When conscious recollection disrupts memory.
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Consciousness Disorders↗
Biomedical subjects
C Frith
Publications and source records attributed to C Frith.
How hallucinations make themselves heard.
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Brain↗
The neural correlates of conscious experience: an experimental framework.
Demonstrating that neural activity 'represents' physical properties of the world such as the orientation of a line in the receptive field of a nerve cell is a standard procedure in neuroscience. However, not all such neural activity will be associated with the mental representations that form the contents of consciousness. In some cases, such as when patients with blindsight correctly 'guess' the location of a stimulus, neural activity is associated with physical stimulation and with appropriate behaviour, but not with awareness. To identify the neural correlates of conscious experience we need to identify patterns of neural activity that are specifically associated with awareness. Experiments aimed at making such identifications require that subjects report some aspect of their conscious experience either verbally or through some pre-arranged non-verbal report while neural activity is measured. If there is some characteristic neural signature of consciousness, then this should be distinguishable from the kinds of neural activity associated with stimulation and/or behaviour in the absence of awareness. It remains to be seen whether the neural signature of consciousness relates to the location of the neural activity, the temporal properties of the neural activity or the form of the interaction between activity in different brain regions.
Journal Article↗
Psychosis and the experience of self. Brain systems underlying self-monitoring.
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Brain↗
Images of psychopathology.
Brain imaging continues to provide important data about brain structure, neurotransmitter function and the physiological basis of cognitive processes, as these relate to schizophrenia and mood disorders. A unifying theoretical perspective, however, that can clarify the precise nature of the biological basis of these diverse psychiatric conditions is lacking. It is becoming increasingly evident that a lesion model is inappropriate and that a more relevant characterisation will be found in terms of disorders of functional interconnections between brain regions.
Depression↗
Brain mechanisms associated with top-down processes in perception.
Perception arises through an interaction between sensory input and prior knowledge. We propose that at least two brain areas are required for such an interaction: the 'site' where analysis of afferent signals occurs and the 'source' which applies the relevant prior knowledge. In the human brain, functional imaging studies have demonstrated that selective attention modifies activity in early visual processing areas specific to the attended feature. Early processing areas are also modified when prior knowledge permits a percept to emerge from an otherwise meaningless stimulus. Sources of this modification have been identified in parietal cortex and in prefrontal cortex. Modification of early processing areas also occurs on the basis of prior knowledge about the predicted sensory effects of the subject's own actions. Activity associated with mental imagery resembles that associated with response preparation (for motor imagery) and selective attention (for sensory imagery) suggesting that mental imagery reflects the effects of prior knowledge on sensory processing areas in the absence of sensory input. Damage to sensory processing areas can lead to a form of sensory hallucination which seems to arise from the interaction of prior knowledge with random sensory activity. In contrast, hallucinations associated with schizophrenia may arise from a failure of prior knowledge about motor intentions to modify activity in relevant sensory areas. When functioning normally, this mechanism permits us to distinguish our own actions from those of independent agents in the outside world. Failure to make this distinction correctly may account for the strong association between hallucinations and paranoid delusions in schizophrenia; the patient not only hears voices, but attributes (usually hostile) intentions to these voices.
Cognition↗
Two modulatory effects of attention that mediate object categorization in human cortex.
Attentional modulation of cortical activity was examined by varying the rate of visual stimuli in object categorization tasks according to single and conjoined features. Activation of dorsolateral frontal cortex was independent of the stimulus presentation rate and elicited by the participant's attention to conjoined compared with single features. Several cortical regions showed attentionally modulated activity. In inferior temporal cortex, modulation was due to an additional bias signal underlying normal rate-correlated activity. In two other regions (premotor cortex and cerebellum), attention modified the correlation of activity and the stimulus presentation rate. Attentional effects in the human cortex are expressed by at least two physiologically distinct mechanisms acting on spatially distributed areas.
Adult↗
'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome.
The ability to attribute mental states to others ('theory of mind') pervades normal social interaction and is impaired in autistic individuals. In a previous positron emission tomography scan study of normal volunteers, performing a 'theory of mind' task was associated with activity in left medial prefrontal cortex. We used the same paradigm in five patients with Asperger syndrome, a mild variant of autism with normal intellectual functioning. No task-related activity was found in this region, but normal activity was observed in immediately adjacent areas. This result suggests that a highly circumscribed region of left medial prefrontal cortex is a crucial component of the brain system that underlies the normal understanding of other minds.
Adult↗
The role of the prefrontal cortex in self-consciousness: the case of auditory hallucinations.
Many patients with schizophrenia report hallucinations in which they hear voices talking to them or about them. Behavioural and physiological studies show that this experience is associated with processes occurring in auditory language systems associated with both the production and the reception of speech. I propose that hallucinations are experienced because patients have difficulty in distinguishing sensations caused by their own actions from those that arise from external influences. This distinction can be made by predicting the sensations that will result from executive commands (forward modelling). If the predicted sensation matches the actual sensation then no outside influences have occurred and perception of change can be 'cancelled'. At the physiological level this mechanism depends upon interactions between the prefrontal areas where the executive commands originate and posterior brain regions concerned with the resultant sensations. Evidence from functional brain imaging confirms that interactions between prefrontal (executive) areas and auditory association areas are abnormal in schizophrenia. However, this account needs to be extended before we can understand why patients experience the voices as emanating, not just from an external source, but from agents who are trying to influence their behaviour. Recent imaging studies suggest that medial prefrontal cortex is engaged when we think about other people, but the precise nature of the interaction of this brain area with other regions remains to be established.
Consciousness↗
A biological marker for dyslexia.
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Biomarkers↗
The role of the prefrontal cortex in higher cognitive functions.
The higher cognitive functions, working memory, mental imagery and willed action, are all intimately associated with consciousness. The common process underlying all these functions is that information is "held in mind" for a period of time. This information, which may be about stimuli or responses, can be derived from the past or generated for the future. Brain imaging studies show that "holding something in mind" is associated with activity in an extended system which involves both prefrontal cortex and more posterior areas whose location is determined by the nature of the information being held in mind. Automatic actions and perceptions which do not involve consciousness are associated with activity in the relevant posterior areas, but not in the prefrontal cortex. These studies demonstrate that activity occurs in the same posterior area whether the associated information comes from the outside world or is internally generated. This raises the problem of how we know whether our experience derives from mental imagery or from something happening in the outside world. There is evidence that patients with schizophrenia have precisely this problem since they perceive their own thoughts and even sub-vocal speech as coming from outside (hallucinations). Recent brain imaging studies suggest that there is a disconnection between prefrontal and posterior areas in these patients which could explain their characteristic misperceptions.
Choice Behavior↗
Neuropsychology of schizophrenia, what are the implications of intellectual and experiential abnormalities for the neurobiology of schizophrenia?
The diagnosis of schizophrenia is largely based on reports of bizarre experiences such as having alien thoughts inserted into one's mind. Many patients with this diagnosis show a marked intellectual decline and particular problems with tasks involving certain kinds of memory or requiring mental flexibility. Similar patterns of performance can be seen in patients with damage in the prefrontal cortex. However, patients with schizophrenia show a very varied pattern of impairments relating to their current mental state. Chronic patients with negative features, such as poverty of speech, are most likely to show poor test performance, while the presence of severe hallucinations and delusions need not be associated with any impairment. A cognitive approach suggests that hallucinations and delusions result from the patient attributing his own actions to an external agency. This error is due to an inability to distinguish between external events and perceptual changes caused by his own actions. The basis of this failure could be a functional disconnection between frontal brain areas concerned with action and posterior areas concerned with perception.
Brain↗
A functional neuroanatomy of hallucinations in schizophrenia.
Hallucinations, perceptions in the absence of external stimuli, are prominent among the core symptoms of schizophrenia. The neural correlates of these brief, involuntary experiences are not well understood, and have not been imaged selectively. We have used new positron emission tomography (PET) methods to study the brain state associated with the occurrence of hallucinations in six schizophrenic patients. Here we present a group study of five patients with classic auditory verbal hallucinations despite medication, demonstrating activations in subcortical nuclei (thalamic, striatal), limbic structures (especially hippocampus), and paralimbic regions (parahippocampal and cingulate gyri, as well as orbitofrontal cortex). We also present a case study of a unique, drug-naive patient with visual as well as auditory verbal hallucinations, demonstrating activations in visual and auditory/linguistic association cortices as part of a distributed cortical-subcortical network. Activity in deep brain structures, identified with group analysis, may generate or modulate hallucinations, and the particular neocortical regions entrained in individual patients may affect their specific perceptual content. The interaction of these distributed neural systems provides a biological basis for the bizarre reports of schizophrenic patients.
Adult↗
Functional imaging and cognitive abnormalities.
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Brain↗
The functional anatomy of recovery from auditory agnosia. A PET study of sound categorization in a neurological patient and normal controls.
H2(15)O-PET was used to investigate the functional anatomy of recovery in a patient (J.B.) with bilateral perisylvian strokes and auditory agnosia, who partially regained the ability to recognize environmental sounds, but remained clinically word-deaf. The patient and a group of six normal volunteers were scanned in the following three conditions: (i) passive listening to environmental sounds; (ii) categorization of environmental sounds; (iii) at rest. In normal subjects, passive listening as compared with rest was associated with significant activations in the auditory cortices and posterior thalami, and in the inferior parietal lobe and anterior insula/frontal opercular region on the right. In J.B., activations were observed in the spared auditory cortex and inferior parietal lobe of the right hemisphere and in regions adjacent to the perisylvian lesion in the left hemisphere (anterior insula/frontal opercular region, middle temporal gyrus and inferior parietal lobe). The recovered function, as measured by categorization of sounds compared with passive listening, in J.B. was associated with bilateral activation of a distributed network comprising (pre)frontal, middle temporal and inferior parietal cortices, as well as the right cerebellum and the right caudate nucleus. In addition, there was a left-sided activation of the anterior cingulate gyrus. In normal subjects, the same categorization task led to activation of a network comprising (pre)frontal, middle temporal and inferior parietal cortices in the left hemisphere only. These results suggest that bilateral activation (with recruitment of areas homologous to those known to be responsible for normal function), the engagement of peri-infarct regions, and the involvement of a more widespread neocortical network, are mechanisms of functional reorganization after injury that may enable recovery from, or compensation for, cognitive deficits.
Agnosia↗
Effect of bleomycin-induced fibrosis on pulmonary metabolism of selected xenobiotics.
Few studies are available characterizing the effects of fibrosis on pulmonary disposition of drugs or environmental pollutants. Two model substrates, p-nitroanisole and carbofuran, were selected to evaluate the effect of bleomycin-induced fibrosis on pulmonary disposition and metabolism using the isolated perfused lung and in vitro enzyme preparations. The rate of p-nitroanisole oxidation in the isolated perfused lung was significantly lower in fibrotic (k = 0.0334 min-1) than in control (k = 0.0493 min-1) lungs. However, there was no difference in the amount of p-nitrophenol formed between control (38 +/- 4 micrograms) and fibrotic (47 +/- 7 micrograms) lungs. Carbofuran clearance was similar in control (t1/2 = 91 min, ke = 0.008 min-1) and fibrotic (t1/2 = 75 min, ke = 0.009 min-1) lungs and was consistent with a one-compartment model. The Km value for p-nitrophenol formation in microsomes (0.185 +/- 0.095 mM) from control lungs was similar to fibrotic lungs (0.054 +/- 0.014 mM); however, Vmax was significantly higher in healthy (34.6 +/- 6.3 pmoles/min per mg microsomal protein) than in fibrotic (11.16 +/- 3.19 pmoles/min per mg microsomal protein) lungs. In vitro carbofuran studies indicated limited metabolism of carbofuran in both healthy and fibrotic microsomal enzyme preparations (< 5% of the administered dose). Lower p-nitroanisole metabolism in fibrotic lungs was consistent with lower levels of cytochrome P-450 2B1/B2 measured in bleomycin-treated lungs. Results suggest that individuals with bleomycin-induced pulmonary fibrosis may be at greater risk when exposed to certain toxic environmental chemicals or drugs that require detoxification by pulmonary microsomal enzymes.
Animals↗
Hypothesis: the bradyphrenia of parkinsonism is a nosological entity.
Reaction time was studied in 103 subjects with idiopathic parkinsonism and 144 without. Central processing time, as measured by the response to a warning, had a component which could be explained by the presence or absence of parkinsonism, but not by the ageing process, a mental test score, or consumption of exogenous substances. Depression did not influence the efficiency of response. Cigarette smoking and anti-parkinsonian medication were associated with greater efficiency.
Adult↗
Positron emission tomography studies of frontal lobe function: relevance to psychiatric disease.
The frontal lobes in man include about one-third of the total cortical area of the cerebrum, a considerably greater proportion than in other primates. It is likely that the frontal lobes subserve the most complex of cognitive functions including will and consciousness. During the performance of willed actions (spontaneous selection of actions without help from external cues) an increase of activity can be observed in dorsolateral prefrontal cortex. Critically, there is no increased activity in this location when the same actions are performed routinely. Such observations, which systematically use positron emission tomography (PET) in conjunction with specific cognitive activations, should make it possible (a) to specify more precisely the cognitive components comprising 'frontal' attributes such as willed behaviour and planning, (b) to relate these components to particular frontal lobe areas, and (c) to show how these frontal lobe areas interact with other parts of the brain. Psychotic patients typically show abnormalities of willed behaviour (e.g. poverty of speech and action) and consciousness (e.g. hallucinations, delusions of control). PET studies of frontal lobe function in patients with these signs and symptoms should not only provide information about the pathophysiology of these disorders, but also increase our knowledge of the brain systems underlying the most complex human faculties.
Attention↗