Disruption of White Matter Integrity in the Inferior Longitudinal Fasciculus in Adolescents With Schizophrenia as Revealed by Fiber Tractography

Ashtari, Manzar; Cottone, John; Ardekani, Babak A.; Cervellione, Kelly; Szeszko, Philip R.; Wu, Jinghui; Chen, Steven; Kumra, Sanjiv

doi:10.1001/archpsyc.64.11.1270

Cited by 160 publications

(130 citation statements)

References 73 publications

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“…Differences in RD are less examined, yet to date increases have been detected in the external capsule (Seal et al, 2008), in the left inferior temporal and left occipital lobe (Ashtari et al, 2007), in temporal WM (Koch et al, 2011), and in the middle cerebellar peduncle (Okugawa et al, 2006), and increased mean diffusivity has been detected in the splenium of the corpus callosum (Foong et al, 2000). The regions reported in these studies were also found in this work.…”

Section: Discussionmentioning

confidence: 99%

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Holleran

Ahmed

Anderson‐Schmidt

et al. 2013

Neuropsychopharmacol

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Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age-and gender-matched healthy controls using a 64 gradient direction sequence, (b ¼ 1300 s/mm 2 ) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.

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Section: Discussionmentioning

confidence: 99%

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Holleran

Ahmed

Anderson‐Schmidt

et al. 2013

Neuropsychopharmacol

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“…This is not the first study pointing to altered diffusion parameters in the thalamus or thalamocortical pathways. DTI findings supporting altered integrity of thalamocortical connectivity in schizophrenia include controversial alterations of fractional anisotropy in the anterior limb of the internal capsule (ALIC) Kubicki et al, 2005;Mamah et al, 2010;Sprooten et al, 2009;Sussmann et al, 2009;Zhang et al, 2010;Zhou et al, 2008, but see Ashtari et al, 2007;Kito et al, 2009;Kyriakopoulos et al, 2008;Szeszko et al, 2005;White et al, 2007 for negative findings in younger individuals and Beasley et al, 2009 for lack of evidence of myelin abnormalities post-mortem), of the tracts connecting to the LPFC (Kim et al, 2008;Oh et al, 2009) and altered FA (Hashimoto et al, 2009) or mean diffusivity in the thalamus itself (Agarwal et al, 2008;Rose et al, 2006;Spoletini et al, 2011). Kim et al (2007) have performed a similar DTI study, with an identical a-priori hypothesis, but found only differences in the thalamic CDR defined by connectivity to the orbitofrontal, parietal, and medial prefrontal cortices.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

Marenco

Stein

Savostyanova

et al. 2011

Neuropsychopharmacol

142

101

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The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age-and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.

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“…Philips Medical Systems (Best, Netherlands) offers a similar software package called PRIDE (Philips Research Integrated Development Environment). Others (e.g., (Ashtari et al, 2007) have used elaborate registration algorithms that permit overlaying of tracts-ofinterest derived from tractography models produced by programs such as DTIStudio, MedINRIA, or PRIDE onto scalar FA maps to determine the structural integrity of the selected tracts. Each of these methods demonstrated the potential utility of using quantitative tractography.…”

Section: Introductionmentioning

confidence: 99%

Quantitative tractography metrics of white matter integrity in diffusion-tensor MRI

et al. 2008

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We present new quantitative diffusion-tensor imaging (DTI) tractography-based metrics for assessing cerebral white matter integrity. These metrics extend prior work in this area. Tractography models of cerebral white matter were produced from each subject's DTI data. The models are a set of curves (e.g., "streamtubes") derived from DTI data that represent the underlying topography of the cerebral white matter. Nine metrics were calculated in whole brain tractography models and in three "tracts-of-interest" (TOI): transcallosal fibers, and the left and right cingulum bundles. The metrics included the number of streamtubes and several metrics based on the summed length of streamtubes in including some that were weighted by scalar anisotropy metrics and normalized for estimated intracranial volume. We then tested whether patients with subcortical ischemic vascular disease (i.e., vascular cognitive impairment or VCI) vs. healthy controls (HC) differed on the metrics. The metrics were significantly lower in the VCI group in whole brain and in transcallosal TOI but not in the left or right cingulum bundles. The metrics correlated significantly with cognitive functions known to be impacted by white matter abnormalities (e.g., processing speed) but not with those more impacted by cortical disease (e.g., naming). These new metrics help bridge the gap between DTI tractography and scalar analytical methods and provide a potential means for examining group differences in white matter integrity in specific tracts-of-interest.

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Disruption of White Matter Integrity in the Inferior Longitudinal Fasciculus in Adolescents With Schizophrenia as Revealed by Fiber Tractography

Cited by 160 publications

References 73 publications

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

Quantitative tractography metrics of white matter integrity in diffusion-tensor MRI

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