White matter integrity associated with volitional motor activity

Variations of white matter integrity have been associated with interindividual differences in brain function. Still, little is known about the impact of white matter integrity on quantitative motor behaviour. Diffusion tensor imaging and continuous wrist actigraphy were measured on the same day in 12 individuals. Fractional anisotropy as measure of white matter integrity was correlated with the motor activity level. Positive correlations of fractional anisotropy and activity level were detected in the cingulum and the right superior longitudinal fasciculus underneath the precentral gyrus. Negative correlations were found in the left corticobulbar tract, in the right posterior corpus callosum and in the left superior longitudinal fasciculus. Volitional motor activity was associated with white matter integrity in motor relevant fiber tracts.

Alterations of white matter integrity related to motor activity in schizophrenia

Altered structural connectivity is a key finding in schizophrenia, but the meaning of white matter alterations for behavior is rarely studied. In healthy subjects, motor activity correlated with white matter integrity in motor tracts. To explore the relation of motor activity and fractional anisotropy (FA) in schizophrenia, we investigated 19 schizophrenia patients and 24 healthy control subjects using Diffusion Tensor Imaging (DTI) and actigraphy on the same day. Schizophrenia patients had lower activity levels (AL). In both groups linear relations of AL and FA were detected in several brain regions. Schizophrenia patients had lower FA values in prefrontal and left temporal clusters. Furthermore, using a general linear model, we found linear negative associations of FA and AL underneath the right supplemental motor area (SMA), the right precentral gyrus and posterior cingulum in patients. This effect within the SMA was not seen in controls. This association in schizophrenia patients may contribute to the well known dysfunctions of motor control. Thus, structural disconnectivity could lead to disturbed motor behavior in schizophrenia.

White matter lesions and intra-arterial thrombolysis

The aim of the study was to assess the influence of white matter lesions in patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). From September 2003 to January 2010, we treated 400 patients with IAT at our institution. Of these patients, 292 were evaluated with MRI scans and included in this observational study. Clinical data were collected prospectively. Outcome after 3 months was measured with the modified Rankin Scale (mRS); mRS 0-1 was considered as favorable outcome. White matter lesions were scored visually by two observers using the semiquantitative Scheltens and Fazekas scores. Logistic regression analysis was used to identify the association of white matter lesions and clinical outcome, recanalization, and cerebral hemorrhage. The severity of white matter lesions was inversely correlated with favorable outcome, survival and successful recanalization. White matter lesions were an independent predictor of outcome (OR 0.569, p = 0.007) and survival (OR 0.550, p = 0.018) and a weak but independent predictor for recanalization (OR 0.949, p = 0.038). Asymptomatic intracerebral bleeding after IAT was associated with white matter lesions in the basal ganglia in the univariate analysis (p = 0.036), but not after multivariable analysis. The severity of white matter lesions independently predicts clinical outcome and survival in patients treated with IAT. White matter lesions are also a weak but independent predictor for recanalization. Symptomatic intracranial bleeding after IAT are not associated with white matter lesions. Therefore, white matter lesions should not be considered as a contraindication against IAT.

Widespread grey matter changes and hemodynamic correlates to interictal epileptiform discharges in pharmacoresistant mesial temporal epilepsy

Focal onset epilepsies most often occur in the temporal lobes. To improve diagnosis and therapy of patients suffering from pharmacoresistant temporal lobe epilepsy it is highly important to better understand the underlying functional and structural networks. In mesial temporal lobe epilepsy (MTLE) widespread functional networks are involved in seizure generation and propagation. In this study we have analyzed the spatial distribution of hemodynamic correlates (HC) to interictal epileptiform discharges on simultaneous EEG/fMRI recordings and relative grey matter volume (rGMV) reductions in 10 patients with MTLE. HC occurred beyond the seizure onset zone in the hippocampus, in the ipsilateral insular/operculum, temporo-polar and lateral neocortex, cerebellum, along the central sulcus and bilaterally in the cingulate gyrus. rGMV reductions were detected in the middle temporal gyrus, inferior temporal gyrus and uncus to the hippocampus, the insula, the posterior cingulate and the anterior lobe of the cerebellum. Overlaps between HC and decreased rGMV were detected along the mesolimbic network ipsilateral to the seizure onset zone. We conclude that interictal epileptic activity in MTLE induces widespread metabolic changes in functional networks involved in MTLE seizure activity. These functional networks are spatially overlapping with areas that show a reduction in relative grey matter volumes.

Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD.

Alterations of white matter connectivity in first episode schizophrenia

Cerebral disconnectivity due to white matter alterations in patients with chronic schizophrenia assessed by diffusion tensor imaging has been reported previously. The aim of this preliminary study is to investigate whether cerebral disconnectivity can be detected as early as the first episode of schizophrenia. Intervoxel coherence values were compared by voxel-based t test in 12 patients with first episode schizophrenia and 12 age- and gender-matched control groups. We detected 14 circumscribed significant clusters (P < 0.02), 3 of them with higher, and 11 of them with lower IC values for patients with schizophrenia than for healthy control groups. We interpret these white matter alterations in different regions to be disconnected fiber tracts already present early in schizophrenic disease progression.

Relation of white matter anisotropy to visual memory in 17 healthy subjects

We performed a Rey visual design learning test (RVDLT) in 17 subjects and measured intervoxel coherence (IC) by DTI as an indication of connectivity to investigate if visual memory performance would depend on white matter structure in healthy persons. IC considers the orientation of the adjacent voxels and has a better signal-to-noise ratio than the commonly used fractional anisotropy index. Voxel-based t-test analysis of the IC values was used to identify neighboring voxel clusters with significant differences between 7 low and 10 high test performers. We detected 9 circumscribed significant clusters (p< .01) with lower IC values in low performers than in high performers, with centers of gravity located in left and right superior temporal region, corpus callosum, left superior longitudinal fascicle, and left optic radiation. Using non-parametric correlation analysis, IC and memory performance were significantly correlated in each of the 9 clusters (r< .61 to r< .81; df=15, p< .01 to p< .0001). The findings provide in vivo evidence for the contribution of white matter structure to visual memory in healthy people.

White matter anisotropy related to electrophysiology of first episode schizophrenia during NoGo inhibition

Patients with schizophrenia have reduced execution functions and white matter alterations indicating cerebral disconnectivity. Here we investigated the relationship between white matter integrity and event related potentials (ERP) during a continuous performance test (CPT). Anisotropy values were correlated with the brain electrical P300 microstate duration and P300 latency associated to the NoGo- and the Go-stimuli of the CPT in 11 patients with first episode schizophrenia and 11 matched healthy controls. Both groups showed significant positive correlations of the NoGo-microstate duration with the white matter signal in the superior frontal region, the optic radiation, the posterior cingulate, and the inferolateral fascicle. In addition, patients with first episode schizophrenia had significant correlations with the right radiation and the left genu of the corpus callosum, bilateral geniculate, and the left middle and the superior temporal regions. We interpreted these findings as a sign of functional correlates of extended circuits for the active inhibition of a motor response in the visual CPT as compared to controls.

Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.

White matter microstructure alterations of the medial forebrain bundle in melancholic depression

BACKGROUND The medial forebrain bundle (MFB) is a key structure of the reward system and connects the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), the medial and lateral orbitofrontal cortex (mOFC, lOFC) and the dorsolateral prefrontal cortex (dlPFC). Previous diffusion tensor imaging (DTI) studies in major depressive disorder point to white matter alterations of regions which may be incorporated in the MFB. Therefore, it was the aim of our study to probe white matter integrity of the MFB using a DTI-based probabilistic fibre tracking approach. METHODS 22 patients with major depressive disorder (MDD) (12 melancholic-MDD patients, 10 non-melancholic-MDD patients) and 21 healthy controls underwent DTI scans. We used a bilateral probabilistic fibre tracking approach to extract pathways between the VTA and NACC, mOFC, lOFC, dlPFC respectively. Mean fractional anisotropy (FA) values were used to compare structural connectivity between groups. RESULTS Mean-FA did not differ between healthy controls and all MDD patients. Compared to healthy controls melancholic MDD-patients had reduced mean-FA in right VTA-lOFC and VTA-dlPFC connections. Furthermore, melancholic-MDD patients had lower mean-FA than non-melancholic MDD-patients in the right VTA-lOFC connection. Mean-FA of these pathways correlated negatively with depression scale rating scores. LIMITATIONS Due to the small sample size and heterogeneous age group comparisons between melancholic and non-melancholic MDD-patients should be regarded as preliminary. CONCLUSIONS Our results suggest that the melancholic subtype of MDD is characterized by white matter microstructure alterations of the MFB. White matter microstructure is associated with both depression severity and anhedonia.

White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

The reward systemin schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approachwe bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), themedial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-valueswere increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments ofwhite matter pathways of the reward systemin schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.