Analyzing structural and functional brain changes related to an integrative cognitive remediation program for schizophrenia: A randomized controlled trial

Cognitive remediation has been shown to improve cognition in schizophrenia, but little is known about the specific functional and structural brain changes related to the implementation of an integrative cognitive remediation program. This study analyzed the functional and structural brain changes identified after implementing an integrative cognitive remediation program, REHACOP, in schizophrenia. The program combined cognitive remediation, social cognitive training, and functional and social skills training. The sample included 59 patients that were assigned to either the REHACOP group or an active control group for 20 weeks. In addition to a clinical and neuropsychological assessment, T1-weighted, diffusion-weighted and functional magnetic resonance images were acquired during a resting-state and during a memory paradigm, both at baseline and follow-up. Voxel-based morphometry, tract-based spatial statistics, resting-state functional connectivity, and brain activation analyses during the memory paradigm were performed. Brain changes were assessed with a 2 × 2 repeated-measure analysis of covariance for group x time interaction. Intragroup paired t-tests were also carried out. Repeated-measure analyses revealed improvements in cognition and functional outcome, but no significant brain changes associated with the integrative cognitive remediation program. Intragroup analyses showed greater gray matter volume and cortical thickness in right temporal regions at post-treatment in the REHACOP group. The absence of significant brain-level results associated with cognitive remediation may be partly due to the small sample size, which limited the statistical power of the study. Therefore, further research is needed to clarify whether the temporal lobe may be a key area involved in cognitive improvements following cognitive remediation.This study has been supported by the Carlos III Health Institute of the Spanish Ministry of Economy and Competitiveness (PI16/01022) and the Department of Education and Science of the Basque Government (Team A; IT946-16). AS was supported by a Fellowship from the Fundación Tatiana Pérez de Guzmán el Bueno. MTE was supported by a Fellowship from University of the Basque Country (UPV/EHU; PIF 19/40). The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cognitive dysfunction in schizophrenia: An expert group paper on the current state of the art.

Cognitive impairment in schizophrenia represents one of the main obstacles to clinical and functional recovery. This expert group paper brings together experts in schizophrenia treatment to discuss scientific progress in the domain of cognitive impairment to address cognitive impairments and their consequences in the most effective way. We report on the onset and course of cognitive deficits, linking them to the alterations in brain function and structure in schizophrenia and discussing their role in predicting the transition to psychosis in people at risk. We then address the assessment tools with reference to functioning and social cognition, examining the role of subjective measures and addressing new methods for measuring functional outcomes including technology based approaches. Finally, we briefly review treatment options for cognitive deficits, focusing on cognitive remediation programs, highlighting their effects on brain activity and conclude with the potential benefit of individualized integrated interventions combing cognitive remediation with other approaches

Exploration de la reconnaissance des émotions en schizophrénie comorbide

La schizophrénie est un trouble mental complexe qui possède plusieurs étiologies possibles, enracinées à la fois dans la biologie et l'environnement. Ce trouble se manifeste par divers symptômes négatifs et positifs ainsi que de nombreux déficits neurocognitifs et sociocognitifs. Pour compliquer les choses, ce trouble est fortement comorbide avec plusieurs autres, dont l'un des plus répandus est le trouble d'abus de substances. La plupart des recherches se sont concentrées soit sur la neurobiologie de cette maladie, soit sur l'identification de structures cérébrales déficientes et la dérégulation de plusieurs systèmes neurotransmetteurs, ou encore sur la neurocognition en essayant de déceler les déficits dans des domaines tels que l'attention, l'apprentissage et la mémoire, via l'usage de technologies modernes telles que l'imagerie cérébrale fonctionnelle. Cependant, des études plus récentes ont démontré que ce qui caractérise le plus la schizophrénie serait plutôt lié au fonctionnement social. De plus, on peut prédire plus facilement le fonctionnement social lorsque l'on examine les domaines sociocognitifs plutôt que les domaines neurocognitifs. Plus précisément, il a été démontré que la capacité à reconnaître les émotions pouvait avoir une très forte association avec le fonctionnement social et les conséquences du trouble. Cependant, en ce qui concerne la reconnaissance des émotions, aucun consensus n’émerge de la littérature scientifique. Certains affirment que les déficits sociocognitifs sont globaux tandis que d'autres suggèrent qu'ils sont spécifiques à une ou certaines émotions. Pourtant, d'autres ont postulé que les résultats hétérogènes dans la reconnaissance des émotions pourraient être dus non pas aux décifits eux-mêmes, mais plutôt aux méthodes utilisées pour mesurer la reconnaissance des émotions. Il est également important de noter que la plupart des études ont porté uniquement sur les personnes atteintes de schizophrénie seule lorsque les statistiques montrent qu'environ 50% de ces personnes souffrent également d'un trouble d'abus de substances. Par conséquent, essayer de déterminer les déficits sociocognitifs dans la schizophrénie seule pourrait ne pas permettre de généraliser les résultats. Notre objectif premier était d'évaluer la reconnaissance des émotions à la fois globale et spécifique, dans la schizophrénie seule et dans la schizophrénie comorbide avec l'abus de substances, en utilisant des avatars virtuels comme outil de mesure (considéré plus naturel) et en examinant l'impact sur le fonctionnement social. Nos résultats pour l'ensemble de l'échantillon composé de personnes atteintes de schizophrénie seule et de schizophrénie et d'abus de substances ont montré une bonne reconnaissance générale des émotions, la tristesse étant la plus facile à identifier et la peur étant la plus difficile. Il y avait aussi des patrons d'interprétation erronés où la peur tendait à être confondue avec la surprise alors que la colère était confondue avec la neutralité. Il y avait une corrélation positive entre l'identification de la tristesse et la fréquence des interactions positives avec la famille et une corrélation négative entre les erreurs d'identification dans la neutralité et la fréquence de l'interaction positive avec la famille. Il est important de noter que les personnes présentant des comorbidités étaient plus à même de reconnaître les émotions négatives comme la colère et la peur, les amenant à interagir davantage avec les autres. Compte tenu de ces résultats paradoxaux, nous avons voulu dans notre deuxième article, mieux comprendre l'impact du trouble d'abus de substances - plus spécifiquement pour la consommation de cannabis qui a été la plus étudiée - sur la schizophrénie afin de donner un sens aux profils sociocognitifs que nous avons trouvé, avec comme objectif principal de trouver des moyens appropriés pour remédier aux déficits. Nous avons exploré différents modèles explicatifs tels que l'hypothèse neuroprotectrice, l'hypothèse de vulnérabilité inférieure et enfin l'hypothèse sociale qui est la plus prometteuse. Enfin, nous avons examiné la littérature pour voir ce qui a été fait le plus souvent en matière de remédiation cognitive en sociocognition. Nous pouvons conclure qu'il serait préférable de créer un programme de remédiation hybride qui inclurait à la fois l'apprentissage via la pratique - en créant un programme d'entrainement à la reconnaissance des émotions adapté aux déficits individuels avec des avatars virtuels - et l'apprentissage stratégique par la thérapie de groupe pour intégrer les compétences sociales une fois la rééducation de la reconnaissance des émotions acquise. En conclusion, alors que notre échantillon était petit, sans pouvoir prédictif ou de comparaison avec un groupe témoin, nos résultats soulignent toutefois l'importance de la remédiation ciblée et l'impact de l'abus de substances comorbides sur les profils sociocognitifs en schizophrénie. Nous suggérons que la schizophrénie est plutôt un «trouble social» qu'un trouble «du cerveau» ou «de la pensée». Nous explorons les diverses étiologies sociales telles que les expériences traumatiques de l'enfance, la déviance de la communication parentale et le concept 'd'émotion exprimée' tout en suggérant que la stigmatisation, l'isolement social et les mauvaises interactions sociales pourraient être à l'origine des nombreux dysfonctionnements. Par conséquent, nous suggérons que l'accent de la recherche future soit mis sur les comorbidités en schizophrénie, sur la cognition sociale et sur les impacts sur le fonctionnement social.Schizophrenia is a complex mental disorder that has multiple possible aetiologies that are rooted in both biology and environment. It is manifested through various negative and positive symptoms as well as many neurocognitive and sociocognitive deficits. To complicate matters, this disorder is highly comorbid with several others, with one of the most prevalent one being substance use disorder. Most research in the past has focused on either the neurobiology of this illness, identifying deficient brain structures and dysregulation in several neurotransmitter systems or on neurocognition trying to decipher the deficits in domains like attention, learning and memory through the use of modern technology such as functioning imaging. However, more recent studies have shown that what could very well be the hallmark of schizophrenia, is rather more linked to social functioning. Furthermore, social functioning can be more readily predicted when we examine sociocognitive domains rather than neurocognitive ones. More specifically, it has been shown that emotion recognition ability could have a very strong association with social functioning and outcomes. However, where emotion recognition is concerned, there is no clear consensus in the literature. Some argue the deficits are global while others suggest that it is emotion specific. Yet others have posited that perhaps, the heterogeneous findings in emotion recognition could be due not to the deficits themselves to rather to the methods used to measure emotion recognition. Also of importance, is the fact that most studies will solely focus on individuals that have schizophrenia alone when statistics show that around 50% of these individuals also suffer from substance use disorder. Therefore, trying to ascertain sociocognitive deficits in schizophrenia alone might not be optimal to generalize the findings. As such, it was our first objective to assess emotion recognition both global and specific, in schizophrenia alone and in comorbid schizophrenia and substance use disorder, using virtual avatars as a more naturalistic measurement tool and also examining the impact of social functioning. Our results for the whole sample comprised of individuals with schizophrenia alone and schizophrenia and substance use disorder, showed good overall emotion recognition with sadness being the easiest to identify and fear the hardest. There were also specific misinterpretation patterns where fear tended to be misidentified as surprise while anger was perceived as neutrality. There was a positive correlation between identification sadness and frequency of positive interaction with family and a negative one between identification errors in neutrality and frequency of positive interaction with family. Importantly, individual with comorbid presentations were better at recognizing negative emotions like anger and fear leading to more interactions with others. Given those paradoxical results, we wanted in our second article, to better understand the impact of substance use disorder – more specifically for cannabis use which has been studied the most – on schizophrenia in order to make sense of the sociocognitive profiles we found, with the main objective of finding appropriate ways to remediate the deficits. We explored various explanatory models such as the neuroprotective hypothesis, the lower vulnerability hypothesis and finally the social hypothesis which is the one that holds the most promise. Finally, we examined the literature to see what was done the most often with regard to cognitive remediation in sociocognition. We can conclude that it would be preferable to create a hybrid remediation program that would include both practice learning – by creating a training program for emotion recognition tailor-fitted to individual deficits with virtual avatars – and strategy learning through group therapy to integrate social skills following retraining of emotion recognition. To conclude, while our sample was small and did not allow us any predictive power or comparison with a control group, our results highlight the importance of targeted remediation and the impact of comorbid substance use disorder on sociocognitive profiles. We suggest that schizophrenia is rather a "social disorder" than it is a "brain" or "thought disorder". We explore the various social aetiologies such as traumatic childhood experiences, communication deviance and expressed emotion for the disorder while proposing that stigmatisation, social isolation and overall poor social interactions could be at the source of the many dysfunctions found in the disorder. Therefore, we suggest that the focus of future research should be on both comorbidities in schizophrenia, social cognition and social functioning outcomes

Exploring Predictors of Outcome in the Psychosis Prodrome: Implications for Early Identification and Intervention

Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth

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

Exercise induced neuroplasticity to enhance therapeutic outcomes of cognitive remediation in schizophrenia: Analyzing the role of brain-derived neurotrophic factor

Cognitive impairment is a major manifestation of schizophrenia and a crucial treatment target as these deficits are closely related to patients' functional outcomes. Cognitive remediation is the gold-standard practice to address cognitive deficits in schizophrenia. There is clear evidence stating that cognitive remediation improves cognitive function and promotes structural neuroplastic changes in patients with schizophrenia, with brain-derived neurotrophic factor (BDNF) expression emerging as a potential biomarker for its efficacy. This is particularly important as there is clear evidence relating atypical BDNF expression to cognitive impairment in patients with schizophrenia. Despite the valuable role of cognitive remediation in the management of schizophrenia, there is still a need to develop methods that allow maximizing its efficacy.info:eu-repo/semantics/publishedVersio

The effect of transcranial direct current stimulation (tDCS) on working memory in schizophrenia

Die vorliegende Dissertation untersucht die Anwendung von tDCS zur Behandlung von kognitiven Defiziten bei Menschen mit Schizophrenie in mehreren Experimenten. Im Experiment von Schwippel und Kollegen wurde die Verbesserung des räumlichen Arbeitsgedächtnisses mit 2 mA tDCS nachgewiesen. Es zeigten sich erste Hinweise darauf, dass die Stimulationswirkung von den allgemeinen kognitiven Fähigkeiten der Patienten und von der Schwierigkeit der Aufgabe beeinflusst wird. Der Stimulationseffekt zeigte sich in der Verbesserung der Fehlerrate in Kombination mit einer Verlangsamung der Reaktionszeit, was für eine Anpassung der Balance zwischen Geschwindigkeit und Genauigkeit spricht. In Bezug auf das verbale Arbeitsgedächtnis wiesen Papazova und Kollegen einen positiven Einfluss von tDCS auf die Arbeitsgedächtnisleistung von Menschen mit Schizophrenie nach. Interessanterweise wurde kein Intensitätseffekt beobachtet, obwohl sich in der post hoc Analyse tDCS in der niedrigeren Intensität (1 mA) als effektiver erwies. Eine Verlangsamung der Reaktionszeit war lediglich numerisch nachweisbar. Zusammenfassend lässt sich konstatieren, dass tDCS die Arbeitsgedächtnisleistung von Menschen mit Schizophrenie verbessern kann. Die optimalen Stimulationsparameter und weitere Prädiktoren für die Wirksamkeit der Stimulation sind Gegenstand der zukünftigen Forschung.The present dissertation presents the application of tDCS for the treatment of cognitive deficits in patients with schizophrenia in two publications. The studies systematically investigate the effect of different stimulation intensities on verbal and spatial working memory in schizophrenia. The investigations are based on preliminary work in healthy volunteers (Ruf et al., 2017). In the experiment by Schwippel and colleagues, improvement of spatial working memory was demonstrated with 2 mA tDCS (Schwippel et al., 2018b). There is first evidence that the stimulation effect is influenced by general cognitive abilities of the patients and by task difficulty. The stimulation effect is manifested in the improvement of the error rate, in combination with a slowing of response time, which is suggestive for a speed-accuracy trade-off. With regard to verbal working memory, Papazova and colleagues showed a beneficial effect of tDCS on working memory performance (Papazova et al., 2018). Interestingly, no effect of intensity was observed, although tDCS with lower intensity (1 mA) proved to be more effective. A slowing of the response time was only numerically present. In summary, tDCS can improve working memory performance in schizophrenia, although the optimal stimulation parameters and predictors of effectiveness remain the subject of future research

Social cognition in early schizophrenia: exploratory factor analysis and subcortical biomarkers

BACKGROUND: One of the central determinants of functional outcome in schizophrenia is social cognition (SC). With the wide array of SC domains, factor-analysis provides a powerful tool to identify commonalities amongst their underlying dysfunctions and its neural underpinnings. METHODS: The present study performed exploratory factor analysis (EFA) on 93 patients with early course schizophrenia using eight validated SC subtests. Factors derived from this analysis were then used to investigate their relationships with neurocognitive performance, clinical symptoms, and functional outcome. Moreover, subsequent shape analysis of the amygdala and hippocampus was performed using the MAGeT Brain pipeline to investigate their relationship to the composite scores of SC factors. RESULTS: EFA revealed a 3-factor solution, representing the domains of emotion management, emotion recognition, and theory of mind-social contextual appraisal, together accounting for 63.58% of the variance. Interestingly, only the theory of mind-social context appraisal factor correlated with measures of functional outcome. Addition analysis revealed that higher score on the theory of mind factor is significantly related with higher functional outcome measures and verbal learning performance, as well as with lower negative symptoms. Both emotion management and emotion perception factors indicated significant positive correlations with attention-vigilance while only emotion perception significantly correlated with visual learning and memory. Outward convexity of the right amygdala was identified to be positively correlated with the theory of mind-social context appraisal factor (p<0.05, FDR corrected), while the left and right hippocampus, specifically greater surface area of the dorsal-medial and ventral-lateral aspect of the hippocampus respectively, were positively correlated with higher composite score on theory of mind factor (p<0.05, FDR corrected). CONCLUSION: Our EFA indicates overlap amongst SC subtests which represent three different SC subdomains. Furthermore, shape analysis reveals that displacement and surface area of the amygdala and hippocampus respectively play a role in theory of mind. In the future, the SC factors that we identified, along with their neural correlates, could provide essential diagnostic tools to assess SC functioning in early schizophrenia patients, as well as identify strategies for potential improvement following cognitive remediation therapy