[Hypofrontality and negative symptoms in schizophrenia: synthesis of anatomic and neuropsychological knowledge and ecological perspectives].Encephale. 2001 Sep-Oct; 27(5):405-15.E
Cognitive deficits in schizophrenia have been observed with neuropsychological tests of executive function, traditionally considered sensitive to frontal lobe damage. These impairments affect planning abilities, as well as the aptitude to initiate and regulate a goal-directed behaviour. On the other hand, negative symptoms of schizophrenia are widely suspected to reflect a frontal lobe dysfunction. Based on a review of a hundred papers, the present article analyses the anatomical and neuropsychological evidence of disturbed frontal lobe functioning in patients with negative schizophrenic symptoms. The phenomenological similarity of some schizophrenic symptoms to the clinical features of patients with prefrontal injury inspired the hypothesis of damaged frontal lobe in the former disorder. The morphological findings of neuroimaging studies brought inconsistent conclusions, with some researchers noting no differences between patients and control subjects while others observing reduced prefrontal volumes in schizophrenia. The functional neuroimaging demonstrated a reduced frontal blood flow relative to the general cerebral perfusion in patients with schizophrenia. Even though the overall neuroimaging literature provides reliable evidence of frontal impairment in schizophrenia, the average magnitude of the difference between patients and healthy controls is insufficient to defend the hypothesis of frontal lobe dysfunction, as far as brain volume, resting metabolism or blood flow are concerned. The only measure, which clearly distinguishes between the patients' and controls' distributions, is the functional neuroimaging of the frontal lobe while subjects are performing an experimentally controlled task. Schizophrenic patients fail to activate their frontal cortex when the task requires it. Analysing executive abilities in relation to symptom expression leads to recognising the fact that frontal dysfunction is a characteristic of only a sub-syndrome of schizophrenia. The factor analysis of the clinical features consistently reveals three syndromes in schizophrenia, termed disorganisation, positive and negative syndromes. The substantial body of evidence that patients exhibit more than one syndrome indicates these are dimensions within a single illness rather than discrete diseases. Liddle labelled the negative syndrome as "psychomotor poverty" and associated it with malfunction of the neuronal projections from dorsal prefrontal cortex to thalamus via striatum, connections involved in the initiation of mental activity. His hypothesis was supported by the work of other, independent research groups. The patients with negative symptoms, in contrast with the nonnegative symptom group, tend to demonstrate reduced neuronal activation of the frontal cortex during executive task realisation. The nonnegative patients are indistinguishable from the healthy control subjects in this region. Neuropsychological studies reveal that severity of psychomotor poverty is associated with slowing of mental processing and deficits in tasks that require planning abilities. These frontal functions are identified with the selection, the initiation and monitoring of a wide variety of behavioural processes. It was hypothesised that executive dysfunction will appear through different patterns across symptom subtypes, but few studies sought to validate this assumption. Finally, researchers make little effort to develop theoretical conceptualisations of the aetiology of negative schizophrenic symptoms, despite the growing body of evidence on its resemblance to the dorsolateral frontal lobe syndrome. Frith proposes that defects in the initiation of spontaneous action underlie these clinical phenomena, but his definition is not specific enough to be confronted to existing literature, neither has been empirically tested. Disturbed executive functioning has detrimental impact on the quality of daily living in patients with schizophrenia. Indirect observation of the latter accounts for defective long-term adaptation, which has been correlated to severity of negative symptoms and, although not consistently, to executive deficit as assessed by neuropsychological testing. Unfortunately, this area of research lacks ecologically valid studies. Measuring executive dysfunction as it occurs in the natural setting of the patient and validating dissocialbility of frontal deficits with respect to the schizophrenic symptomatology could lead to greater individualization of treatment plans and therefore to more efficient therapy outcome.