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Reduced Laterality as a Trait Marker of Schizophrenia-Evidence from Structural and Functional Neuroimaging

Neurophysiology and Neuroimaging Laboratory, Department of Psychiatry, Goethe University, 60528 Frankfurt/Main, Germany.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 02/2010; 30(6):2289-99. DOI: 10.1523/JNEUROSCI.4575-09.2010
Source: PubMed

ABSTRACT Laterality is a characteristic principle of the organization of the brain systems for language, and reduced hemispheric asymmetry has been considered a risk factor for schizophrenia. Here we sought support for the risk factor hypothesis by investigating whether reduced asymmetry of temporal lobe structure and function is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age-matched first-degree relatives, and 15 healthy controls underwent high-resolution three-dimensional anatomical imaging and functional magnetic resonance imaging during auditory stimulation. Both the overall auditory cortex and planum temporale volumes and the lateralization to the left hemisphere were markedly reduced in patients. The decrease of lateralization correlated with increased severity of symptoms. In addition, both the overall functional activation in response to auditory stimulation and its asymmetry were reduced in the patients. Relatives had intermediate values between patients and controls on both structural and functional measures. This study provides added support for the idea that reduced hemispheric asymmetry is a biological risk factor for schizophrenia.

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    • "An extreme example of a lateralized function is human language, although asymmetry in other functions including aspects of memory and emotion have been described (Kavcic et al. 2003; Hugdahl, 2005; Lowell et al. 2012; Smaers et al. 2012). Perception and cognition can remain relatively intact in unilateral or split brain subjects (Gordon & Sperry, 1969), whereas cerebral lateralization can enhance performance and reduced bilateral communication can impair cognition (Arora & Meltzer, 1991; Carlson & Glick, 1991; Hill et al. 2009; Shi et al. 2009; Oertel et al. 2010; Long et al. 2013). Although not a typical thalamocortical sensory system, the olfactory system may also demonstrate asymmetry, especially in humans (Bellas et al. 1989; Zucco & Tressoldi, 1989; Zatorre et al. 1992; Jones-Gotman & Zatorre, 1993; Herz et al. 1999; Brand & Jacquot, 2001; Royet & Plailly, 2004; Thuerauf et al. 2008; Hudry et al. 2014). "
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    ABSTRACT: Bilateral cortical circuits are not necessarily symmetrical. Asymmetry, or cerebral lateralization, allows functional specialization of bilateral brain regions and has been described in humans for such diverse functions as perception, memory and emotion. There is also evidence for asymmetry in the human olfactory system, though evidence in non-human animal models is lacking. Here, we took advantage of the known changes in olfactory cortical local field potentials that occur over the course of odor discrimination training to test for functional asymmetry in piriform cortical activity during learning. Both the right and left piriform cortex local field potential activities were recorded. The results demonstrate robust inter-hemispheric asymmetry in anterior piriform cortex activity that emerges during specific stages of odor discrimination learning, with a transient bias toward the left hemisphere. This asymmetry is not apparent during error trials. Furthermore, functional connectivity (coherence) between the bilateral anterior piriform cortices is learning- and context-dependent. Steady-state inter-hemispheric anterior piriform cortex coherence is reduced during initial stages of learning and then recovers as animals acquire competent performance. The decrease in coherence is seen relative to bilateral coherence expressed in the home cage, which remains stable across conditioning days. Similarly, transient, trial-related inter-hemispheric coherence increases with task competence. Together the results demonstrate transient asymmetry in piriform cortical function during odor discrimination learning until mastery, and suggests that each PCX may contribute something unique to odor memory.This article is protected by copyright. All rights reserved
    The Journal of Physiology 01/2015; 593(7). DOI:10.1113/jphysiol.2014.288381
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    • "In these areas, we found significant group differences between patients and controls, and between unaffected relatives and controls, but no significant differences between relatives and patients. This finding may indicate that unaffected first-degree relatives of SZ patients have a pattern of resting-state activation comparable to that of SZ patients, which also conforms to several other resting-state (Whitfield-Gabrieli et al., 2009; Gavrilescu et al., 2010; Jang et al., 2011; Repovs et al., 2011) and task-related fMRI studies (Kasai et al., 2003; Kawasaki et al., 2008; Oertel et al., 2010). In contrast, left anterior cingulate cortex showed higher HG-seeded functional connectivity in SZ patients in comparison to relatives and controls. "
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    ABSTRACT: We have previously reported altered functional asymmetry of the primary auditory cortex (Heschl's gyrus) of patients with schizophrenia (SZ) and their relatives during auditory processing. In this study, we investigated whether schizophrenia patients have altered intrinsic functional organization of Heschl's gyrus (HG) during rest. Using functional magnetic resonance imaging (fMRI), we measured functional connectivity between bilateral HG and the whole brain in 24 SZ patients, 22 unaffected first-degree relatives and 24 matched healthy controls.SZ patients and relatives showed altered functional asymmetry in HG and altered connectivity between temporal and limbic areas in the auditory network during resting-state in comparison with healthy controls. These changes in functional connectivity correlated with predisposition towards hallucinations in patients and relatives and with acute positive symptoms in patients.The results are in line with the results from task-related and symptom-mapping studies that investigated the neural correlates of positive symptoms, and suggest that individual psychopathology is associated with aberrant intrinsic organization of auditory regions in schizophrenia. This might be evidence that reduced hemispheric lateralization and reduced functional connectivity of the auditory network are trait markers of schizophrenia.
    Schizophrenia Research 11/2014; 160(1-3). DOI:10.1016/j.schres.2014.10.036
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    • "Although unaffected siblings of patients do not develop schizophrenia , they share 50% of their genes with the patients [Brunelin , et al., 2008] and may have similar but less severe impairments [Karlsgodt, et al., 2007]. Consequently, the estimated values of trait markers in unaffected siblings should be similar to those of patients and intermediate between those of controls and patients [Knochel, et al., 2012; Oertel, et al., 2010]. For instance, Brunelin et al. [2007] and Marcelis et al. [2004] studied metabolite elevation in response to stress, and found that siblings showed a response which was intermediate between patients and controls. "
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    ABSTRACT: Trait markers of schizophrenia aid the dissection of the heterogeneous phenotypes into distinct subtypes and facilitate the genetic underpinning of the disease. The microstructural integrity of the white matter tracts could serve as a trait marker of schizophrenia, and tractography-based analysis (TBA) is the current method of choice. Manual tractography is time-consuming and limits the analysis to preselected fiber tracts. Here, we sought to identify a trait marker of schizophrenia from among 74 fiber tracts across the whole brain using a novel automatic TBA method. Thirty-one patients with schizophrenia, 31 unaffected siblings and 31 healthy controls were recruited to undergo diffusion spectrum magnetic resonance imaging at 3T. Generalized fractional anisotropy (GFA), an index reflecting tract integrity, was computed for each tract and compared among the three groups. Ten tracts were found to exhibit significant differences between the groups with a linear, stepwise order from controls to siblings to patients; they included the right arcuate fasciculus, bilateral fornices, bilateral auditory tracts, left optic radiation, the genu of the corpus callosum, and the corpus callosum to the bilateral dorsolateral prefrontal cortices, bilateral temporal poles, and bilateral hippocampi. Posthoc between-group analyses revealed that the GFA of the right arcuate fasciculus was significantly decreased in both the patients and unaffected siblings compared to the controls. Furthermore, the GFA of the right arcuate fasciculus exhibited a trend toward positive symptom scores. In conclusion, the right arcuate fasciculus may be a candidate trait marker and deserves further study to verify any genetic association. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 11/2014; 36(3). DOI:10.1002/hbm.22686
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