Association between reduced white matter integrity in the corpus callosum and serotonin transporter gene DNA methylation in medication-naive patients with major depressive disorder.

Previous evidence suggests that the serotonin transporter gene (SLC6A4) is associated with the structure of brain regions that are critically involved in dysfunctional limbic-cortical network activity associated with major depressive disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics were used to investigate changes in white matter integrity in patients with MDD compared with healthy controls. A possible association between structural alterations in white matter tracts and DNA methylation of the SLC6A4 promoter region was also assessed. Thirty-five medication-naive patients with MDD (mean age: 40.34, male/female: 10/25) and age, gender and education level matched 49 healthy controls (mean age: 41.12, male/female: 15/34) underwent DTI. SLC6A4 DNA methylation was also measured at five CpG sites of the promoter region, and the cell type used was whole-blood DNA. Patients with MDD had significantly lower fractional anisotropy (FA) values for the genu of the corpus callosum and body of the corpus callosum than that in healthy controls (family-wise error corrected, P<0.01). Significant inverse correlations were observed between SLC6A4 DNA methylation and FA (CpG3, Pearson's correlation: r=-0.493, P=0.003) and axial diffusivity (CpG3, Pearson's correlation: r=-0.478, P=0.004) values of the body of the corpus callosum in patients with MDD. These results contribute to evidence indicating an association between epigenetic gene regulation and structural brain alterations in depression. Moreover, we believe this is the first report of a correlation between DNA methylation of the SLC6A4 promoter region and white matter integrity in patients with MDD.

Applicability of the Sparse Temporal Acquisition Technique in Resting-State Brain Network Analysis.

BACKGROUND AND PURPOSE: The ability of sparse temporal acquisition to minimize the effect of scanner background noise is of utmost importance in auditory fMRI; however, it has considerably lower temporal efficiency and resolution than the conventional continuous acquisition method. The purpose of this study was to determine whether sparse sampling could be applied to resting-state research by comparing its results with those obtained by using continuous acquisition. MATERIALS AND METHODS: We identified resting-state networks by using independent component analysis and measured their functional connectivity strength in 14 healthy subjects who underwent two 6-minute sparse (60 volumes) and continuous (360 volumes) imaging sessions. To account for the sample size difference, an additional continuous dataset was generated by temporally matching the continuous dataset to 60 volumes of the sparse dataset. RESULTS: Consistent resting-state network maps were produced through all 3 datasets. Scanner background noise did not appear to affect the spatial constitution of the networks, whereas a larger sample size influenced it substantially. The strength of the intranetwork connectivity was similar through the 3 datasets. CONCLUSIONS: Our results indicated that continuous acquisition is a recommended technique that should be applied in most of the resting-state studies due to its superior temporal efficiency and increased statistical power. The use of sparse temporal acquisition should be restricted to very particular conditions when continuous scanner noise is unacceptable.

Hippocampal shape deformation in female patients with unremitting major depressive disorder.

BACKGROUND AND PURPOSE: The hippocampal atrophy of MDD has been known, but the region shape contractions of the hippocampus in MDD were inconsistent. Spheric harmonic shape analysis was applied to the hippocampus in female patients with unremitting MDD to evaluate morphometric changes of the hippocampus. MATERIALS AND METHODS: Shape analysis was performed by using T1-weighted MR imaging in 21 female patients with MDD and 21 age- and sex-matched healthy controls. Manually segmented hippocampi were parameterized, and the point-to-point-based group difference was compared by using the Hotelling T-squared test. The partial correlation analyses were tested between clinical variables and shape changes. RESULTS: Both hippocampal volumes were small in patients with MDD compared with healthy controls, and the right hippocampal volume was negatively correlated with the number of episodes at marginal significance. Regional shape contractions were found in the ambient gyrus, basal hippocampal head, posterior subiculum, and dorsal hippocampus of the left hemisphere. The right hippocampus showed a similar pattern but was less atrophic compared with the left hippocampus. A negative correlation was found between the HDRS and shape deformation in the CA3, ambient gyrus, posterior subiculum, and gyrus fasciolaris of the left hippocampus. CONCLUSIONS: We showed atrophy and regional shape contractions in the hippocampi of patients with MDD, which were more dominant on the left side. The causes of hippocampal damage could be the hypersecretion of glucocorticoids contributing to neuronal death or the failing of adult neurogenesis in the dentate gyrus.

Regional volume analysis of the Parkinson disease brain in early disease stage: gray matter, white matter, striatum, and thalamus.

BACKGROUND AND PURPOSE: Loss of dopaminergic neurons in the nigrostriatal pathway is well-documented in PD, whereas neuronal changes beyond the nigrostriatal pathway are uncertain. The purpose of our study was to estimate volume changes in the striatum and thalamus, which are areas of the basal ganglia, as well as in GM and WM located beyond the nigrostriatal pathway, in early-stage PD. MATERIALS AND METHODS: We enrolled 30 participants (15 healthy controls and 15 patients with PDND with H & Y stage I or II). Cognitive function was assessed by using the MMSE. ICV and the volumes of the caudate nucleus, putamen, thalamus, GM, and WM were calculated via 3D volume analysis by using MR imaging. RESULTS: A comparison of the PD group with the control group revealed an absence of significant differences between them regarding age and MMSE scores. Comparison of the volumes of regional brain structures of patients with PD with those of controls revealed the presence of significant differences in the caudate nucleus, thalamus, and WM (P<.05) between the groups. However, there were no significant differences in the volumes of the putamen and GM or in ICV between patients with PD and controls. The results of ANCOVA by using the covariates of age and ICV showed a significant difference in the caudate nucleus, thalamus, and WM between patients with PD and controls (P<.05). CONCLUSIONS: We suggest that loss of WM volume may occur in early disease stages and that variation of the volumes of the caudate nucleus and thalamus may be an early phenomenon of disease progression.

Ictal hyperperfusion of cerebellum and basal ganglia in temporal lobe epilepsy: SPECT subtraction with MRI coregistration.

UNLABELLED: The ictal hyperperfusion (compared with the interictal state) of the cerebellum and basal ganglia has not been investigated systematically in patients with temporal lobe epilepsy (TLE). Their ictal perfusion patterns were analyzed in relation to temporal and frontal hyperperfusion during TLE seizures using SPECT subtraction. METHODS: Thirty-three TLE patients had interictal and ictal SPECT, video-electroencephalographic (EEG) monitoring, and volumetric MRI. SPECT subtraction with MRI coregistration was performed using commercial software. The presence of ictal hyperperfusion was determined in the ipsilateral and contralateral temporal lobe, frontal lobe, cerebellum, and basal ganglia. RESULTS: All patients showed ictal hyperperfusion in the temporal lobe of seizure origin. Vermian cerebellar hyperperfusion (CH) was observed in 26 patients (78.8%) and hemispheric CH was found in 25 (75.8%). Compared with the side of the epileptogenic temporal lobe, there were 7 patients with ipsilateral hemispheric CH (28.0%), 15 with contralateral hemispheric CH (60.0%), and 3 with bilateral hemispheric CH (12.0%). CH was observed more frequently in patients with additional frontal hyperperfusion (14/15, 93.3%; 2 ipsilateral to the seizure focus, 10 contralateral, and 2 bilateral) than in patients without frontal hyperperfusion (11/18, 61.1%). Among 18 patients with temporal hyperperfusion without frontal hyperperfusion, 11 patients showed hemispheric CH (5 ipsilateral to seizure focus, 5 contralateral, 1 bilateral). Hyperperfusion in the basal ganglia (BGH) was seen in 11 of the 15 patients with temporal and frontal hyperperfusion (73.3%) and in 11 of the 18 with only temporal hyperperfusion (61.1%). In 17 patients with unilateral BGH (13 ipsilateral to the seizure focus, 4 contralateral), CH contralateral to the BGH was observed in 14 (82.5%), CH ipsilateral to the BGH was found in 2 (11.8%), and CH bilateral to the BGH was found in 1 (5.9%). CONCLUSION: During TLE seizures, hemispheric CH occurred not only in contralateral but also in ipsilateral or bilateral cerebellar hemispheres to the side of seizure origin. Although temporal lobe origin seizures associated with additional frontal hyperperfusion produced more frequent hemispheric CH, seizures showing only temporal hyperperfusion without frontal hyperperfusion could produce BGH and CH. To determine the side of hemispheric CH, the most important factor appears to be the side of BGH, not the side of seizure origin.

Opposite ictal perfusion patterns of subtracted SPECT. Hyperperfusion and hypoperfusion.

To investigate the patterns of ictal perfusion and related clinical factors, single photon emission computed tomography (SPECT) subtraction was performed in 61 patients who had undergone epilepsy surgery. In addition to the ictal hyperperfusion region, the ictal hypoperfusion area was obtained by SPECT subtraction. The ictal perfusion patterns of subtracted SPECT were classified into focal hyperperfusion, hyperperfusion-plus, combined hyperperfusion-hypoperfusion and focal hypoperfusion only. The concordance rate of seizure localization was 91.8% in the combined analysis of ictal hyperperfusion-hypoperfusion by SPECT subtraction, 85.2% in hyperperfusion images of SPECT subtraction and 68.9% in the visual inspection of ictal SPECT. Ictal hypoperfusion occurred less frequently in temporal lobe epilepsy (TLE) than in extra-TLE. Mesial temporal hyperperfusion alone was seen only in mesial TLE while lateral temporal hyperperfusion alone was observed only in neocortical TLE. Hippocampal sclerosis had a much lower incidence of ictal hypoperfusion than other pathologies. Some patients showed ictal hypoperfusion at the epileptic focus with ictal hyperperfusion in the neighbouring brain regions where ictal discharges propagated. Hypoperfusion as well as hyperperfusion in ictal SPECT should be considered for localizing epileptic focus. The mechanism of ictal hypoperfusion could be an intra-ictal early exhaustion of seizure focus or a steal phenomenon associated with the propagation of ictal discharges to adjacent brain areas.

Mapping of functional organization in human visual cortex: electrical cortical stimulation.

OBJECTIVES: To investigate the pattern of functional organization in the human visual cortex through electrical cortical stimulation. METHODS: Electrical cortical stimulation was applied to the occipital cortex and adjacent cortices using subdural grid electrodes in 23 epilepsy patients. Diverse visual responses were recorded. These responses were divided into different categories according to the specific response modalities, such as form, color, and motion. Form visual responses were further subdivided into simple, intermediate, and complex responses. The cortical localization of subdural electrodes was identified using MRI-CT coregistration. The cortical distribution of different visual responses was projected into three-dimensional surface renderings of the brain. The distribution and frequency of subdural electrodes showing different visual responses were quantified by calculating the percentage of the number of electrodes showing one specific type of visual response at the corresponding anatomic region to the total number of electrodes in all brain regions that produced the same response. RESULTS: Simple form responses were obtained mostly at the occipital pole and the inferior occipital gyrus (47.4%) and the striate cortex (42.4%). Intermediate form responses occurred mainly on the peristriate cortex (52.5%) and the lateral occipital (28.0%) and fusiform gyri (19.5%). Complex forms were produced by stimulation of the basal temporo-occipital region (57.6%) and the lateral temporal or lateral temporo-occipital junctional region (42.4%). Color responses occurred on the basal occipital area, mostly at the fusiform (40.0%) and lingual gyri (36.0%). Moving sensations were evoked by stimulation of the basal temporo-occipital (28.4%) and the mesial parieto-occipital or temporo-parieto-occipital junctional regions (23.9%). CONCLUSIONS: Different modalities of vision, such as form, color, and moving sensation, appeared to be distributed and organized in different areas of the human visual cortex.

Partial seizures manifesting as apnea only in an adult.

PURPOSE: Although several cases of apneic seizures have been reported in neonates, epileptic seizures presenting as apnea only in adults are very rare. We present a case report of a 19-year-old man with viral encephalitis and frequent episodes of apneic seizures. METHODS: Prolonged electroencephalograms (EEGs), respiratory monitorings, and imaging including ictal-interictal subtraction single photon emission computed tomography (SPECT) coregistered with magnetic resonance imaging (MRI) were performed. RESULTS: Ictal EEGs recorded during apneic episodes showed repetitive sharp waves or rhythmic theta activity arising from the left or right independent bitemporal region. Ictal SPECT was performed during one episode of apnea that showed ictal EEG discharges arising from the left posterior temporal area. Ictal-interictal subtraction SPECT coregistered with MRI revealed that the seizures originated from the left, posterior, midlateral temporal cortex. CONCLUSIONS: Previous studies with ictal EEG or brain stimulation suggest that apneic seizures might be mediated through the limbic and associated cortical systems. Our study reports on a very rare case of partial seizures with apnea only in an adult patient and is supported by ictal EEG and ictal-interictal subtraction SPECT coregistered with MRI.