Neuroimaging studies of cognitive remediation in schizophrenia: A systematic and critical review

AIM: To examine the effects of cognitive remediation therapies on brain functioning through neuroimaging procedures in patients with schizophrenia. METHODS: A systematic, computerised literature search was conducted in the PubMed/Medline and PsychInfo databases. The search was performed through February 2016 without any restrictions on language or publication date. The search was performed using the following search terms: [('cogniti*' and 'remediation' or 'training' or 'enhancement') and ('fMRI' or 'MRI' or 'PET' or 'SPECT') and (schizophrenia or schiz*)]. The search was accompanied by a manual online search and a review of the references from each of the papers selected, and those papers fulfilling our inclusion criteria were also included. RESULTS: A total of 101 studies were found, but only 18 of them fulfilled the inclusion criteria. These studies indicated that cognitive remediation improves brain activation in neuroimaging studies. The most commonly reported changes were those that involved the prefrontal and thalamic regions. Those findings are in agreement with the hypofrontality hypothesis, which proposes that frontal hypoactivation is the underlying mechanism of cognitive impairments in schizophrenia. Nonetheless, great heterogeneity among the studies was found. They presented different hypotheses, different results and different findings. The results of more recent studies interpreted cognitive recovery within broader frameworks, namely, as amelioration of the efficiency of different networks. Furthermore, advances in neuroimaging methodologies, such as the use of whole-brain analysis, tractography, graph analysis, and other sophisticated methodologies of data processing, might be conditioning the interpretation of results and generating new theoretical frameworks. Additionally, structural changes were described in both the grey and white matter, suggesting a neuroprotective effect of cognitive remediation. Cognitive, functional and structural improvements tended to be positively correlated

Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect

Background: The negative symptoms of schizophrenia have been proposed to reflect prefrontal cortex dysfunction. However, this proposal has not been consistently supported in functional imaging studies, which have also used executive tasks that may not capture key aspects of negative symptoms such as lack of volition. Method: Twenty-four DSM-5 schizophrenic patients with high negative symptoms (HNS), 25 with absent negative symptoms (ANS) and 30 healthy controls underwent fMRI during performance of the Computerized Multiple Elements Test (CMET), a task designed to measure poor organization of goal directed behaviour or 'goal neglect'. Negative symptoms were rated using the PANSS and the Clinical Assessment Interview for Negative Symptoms (CAINS). Results: On whole brain analysis, the ANS patients showed no significant clusters of reduced activation compared to the healthy controls. In contrast, the HNS patients showed hypoactivation compared to the healthy controls in the left anterior frontal cortex, the right dorsolateral prefrontal cortex (DLPFC), the anterior insula bilaterally and the bilateral inferior parietal cortex. When compared to the ANS patients, the HNS patients showed reduced activation in the left anterior frontal cortex, the left DLPFC and the left inferior parietal cortex. After controlling for disorganization scores, differences remained in clusters in the left anterior frontal cortex and the bilateral inferior parietal cortex. Conclusions: This study provides evidence that reduced prefrontal activation, perhaps especially in the left anterior frontal cortex, is a brain functional correlate of negative symptoms in schizophrenia. The simultaneous finding of reduced inferior parietal cortex activation was unexpected, but could reflect this region's involvement in cognitive control, particularly the 'regulative' component of this

Abnormalities of brain structure and lateralisation in schizophrenia

Researchers have proposed that schizophrenia is a disease related to abnormal cerebral lateralisation following findings of increased "schizophrenia-like" symptoms in left-hemisphere epileptics. Theories regarding abnormal brain structural asymmetries in schizophrenia suggest either ambiguous or extreme motor asymmetry. These theories are conceptually similar to ones proposed to explain non-right-handedness in normal subjects. In this thesis I objectively evaluate these hypotheses. Firstly, I critically survey the neuropsychological literature and find the evidence for lateralised cognitive deficit to be inconclusive. Next, a meta-analysis of studies reporting the finding of ventricular enlargement in schizophrenia is carried out and it is found that findings are highly influenced by methodological factors. A review of the literature concerning lateralised neuropathologies from brain imaging and postmortem studies similarly finds the evidence to be hindered by differences in experimental methodology. Furthermore, there is much disagreement between researchers regarding which asymmetries are empirically or theoretically meaningful. The next chapter concentrates exclusively with the experimental measurement of hand performance. The Annett pegboard, the Tapley and Bryden circle marking, and the Bishop square tracing tasks of hand performance are extended and used to test hand performance in normal subjects as a function of increasing task difficulty. Pursuit tracking is used to consider the Fourier spectrum and sub-components of relative hand performance. The differences between the hands on the conventional and tracking tasks are then subjected to factor analyses. Surprising results are obtained in which performance tasks show moderate-to-high internal reliability but correlate poorly with one another. Their relevance to handedness and motor research is then discussed. Schizophrenic hand preference is investigated in a meta-analytic assessment of studies reporting an increased incidence of non-dextral hand preference in schizophrenia. This is examined with respect to the definition and methods of measurement in these studies. Finally, the hand performance of schizophrenics is investigated. Testing hand performance, in conjunction with hand preference measures, allows for greater reliability in the evaluation of the notion of abnormal handedness in schizophrenia. Patients show poorer overall performance on all of the tasks, but show no significant differences in their degree of handedness as compared to normals. Conclusions are drawn that associations between abnormal handedness and disorders of brain structural asymmetry in schizophrenic patients are unlikely. Further implications for abnormalities of cerebral dominance and schizophrenia are considered

Computer-aided segmentation and estimation of indices in brain CT scans

The importance of neuro-imaging as one of the biomarkers for diagnosis and prognosis of pathologies and traumatic cases is well established. Doctors routinely perform linear measurements on neuro-images to ascertain severity and extent of the pathology or trauma from significant anatomical changes. However, it is a tedious and time consuming process and manually assessing and reporting on large volume of data is fraught with errors and variation. In this paper we present a novel technique for segmentation of significant anatomical landmarks using artificial neural networks and estimation of various ratios and indices performed on brain CT scans. The proposed method is efficient and robust in detecting and measuring sizes of anatomical structures on non-contrast CT scans and has been evaluated on images from subjects with ages between 5 to 85 years. Results show that our method has average ICC of ≥0.97 and, hence, can be used in processing data for further use in research and clinical environment

Psychiatric, psychometric and MRI abnormalities in multiple sclerosis

Study 1. Forty two patients with acute optic neuritis were compared to matched, normal controls on tests of attention/information processing speed and anxiety/depression. Approximately half the sample had brain magnetic resonance imaging (MRI) abnormalities and were more impaired across a variety of psychometric tests compared to patients without brain lesions or controls. There were no psychometric differences between controls and optic neuritis patients without brain involvement. Total lesion area correlated significantly with some tests of attention. Psychiatric morbidity did not differ between optic neuritis patients, irrespective of the presence of brain lesions, and controls. Study 2. Forty eight patients with clinically isolated lesions (eg. optic neuritis) were followed up after 4 years with respect to MRI, psychometric and psychiatric abnormalities. Approximately half the sample had developed clinically definite multiple sclerosis (MS), with memory deficits becoming apparent. Attention deficits documented at initial assessment were present, but unchanged in those who remained with a clinically isolated lesion status. After dividing MS patients into a relapsing-remitting or chronic-progressive group, the latter were found to have significantly deteriorated on auditory attention tasks. Study 3. Over 6 months, 5 patients with early relapsing-remitting MS and 5 with long standing, "benign" MS underwent serial psychometric testing and contrast enhanced brain MRI at 2 weekly/monthly intervals respectively. All patients were individually matched with healthy controls who completed the same psychometric procedure. As a group, MS patients made more errors and/or performed slower on all tasks. In patients with stable brain lesion scores, no consistent deterioration occurred in any test and the overall pattern was one of improvement over time. However, patients with deteriorating lesion scores either showed a significant fall- off in performance on some psychomotor tasks or an impaired ability to improve performance with practice. Study 4. Ten psychotic MS patients were assessed retrospectively with the Present State Examination and matched according to demographic and disease characteristics with 10 MS patients without psychosis. Both groups underwent brain MRI. There was a trend for the psychotic group to have a higher periventricular and total lesion score. This reached statistically significance for temporal horn scores. Clinical and MRI data pointed to an aetiological association between MS and psychosis

What Investigations Are Ordered in Patients with First-episode Psychosis?

Psychiatrists are often left with the dilemma of which investigations to order in adolescents presenting with a first episode of psychosis. Blood work, urine studies, and neuroimaging studies were tracked in 13 adolescents admitted with a diagnosis of first-episode psychosis over a 13-month period to the Children’s Hospital of Eastern Ontario. Variation was found in the amount of investigation ordered: 85% of patients received a drug screen; 54% a CT scan; 8% an MRI; 92% a CBC with differential; 92% electrolytes. Abnormalities of CT scans were detected in 2 patients (29%); in neither case did the result lead to a diagnosis of brain-lesion-related psychosis, nor did it affect the clinical care of the patient. This study highlights the need to develop clinical practice-guidelines for the workup of first-episode psychosis in adolescents

Pathological regional blood flow in opiate-dependent patients during withdrawal: A HMPAO-SPECT study

The aims of the present study were to investigate regional cerebral blood flow (rCBF) in heroin-dependent patients during withdrawal and to assess the relation between these changes and duration of heroin consumption and withdrawal data. The rCBF was measured using brain SPECT with Tc-99m-HMPAO in 16 heroin-dependent patients during heroin withdrawal. Thirteen patients received levomethadone at the time of the SPECT scans. The images were analyzed both visually and quantitatively, a total of 21 hypoperfused brain regions were observed in 11 of the 16 patients. The temporal lobes were the most affected area, hypoperfusions of the right and left temporal lobe were observed in 5 and 5 patients, respectively. Three of the patients had a hypoperfusion of the right frontal lobe, 2 patients showed perfusion defects in the left frontal lobe, right parietal lobe and left parietal lobe. The results of the quantitative assessments of the rCBF were consistent with the results of the qualitative findings. The stepwise regression analysis showed a significant positive correlation (r = 0.54) between the dose of levomethadone at the time of the SPECT scan and the rCBF of the right parietal lobe. Other significant correlations between clinical data and rCBF were not found. The present results suggest brain perfusion abnormalities during heroin withdrawal in heroin-dependent patients, which are not due to the conditions of withdrawal

Executive function in first-episode schizophrenia

BACKGROUND: We tested the hypothesis that schizophrenia is primarily a frontostriatal disorder by examining executive function in first-episode patients. Previous studies have shown either equal decrements in many cognitive domains or specific deficits in memory. Such studies have grouped test results or have used few executive measures, thus, possibly losing information. We, therefore, measured a range of executive ability with tests known to be sensitive to frontal lobe function. METHODS: Thirty first-episode schizophrenic patients and 30 normal volunteers, matched for age and NART IQ, were tested on computerized test of planning, spatial working memory and attentional set shifting from the Cambridge Automated Neuropsychological Test Battery. Computerized and traditional tests of memory were also administered for comparison. RESULTS: Patients were worse on all tests but the profile was non-uniform. A componential analysis indicated that the patients were characterized by a poor ability to think ahead and organize responses but an intact ability to switch attention and inhibit prepotent responses. Patients also demonstrated poor memory, especially for free recall of a story and associate learning of unrelated word pairs. CONCLUSIONS: In contradistinction to previous studies, schizophrenic patients do have profound executive impairments at the beginning of the illness. However, these concern planning and strategy use rather than attentional set shifting, which is generally unimpaired. Previous findings in more chronic patients, of severe attentional set shifting impairment, suggest that executive cognitive deficits are progressive during the course of schizophrenia. The finding of severe mnemonic impairment at first episode suggests that cognitive deficits are not restricted to one cognitive domain

Peter Josef Ell : discurs llegit a la cerimònia d'investidura celebrada a l'aula magna de Casa Convalescència el dia 5 d'abril de l'any 2005

Peter Josef Ell , nascut el 7 de maig de 1944, és professor de Medicina Nuclear a la Universitat de Londres des de 1987, director del Institute of Nuclear Medicine, UCL, des de 1986, Honorary Consultant Physician del Middlesex Hospital des de 1976, i Clinical Director del UCLH NHS Trust des de 2001. El professor Ell és una de les figures més rellevants del món en l'àrea de la medicina nuclear i del diagnòstic per la imatge. La seva formació, variada i europeista, inclou una llicenciatura en Medicina per la Universitat de Lisboa, un màster en Ciències per la Universitat de Londres i un doctorat per la Universitat de Berna. No solament parla diverses llengües, sinó que ha integrat les cultures portuguesa, alemanya i anglesa. És director del Institute of Nuclear Medicine del UCL, un dels serveis més grans d'Anglaterra en l'especialitat, i catedràtic de Medicina Nuclear en aquest mateix centre. És autor de més de cinc-centes publicacions científiques, moltes d'elles en les revistes de més factor d'impacte (Lancet, JCO, JACC, etc.), i és editor/autor de dotze llibres de text, i de múltiples comunicacions i presentacions a congressos. Ha estat convidat a pronunciar nombroses conferències arreu del món. La seva multiculturalitat li ha permès de tenir un paper central en la creació i formació de la Societat Europea de Medicina Nuclear (EANM), de la qual va ser autor de molts dels documents fundacionals, i de la qual ha estat president entre 1994 i 1996. Ha estat quinze anys redactor en cap del European Journal of Nuclear Medicine and Molecular Imaging, revista que, sota la seva direcció, s'ha consolidat com una de les més importants del món en aquesta àrea científica.Nomenament 10/11/2004. A proposta de Facultat de Medicina. Investidura 05/05/2005. Padrí: Ignasi Carri