Objective: Patients with schizophrenia are characterized by neurological abnormalities, which can be assessed by bedside clinical examination. These abnormalities have been argued to represent core features of the illness. We review studies published since our last review in 1988 that address the validity of neurological signs as a trait feature of schizophrenia. Methods: We conducted a literature search in the following computer databases: MEDLINE, PSYCHLIT, EMBASE, and COCHRANE. The search was limited to articles published from January 1988 to May 2005. Results: Neurological signs occur in the majority of patients with schizophrenia. Their occurrence is independent of demographic and most medication variables. Neurological signs are strongly associated with negative symptoms and cognitive impairments. There is also evidence to suggest that their occurrence is under genetic control. Conclusions: There is compelling evidence to suggest the hypothesis that neurological signs represent a trait feature of schizophrenia.

/pdf/significance-and-meaning-of-neurological-signs-in-39fgxgq8qu.pdf

Significance and Meaning of Neurological Signs in Schizophrenia: Two Decades Later

Structural Brain Anomalies and Chronic Pain: A Quantitative Meta-Analysis of Gray Matter Volume

Background The results of one randomised control trial testing a psychological rehabilitation programme aimed at information processing strategies showed improvements in cognition posttreatment. Aims To determine whether there are concomitant brain activation changes as a result of engaging in cognitive remediation therapy (CRT). Method Three groups (patients receiving control therapy or CRTand a healthy control group) were investigated in a repeated measures design using the two-back test. Functional magnetic resonance imaging (fMRI) data and a broad assessment of executive functioning were completed at baseline and posttreatment. Brain activation changes were identified after accounting for possible task-correlated motion artefact. Results fMRI analyses indicate that the control group showed decreased activation but the two patient groups showed an increase in activation over time. The patient group that received successful CRT had significantly increased brain activation in regions associated with working memory, particularly the frontocortical areas. Conclusions This is the first time that brain activation changes in a seriously disabled group of patients with schizophrenia can be associated clearly with psychological rather than pharmacological therapy Declaration of interest This work was supported by the WellcomeTrust.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/285B89E03F29EB001EA45B768776BEA3/S0007125000161872a.pdf/div-class-title-effects-on-the-brain-of-a-psychological-treatment-cognitive-remediation-therapy-div.pdf

Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia.

Patients with schizophrenia and related psychoses have an excess of minor neurological abnormalities (neurological soft signs) of unclear neuropathological origin. These include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing complex motor tasks. Neurological soft signs seem not to reflect primary tract or nuclear pathology. It still has to be established whether neurological soft signs result from specific or diffuse brain structural abnormalities. Studying their anatomical correlates can provide not only a better understanding of the aetiopathogenesis of soft signs, but also of the pathophysiology of schizophrenia. Surprisingly few studies have investigated the brain correlates of neurological soft signs. In the present study, we investigated the relationship between brain structure and neurological soft signs in an epidemiologically based sample of 77 first-episode psychosis patients. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of soft neurological signs (both motor and sensory) were associated with a reduction of grey matter volume of subcortical structures (putamen, globus pallidus and thalamus). Signs of sensory integration deficits were additionally associated with volume reduction in the cerebral cortex, including the precentral, superior and middle temporal, and lingual gyri. Neurological soft signs and their associated brain changes were independent of antipsychotic exposure. We conclude that neurological soft signs are associated with regional grey matter volume changes and that they may represent a clinical sign of the perturbed cortical-subcortical connectivity that putatively underlies psychotic disorders.

The structural brain correlates of neurological soft signs in ÆSOP first-episode psychoses study

Meta-analysis of brain and cranial size in schizophrenia

Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT (computerized tomography) and rCBF (regional cerebral blood flow) as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.

Neurological abnormalities in patients with schizophrenia or schizophreniform disorder at first admission to hospital: correlations with computerized tomography and regional cerebral blood flow findings.

Fifty newly diagnosed, briefly treated or drug-naive patients with schizophrenia or schizophreniform disorder were examined by psychopathology scales for positive (SAPS), negative (SANS) and overall psychotic symptoms (PSE and BPRS). CT-scan and regional cerebral blood flow (rCBF) measurement by 99mTc-HMPAO SPECT during rest and mental activation by Wisconsin Card Sorting Test was performed as well. Twenty-five age-matched normal healthy volunteers served as controls. Thought disorders and fundamental symptoms correlated positively with relatively high, though subnormal prefrontal (PFC) rCBF and high rCBF in temporal cortex; positive symptoms correlated positively with high rCBF in the striatum and temporal cortex during activation. Negative symptoms correlated with high prefrontal rCBF. The patients had sulcal enlargement and smaller brain volume compared with the healthy volunteers. There were no signs of ventricular enlargement. Neither total negative symptoms, thought disorder nor fundamental symptoms correlated with any CT measurements. Total positive symptoms correlated negatively with the size of the temporal horns. The relatively high rCBF in PFC and temporal cortex of cases with pronounced positive and negative symptoms and thought disorder may imply that an aberrant cortical network has to be active to express a malattuned clinical output. The striatal hyperfunction mainly in productive cases may be a secondary phenomenon and more pronounced in cases where no signs of subcortical atrophy has (yet?) ensued.

Relationship between brain structure and function in disorders of the schizophrenic spectrum: single positron emission computerized tomography, computerized tomography and psychopathology of first episodes

Schizophrenia has the quality of a 'top-down' disorder with perturbation of self, and malattuned appraisal of basic experience of the outside world, and of intentionality. There is dissonance between the faculties of consciousness. The neuronal cortical network displays distributed activation of the sensory cortices during perception, and retroactivation during recall. This multimodal organization is sensitive to aberrations of structure and informational content during the metabolically dynamic phases of expansion and pruning in childhood and adolescence. There is substantial evidence of deviant function of the cortical network in schizophrenia. This includes increased neuronal density, reduced prefrontal capacity for activation, impaired fronto-temporal interaction during language production, defect monitoring of inner speech, activation of secondary sensory cortices during hallucinations, reduced cortical and thalamic volume, reduced thalamic activation (filtering) and sensitization of dopaminergic modulation. As a hypothesis the cortical defects lead to secondary causation of abnormalities at the levels of neuroplasticity, symptomatology and social competence. Suggestions for empirical testing are presented for the hypothesis that neocortical defects are primary, thalamic defects secondary and dopaminergic aberrations tertiary in the schizophrenic process. This testing of hypotheses involves prospective studies of patient groups at various ages of onset, as well as comparison of neurobiological measures in remitting vs. treatment-resistant cases.

Cortical brain dysfunction in early schizophrenia: secondary pathogenetic hierarchy of neuroplasticity, psychopathology and social impairment

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Neurological abnormalities in patients with schizophrenia or schizophreniform disorder at first admission to hospital: correlations with computerized tomography and regional cerebral blood flow findings.

Relationship between brain structure and function in disorders of the schizophrenic spectrum: single positron emission computerized tomography, computerized tomography and psychopathology of first episodes

Cortical brain dysfunction in early schizophrenia: secondary pathogenetic hierarchy of neuroplasticity, psychopathology and social impairment