functional unit along with the ACC provides an integrated understanding of the role of the insula in information processing. In this review, we bring together evidence from imaging studies to understand the role of the salience network in schizophrenia and propose a model of insular dysfunction in psychosis.

Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or disease specificity?

Neurophysiological deficits in the left dorsolateral prefrontal cortex (DLPFC) have been described in positron emission tomography studies of schizophrenia and depression. In schizophrenia and depression this deficit has been associated with the syndromes of psychomotor poverty and psychomotor retardation, respectively. Such findings lead to a prediction that DLPFC dysfunction is symptom rather than disease related. This prediction was empirically tested in a retrospective study that pooled data from 40 patients meeting research diagnostic criteria for depression and 30 patients meeting DSM-III R criteria for schizophrenia. The patients were categorised into those with and without poverty of speech, a symptom that is an observable manifestation of psychomotor impairment. The profile of regional cerebral blood flow (rCBF), measured in all subjects under resting conditions, was subsequently compared in these two groups. Patients with poverty of speech had significantly lower rCBF in the left DLFPC. This reduction of rCBF was independent of diagnosis. The findings support the view that the study of symptoms, or symptom clusters, can provide information additional to that of traditional diagnostic systems in the study of the major psychoses.