DOI 10.1007/s10517-015-2881-1 Bulletin of Experimental Biology and Medicine, Vol. 159, No. 1, May, 2015 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY

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Characteristics of Diffusion in the Corticospinal Tract of Patients with Early Stage of Schizophrenia: Diffusion Tensor Magnetic Resonance Imaging M. V. Ublinskii*,**, N. A. Semenova*,**, O. V. Lukovkina*, S. V. Sidorin*,**, I. S. Lebedeva***, V. G. Kaleda***, A. N. Barkhatova***, and T. A. Akhadov* Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 159, No. 1, pp. 36-39, January, 2015 Original article submitted February 14, 2014 Specific features of diffusion in the cerebral corticospinal tract of patients with early stages of schizophrenia were studied using methods of diffusion tensor magnetic-resonance imaging and magnetic resonance spectroscopy. A decrease in the coefficient of fractional anisotropy in the posterior limb of the internal capsule and an increase in diffusion coefficient in the radiate crown and motor cortex were observed. The results reflect different mechanisms of changes in water diffusion in various areas of the corticospinal tract: changes in nerve fiber microstructure in the internal capsule of the left hemisphere and a decrease in their density in the motor cortex and radiate crown. Key Words: diffusion tensor magnetic resonance imaging; schizophrenia; corticospinal tract Endogenous psychoses, e.g. schizophrenia, are a pressing problem of modern medicine and biology. Among various neurobiological models of schizophrenia, much attention is paid to disturbances in the structure and connections in the white matter of the brain [5,7,9,14]. Our previous functional magnetic-resonance imaging (fMRI) studies have demonstrated that hemodynamic response of the motor cortex to presentation of a relevant stimulus during performance of the task for selective attention and motor reaction (oddball paradigm) was decreased in patients with schizophrenia [2]. We continue these experiments and here we focused on the state of conductive pathways related to motor functions of the brain. Method of diffusion tensor MRI (DT-MRI) consisting in measurement of the rate and direction of *Research Institute of Urgent Children Surgery and Traumatology; **N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; ***Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow, Russia. Address for correspondence: [email protected] T. A. Akhadov

water diffusion in tissues was used. This method allows intravital and non-invasive study of brain tissue microstructure and analysis of local parameters of diffusion using the tensor method [7] as was described previously [3]. The corticospinal tract (CST) is the most important pyramid pathway of the brain responsible for impulse transduction during motion regulation [1]. CST starts from the giant pyramidal cells of the anterior central gyrus, passes the radiate crown, descends to the internal capsule, and occupies 2/3 of the posterior limb of internal capsule. Then CST fibers pass the middle of the base of cerebral peduncle, ventral pons, and form pyramids near the ventral surface of the spinal bulb (brainstem basis). The only published study of various areas of the CST was performed in healthy volunteers. Functional asymmetry (FA) and diffusion coefficient (DC) were measured in all CST in the left and right hemispheres [15]. The results of detailed analysis of CST in patients with schizophrenia have not been published yet. However, there are data on significant decrease in FA in some areas of the brain of these patients, in particu-

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Bulletin of Experimental Biology and Medicine, Vol. 159, No. 1, May, 2015 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY

DT-images of the brain were analyzed using Extended MR Workspace 2.6.3.4 (Philips), Fiber Track option, and 3D anatomical image overlap. Five areas most significant for CST analysis (Fig. 1) were chosen in the axial sections of each participant for analysis of DT-MRI data. DC and FA were measured in the left and right hemispheres. Statistical analysis of the obtained results was performed using Statistica 6.0 software. Betweengroup differences were estimated using Mann– Whitney U test.

RESULTS Fig. 1. Studied areas of in the corticospinal tract.

lar in CST (localization not specified) in comparison with the normal [12,13]. Here we studied specific features of diffusion in CST in patients with early stage of schizophrenia.

MATERIALS AND METHODS The study was included 13 men with juvenile paroxysmal schizophrenia (duration of diseases starting from the first manifestation did not exceed 5 years) aging 17-27 years (mean age 22.0±3.1 years). Mentally healthy volunteers (15 men, mean age 24.9±4.1 years) comprised the control group. All participants gave written informed consent. MRI was performed on an Achieva 3.0T tomograph (Philips) with DualQuasar gradient system and 8-channel radio-frequency receiver coil for the head. DT-images were acquired in the axial plane using echoplanar impulse sequence: TR=9431 msec; TE=70 msec; matrix 120/144 pixels, field of view 240 mm; voxel size 2×2×2 mm; acceleration factor 63; gap 0; accumulation number 2. Diffusion gradient were applied in 32 non-collinear directions.

Statistically significant decrease in FA in patients with schizophrenia was found only in the left posterior limb of the internal capsule. In other areas of CST, the differences were insignificant (Table 1). Between-group differences of DC were more pronounced. They were significant in three areas: motor cortex of the left and right hemispheres and in the radiate crown of the right hemisphere (Table 2). No differences in DC between the left and right hemispheres were found in patients with schizophrenia. According to FA definition, the decrease in this parameter is determined by an increase in the rate of radial diffusion in comparison with axial diffusion [11]. It can be related to several factors including normal ontogenetic changes. Previous data [4,10,13] show the increase in FA correlates with the process of brain maturation: at the age of 5-18 years, FA increases in the thalamus, corpus callosum, basal ganglia, and posterior limb of the internal capsule. Thus, it can be suggested that FA in the area of the internal capsule is a marker of structuring and development of the white matter of the brain. The decrease of FA in conductive pathways connecting the internal capsule with some areas of the cerebral cortex was previously shown in severe psy-

TABLE 1. FA Level in Various Areas of CST and Results of Between-Group Comparison (M±SD) Left CST

Right CST

CST area schizophrenia

control

p

schizophrenia

control

p

Motor area

0.473±0.061

0.495±0.044

0.27

0.467±0.027

0.501±0.067

0.136

Radiate crown

0.618±0.052

0.599±0.06

0.377

0.589±0.030

0.593±0.063

0.89

Posterior limb of internal capsule

0.725±0.045

0.759±0.024

0.024

0.707±0.029

0.735±0.046

0.164

Cerebral peduncle

0.775±0.045

0.769±0.051

0.698

0.756±0.021

0.777±0.051

0.25

Pyramids of the medulla oblongata

0.463±0.081

0.461±0.074

0.957

0.451±0.044

0.431±0.078

0.5

M. V. Ublinskii, N. A. Semenova, et al.

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TABLE 2. DC Level in Various Areas of CST and Results of Between-Group Comparison (M±SD) Left CST

Right CST

CST region schizophrenia

control

p

schizophrenia

control

p

Motor area

0.743±0.032

0.719±0.026

0.044

0.765±0.028

0.731±0.029

0.004

Radiate crown

0.724±0.023

0.720±0.014

0.765

0.742±0.023

0.721±0.028

0.029

Posterior limb of internal capsule

0.745±0.032

0.747±0.034

0.87

0.739±0.284

0.737±0.031

0.85

Cerebral peduncle

0.765±0.059

0.791±0.061

0.26

0.800±0.051

0.778±0.053

0.27

Pyramids of the medulla oblongata

0.822±0.072

0.800±0.067

0.43

0.817±0.114

0.809±0.058

0.82

chical disorder such as schizophrenia (in patients with chronic disease [6]). According to our findings, changes in FA and DC appear even at the early stage of the disease. They can be associated with the pathology related to death or damage to axons, impaired myelination, or changes in spatial organization of fibers. It should be emphasized that the increase in DC reflects enhanced water mobility due to the decrease in structural organization of the white matter in the radiate crown and motor cortex. However, the major direction of diffusion in these areas of CST does not change, which is seen from normal FA. Thus, the increase in DC is determined by a decrease in the density of nerve fibers in CST. The absence of changes in DC in the internal capsule and decreased FA reflect impairment of the microstructure of nerve fibers and unchanged density of these fibers. The internal capsule is a key structure in the system of conductive pathways in the brain, and changes in the microstructure of the white matter in this area can be one of the neurobiological factors related to the pathogenesis of schizophrenia. Thus, first gradual investigation of the CST was performed in patients with early stage of schizophrenia. Different mechanisms of changes in water diffusion were observed in various areas of the CST: impairments in microstructure of nerve fibers were found in the internal capsule of the left hemisphere, and their reduced density was observed in the motor cortex and radiate crown. Physical and chemical mechanisms of these changes require further investigation.

Experiments were supported by the Presidium of the Russian Academy of Science (grant No. 05-RAN22) and Russian Foundation for Basic Research (grant No. 12-06-00284-a).

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Characteristics of Diffusion in the Corticospinal Tract of Patients with Early Stage of Schizophrenia: Diffusion Tensor Magnetic Resonance Imaging.

Specific features of diffusion in the cerebral corticospinal tract of patients with early stages of schizophrenia were studied using methods of diffus...
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