Neurological signs and morphological cerebral changes in schizophrenia: An analysis of NSS subscales in patients with first episode psychosis

Section of Geriatric Psychiatry, University of Heidelberg, Germany.
Psychiatry Research (Impact Factor: 2.47). 05/2011; 192(2):69-76. DOI: 10.1016/j.pscychresns.2010.11.009
Source: PubMed


Neurological soft signs (NSS) comprise a broad range of minor motor and sensory deficits which are frequently found in schizophrenia. However, the cerebral changes underlying NSS are only partly understood. We therefore investigated the cerebral correlates of NSS by using magnetic resonance imaging (MRI) in 102 patients with first episode schizophrenia. NSS were assessed after remission of acute psychotic symptoms using the Heidelberg scale (HS), which consists of five NSS subscales ("motor coordination", "complex motor tasks", "orientation", "integrative functions", and "hard signs"). Correlations between NSS scores and cerebral changes were established by optimized voxel-based morphometry. NSS total scores were significantly associated with reduced gray matter densities in the precentral and postcentral gyri, the inferior parietal lobule and the inferior occipital gyrus. Both of the NSS subscales "motor coordination" and "complex motor tasks", referred to motor strip changes but showed differential correlations with parietal, insular, cerebellar or frontal sites, respectively. The NSS subscales "orientation" and "integrative functions" were associated with left frontal, parietal, and occipital changes or bihemispheric frontal changes, respectively. The NSS subscale "hard signs" was associated with deficits in the right cerebellum and right parastriate cortex. Repeated analyses for white matter changes revealed similar results. These findings confirm the associations between NSS and cerebral changes in areas important for motor and sensory functioning. This variety of cerebral sites corresponds to the heterogeneity of NSS and are consistent with the hypothesis that NSS reflect both a rather generalized cerebral dysfunction and localized deficits specific for particular signs.

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    • "NSS refer to difficulties in motor coordination, sensory integration and movement sequencing . It is assumed that NSS include both global, cerebral changes associated with schizophrenia itself, but also localized changes in brain regions related to affected motor or sensory function (Heuser et al., 2011). Thus, NSS are seen not as a result of adverse side effects of antipsychotic medication, but rather reflecting the underlying neurobiology of schizophrenia illness (Chan et al., 2010), or its subtype. "
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    ABSTRACT: Movement sequencing difficulties are part of the neurological soft signs (NSS), they have high clinical value because they are not always present in schizophrenia. We investigated the neuronal correlates of movement sequencing in 24 healthy controls and 24 schizophrenia patients, with (SZP SQ +) or without (SZP SQ −) sequencing difficulties. We characterized simultaneous and lagged functional connectivity between brain regions involved in movement sequencing using psychophysiological interaction (PPI) and the Granger causality modeling (GCM), respectively. Left premotor cortex (PMC) and superior parietal lobule (SPL) were specifically activated during sequential movements in all participants. Right PMC and precuneus, ipsilateral to the hand executing the task, activated during sequential movements only in healthy controls and SZP SQ −. SZP SQ + showed hyperactivation in contralateral PMC, as compared to the other groups. PPI analysis revealed a deficit in inhibitory connections within this fronto-parietal network in SZP SQ + during sequential task. GCM showed a significant lagged effective connectivity from right PMC to left SPL during task and rest periods in all groups and from right PMC to right precuneus in SZP SQ + group only. Both SZP groups had a significant lagged connectivity from right to left PMC, during sequential task. Our results indicate that aberrant fronto-parietal network connectivity with cortical inhibition deficit and abnormal reliance on previous network activity are related to movement sequencing in SZP. The overactivation of motor cortex seems to be a good compensating strategy, the hyperactivation of parietal cortex is linked to motor deficit symptoms.
    Full-text · Article · Jan 2016 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
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    • "Furthermore, all the aforementioned neuroimaging studies in schizophrenia patients used conventional subtraction analysis and did not examine the underlying connectivity between the brain regions identified. Given that some NSS, such as the Fist–Edge–Palm (FEP) task (first described by Luria, see Heuser et al., 2011), involve the functional integration or regulation of areas involved in motor sequencing rather than being directly activated, a connectivity approach is more appropriate to identify the specific network involved. Only one study (Rao et al., 2008) adopted a psychophysiological interaction (PPI) (Friston et al., 1997) method to re-analyze their previous findings on the FEP task in healthy volunteers (Chan et al., 2006). "
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    ABSTRACT: Neurological soft signs have been considered one of the promising neurological endophenotypes for schizophrenia. However, most previous studies have employed clinical rating data only. The present study aimed to examine the neurobiological basis of one of the typical motor coordination signs, the Fist-Edge-Palm task (FEP), in patients with first-episode schizophrenia and their non-psychotic first degree relatives. Thirteen patients with first-episode schizophrenia, 14 non-psychotic first-degree relatives and 14 healthy controls were recruited. All of them were instructed to perform the FEP task in a 3T GE Machine. Psychophysiological interaction (PPI) analysis was used to evaluate the functional connectivity between the sensorimotor cortex and frontal regions when participants performed the FEP task compared to simple motor tasks. In the contrast of palm-tapping (PT) vs. rest, activation of the left frontal-parietal region was lowest in the schizophrenia group, intermediate in the relative group and highest in the healthy control group. In the contrast of FEP vs. PT, patients with schizophrenia did not show areas of significant activation, while relatives and healthy controls showed significant activation of the left middle frontal gyrus. Moreover, with increase in task complexity, significant functional connectivity was observed between the sensorimotor cortex and the right frontal gyrus in healthy controls but not in patients with first episode schizophrenia. These findings suggest that activity of the left frontal-parietal and frontal regions may be neurofunctional correlates of neurological soft signs, which in turn may be a potential endophenotype of schizophrenia. Moreover, the right frontal gyrus may play a specific role in the execution of the FEP task in schizophrenia spectrum disorders.
    Full-text · Article · Sep 2015 · Clinical neuroimaging
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    • "This result is in line with morphological studies (Heuser et al. 2011; Exner et al. 2006). Exner et al. (2006) found structural abnormality in the left pre-SMA in first-episode SCZ patients, and Heuser et al. (2011) "
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    ABSTRACT: Previous studies suggested that the topological properties of brain anatomical networks may be aberrant in schizophrenia (SCZ), and most of them focused on the chronic and antipsychotic-medicated SCZ patients which may introduce various confounding factors due to antipsychotic medication and duration of illness. To avoid those potential confounders, a desirable approach is to select medication-naïve, first-episode schizophrenia (FE-SCZ) patients. In this study, we acquired diffusion tensor imaging datasets from 30 FE-SCZ patients and 34 age- and gender-matched healthy controls. Taking a distinct gray matter region as a node, inter-regional connectivity as edge and the corresponding streamline counts as edge weight, we constructed whole-brain anatomical networks for both groups, calculated their topological parameters using graph theory, and compared their between-group differences using nonparametric permutation tests. In addition, network-based statistic method was utilized to identify inter-regional connections which were impaired in the FE-SCZ patients. We detected only significantly decreased inter-regional connections in the FE-SCZ patients compared to the controls. These connections were primarily located in the frontal, parietal, occipital, and subcortical regions. Although small-worldness was conserved in the FE-SCZ patients, we found that the network strength and global efficiency as well as the degree were significantly decreased, and shortest path length was significantly increased in the FE-SCZ patients compared to the controls. Most of the regions that showed significantly decreased nodal parameters belonged to the top-down control, sensorimotor, basal ganglia, and limbic-visual system systems. Correlation analysis indicated that the nodal efficiency in the sensorimotor system was negatively correlated with the severity of psychosis symptoms in the FE-SCZ patients. Our results suggest that the network organization is changed in the early stages of the SCZ disease process. Our findings provide useful information for further understanding the brain white matter dysconnectivity of schizophrenia.
    Full-text · Article · Jan 2014 · Brain Structure and Function
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