Evidence against functionalism from neuroimaging of the alien colour effect in synaesthesia.

Coloured hearing synaesthetes experience colours to heard words, as confirmed by reliability of self-report, psychophysical testing and functional neuroimaging data. Some also describe the 'alien colour effect' (ACE): in response to colour names, they experience colours different from those named. We have previously reported that the ACE slows colour naming in a Stroop task, reflecting cognitive interference from synaesthetically induced colours, which depends upon their being consciously experienced. It has been proposed that the hippocampus mediates such consciously experienced conflict. Consistent with this hypothesis, we now report that, in functional magnetic resonance imaging of the Stroop task, hippocampal activation differentiates synaesthetes with the ACE from those without it and from non-synaesthete controls. These findings confirm the reality of coloured hearing synaesthesia and the ACE, phenomena which pose major challenges to the dominant contemporary account of mental states, functionalism. Reductive functionalism identifies types of mental states with causal roles: relations to inputs, outputs and other states. However, conscious mental states, such as experiences of colour, are distinguished by their qualitative properties or qualia. If functionalism is applied to conscious mental states, it identifies the qualitative type of an experience with its causal role or function. This entails both that experiences with disparate qualitative properties cannot have the same functional properties, and that experiences with disparate functional properties cannot have the same qualitative properties. Challenges to functionalism have often denied the first entailment. Here, we challenge the second entailment on empirical grounds. In coloured hearing synaesthesia, colour qualia are associated with both hearing words and seeing surfaces; and, in the ACE, these two functions act in opposition to one another. Whatever its merits as an account of other mental states, reductive functionalism cannot be the correct account of conscious experiences.

An fMRI study of verbal self-monitoring: neural correlates of auditory verbal feedback.

The ability to recognize one's own inner speech is essential for a sense of self. The verbal self-monitoring model proposes that this process entails a communication from neural regions involved in speech production to areas of speech perception. According to the model, if the expected verbal feedback matches the perceived feedback, then there would be no change in activation in the lateral temporal cortices. We investigated the neural correlates of verbal self-monitoring in a functional magnetic resonance (fMRI) study. Thirteen healthy male volunteers read aloud presented adjectives and heard their auditory feedback which was experimentally modified. Decisions about the source of the feedback were made with a button-press response. We used a 'clustered' fMRI acquisition sequence, consisting of periods of relative silence in which subjects could speak aloud and hear the feedback in the absence of scanner noise, and an event-related design which allowed separate analysis of trials associated with correct attributions and misattributions. Subjects made more misattribution responses when the feedback was a distorted version of their voice. This condition showed increased superior temporal activation relative to the conditions of hearing their own voice undistorted and hearing another person's voice. Furthermore, correct attributions during this condition were associated with greater temporal activation than misattributions. These findings support the self-monitoring model as mismatches between expected and actual auditory feedback were associated with greater temporal activation.

Effects of psychotic state and task demand on prefrontal function in schizophrenia: an fMRI study of overt verbal fluency.

OBJECTIVE: Impaired prefrontal cortical function is regarded as a central feature of schizophrenia. Although many neuroimaging studies have found evidence of abnormal prefrontal activation when patients with schizophrenia perform cognitive tasks, the extent to which this abnormality depends on the presence of active psychotic symptoms and on the demands of the task is unclear. The authors tested the hypothesis that prefrontal functional abnormalities in schizophrenia would be more evident in patients with active psychosis than in patients who were in remission and would become more apparent in the face of increasing task demands. METHOD: The authors used functional magnetic resonance imaging (fMRI) to examine prefrontal cortical activity during a paced letter verbal fluency task in three groups of subjects: acutely psychotic patients with schizophrenia, schizophrenia patients in remission, and healthy volunteers. Online subject performance was measured by utilizing a clustered fMRI acquisition sequence that allowed overt verbal responses to be made in the relative absence of scanner noise. RESULTS: Patients with schizophrenia showed less activation than the healthy comparison subjects in the anterior cingulate and the inferior frontal and right middle frontal cortices, independent of psychotic state and task demand. Acutely psychotic patients showed less activation than the healthy comparison subjects, but these differences were less marked than the differences between the patients in remission and the healthy comparison subjects. Acutely psychotic patients had less activation than the comparison subjects in the anterior cingulate but no significant difference in lateral prefrontal activation. Increasing task demand led to greater anterior cingulate and middle frontal activation in patients with active psychosis than in patients in remission. CONCLUSIONS: Schizophrenia is associated with impaired prefrontal function, but its manifestation depends on the severity of psychotic symptoms and the level of task difficulty.

Misattribution of external speech in patients with hallucinations and delusions.

BACKGROUND: One of the main cognitive models of positive symptoms in schizophrenia proposes that they arise through impaired self-monitoring. This is supported by evidence of behavioural deficits on tasks designed to engage self-monitoring, but these deficits could also result from an externalising response bias. We examined whether patients with hallucinations and delusions would demonstrate an externalising bias on a task that did not involve cognitive self-monitoring. METHOD: Participants passively listened (without speaking) to recordings of single adjectives spoken in their own and another person's voice, and made self/nonself judgements about their source. The acoustic quality of recorded speech was experimentally manipulated by altering the pitch. Fifteen patients with schizophrenia who were currently experiencing hallucinations and delusions, 13 patients with schizophrenia not experiencing current hallucinations and delusions and 15 healthy controls were compared. RESULTS: When listening to distorted words, patients with hallucinations and delusions were more likely than both the group with no hallucinations and delusions and the control group to misidentify their own speech as alien (i.e. spoken by someone else). Across the combined patient groups, the tendency to misidentify self-generated speech as alien was positively correlated with current severity of hallucinations but not with ratings of delusions or positive symptoms in general. CONCLUSIONS: These findings indicate that patients with hallucinations and delusions are prone to misidentifying their own verbal material as alien in a task which does not involve cognitive self-monitoring. This suggests that these symptoms are related to an externalising bias in the processing of sensory material, and not solely a function of defective self-monitoring.

Allocentric spatial memory activation of the hippocampal formation measured with fMRI.

Hippocampal activation was investigated, comparing allocentric and egocentric spatial memory. Healthy participants were immersed in a virtual reality circular arena, with pattern-rendered walls. In a viewpoint-independent task, they moved toward a pole, which was then removed. They were relocated to another position and had to move to the prior location of the pole. For viewpoint-dependent memory, the participants were not moved to a new starting point, but the patterns were rotated to prevent them from indicating the final position. Hippocampal and parahippocampal activation were found in the viewpoint-independent memory encoding phase. Viewpoint-dependent memory did not result in such activation. These results suggest differential activation of the hippocampal formation during allocentric encoding, in partial support of the spatial mapping hypothesis as applied to humans.

Cognitive effects of nicotine in humans: an fMRI study.

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric "n-back" task in healthy nonsmoking males after the administration of nicotine (12 microg/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy (P = 0.008) in all active conditions (2%-11%), and had a load-specific effect on latency (P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task (P < 0.05, corrected at the voxel level), nicotine produced an increased response (P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest (P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects.

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.

A functional magnetic resonance imaging study of overt letter verbal fluency using a clustered acquisition sequence: greater anterior cingulate activation with increased task demand.

Regional cerebral activation during a cognitive task can vary with task demand and task performance. In a functional magnetic resonance imaging study, we examined the effect of manipulating task demand on activation during verbal fluency by using "easy" and "hard" letters. A "clustered" image acquisition sequence allowed overt verbal responses to be made in the absence of scanner noise which facilitated "on-line" measurement of task performance. Eleven right-handed, healthy male volunteers participated. Twice as many errors were produced with hard as with easy letters (20.8 +/- 13.6 and 10.1 +/- 10.7% errors, respectively). For both conditions, the distribution of regional activation was comparable to that reported in studies of covert verbal fluency, but with greater engagement of subcortical areas. The hard condition was associated with greater dorsal anterior cingulate activation than the easy condition. This may reflect the greater demands of the former, particularly in terms of arousal responses with increased task difficulty and the monitoring of potential response errors.

Procedural learning in schizophrenia: a functional magnetic resonance imaging investigation.

Procedural learning (PL) is a type of rule-based learning in which performance facilitation occurs with practice on task without the need for conscious awareness. Schizophrenic patients have often (though not invariably) been found to show impaired PL. We performed functional magnetic resonance imaging (fMRI) during a blocked, periodic sequence-learning task with groups of: (i) healthy subjects, and (ii) schizophrenic patients on conventional antipsychotics. Healthy subjects showed significant PL, but patients did not. In healthy subjects, PL was associated with increased activation in the striatum, thalamus, cerebellum, precuneus, medial frontal lobe, and cingulate gyrus. The power of activation in the thalamus, striatum, precuneus, cingulate gyrus and BA 6 was related to the magnitude of PL in these subjects. No regions, except the anterior inferior gyrus, were significantly activated in patients. The caudate nucleus, thalamus, precuneus, and sensorimotor regions were activated significantly differently between the two groups. The findings demonstrate the involvement of the striatum, cerebellum, thalamus, cingulate gyrus, precuneus, and sensorimotor regions in PL. Further fMRI studies of PL in normal subjects treated with conventional antipsychotics, drug naïve patients, and patients given atypical antipsychotics would help to clarify the roles of schizophrenic disease processes and antipsychotic medication in impaired PL and associated brain abnormalities in schizophrenia.