Michal Mikl

Combined event-related fMRI and intracerebral ERP study of an auditory oddball task.

Event-related fMRI (efMRI) has been repeatedly used to seek the neural sources of endogenous event-related potentials (ERP). However, significant discrepancies exist between the efMRI data and the results of previously published intracranial ERP studies of oddball task. To evaluate the capacity of efMRI to define the sources of the P3 component of ERP within the human brain, both efMRI and intracerebral ERP recordings were performed in eight patients with intractable epilepsy (five males and three females) during their preoperative invasive video-EEG monitoring. An identical auditory oddball task with frequent and target stimuli was completed in two sessions. A total of 606 intracerebral sites were electrophysiologically investigated by means of depth electrodes. In accordance with the finding of multiple intracerebral generators of P3 potential, the target stimuli evoked MRI signal increase in multiple brain regions. However, regions with evident hemodynamic and electrophysiological responses overlapped only partially. P3 generators were always found within hemodynamic-active sites, if these sites were investigated by means of depth electrodes. On the other hand, unequivocal local sources of P3 potential were apparently also located outside the regions with a significant hemodynamic response (typically in mesiotemporal regions). Both methods should thus be viewed as mutually complementary in investigations of the spatial distribution of cortical and subcortical activation during oddball task.

The default mode network integrity in patients with Parkinson’s disease is levodopa equivalent dose-dependent

Disturbances in the default mode network (DMN) have been described in many neurological and psychiatric disorders including Parkinson’s disease (PD). The DMN is characterized by basal activity that increases during rest or passive visual fixation and decreases (“deactivates”) during cognitive tasks. The network is believed to be involved in cognitive processes. We examined the DMN in PD patients on dopaminergic medication with normal cognitive performance compared to age- and gender-matched healthy controls (HC) using fMRI and three methodological procedures: independent component analysis of resting-state data, analysis of deactivation during a complex visual scene-encoding task, and seed-based functional connectivity analysis. In the PD group, we also studied the effect of dopaminergic medication on the DMN integrity. We did not find any difference between the PD and HC groups in the DMN, but using the daily levodopa equivalent dose as a covariate, we observed an enhanced functional connectivity of the DMN in the posterior cingulate cortex and decreased activation in the left parahippocampal gyrus during the cognitive task. We conclude that dopaminergic therapy has a specific effect on both the DMN integrity and task-related brain activations in cognitively unimpaired PD patients, and these effects seem to be dose-dependent.

Reorganization of language‐related neuronal networks in patients with left temporal lobe epilepsy – an fMRI study

To investigate the inter‐ and intrahemispheric reorganization of the language cortex in left temporal lobe epilepsy (TLE) with left‐sided hippocampal sclerosis. A functional magnetic resonance imaging was performed on 13 right‐handed patients suffering from medically intractable left TLE, and in 13 sex‐ and age‐matched healthy controls. The activation paradigm used was a silent word generation task. A language laterality index (LI) was calculated from the number of activated voxels in the right and left anterior two‐thirds of the hemispheres. Significant differences between the patients and the controls were observed in the activation of the left‐sided inferior frontal gyrus. Less consistent findings in this region, as well as the relative protection of Brocas area from the activation, were revealed in the patients. In addition, different patterns of activation were proven in the cerebellum and other cortical as well as subcortical brain structures within both hemispheres. Significant differences were also found in the values of the language LIs between the investigated groups: these values suggested a more bihemispheric language representation in the patients. As anticipated, lateralization of the language functions in the epileptics significantly decreased in connection with an earlier age of initial insult. Our results support the hypothesis of a significant intra‐ and interhemispheric functional reorganization of language‐related neuronal networks in left TLE.

Effective connectivity in target stimulus processing: A dynamic causal modeling study of visual oddball task

PURPOSE To investigate the fundamental connectivity architecture of neural structures involved in the goal-directed processing of target events. METHODS Twenty healthy volunteers underwent event-related functional magnetic resonance imaging (fMRI) while performing a standard oddball task. In the task, two types of visual stimuli - rare (target) and frequent - were randomly presented, and subjects were instructed to mentally count the target stimuli. Dynamic causal modeling (DCM), in combination with Bayes factors was used to compare competing neurophysiological models with different intrinsic connectivity structures and input regions within the network of brain regions underlying target stimulus processing. RESULTS Conventional analysis of fMRI data revealed significantly greater activation in response to the target stimuli (in comparison to the frequent stimuli) in several brain regions, including the intraparietal sulci and supramarginal gyri, the anterior and posterior cingulate gyri, the inferior and middle frontal gyri, the superior temporal sulcus, the precuneus/cuneus, and the subcortical grey matter (caudate and thalamus). The most extensive cortical activations were found in the right intraparietal sulcus (IPS), the anterior cingulate cortex (ACC), and the right lateral prefrontal cortex (PFC). These three regions were entered into the DCM. A comparison on a group level revealed that the dynamic causal models in which the ACC and alternatively the IPS served as input regions were superior to a model in which the PFC was assumed to receive external inputs. No significant difference was observed between the fully connected models with ACC and IPS as input regions. Subsequent analysis of the intrinsic connectivity within two investigated models (IPS and ACC) disclosed significant parallel forward connections from the IPS to the frontal areas and from the ACC to the PFC and the IPS. CONCLUSION Our findings indicate that during target stimulus processing there is a bidirectional frontoparietal information flow, very likely reflecting parallel activation of two distinct but partially overlapping attentional or attentional/event-encoding neural systems. Additionally, a simple hierarchy within the right frontal lobe is suggested with the ACC exerting influence over the PFC.

Default Mode Network and Extrastriate Visual Resting State Network in Patients with Parkinson’s Disease Dementia

Aims: Using fMRI, we evaluated the default mode network (DMN) and the extrastriate visual resting state network (ESV-RSN) in 14 patients with Parkinson’s disease dementia (PDD) as compared with 18 patients with Parkinson’s disease (PD) without dementia and 18 healthy controls (HC). Methods: We analyzed the seed-based functional connectivity of both resting state data and deactivations during a visual complex scene-encoding task. Results: Using the posterior cingulate cortex/precuneus as a seed for the DMN analysis, we observed significant decreases of connectivity in the right inferior frontal gyrus in PDD as compared to PD and HC. Using the caudate nucleus as a seed for the ESV-RSN analysis, we found significant decreases of connectivity in the left and right inferior occipital gyrus in PDD as compared to HC. Conclusion: Differences in functional connectivity patterns between PDD and PD/HC were observed in areas known to be engaged in stimulus-driven reorienting of attention and in visual processing.

Prefrontal but not temporal grey matter changes in males with first-episode schizophrenia.

INTRODUCTION Changes of brain morphology are now considered as a part of the pathology of schizophrenia. Voxel-based morphometry may be used to study regional changes of the grey matter in the whole brain. It is advantageous to study first-episode patients to prevent the influence of many possible biasing factors when trying to identify primary pathological processes underlying the manifestation of the illness. OBJECTIVE To investigate regional grey matter changes in the first-episode schizophrenia patients. METHODS Optimized voxel-based morphometry was used to detect changes in grey matter volume in 22 patients with first-episode schizophrenia compared with 18 healthy volunteers of comparable age, gender and handedness. RESULTS The first-episode schizophrenia group had significantly reduced grey matter volume in the prefrontal cortex (inferior and middle prefrontal gyrus, cingulate gyrus). We identified no differences in the temporal cortex. CONCLUSION Our data support the theoretical assumption that prefrontal dysfunction underlines the primary pathology and clinical manifestation of schizophrenia. We are inclined to explain the differences in the pattern of morphological changes reported in other first-episode studies--especially the lack of changes in the temporal cortex--by heterogeneity of schizophrenia, potential progression and antipsychotic medication effect.

An optimized voxel-based morphometric study of gray matter changes in patients with left-sided and right-sided mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS)

Purpose:  To determine whether changes in gray matter volume (GMV) differ according to the affected side in mesial temporal lobe epilepsy/hippocampal sclerosis (MTLE/HS) syndrome, and moreover to test the hypothesis of more pronounced structural changes in right‐sided MTLE/HS. This hypothesis (especially that the contralateral thalamus is more affected in right‐sided MTLE/HS) arose from the results of our recent study, wherein more expressed structural and functional changes were observed in a small sample of patients with right‐sided MTLE/HS ( Brázdil et al., 2009 ).

Functional Abnormalities in the Primary Orofacial Sensorimotor Cortex During Speech in Parkinson's Disease

Parkinsons disease (PD) affects speech, including respiration, phonation, and articulation. We measured the blood oxygen level‐dependent (BOLD) response to overt sentence reading in: (1) 9 treated female patients with mild to moderate PD (age; mean 66.0 ± 11.6 years, mean levodopa equivalent 583.3 ± 397.9 mg) and (2) 8 age‐matched healthy female controls (age; mean 62.2 years ± 12.3). Speech was recorded in the scanner to assess which brain regions underlie variations in the initiation and paralinguistic aspects (e.g., pitch, loudness, and rate) of speech production in the two groups. There were no differences in paralinguistic aspects of speech except for speech loudness; it was lower in PD patients compared with that in controls, when age was used as a covariate. In both groups, we observed increases in the BOLD response (reading‐baseline) in brain regions involved in speech production and perception. In PD patients, as compared with controls, we found significantly higher BOLD signal in the right primary orofacial sensorimotor cortex and more robust correlations between the measured speech parameters and the BOLD response to reading, particularly, in the left primary orofacial sensorimotor cortex. These results might reflect compensatory mechanisms and/or treatment effects that take place in mild to moderately ill PD patients with quality of speech yet comparable with that of age‐matched controls.

Source-based morphometry of gray matter volume in men with first-episode schizophrenia.

Objectives: There is a lot of variability between the results of studies reporting the pattern of gray matter volume changes in schizophrenia. Methodological issues may play an important role in this heterogeneity. The aim of the present study was to replicate the better performance of multivariate “source‐based morphometry” (SBM) over the mass‐univariate approach. Experimental design: Voxel‐based morphometry of Jacobian‐modulated gray matter volume images, using voxel and cluster level inference, and SBM were performed in a group of first‐episode schizophrenia patients (N = 49) and healthy controls (N = 127). Results: Using SBM we were able to find a significant reduction of gray matter volume in fronto‐temporo‐cerebellar areas whereas no significant results were obtained using voxel‐based morphometry. Conclusion: Multivariate analysis of gray matter volume seems to be a suitable method for characterization of the pattern of changes at the beginning of the illness in schizophrenia subjects. Hum Brain Mapp, 2010.

Functional Imaging of the Cerebellum and Basal Ganglia During Predictive Motor Timing in Early Parkinson's Disease

The basal ganglia and the cerebellum have both emerged as important structures involved in the processing of temporal information.