Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study.

BACKGROUND: In vivo magnetic resonance studies have found that cocaine dependence is associated with T2 signal hyperintensities and metabolite abnormalities in cerebral white matter (WM). Functional neuroimaging studies have suggested that chronic cocaine use is primarily associated with frontal lobe deficits in regional cerebral blood flow and brain glucose metabolism levels; however, the effects of cocaine dependence, if any, on frontal WM microstructure are unknown. Thus, we sought to examine the effects of cocaine dependence on frontal WM integrity. METHODS: Diffusion tensor imaging was employed to examine the WM integrity of frontal regions at four levels: 10 mm above, 5 mm above, 0 mm above, and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. The fractional anisotropy (FA) of 12 cocaine-dependent patients and 13 age-similar control subjects was compared. RESULTS: The cocaine-dependent patients had significantly reduced FA in the frontal WM at the AC-PC plane and a trend toward reduced FA at 5 mm below the AC-PC plane, suggestive of reduced WM integrity in these regions. CONCLUSIONS: These findings were consistent with the hypothesis that cocaine dependence involves alterations in orbitofrontal connectivity, which may be involved in the decision-making deficits seen in this disorder.     

White matter integrity of the whole brain is disrupted in first-episode schizophrenia

Diffusion tensor imaging studies in schizophrenia have demonstrated lower diffusion anisotropy within white matter that provides information about brain white matter integrity. We have examined whether white matter is abnormal in first-episode schizophrenia by using diffusion tensor imaging. Twenty-one schizophrenic patients and healthy controls underwent diffusion tensor imaging scans that analyzed by using a rigorous voxel-based approach. We found that fractional anisotropy in white matter of the patients was lower than that in controls at the cerebral peduncle, frontal regions, inferior temporal gyrus, medial parietal lobes, hippocampal gyrus, insula, right anterior cingulum bundle and right corona radiata. These results suggested that white matter integrity of the whole brain was disrupted in early illness onset of schizophrenia.     

Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging

BACKGROUND: Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. METHODS: Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. RESULTS: Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. CONCLUSIONS: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.     

Associations of White Matter Integrity and Cortical Thickness in Patients With Schizophrenia and Healthy Controls

Typical brain development includes coordinated changes in both white matter (WM) integrity and cortical thickness (CT). These processes have been shown to be disrupted in schizophrenia, which is characterized by abnormalities in WM microstructure and by reduced CT. The aim of this study was to identify patterns of association between WM markers and cortex-wide CT in healthy controls (HCs) and patients with schizophrenia (SCZ). Using diffusion tensor imaging and structural magnetic resonance imaging data of the Mind Clinical Imaging Consortium study (130 HC and 111 SCZ), we tested for associations between (a) fractional anisotropy in selected manually labeled WM pathways (corpus callosum, anterior thalamic radiation, and superior longitudinal fasciculus) and CT, and (b) the number of lesion-like WM regions (“potholes”) and CT. In HC, but not SCZ, we found highly significant negative associations between WM integrity and CT in several pathways, including frontal, temporal, and occipital brain regions. Conversely, in SCZ the number of WM potholes correlated with reduced CT in the left lateral temporal gyrus, left fusiform, and left lateral occipital brain area. Taken together, we found differential patterns of association between WM integrity and CT in HC and SCZ. Although the pattern in HC can be explained from a developmental perspective, the reduced gray matter CT in SCZ patients might be the result of focal but spatially heterogeneous disruptions of WM integrity.Key words: cortical thickness, fractional anisotropy, structural MRI, DTI, schizophrenia     

Diffusion tensor imaging in schizophrenia.

BACKGROUND: Alignment of white matter axons as inferred from diffusion tensor imaging has indicated changes in schizophrenia in frontal and frontotemporal white matter. METHODS: Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired in 64 patients with schizophrenia and 55 normal volunteers. Anatomical images were acquired with a magnetization prepared rapid gradient echo sequence, and diffusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and anisotropy in normal volunteers and patients was compared using significance probability mapping. RESULTS: Patients showed widespread areas of reduced anisotropy, including the frontal white matter, the corpus callosum, and the frontal longitudinal fasciculus. CONCLUSIONS: These findings, which are consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions.     

MRI study of white matter diffusion anisotropy in schizophrenia

Diffusion tensor imaging (DTI) can provide information about brain white matter integrity. The results of DTI studies in schizophrenia are somewhat variable and could benefit from standardized image processing methods. Fourteen patients with schizophrenia or schizoaffective disorder and 14 healthy volunteers underwent DTI. Scans were analyzed using a rigorous voxelwise approach. The key dependent variable, fractional anisotropy, was lower for patients in the corpus callosum, left superior temporal gyrus, parahippocampal gyri, middle temporal gyri, inferior parietal gyri, medial occipital lobe, and the deep frontal perigenual region. Regions showing reduced white matter fractional anisotropy are known to be abnormal in schizophrenia. The voxelwise method used in the current study can provide the basis for hypothesis-driven research.     

White matter abnormalities in children with and at risk for bipolar disorder

OBJECTIVES: Diffusion tensor magnetic resonance imaging (DT-MRI) assesses the integrity of white matter (WM) tracts in the brain. Children with bipolar disorder (BPD) may have WM abnormalities that precede illness onset. To more fully examine this possibility, we scanned children with DSM-IV BPD and compared them to healthy peers and children at risk for BPD (AR-BPD), defined as having a first-degree relative with the disorder. METHODS: Ten children with BPD, eight healthy controls (HC), and seven AR-BPD, similar in age, had MRI scans on a 1.5 Tesla GE scanner, including a standard DT-MRI sequence (T2-EPI) with 25 axial slices. Fractional anisotropy (FA) values were compared between groups to determine regions of significant difference (p < 0.05). RESULTS: Compared to HC, children with BPD had decreased FA in right and left superior frontal tracts, including the superior longitudinal fasciculus I (SLF I) and the cingulate-paracingulate WM (CG-PAC(WM)). In addition, the BPD group had reduced FA in left orbital frontal WM and the right corpus callosum body. Compared to AR-BPD, children with BPD showed reduced FA in the right and left CG-PAC(WM). Both the BPD and AR-BPD groups showed reduced FA relative to HC in bilateral SLF I. CONCLUSIONS: The bilateral SLF I finding in both the BPD and AR-BPD groups may represent a trait-based marker or endophenotype of the disorder. The finding of decreased FA in the right and left CG-PAC(WM) in children with BPD compared to the other two groups may represent a disease-state related finding.     

White Matter Alterations in Early Stages of Schizophrenia: A Systematic Review of Diffusion Tensor Imaging Studies

Several lines of evidence suggest that the normal integration of cerebral communication may be compromised in schizophrenia, with white matter (WM) abnormalities being integral to these functional deficits. Diffusion tensor imaging (DTI) is a neuroimaging technique which has increasingly been used to study WM through quantitative indices of its structural and orientational characteristics. Identifying the WM differences early in the course of schizophrenia may assist in prevention, early diagnosis and identification of treatment targets. In that respect, the aims of the present study were to (a) systematically review WM integrity in the early stages of schizophrenia as inferred by DTI and (b) specifically examine parameters that may affect WM: age, duration of illness and treatment. In summary, DTI studies in early schizophrenia suggest that structural dysconnectivity may be already present in recent‐onset and drug‐naïve patients, as well as in individuals clinically at high risk for developing schizophrenia. Although the pattern of WM differences is not totally consistent frontal, fronto‐temporal and fronto‐limbic connections, with tracts including the superior longitudinal fasciculus, cingulum bundle, uncinate fasciculus and corpus callosum seem to be affected. These differences may depend on the developmental stage of the subjects, the duration of illness and exposure to antipsychotic medication.     

Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging study.

BACKGROUND: The purpose of this study was to explore whether there are white matter (WM) abnormalities in children with attention-deficit/hyperactivity disorder (ADHD) using diffusion tensor imaging. Based upon the literature, we predicted decreased fractional anisotropy (FA) findings in the frontal and cerebellar regions. METHODS: Eighteen patients with ADHD and 15 age- and gender-matched healthy volunteers received DTI assessments. Fractional anisotropy maps of WM were compared between groups with a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Children with ADHD had decreased FA in areas that have been implicated in the pathophysiology of ADHD: right premotor, right striatal, right cerebral peduncle, left middle cerebellar peduncle, left cerebellum, and left parieto-occipital areas. CONCLUSIONS: These preliminary data support the hypothesis that alterations in brain WM integrity in frontal and cerebellar regions occur in ADHD. The pattern of decreased FA might implicate the corticopontocerebellar circuit in the pathophysiology of ADHD.     

White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia.