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Journal ArticleDOI

Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London.

01 Dec 1992-Archives of General Psychiatry (American Medical Association)-Vol. 49, Iss: 12, pp 943-958
TL;DR: The results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.
Abstract: The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.
Citations
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Journal ArticleDOI
01 Feb 1995-Brain
TL;DR: The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulates cortex in movement, affect and social behaviours.
Abstract: Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into ‘affect’ and ‘cognition’ components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal—infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive—compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours. The anterior cingulate cortex is part of a larger matrix of structures that are engaged in similar functions. These structures form the rostral limbic system and include the amygdala, periaqueductal grey, ventral striatum, orbitofrontal and anterior insular cortices. The system formed by these interconnected areas assesses the motivational content of internal and external stimuli and regulates context-dependent behaviours.

3,245 citations

Journal ArticleDOI
TL;DR: The peak age of onset for many psychiatric disorders is adolescence, a time of remarkable physical and behavioural changes and answers to these questions might enable the understanding of mental health during adolescence.
Abstract: The peak age of onset for many psychiatric disorders is adolescence, a time of remarkable physical and behavioural changes. The processes in the brain that underlie these behavioural changes have been the subject of recent investigations. What do we know about the maturation of the human brain during adolescence? Do structural changes in the cerebral cortex reflect synaptic pruning? Are increases in white-matter volume driven by myelination? Is the adolescent brain more or less sensitive to reward? Finding answers to these questions might enable us to further our understanding of mental health during adolescence.

2,436 citations

Journal ArticleDOI
TL;DR: The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000 and have led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research.

2,298 citations


Cites background from "Hypofrontality in neuroleptic-naive..."

  • ...…lobe damage (e.g. Wisconsin Card Sorting Task, eye tracking abnormalities, spatial working memory deficits, PET and fMRI functional measures showing hypo and hyperfrontality—see review in Wible et al., 1995, 1997, see also Andreasen et al., 1992; Goldberg et al., 1987; Weinberger et al., 1992)....

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Journal ArticleDOI
TL;DR: Some of the new anatomical, physiological and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex are reviewed.

1,824 citations

Journal ArticleDOI
TL;DR: To support the contention that NMDA receptor antagonist administration represents a viable model of schizophrenia, the behavioral and neurobiological effects of these drugs are discussed, especially with regard to differing profiles following single-dose and long-term exposure.

1,285 citations


Cites background from "Hypofrontality in neuroleptic-naive..."

  • ...The finding that repeated exposures to PCP reduces frontal blood flow is consistent with the observation that some components of the cognitive dysfunction of schizophrenia are associated with reduced frontal blood flow, so-called “hypofrontality” (Ingvar and Franzen 1974; Weinberger et al. 1986; Andreasen et al. 1992; Weinberger and Berman 1996)....

    [...]

  • ...…frontal blood flow is consistent with the observation that some components of the cognitive dysfunction of schizophrenia are associated with reduced frontal blood flow, so-called “hypofrontality” (Ingvar and Franzen 1974; Weinberger et al. 1986; Andreasen et al. 1992; Weinberger and Berman 1996)....

    [...]

References
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Journal ArticleDOI
TL;DR: The present scale has been devised for use only on patients already diagnosed as suffering from affective disorder of depressive type, used for quantifying the results of an interview, and its value depends entirely on the skill of the interviewer in eliciting the necessary information.
Abstract: Types of Rating Scale The value of this one, and its limitations, can best be considered against its background, so it is useful to consider the limitations of the various rating scales extant. They can be classified into four groups, the first of which has been devised for use on normal subjects. Patients suffering from mental disorders score very highly on some of the variables and these high scores serve as a measure of their illness. Such scales can be very useful, but have two defects: many symptoms are not found in normal persons; and less obviously, but more important, there is a qualitative difference between symptoms of mental illness and normal variations of behaviour. The difference between the two is not a philosophical problem but a biological one. There is always a loss of function in illness, with impaired efficiency. Self-rating scales are popular because they are easy to administer. Aside from the notorious unreliability of self-assessment, such scales are of little use for semiliterate patients and are no use for seriously ill patients who are unable to deal with them. Many rating scales for behaviour have been devised for assessing the social adjustment of patients and their behaviour in the hospital ward. They are very useful for their purpose but give little or no information about symptoms. Finally, a number of scales have been devised specifically for rating symptoms of mental illness. They cover the whole range of symptoms, but such all-inclusiveness has its disadvantages. In the first place, it is extremely difficult to differentiate some symptoms, e.g., apathy, retardation, stupor. These three look alike, but they are quite different and appear in different settings. Other symptoms are difficult to define, except in terms of their settings, e.g., mild agitation and derealization. A more serious difficulty lies in the fallacy of naming. For example, the term "delusions" covers schizophrenic, depressive, hypochrondriacal, and paranoid delusions. They are all quite different and should be clearly distinguished. Another difficulty may be summarized by saying that the weights given to symptoms should not be linear. Thus, in schizophrenia, the amount of anxiety is of no importance, whereas in anxiety states it is fundamental. Again, a schizophrenic patient who has delusions is not necessarily worse than one who has not, but a depressive patient who has, is much worse. Finally, although rating scales are not used for making a diagnosis, they should have some relation to it. Thus the schizophrenic patients should have a high score on schizophrenia and comparatively small scores on other syndromes. In practice, this does not occur. The present scale has been devised for use only on patients already diagnosed as suffering from affective disorder of depressive type. It is used for quantifying the results of an interview, and its value depends entirely on the skill of the interviewer in eliciting the necessary information. The interviewer may, and should, use all information available to help him with his interview and in making the final assessment. The scale has undergone a number of changes since it was first tried out, and although there is room for further improvement, it will be found efficient and simple in use. It has been found to be of great practical value in assessing results of treatment.

29,488 citations

Journal ArticleDOI
TL;DR: The Brief Psychiatric Rating Scale (BRS) as mentioned in this paper was developed to provide a rapid assessment technique particularly suited to the evaluation of patient change, and it is recommended for use where efficiency, speed, and economy are important considerations.
Abstract: The Brief Psychiatric Rating Scale was developed to provide a rapid assessment technique particularly suited to the evaluation of patient change. Sixteen symptom constructs which have resulted from factor analyses of several larger sets of items, principally Lorr's Multidimensional Scale for Rating Psychiatric Patients (MSRPP) (1953) and Inpatient Multidimensional Psychiatric Scale (IMPS) (1960), have been included for rating on 7-point ordered category rating scales. The attempt has been to include a single scale to record degree of symptomacology in each of the relatively independent symptom areas which have been identified. Some of the preliminary work which has led to the identification of primary symptom constructs has been published (Gorham & Overall, 1960, 1961, Overall, Gorharn, & Shawver, 1961). While other reports are in preparation, applications of the Brief Scale in both pure and applied research suggest the importance of presenting the basic instrument to the wider scientific audience at this time, together with recommendations for its standard use. The primary purpose in developing the Brief Scale has been the development of a highly efficient, rapid evaluation procedure for use in assessing treatment change in psychiatric patients while at the same time yielding a rather comprehensive description of major symptom characteristics. It is recommended for use where efficiency, speed, and economy are important considerations, while more detailed evaluation procedures, such as those developed by Lorr (1953, 1961) should perhaps be wed in other cases. In order to achieve the maximum effectiveness in use of the Brief Scale, a standard interview procedure and more detailed description of rating concepts are included in this report. In addition, each symptom concept is defined briefly in the rating scale statements themselves. Raters using the scale should become thoroughly familiar with the scale definitions presented herein, after which the rating scale statements should be sufficient to provide recall of the nature and delineation of each symptom area. , To increase the reliability of ratings, it is recommended that patients be interviewed jointly by a team of two clinicians, with the two raters making independent ratings at the completion of the interview. An alternative procedure which has been recommended by some is to have raters discuss and arrive at a

10,457 citations

Journal ArticleDOI
TL;DR: The relative simplicity, reliability, and validity of the GAS suggests that it would be useful in a wide variety of clinical and research settings.
Abstract: † The Global Assessment Scale (GAS) is a rating scale for evaluating the overall functioning of a subject during a specified time period on a continuum from psychological or psychiatric sickness to health. In five studies encompassing the range of populations to which measures of overall severity of illness are likely to be applied, the GAS was found to have good reliability. GAS ratings were found to have greater sensitivity to change over time than did other ratings of overall severity or specific symptom dimensions. Former inpatients in the community with a GAS rating below 40 had a higher probability of readmission to the hospital than did patients with higher GAS scores. The relative simplicity, reliability, and validity of the GAS suggests that it would be useful in a wide variety of clinical and research settings.

4,799 citations

Journal ArticleDOI
TL;DR: An information-processing model is outlined that predicts that performance on non-routine tasks can be impaired independently of performance on routine tasks, related to views on frontal lobe functions, particularly those of Luria.
Abstract: An information-processing model is outlined that predicts that performance on non-routine tasks can be impaired independently of performance on routine tasks. The model is related to views on frontal lobe functions, particularly those of Luria. Two methods of obtaining more rigorous tests of the model are discussed. One makes use of ideas from artificial intelligence to derive a task heavily loaded on planning abilities. A group of patients with left anterior lesions has a specific deficit on the task. Subsidiary investigations support the inference that this is a planning impairment.

3,591 citations

Journal ArticleDOI
TL;DR: A modification of an earlier rating scale for extrapyramidal system disturbance is described, and evidence for the validity and reliability of the scale is presented.
Abstract: SUMMARY A modification of an earlier rating scale for extrapyramidal system disturbance is described, and evidence for the validity and reliability of the scale is presented. The usefulness of the scale in studies of neuroleptic drugs is discussed. By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors.

3,135 citations