Objectives Healthy people have a slight leftward bias of spatial attention as measured on the Landmark task. Former studies indicated that lateralisation of brain activation contributes to this attentional bias. In this study we hypothesised that if the spatial bias was consistent over several measurements there would be structural background of it. Methods Reproducibility of the spatial bias of visuo-spatial attention was measured in twenty healthy subject in a Landmark task over three consecutive days. In order to evaluate the correlation between the spatial attentional bias and the white matter microstructure high angular resolution diffusion MRI was acquired for each subjects. The Track Based Spatial Statistics method was used to measure the hemispheric differences of the white matter microstructure. Probabilistic tractography was used to reveal the connection of the identified regions. Results The analysis showed correlation between the behavioural scores and the lateralisation of the white matter microstructure in the parietal white matter (p< 0.05, corrected for multiple correlations). Higher FA values on the left are associated to rightward bias. The parietal cluster showed connectivity along the superior longitudinal fascicle on one end to posterior parietal cortex and anteriorly to the putative frontal eye field. From the frontal eye field some of the fibres run towards the nodes of the dorsal attention network to the intraparietal suclus, while some of the fibres travelled toward to ventral attention network to the temporo-parietal junction. Conclusions These results indicate that the structural integrity dorsal fronto-parietal network and the connection between the dorsal and ventral attention networks are responsible for the attentional bias in normal healthy controls.

Background Previous functional and structural imaging studies have revealed that subcortical structures play a key a role in pain processing. The recurring painful episodes might trigger maladaptive plasticity or alternatively degenerative processes that might be detected by MRI as changes in size or microstructure. In the current investigation, we aimed to identify the macro- and microstructural alterations of the subcortical structures in episodic cluster headache. Methods High-resolution T1-weighted and diffusion-weighted MRI images with 60 gradient directions were acquired from 22 patients with cluster headache and 94 healthy controls. Surface-based segmentation analysis was used to measure the volume of the subcortical nuclei, and mean diffusion parameters (fractional anisotropy, mean, radial and axial diffusivity) were determined for these structures. In order to understand whether the size and diffusion parameters could be investigated in a headache lateralised manner, first the asymmetry of the size and diffusion parameters of the subcortical structures was analysed. Volumes and diffusion parameters were compared between groups and correlated with the cumulative number of headache days. To account for the different size of the patient and control group, a bootstrap approach was used to investigate the stability of the findings. Results A significant lateralisation of the size (caudate, putamen and thalamus) and the diffusion parameters of the subcortical structures were found in normal controls. In cluster headache patients, the mean fractional anisotropy of the right amygdalae, the mean axial and mean diffusivity of the right caudate nucleus and the radial diffusivity of the right pallidum were higher. The mean anisotropy of the right pallidum was lower in patients. Conclusion The analysis of the pathology in the subcortical structures in episodic cluster headache reveals important features of the disease, which might allow a deeper insight into the pathomechanism of the pain processing in this headache condition.

Background: Formerly white matter abnormalities in a mixed group of migraine patients with and without aura were shown. Here, we aimed to explore white matter alterations in a homogeneous group of migraineurs with aura and to delineate possible relationships between white matter changes and clinical variables. Methods: Eighteen patients with aura, 25 migraine patients without aura and 28 controls were scanned on a 1.5T MRI scanner. Diffusivity parameters of the white matter were estimated and compared between patients' groups and controls using whole-brain tract-based spatial statistics. Results: Decreased radial diffusivity (p < 0.036) was found bilaterally in the parieto-occipital white matter, the corpus callosum, and the cingular white matter of migraine with aura (MwA) patients compared to controls. Migraine without aura (MwoA) patients showed no alteration compared to controls. MwA compared to MwoA showed increased fractional anisotropy (p < 0.048) in the left parieto-occipital white matter. In MwA a negative correlation was found between axial diffusivity and disease duration in the left superior longitudinal fascicle (left parieto-occipital region) and in the left corticospinal tract (p < 0.036) and with the number of the attacks in the right superior longitudinal fascicle (p < 0.048). Conclusion: We showed for the first time that there are white matter microstructural differences between these two subgroups of migraine and hence it is important to handle the two groups separately in further researches. We propose that degenerative and maladaptive plastic changes coexist in the disease and the diffusion profile is a result of these processes.

Migraine is one of the most severe primary headache disorders. The nature of the headache and the associated symptoms during the attack suggest underlying functional alterations in the brain. In this study, we examined amplitude, the resting state fMRI fluctuation in migraineurs with and without aura (MWA, MWoA respectively) and healthy controls.

The pathomechanism of cluster headache (CH) is not entirely understood, but central and peripheral components were suggested. A recent report showed that transcranial magnetic stimulation measured cortical excitability was increased in the hemisphere ipsilalteral to the pain. In the current study we set out to investigate the amplitude of resting brain fMRI activity to find signatures of the increased excitability. High resolution T1 weighted and resting state functional MRI images were acquired from seventeen patients with CH in pain free period and from twenty-six healthy volunteers. Patients' data were normalized (e.g. inverted along the midsagittal axis) according to the headache side. Independent component analysis and a modified dual regression approach were used to reveal the differences between the resting state networks. Furthermore, the timecourses were decomposed into five frequency bands by discrete wavelet decomposition and were also re-regressed to the original data to reveal frequency specific resting activity maps. Two of the identified resting state networks showed alterations in CH. When the data were inverted to have patients' headaches on the left, the ipsilateral attention network showed increased connectivity in 0.08-0.04 Hz frequency band in the in CH group. In the same dataset, cerebellar network showed higher functional connectivity in 0.02-0.01 Hz range in the ipsilateral cerebellum. When the data of patients having headache on the left were inverted to the right, similar increased signal was found in the ipsilateral attention network in 0.08-0.04 Hz band. The cerebellar network showed increased connectivity in the cerebellum in 0.02-0.01 Hz band in patients. The Fourier analysis of these area revealed increased power in CH at all cases. Our results showed alterations of brain functional networks in CH. The alterations of resting state activity were found in the hemisphere ipsilateral to the pain, signifying the altered cortical processing in the pathomechanism of CH.

Visual categorization plays an important role in fast and efficient information processing; still the neuronal basis of fast categorization has not been established yet. There are two main hypotheses known; both agree that primary, global impressions are based on the information acquired through the magnocellular pathway (MC). It is unclear whether this information is available through the MC that provides information (also) for the ventral pathway or through top-down mechanisms by connections between the dorsal pathway and the ventral pathway via the frontal cortex. To clarify this, a categorization task was performed by 48 subjects; they had to make decisions about objects' sizes. We created stimuli specific to the magno- and parvocellular pathway (PC) on the basis of their spatial frequency content. Transcranial direct-current stimulation was used to assess the role of frontal areas, a target of the MC. Stimulation did not bias the accuracy of decisions when stimuli optimized for the PC were used. In the case of stimuli optimized for the MC, anodal stimulation improved the subjects' accuracy in the behavioral test, while cathodal stimulation impaired accuracy. Our results support the hypothesis that fast visual categorization processes rely on top-down mechanisms that promote fast predictions through coarse information carried by MC via the orbitofrontal cortex.

Objective: Cortical pathology, periventricular demyelination, and lesion formation in multiple sclerosis (MS) are related (Hypothesis 1). Factors in the cerebrospinal fluid close to these compartments could possibly drive the parallel processes. Alternatively, the cortical atrophy could be caused by remote axonal transection (Hypothesis 2). Since MRI can differentiate between demyelination and axon loss, we used this imaging modality to investigate the correlation between the pattern of diffusion parameter changes in the periventricular- and deep white matter and the gray matter atrophy. Methods: High-resolution T1-weighted, FLAIR, and diffusion MRI images were acquired in 52 RRMS patients and 50 healthy, age-matched controls. We used EDSS to estimate the clinical disability. We used Tract Based Spatial Statistics to compare diffusion parameters (fractional anisotropy, mean, axial, and radial diffusivity) between groups. We evaluated global brain, white, and gray matter atrophy with SIENAX. Averaged, standard diffusion parameters were calculated in four compartment: periventricular lesioned and normal appearing white matter, non-periventricular lesioned and normal appearing white matter. PLS regression was used to identify which diffusion parameter and in which compartment best predicts the brain atrophy and clinical disability. Results: In our diffusion tensor imaging study compared to controls we found extensive alterations of fractional anisotropy, mean and radial diffusivity and smaller changes of axial diffusivity (maximal p > 0.0002) in patients that suggested demyelination in the lesioned and in the normal appearing white matter. We found significant reduction in total brain, total white, and gray matter (patients: 718.764 ± 14.968, 323.237 ± 7.246, 395.527 ± 8.050 cm3, controls: 791.772 ± 22.692, 355.350 ± 10.929, 436.422 ± 12.011 cm3; mean ± SE), (p < 0.015; p < 0.0001; p < 0.009; respectively) of patients compared to controls. The PLS analysis revealed a combination of demyelination-like diffusion parameters (higher mean and radial diffusivity in patients) in the lesions and in the non-lesioned periventricular white matter, which best predicted the gray matter atrophy (p < 0.001). Similarly, EDSS was best predicted by the radial diffusivity of the lesions and the non-lesioned periventricular white matter, but axial diffusivity of the periventricular lesions also contributed significantly (p < 0.0001). Interpretation: Our investigation showed that gray matter atrophy and white matter demyelination are related in MS but white matter axonal loss does not significantly contribute to the gray matter pathology.

Subdominant hemispheric lesion results neglect syndrome, where the processing of the visual information coming from the contralateral side is damaged. A similar phenomenon is known in healthy subjects, called pseudo-neglect. In line bisection task there is a tendency to pay more attention to the left side of space. We involved 29 healthy subjects. Landmark task was used in a forced choice paradigm to determine the preferred space side. Then cathodal transcranial direct–current stimulation was used in the right region of posterior–parietal cortex. Landmark task was repeated. Fierro score was used to describe the precise choices and the reaction time was calculated. 67% of the subjects showed left pseudo-neglect, 22% showed right pseudo-neglect and in 11% pseudo-neglect was not detected. After the stimulation the number of the incorrect choices was increased (p < 0.0362) and the reaction time increased in the case of the middle-sectioned line (p < 0.0126) and in the case of the right-sectioned line (p < 0.0099). Parietal lobe has a crucial role in spatial attention. It can be measured by neurocognitive tests that might serve as a test for the early detection of cognitive impairment. Cathodal stimulation of the parietal lobe can induce a neglect-like symptom.

Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson's disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders.

Background: Episodic memory disturbances were found to constitute a potential trait marker for major depression (MD). The recall of positive or rewarding information in a relational context is specifically impaired. Eye-movement recording constitutes a novel, direct approach to examine implicit memory performance. Here we aimed to assess the effect of emotional context and implicit virtual monetary reward or loss on viewing patterns in association with relational memory in a 6-months follow-up study in MD. Materials and Methods: Twenty-eight patients with MD and 30 healthy participants were trained to associate a face (happy/sad/neutral) with a background scene. After each pair a virtual monetary reward or loss appeared briefly. During testing, scenes were presented as a cue and then overlaid with three previously studied faces. Participants were asked to recall the matching face if present (Match trials), with eye-movements and subsequent forced-choice recognition being recorded. Results: Explicit recognition of the matching face was impaired in the MD group as compared to controls. In correlation with this, viewing of the matching face was significantly reduced in the MD group. We found a significant interaction of group (MD vs HC) with the relational memory condition (Match and Non-match), facial emotion and monetary reward and loss. MD patients attended longer to previously rewarded stimuli, but significantly less to sad faces in the Match condition. The relational memory impairment persisted at follow-up and correlated with symptom severity both at baseline and follow-up. Viewing patterns associated with previous virtual reward were associated with clinical symptoms at follow-up. Conclusion: Our current results provide novel evidence for a specific relational memory impairment in MD as supported by abnormal eye-movement behavior and a deficit in explicit recognition. MD patients showed an attentional bias to rewarded stimuli and decreased viewing of sad faces when relational memory information was present.

Background Huntington's disease is a progressive disease in which neurodegeneration is on-going from the early presymptomatic phase. Development of sensitive biomarkers in this presymptomatic stage that are able to monitor the disease progression and test the efficacy of putative neuroprotective treatments are essential.Methods Seven presymptomatic Huntington mutation carriers and ten age-matched healthy controls were recruited. Six of the patients participated in a 24 months longitudinal study having MRI scans 12 and 24 months after the baseline measurements. High resolution T1 weighted images were carried out and voxel based morphometry was used to analyse the data. Apart of group differences, correlation of CAG repeat number with focal cortical thickness and with global gray matter volume was calculated.Results Focal cortical atrophy was found bilaterally in the superior temporal sulcus and in the left middle frontal gyrus in presymptomatic Huntington patients in whom no sign of cognitive or motor deterioration was detected. Global gray matter atrophy (p<0.048) and decreased total brain volume was found. The number of CAG triplets showed no correlation with the focal gray matter atrophy and total brain volume. Strong correlation between the CAG repeat number and global gray matter volume was found (p<0.016).Conclusion Cortical atrophy is apparent in the early, presymptomatic stage of the disease. With further validation in large patient sample atrophy measure could be biomarker of disease progression and putatively of neurodegeneration.

Visual categorization plays an important role in the fast and efficient processing of information surrounding us, still the neuronal basis of fast categorization has not been established. Two main hypotheses are known, both agree that the primary impressions are based on information acquired through the Magnocellular Pathway (MP). It is unclear whether this information is due to the MP running parallel to the ventral pathway or to the top-down mechanisms executed through the connections of the dorsal pathway and the frontal cortex. A categorization task was performed by 39 subjects, who decided about the size of objects based on their first impression. Stimuli used for the MP and Parvocellular Pathways (PP) were discriminated by their spatial frequency content. transcranial Direct-Current Stimulation (tDCS) were used to assess the role of frontal areas. Stimulation did not bias the accuracy of decision for stimuli optimized for the PP. In case of stimuli optimized for the MP, cathodal stimulation decreased the subjects’ performance, whereas the anodal stimulation increased their performance. Our results support the hypothesis that top-down mechanisms, which promote fast predictions through coarse information carried to the Orbito-Frontal Cortex (OFC) by the MP, are crucial in fast categorization processes.

Audio-visual integration has been shown to be present in a wide range of different conditions, some of which are processed through the dorsal, and others through the ventral visual pathway. Whereas neuroimaging studies have revealed integration-related activity in the brain, there has been no imaging study of the possible role of segregated visual streams in audio-visual integration. We set out to determine how the different visual pathways participate in this communication. We investigated how audio-visual integration can be supported through the dorsal and ventral visual pathways during the double flash illusion. Low-contrast and chromatic isoluminant stimuli were used to drive preferably the dorsal and ventral pathways, respectively. In order to identify the anatomical substrates of the audio-visual interaction in the two conditions, the psychophysical results were correlated with the white matter integrity as measured by diffusion tensor imaging.The psychophysiological data revealed a robust double flash illusion in both conditions. A correlation between the psychophysical results and local fractional anisotropy was found in the occipito-parietal white matter in the low-contrast condition, while a similar correlation was found in the infero-temporal white matter in the chromatic isoluminant condition. Our results indicate that both of the parallel visual pathways may play a role in the audio-visual interaction.

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Visual perception declines with age. Perceptual deficits may originate not only in the optical system serving vision but also in the neural machinery processing visual information. Since homologies between monkey and human vision permit extrapolation from monkeys to humans, data from young, middle aged and old monkeys were analyzed to show age-related changes in the neuronal activity in the inferotemporal cortex, which is critical for object and shape vision. We found an increased neuronal response latency, and a decrease in the stimulus selectivity in the older animals and suggest that these changes may underlie the perceptual uncertainties found frequently in the elderly.