Isabelle Amado

Correlation between clinical syndromes and neuropsychological tasks in unmedicated patients with recent onset schizophrenia

The aim of this study is to circumscribe the cognitive deficits according to schizophrenic syndromes in a population of sub-acute untreated patients. We have studied the cross-sectional correlation between cognitive deficits and schizophrenic symptoms, in a group of 24 untreated patients (including 17 neuroleptic-naive patients) with recent onset of the disease. A task of alertness, a working memory (WM) test (including two levels of difficulty) and an abbreviated version of the Wisconsin Card Sorting Test (WCST) were selected. WM deficits and poor performance on the WCST were highly correlated with disorganized symptoms, modestly with the positive syndrome and not with the negative syndrome. Thus, disorganized symptoms, more than any other, appear to be related to the impairment of executive function and WM in recent onset unmedicated patients with schizophrenia.

Memory-guided saccade abnormalities in schizophrenic patients and their healthy, full biological siblings

BACKGROUNDnOcular-motor inhibition errors and saccadic hypometria occur at elevated rates in biological relatives of schizophrenic patients. The memory-guided saccade (MS) paradigm requires a subject to inhibit reflexive saccades (RSs) and to programme a delayed saccade towards a remembered target.nnnMETHODnMS, RS, and central fixation (CF) tasks were administered to 16 patients who met the criteria for DSM-IV schizophrenia, 19 of their psychiatrically healthy siblings, and 18 controls.nnnRESULTSnPatients and siblings showed elevated MS error rates reflecting a failure to inhibit RSs to a visible target, as required by the task. In contrast to controls, prior errors did not improve MS accuracy in patients and siblings.nnnCONCLUSIONSnThe specific characteristics of the elevated MS error rate help to clarify the nature of the disinhibition impairment found in schizophrenics and their healthy siblings. Failure to inhibit premature saccades and to improve the accuracy of subsequent volitional saccades implicates a deficit in spatial working-memory integration, mental representation and/or motor learning processes in schizophrenia.

Visuo-spatial cognition in schizophrenia: Confirmation of a preference for local information processing

During visuo-spatial cognitive tasks, patients with schizophrenia show a preference for local (detailed) rather than global (holistic) information processing. The efficiency of such information processing is influenced by task difficulty. We tested whether patients preference for local processing would persist if task demands favored global or local processing. Twenty-four stabilized patients with schizophrenia (SZ) and 25 healthy, matched controls (C) were tested in a mental mirroring task. Task difficulty was manipulated while stimulus surface structures were maintained unchanged. Information processing was assessed by recording eye movements. SZ were slower than C in the easiest condition but they made more errors than C in the more difficult conditions. Further, SZ did not adapt their average fixation duration to task demands resulting in longer fixation duration in the easiest condition and shorter fixation duration in the most difficult condition compared to C. These findings suggest that patients employ local information processing even when it is maladaptive for task demands. That is, patients do not adapt their fixation duration to task demands implicating (i) a preference for scanning local stimuli features and (ii) information processing inflexibility. These features need to be taken into account when evaluating visuo-spatial cognitive performance in schizophrenia.

Cognitive remediation therapy (CRT) benefits more to patients with schizophrenia with low initial memory performances.

Abstract Purpose: Cognitive deficits in schizophrenia mainly affect memory, attention and executive functions. Cognitive remediation is a technique derived from neuropsychology, which aims to improve or compensate for these deficits. Working memory, verbal learning, and executive functions are crucial factors for functional outcome. Our purpose was to assess the impact of the cognitive remediation therapy (CRT) program on cognitive difficulties in patients with schizophrenia, especially on working memory, verbal memory, and cognitive flexibility. Methods: We collected data from clinical and neuropsychological assessments in 24 patients suffering from schizophrenia (Diagnostic and Statistical Manual of mental Disorders-Fourth Edition, DSM-IV) who followed a 3-month (CRT) program. Verbal and visuo-spatial working memory, verbal memory, and cognitive flexibility were assessed before and after CRT. Results: The Wilcoxon test showed significant improvements on the backward digit span, on the visual working memory span, on verbal memory and on flexibility. Cognitive improvement was substantial when baseline performance was low, independently from clinical benefit. Conclusions: CRT is effective on crucial cognitive domains and provides a huge benefit for patients having low baseline performance. Such cognitive amelioration appears highly promising for improving the outcome in cognitively impaired patients. Implications for Rehabilitation Cognitive impairment is observed in 70–80% of patients with schizophrenia a devastating disorder with high direct and indirect social costs and cognitive alterations are a crucial predictive factor for an inability to work. Cognitive remediation is an efficient technique to improve cognition, autonomy, and social functioning in patients. Individual structure programs are successful to improve working memory, verbal learning and flexibility in this study.

Signes neurologiques mineurs et troubles envahissants du développement

BACKGROUNDnMany studies have focused on specific motor signs in autism and Aspergers syndrome, but few has been published on the complete range of neurological soft signs (NSS) in children with pervasive developmental disorder (PDD). Scarce are the studies evaluating NSS in children suffering from PDD not otherwise specified (PDDNOS).nnnMETHODSnThis study compared performance of 11 autistic children (AD) and 10 children with PDDNOS, with controls matched on age, sex and cognitive performance on Krebs et al.s NSS scale. Because of the duration of the assessments and specific difficulties encountered in managing some items, an adaptation of the scale had to be made during a pilot study with the agreement of the author. To be eligible, patients had to meet the following inclusion criteria: an age range of 6-16 years, a diagnosis of autistic disorder or PDDNOS based on the DSMxa0IV criteria (American Psychiatric Association 1994). The autism diagnostic interview-revised (ADI-R) was used in order to confirm the diagnosis and to evaluate the association of the symptoms to the severity of the NSS. The childhood autism rating scale (CARS) was completed for the patients in order to evaluate symptoms at the time of the NSS examination. Cognitive ability was assessed with Ravens progressive matrices. Were excluded patients with: history of cerebral palsy, congenital anomaly of the central nervous system, epilepsy, known genetic syndrome, tuberous sclerosis, neurofibromatosis, antecedent of severe head trauma, Aspergers syndrome, obvious physical deformities or sensory deficits that would interfere with neurological assessment, deep mental retardation and recent or chronic substance use or abuse. Healthy controls shared the same exclusion criteria, with no personal history of neurological, psychiatric disorder or substance abuse, no family history of psychiatric disorder and normal or retardation in schooling. All study procedures were approved by the local Ethics Committee (Comité déthique, Razi Hospital), according to the declaration of Helsinki.nnnRESULTSnThere was no difference between patients and controls with respect to sex, age and cognitive function. All children had an IQ higher than 81. Significant differences were found between AD children and control group in the motor integration function and sensory integration function. Different NSS scores were significantly higher in the PDDNOS group than in controls: the total scores, motor coordination, motor integration function, sensory integration and abnormal movements. Lower performance in motor coordination skills was associated with higher ADI-R communication score in the AD group. No relationship was found between NSS and CARS total sore.nnnCONCLUSIONnThis study confirms the impaired neurological functioning in autistic as well as PDDNOS children. The association of motor impairment with autistic symptoms highlights the argument that motor control problems can be part of the autism spectrum disorders. The lack of relationship between NSS and intellectual aptitude in the clinical sample provides new elements for the neurodevelopment model of the autism spectrum.

Correlates between neurological soft signs and saccadic parameters in schizophrenia

OBJECTIVEnNeurological Soft Signs (NSS) and impairments in oculomotor saccadic paradigms are both frequent in patients with schizophrenia but their correlation has never been explored.nnnMETHODSn78 patients with DSM-IV schizophrenia (including 43 non-treated) and 41 matched healthy controls were tested for NSS, and on three saccadic tasks: prosaccades, predictive saccades and memory-guided saccades) using infrared oculometry. We analyzed correlations between NSS scores and latencies in all three tasks, rate of errors in memory-guided saccades, and rate of anticipated predictive saccades.nnnRESULTSnNo correlations were found in healthy controls. In the patient group, the NSS total and motor coordination scores were positively correlated with three saccadic variables: the latency of prosaccades (r=0.36, p<0.01 and r=0.36, p<0.01 respectively), of memory-guided saccades (r=0.35, p<0.01 and r=0.32, p<0.05 respectively) and, negative correlations were found, with the rate of anticipated predictive saccades (r=-0.33, p<0.01; r=-0.35, p<0.01 respectively). NSS total, motor coordination and sensory integration scores were correlated to the latency of non-anticipated predictive saccades (r=0.34, p<0.01; r=0.24, p<0.05 and r=0.40, p<0.001 respectively). The NSS total, motor integration and sensory integration scores were correlated with the rate of errors in memory-guided saccades (r=0.38, p<0.01; r=0.37, p<0.01 and r=0.34, p<0.01 respectively).nnnCONCLUSIONSnThese results support a common pathological mechanism with partial overlapping neural substrates between NSS and saccades in schizophrenia.

Conscious and unconscious performance monitoring: Evidence from patients with schizophrenia

ABSTRACT The ability to detect our own errors is an essential component of action monitoring. Using a masking paradigm in normal adults, we recently discovered that some error‐detection processes can proceed without awareness, while other markers of performance monitoring such as the Error‐Related Negativity (ERN) are tightly linked to conscious perception. Interestingly, research on cognitive deficit in schizophrenia has shown that the ERN is altered in these patients. In the present study, we therefore tested if the error detection impairment in schizophrenia is specific to conscious perception or is also found under non‐conscious conditions, probing whether these performance monitoring processes are truly distinct. Thirteen patients with schizophrenia and thirteen age‐matched healthy control subjects performed a speeded number comparison task on masked stimuli while EEG and MEG signals were recorded. Conscious perception and error‐detection were assessed on a trial‐by‐trial basis using subjective reports of visibility and confidence. We found that patients with schizophrenia presented altered cingulate error‐detection responses in conscious trials, as reflected by a decreased ERN. By contrast, on unconscious trials, both controls and schizophrenia patients performed above chance in evaluating the likelihood of having made an error. This dissociation confirms the existence of two distinct performance monitoring systems, and suggests that conscious metacognition in schizophrenia is specifically altered while non‐conscious performance monitoring remains preserved.

Reading impairment in schizophrenia: dysconnectivity within the visual system.

Patients with schizophrenia suffer from perceptual visual deficits. It remains unclear whether those deficits result from an isolated impairment of a localized brain process or from a more diffuse long-range dysconnectivity within the visual system. We aimed to explore, with a reading paradigm, the functioning of both ventral and dorsal visual pathways and their interaction in schizophrenia. Patients with schizophrenia and control subjects were studied using event-related functional MRI (fMRI) while reading words that were progressively degraded through word rotation or letter spacing. Reading intact or minimally degraded single words involves mainly the ventral visual pathway. Conversely, reading in non-optimal conditions involves both the ventral and the dorsal pathway. The reading paradigm thus allowed us to study the functioning of both pathways and their interaction. Behaviourally, patients with schizophrenia were selectively impaired at reading highly degraded words. While fMRI activation level was not different between patients and controls, functional connectivity between the ventral and dorsal visual pathways increased with word degradation in control subjects, but not in patients. Moreover, there was a negative correlation between the patients behavioural sensitivity to stimulus degradation and dorso-ventral connectivity. This study suggests that perceptual visual deficits in schizophrenia could be related to dysconnectivity between dorsal and ventral visual pathways.

A Serious Game to Improve Cognitive Functions in Schizophrenia: A Pilot Study

Cognitive deficits in schizophrenia impair everyday functioning and instrumental daily living activities. These disabilities can be partly responsible for chronicity and institutionalization. We present here a virtual reality (VR) tool in which patients with schizophrenia performed a virtual game in an imaginary town during a 3-month program. In a pilot study, seven patients with schizophrenia (DSM-5), institutionalized for many years, attended weekly 1-h-and-a-half sessions organized by two clinicians. During the first sessions, they listed together the difficulties they experienced in everyday organization and planning. After being familiarized with the joystick and the VR environment, they navigated in the town, and planned actions that were difficult for them to carry out in their usual life (e.g., shopping, memorizing the way to the supermarket or being on time at a meeting point). They had to look for alternative routes and practice a switch from a 2D Map to the 3D Map. They also gathered their efforts to share strategies for each action, or discussed the action plan they could generate to solve concrete problems. The pre/post-neuropsychological evaluations showed attention, working memory, prospective, and retrospective memory benefits, but no improvement in planning as assessed by the Zoo map test and the action program subtest of Behavioral Assessment of the Dysexecutive Syndrome. Patients also clinically and functionally improved, gaining autonomy. Pragmatically, they reported a strong energy to elaborate concrete plans to search for jobs, or return to activities in the community. Qualitative assessments showed a benefit in sparing time, planning better, enriched relatedness, and better management of their housework. This VR game opens avenue to rehabilitation for patients with schizophrenia experiencing chronicity in their life, less attendance in daycare units, and a better community living. This program might reduce neurocognitive difficulties and might evolve into a true method for cognitive remediation (trial n° 2011-A00988-33).

Traitement du contexte visuospatial chez des patients schizophrènes non traités – influence de la désorganisation

Resume Differentes etudes suggerent que les patients schizophrenes presentent une defaillance des strategies de selection et d’inhibition, des difficultes de retention temporaire de l’information visuospatiale lors de l’interference contextuelle.Nous proposons d’explorer les performances des patients schizophrenes non traites a l’aide de 2 epreuves evaluant la detection et la retention d’images complexes en situation d’interference contextuelle et la dependance-independance a l’egard du champ perceptif ainsi que l’influence de la desorganisation clinique sur ces performances. Le test de Recherche de Figures (RF) et le Group Embbeded Figure Test (GEFT) ont ete etudies chez 36 patients schizophrenes non traites, evalues cliniquement a l’aide de la Positive and Negative Syndrome Scale (PANSS) et apparies pour l’âge, le sexe et le niveau d’etudes a un groupe de sujets temoins. Si l’ensemble des patients montre des performances comparables aux temoins, le sous groupe des patients schizo phrenes desorganises obtient des scores aux deux tâches significativement plus faibles que les patients peu desorganises et les temoins. Lorsque le QI logico abstrait est introduit en covariable, cette difference disparait partiellement. Ces resultats soulignent l’atteinte des capacites d’integration de figures complexes en memoire visuospatiale chez les patients desorganises, liee vraisemblablement a un deficit de la composante visuospatiale de la memoire de travail qui pourrait renvoyer a un dysfonctionnement du cortex frontal dorsolateral.