Neurological Soft Signs Are Not "Soft" in Brain Structure and Functional Networks: Evidence From ALE Meta-Analysis

Background: Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. Method: We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic -resonance imaging (fMRI) studies were included. Results: The results from meta-analysis of the sMRI studies-indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Conclusions: Ourfindings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders

Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia

Psychotic illness is associated with cognitive control deficits and abnormal recruitment of neural circuits subserving cognitive control. It is unclear to what extent this dysfunction underlies the development and/or maintenance of positive and negative symptoms typically observed in schizophrenia. In this study we compared fMRI activation on a standard Stroop task and its relationship with positive and negative symptoms in early psychosis (EP, N = 88) and chronic schizophrenia (CHR-SZ, N = 38) patients. CHR-SZ patients showed reduced frontal, striatal, and parietal activation across incongruent and congruent trials compared to EP patients. Higher positive symptom severity was associated with reduced activation across both trial types in supplementary motor area (SMA), middle temporal gyrus and cerebellum in EP, but not CHR-SZ patients. Higher negative symptom severity was associated with reduced cerebellar activation in EP, but not in CHR-SZ patients. A negative correlation between negative symptoms and activation in SMA and precentral gyrus was observed in EP patients and in CHR-SZ patients. The results suggest that the neural substrate of positive symptoms changes with illness chronicity, and that cognitive control related neural circuits may be most relevant in the initial development phase of positive symptoms. These findings also highlight a changing role for the cerebellum in the development and later maintenance of both positive and negative symptoms

Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia

Psychotic illness is associated with cognitive control deficits and abnormal recruitment of neural circuits subserving cognitive control. It is unclear to what extent this dysfunction underlies the development and/or maintenance of positive and negative symptoms typically observed in schizophrenia. In this study we compared fMRI activation on a standard Stroop task and its relationship with positive and negative symptoms in early psychosis (EP, N = 88) and chronic schizophrenia (CHR-SZ, N = 38) patients. CHR-SZ patients showed reduced frontal, striatal, and parietal activation across incongruent and congruent trials compared to EP patients. Higher positive symptom severity was associated with reduced activation across both trial types in supplementary motor area (SMA), middle temporal gyrus and cerebellum in EP, but not CHR-SZ patients. Higher negative symptom severity was associated with reduced cerebellar activation in EP, but not in CHR-SZ patients. A negative correlation between negative symptoms and activation in SMA and precentral gyrus was observed in EP patients and in CHR-SZ patients. The results suggest that the neural substrate of positive symptoms changes with illness chronicity, and that cognitive control related neural circuits may be most relevant in the initial development phase of positive symptoms. These findings also highlight a changing role for the cerebellum in the development and later maintenance of both positive and negative symptoms

Mediating effect of symptom severity on the relationship between aggression, impulsivity and quality of life outcomes among patients with schizophrenia and related psychoses

AimsAggression and impulsivity among individuals with schizophrenia have been associated with poor clinical outcomes including worsening of symptoms and substance abuse which have been linked to a lower quality of life (QoL). The current study aimed to look at the mediating effect of symptom severity on the relationship between aggression, impulsivity and QoL among outpatients with schizophrenia and related psychoses in a multi-ethnic Asian population.MethodsData (n = 397) were collected from outpatients seeking treatment at the Institute of Mental Health. The World Health Organization quality of life-BREF (WHOQOL-BREF) scale, the symptoms checklist-90 revised (SCL-90-R), Buss Perry aggression questionnaire (BPAQ), and the Barratt impulsiveness scales (BIS) were used to assess subjective well-being, symptom severity, aggression, and impulsivity, respectively. Mediation analysis was performed using the PROCESS macro to understand the mediating effect of symptom severity.ResultsMotor impulsivity (MI) was indirectly associated with both the physical and psychological health domains of QoL while self-control was indirectly associated with the physical, psychological, and environmental health QoL domains through increased symptom severity.ConclusionThe significant indirect effect of symptom severity in our study highlights one potential pathway through which impulsivity impacts the QoL of individuals with schizophrenia and related psychoses. Elucidating other factors besides symptom severity that have an indirect effect on the QoL of individuals provides alternative approaches for treatment through which better clinical outcomes can be achieved

Functional cerebral asymmetries of emotional processes in the healthy and bipolar brain

The perception and processing of emotions are of primary importance for social interaction, which confers faculties such as inferring what another person’s feels. Brain organisation of emotion perception has shown to primarily involve right hemisphere functioning. However, the brain may be functionally organised according to fundamental aspects of emotion such as valence, rather than involving processing of emotions in general. It should be noted, however, that emotion perception is not merely a perceptual process consisting in the input of emotional information, but also involves one’s emotional response. Therefore, the functional brain organisation of emotional processing may also be influenced by emotional experience. An experimental model for testing functional cerebral asymmetries (FCAs) of valenced emotional experience is uniquely found in bipolar disorder (BD) involving impaired ability to regulate emotions and eventually leading to depressive or manic episodes. Previous models have only explained hemispheric asymmetries for manic and depressive mood episodes, but not for BD euthymia. The present thesis sought to investigate FCAs in emotional processing in two major ways. First, FCAs underlying facial emotion perception under normal functioning was examined in healthy controls. Secondly, functional brain organisation in emotional processing was further investigated by assessing FCAs in the bipolarity continuum, used as an experimental model for studying the processing of emotions. In contrast with previous asymmetry models, results suggested a right hemisphere involvement in emotional experience regardless of valence. Atypical FCAs were found in euthymic BD patients reflecting inherent aspects of BD functional brain organisation that are free of symptomatic influence. Also, BD patients exhibited atypical connectivity in a default amygdala network particularly affecting the right hemisphere, suggesting intrinsic mechanisms associated with internal emotional states. Last, BD patients were associated with a reduced right hemisphere specialisation in visuospatial attention, therefore suggesting that right hemisphere dysfunction can also affect non-emotional processes. Taken together, the findings emphasize a BD continuum model relying on euthymia as a bridging state between usual mood and acute mood phases

Aufmerksamkeitskontrolle von Attributionsprozessen in Schizophrenie

In patients with schizophrenia, the misattribution of self-generated events to an external source is associated with self-recognition deficits and the presence of psychotic symptoms. The aim of the present study was to investigate how this misattribution is influenced by dysfunction of attentional processing, which is also impaired in schizophrenia. I conducted two different studies. In both studies participant’s expectancies were manipulated using visual cues that were either congruent (valid) or incongruent (invalid) with the speech. The source (self/alien) and the acoustic quality (undistorted/distorted) of the speech were also manipulated. First, twentythree patients with schizophrenia, with hallucinations and delusions (H/D patients) and twentythree matched healthy controls (HC) were tested for the behavioral study. Later on, twenty patients with first episode psychosis (FEP) and twenty matched healthy controls (HC) underwent functional Magnetic Resonance Imaging (fMRI) while listening to prerecorded speech. The results of the behavioral part of the study showed that H/D patients exhibited increased error rates comparing to HC, when listening to the distorted self spoken words, misidentifying their own speech as produced by others. Importantly, patients made significantly more errors across all the invalid cue conditions. This suggested not only the presence of pathological misattribution bias, but also an inadequate balance between top-down and bottom-up attentional processes in patients, which could be responsible for misattribution of the ambiguous sensory material. Analysis of fMRI data showed that FEP patients when listening to self-generated speech preceded by an invalid (alien) cue, relative to HC showed a strong trend to misidentify their own speech as an other person's. The patient group had reduced activation in the right middle temporal gyrus (MTG) and left precuneus (Pc) relative to HC. Within the FEP group, the level of activation in the right MTG was negatively correlated with the severity of their positive psychotic symptoms. I conclude that impaired attentional modulation in schizophrenia may contribute to the tendency for FEP patients to misattribute the source of self-generated material, and this may be mediated through the right MTG and Pc, regions that are involved in both self-referential processing and the integration of sensory information.Schizophrene Patienten neigen dazu selbstgenerierte Handlungen auf externe Quellen zu misattribuieren. Dieser Bias ist assoziiert mit kognitiven Defiziten im Bereich der Selbsterkennung sowie mit psychotischen Symptomen. Das Ziel der präsentierten Studien ist es, zu untersuchen in wie weit dieser Misattributionsbias durch Aufmerksamkeitsprozesse beeinflusst wird, welche ebenfalls in schizophrenen Patienten beeinträchtigt sind. Ich führte zwei Studien durch in welchen die Probanden unterscheiden sollten, ob ein auditiv präsentiertes Wort in der eigenen Stimme oder einer fremden Stimme dargeboten wurde. Dabei wurden die Erwartungen der Probanden manipuliert durch visuelle Hinweisreize die entweder kongruent oder inkongruent zu einem auditiven Stimulus waren. Zudem wurde die akustische Qualität (unverzerrt / verzerrt) manipuliert. In der ersten Studie wurden 23 Patienten mit Schizophrenie sowie 23 gesunde Probanden in einem behavioralen Design untersucht. In der zweiten Studie wurden bei 20 Patienten mit Schizophrenie sowie bei 20 gesunden Probanden das gleiche Paradigma mittels fMRT untersucht. In der behavioralen Studie zeigte sich bei Patienten mit Schizophrenie im Vergleich zu gesunden Probanden eine erhöhte Fehlerrate und somit eine Tendenz die eigene Stimme zu missattribuieren, wenn selbstgesprochene Wörter verzerrt präsentiert wurden. Interessanterweise zeigten Patienten in allen Bedingungen mit inkongruenten Hinweisreizen eine signifikant erhöhte Fehlerrate. Dies lässt vermuten, dass bei schizophrenen Patienten ein generelles Muster kognitiver Beeinträchtigung vorliegt. Möglicherweise zeigen Patienten auf Grund einer Dysbalance von top-down und bottom-up gesteuerten Aufmerksamkeitsprozessen, eine beeinträchtigte Leistung bei der Attribuierung inkongruenter Stimuli. In der fMRT-Studie zeigten schizophrene Patienten eine ausgeprägte Tendenz ihre eigene Stimme als eine fremde Stimme zu misattribuieren, wenn inkongruente Hinweisreize präsentiert wurden. Dabei zeigten Patienten eine reduzierte Aktivität im rechten mittleren Temporallappen sowie im linken Precuneus. Zudem zeigte sich eine negative Korrelation zwischen der Aktivität im rechten mittleren Temporallappen und der Ausprägung der positiven Symptomatik. Daher ist anzunehmen, dass möglichweise eine beeinträchtigte Balance zwischen top-down und bottom-up gesteuerten Aufmerksamkeitsprozessen zum Misattributionbias in schizophrenen Patienten beiträgt. Zudem ist dieser Einfluss assoziiert mit Aktivität in Hirnregionen, die in der Integration sensorischer Information sowie in der Verabeitung selbstreferentieller Information involviert sind, wie der rechte mittlere Temporallappen sowie der Precuneu

Neurocognitive Insights in Nicotine Addiction

In the Netherlands, 27% of the population is currently smoking. Nicotine is among the most addictive substances of abuse. Thirty-two percent of the people who tried smoking develop nicotine dependence within ten year. This percentage is higher for nicotine than for other substances of abuse (e.g., 23 for heroin: Anthony, et al. 1994). Eighty percent of the smokers intend to quit smoking in the future while only 25% actually attempt to quit every year. Most of these quit attempts fail as 88-95% of the quitters smoke again in the year following the quit attempt (International Tobacco Control Policy Evaluation Project 2011). Although smoking rates are decreasing since 1970, the decline in smoking rates is less distinct in populations with a lower social economic status. Youngsters with lower educational levels start smoking more often and it could be that those with lower social economic status have more difficulties giving up smoking. Nicotine dependence is currently included in the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV-TR) as a ‘substance use disorder’. Examples of diagnostic criteria are tolerance, withdrawal, smoking more than one intended, and the continuation of smoking despite knowledge of adverse consequences. Although nicotine dependence is included in the DSM-IV, nicotine dependence is rarely diagnosed. In addition, many smokers do not meet the diagnostic criteria, although they do experience problems giving up smoking (Schmitz, et al. 2003) and have increased risks for serious health problems. All these characteristics of smoking imply that smoking is a serious and chronic condition that occurs in a substantial part of the population