Lajos R. Kozák

Using diffusion MRI for measuring the temperature of cerebrospinal fluid within the lateral ventricles

Aim:  Hypothermia is often induced to reduce brain injury in newborns, following perinatal hypoxic–ischaemic events, and in adults following traumatic brain injury, stroke or cardiac arrest. We aimed to devise a method, based on diffusion‐weighted MRI, to measure non‐invasively the temperature of the cerebrospinal fluid in the lateral ventricles.

Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls—A Voxel Based Morphometry Study

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender.

Levetiracetam reduces abnormal network activations in temporal lobe epilepsy

Objective: We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). Methods: In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. Results: We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. Conclusions: Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. Classification of evidence: This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures.

Evoked effective connectivity of the human neocortex

The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico‐cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an inverse relationship to distance between sites. Coregistration to Brodmann areas (BA) permitted group analysis. Connections were frequently directional with 43% of early responses and 50% of late responses of connections reflecting relative dominance of incoming or outgoing connections. The most consistent connections were seen as outgoing from motor cortex, BA6–BA9, somatosensory (SS) cortex, anterior cingulate cortex, and Brocas area. Network topology revealed motor, SS, and premotor cortices along with BA9 and BA10 and language areas to serve as hubs for cortical connections. BA20 and BA39 demonstrated the most consistent dominance of outdegree connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated relatively greater indegree. This multicenter, large‐scale, directional study of local and long‐range cortical connectivity using direct recordings from awake, humans will aid the interpretation of noninvasive functional connectome studies. Hum Brain Mapp 35:5736–5753, 2014.

Learning to filter out visual distractors

When learning to master a visual task in a cluttered natural environment, it is important to optimize the processing of task‐relevant information and to efficiently filter out distractors. However, the mechanisms that suppress task‐irrelevant information are not well understood. Here we show that training leads to a selective increase in motion coherence detection thresholds for task‐irrelevant motion directions that interfered with the processing of task‐relevant directions during training. Furthermore, using functional magnetic resonance imaging we found that training attenuated neural responses associated with the task‐irrelevant direction compared with the task‐relevant direction in the visual cortical areas involved in processing of visual motion. The strongest suppression of functional magnetic resonance imaging responses to task‐irrelevant motion information was observed in human area MT+. These findings reveal that perceptual learning leads to the suppression and efficient filtering of task‐irrelevant visual information.

Type of Featural Attention Differentially Modulates hMT+ Responses to Illusory Motion Aftereffects

Activity in the human motion complex (hMT(+)/V5) is related to the perception of motion, be it either real surface motion or an illusion of motion such as apparent motion (AM) or motion aftereffect (MAE). It is a long-lasting debate whether illusory motion-related activations in hMT(+) represent the motion itself or attention to it. We have asked whether hMT(+) responses to MAEs are present when shifts in arousal are suppressed and attention is focused on concurrent motion versus nonmotion features. Significant enhancement of hMT(+) activity was observed during MAEs when attention was focused either on concurrent spatial angle or color features. This observation was confirmed by direct comparison of adapting (MAE inducing) versus nonadapting conditions. In contrast, this effect was diminished when subjects had to report on concomitant speed changes of superimposed AM. The same finding was observed for concomitant orthogonal real motion (RM), suggesting that selective attention to concurrent illusory or real motion was interfering with the saliency of MAE signals in hMT(+). We conclude that MAE-related changes in the global activity of hMT(+) are present provided selective attention is not focused on an interfering feature such as concurrent motion. Accordingly, there is a genuine MAE-related motion signal in hMT(+) that is neither explained by shifts in arousal nor by selective attention.

Peripheral influences on motion integration in foveal vision are modulated by central local ambiguity and center-surround congruence.

PURPOSE To study how central visual motion integration and segmentation processes are influenced by the congruence or incongruence of peripheral contextual moving surrounds and to determine their clinical relevance. METHODS Nine subjects participated in experiments 1 and 2 (12-second blocks containing 2-second static fixation and 10-second surface plaid movement) and 15 in experiment 3 (72-second blocks, with 12-second fixation, and 60-second motion). Observers reported whether they perceived nontransparent (corresponding to visual integration of motion cues into one surface) or transparent (segmentation of two surfaces from motion cues) plaid motion within a 5 degrees central circular region. Surround stimuli were 20 degrees transparent or nontransparent moving plaids. RESULTS Contextual effects required the presence of both local and global ambiguity. If central local motion became unambiguous, then surrounds became ineffective. Under local and global ambiguity, transparent surrounds invariably induced central congruence while also strongly suppressing incongruent percepts. Nontransparent surrounds produced similar but less consistent congruent bias, especially for longer viewing times. In the latter case, however, suppression of incongruent central interpretations became barely detectable compared to the observed significant facilitation of congruent percepts. CONCLUSIONS Local ambiguity is critical in contextual modulation, and the peripheral enhancement or suppression of central motion integration depends both on transparency bias and center-surround congruence. The importance of local ambiguity in contextual modulation is clinically relevant, because it implies that contextual effects will be stronger in disorders with impaired central vision, such as macular degeneration. Moreover, the increased efficacy of global context under conditions of increased local ambiguity may be useful in future rehabilitation approaches.

Investigating the need of triggering the acquisition for infant diffusion MRI: A quantitative study including bootstrap statistics

Diffusion weighted magnetic resonance imaging is increasingly being used for neonatal and young pediatric subjects. Our purpose was to investigate a) whether cardiac triggering was needed to reduce variability of diffusion (tensor) imaging data, b) how pulsation artifacts affect the fitted diffusion tensor when triggering is not used and c) the feasibility of triggered data acquisition in neonates and young children. Data were collected from 11 infants and 7 adults. In seven infants and seven adults, diffusion encoding was applied solely along the z gradient direction with and without cardiac triggering. Non-parametric bootstrap statistical methods were applied to investigate the dependence of variance on triggering. One infant and all adults served as test–retest controls. From the remaining three infants diffusion tensor imaging data were acquired with and without triggering. Our findings that used the repeated measurements in a single diffusion-encoding direction indicated that without triggering the variability in the data was increased significantly both in infants and adults. When collecting diffusion tensor data in infants, this increased variability results in erroneous fractional anisotropy values and artifactual fiber direction estimates. Contrary to previous reports but supported by our findings involving adults, pulsation artifacts were present in a larger extent of the brain in the infant population. In conclusion, triggering is feasible in young subjects and is preferred when acquiring diffusion MRI data. In doing so, the amount of erroneous estimations due to image artifacts will be minimized, which in turn will lead to more specific and less ambiguous interpretations. Although fitting the pulse-monitoring device requires additional set-up time, the total imaging time is usually shorter than acquiring multiple data sets to compile a single, artifact-free set.

Trait Rumination Influences Neural Correlates of the Anticipation but Not the Consumption Phase of Reward Processing

Cumulative evidence suggests that trait rumination can be defined as an abstract information processing mode, which leads people to constantly anticipate the likely impact of present events on future events and experiences. A previous study with remitted depressed patients suggested that enhanced rumination tendencies distort brain mechanisms of anticipatory processes associated with reward and loss cues. In the present study, we explored the impact of trait rumination on neural activity during reward and loss anticipation among never-depressed people. We analyzed the data of 37 healthy controls, who performed the monetary incentive delay (MID) task which was designed for the simultaneous measurement of the anticipation (motivational) and consumption (hedonic) phase of reward processing, during functional magnetic resonance imaging (fMRI). Our results show that rumination—after controlling for age, gender, and current mood—significantly influenced neural responses to reward (win) cues compared to loss cues. Blood-oxygenation-level-dependent (BOLD) activity in the left inferior frontal gyrus (IFG) triangularis, left anterior insula, and left rolandic operculum was positively related to Ruminative Response Scale (RRS) scores. We did not detect any significant rumination-related activations associated with win-neutral or loss-neutral cues and with reward or loss consumption. Our results highlight the influence of trait rumination on reward anticipation in a non-depressed sample. They also suggest that for never-depressed ruminators rewarding cues are more salient than loss cues. BOLD response during reward consumption did not relate to rumination, suggesting that rumination mainly relates to processing of the motivational (wanting) aspect of reward rather than the hedonic (liking) aspect, at least in the absence of pathological mood.

What can DTI tell about early cognitive impairment? – Differentiation between MCI subtypes and healthy controls by diffusion tensor imaging

Mild cognitive impairment (MCI) gained a lot of interest recently, especially that the conversion rate to Alzheimer Disease (AD) in the amnestic subtype (aMCI) is higher than in the non-amnestic subtype (naMCI). We aimed to determine whether and how diffusion-weighted MRI (DWI) using the diffusion tensor model (DTI) can differentiate MCI subtypes from healthy subjects. High resolution 3D T1W and DWI images of patients (aMCI, n = 18; naMCI, n = 20; according to Petersen criteria) and controls (n = 27) were acquired at 3T and processed using ExploreDTI and SPM. Voxel-wise and region of interest (ROI) analyses of fractional anisotropy (FA) and mean diffusivity (MD) were performed with ANCOVA; MD was higher in aMCI compared to controls or naMCI in several grey and white matter (GM, WM) regions (especially in the temporal pole and the inferior temporal lobes), while FA was lower in WM ROI-s (e.g. left Cingulum). Moreover, significant correlations were identified between verbal fluency, visual and verbal memory performance and DTI metrics. Logistic regression showed that measuring FA of the crus of fornix along GM volumetry improves the discrimination of aMCI from naMCI. Additional information from DWI/DTI aids preclinical detection of AD and may help detecting early non-Alzheimer type dementia, too.