Heritability of Subcortical Grey Matter Structures.

Background and Objectives: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age, and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes (the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens) and four general brain volumes (the total intra-cranial volume and the grey matter, white matter, and cerebrospinal fluid (CSF) volume) in twins. Materials and Methods: A total of 118 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 32 dizygotic; median age 50 ± 27 years) underwent brain magnetic resonance imaging. Two automated volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain, were used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated, and the univariate ACE model was applied. Pearson's correlation test was used to compare the results obtained by the two pipelines. Results: The age- and sex-adjusted heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens, were between 0.75 and 0.95. The thalamus volume was more strongly influenced by common environmental factors (C = 0.45-0.73). The heritability estimates, using volBrain, were between 0.69 and 0.92 for the nucleus accumbens, pallidum, putamen, right amygdala, and caudate nucleus. The left amygdala and thalamus were more strongly influenced by common environmental factors (C = 0.72-0.85). A strong correlation between CAT12 and volBrain (r = 0.74-0.94) was obtained for all volumes. Conclusions: The majority of examined subcortical volumes appeared to be strongly heritable. The thalamus was more strongly influenced by common environmental factors when investigated with both segmentation methods. Our results underline the importance of identifying the relevant genes responsible for variations in the subcortical structure volume and associated diseases.

Genetic and Environmental Effects on the Development of White Matter Hyperintensities in a Middle Age Twin Population.

Introduction: White matter hyperintensities (WMH) indicate white matter brain lesions in magnetic resonance imaging (MRI), which can be used as a marker for brain aging and cerebrovascular and neurodegenerative disorders. Twin studies revealed substantial but not uniform WMH heritability in elderly twins. The objective of our study was to investigate the genetic and environmental components of WMH, as well as their importance in a healthy twin population, utilizing 3T MRI scanners in a middle-aged twin population. Methods: Brain MRI was performed on 120 healthy adult twins from the Hungarian Twin Registry on a 3T scanner (86 monozygotic, MZ and 34 dizygotic, DZ twins; median age 50 ± 26.5 years, 72.5% female and 27.5% male). The count of WMH on FLAIR images was calculated using an automated volumetry pipeline (volBrain) and human processing. The age- and sex-adjusted MZ and DZ intra-pair correlations were determined and the total variance was decomposed into genetic, shared and unique environmental components using structural equation modeling. Results: Age and sex-adjusted MZ intrapair correlations were higher than DZ correlations, indicating moderate genetic influence in each lesion (rMZ = 0.466, rDZ = -0.025 for total count; rMZ = 0.482, rDZ = 0.093 for deep white matter count; rMZ = 0.739, rDZ = 0.39 for infratentorial count; rMZ = 0.573, rDZ = 0.372 for cerebellar count and rMZ = 0.473, rDZ = 0.19 for periventricular count), indicating a moderate heritability (A = 40.3%, A = 45%, A = 72.7% and A = 55.5%and 47.2%, respectively). The rest of the variance was influenced by unique environmental effects (E between 27.3% and 59.7%, respectively). Conclusions: The number of WMH lesions is moderately influenced by genetic effects, particularly in the infratentorial region in middle-aged twins. These results suggest that the distribution of WMH in various brain regions is heterogeneous.

Microstructural alterations measured by diffusion tensor imaging following transcatheter aortic valve replacement and their association with cerebral ischemic injury and cognitive function - a prospective study.

PURPOSE: We assessed diffusion tensor imaging (DTI) metric changes of the corpus callosum and cingulum correlated to postprocedural ischemic lesion load (ILL) and cognitive performance in transcatheter aortic valve replacement (TAVR). METHODS: TAVR subjects had DTI post-TAVR (≤ 8 days) and at 6 months (78 participants, males 56%, age 78.8 years ± 6.3) and four neurocognitive tests (pre-TAVR, post-TAVR, 6 months, 1 year). DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were calculated for 7 regions: corpus callosum (genu, body, splenium) and cingulum (cingulate gyrus, parahippocampal cingulum bilaterally). DTI metrics post-TAVR and at 6 months were compared with Student's t-test (p < 0.0071) and ANOVA covarying for sex, ILL (p < 0.05) with post hoc analysis of ILL groups (p < 0.0167). Repeated-measures linear mixed-effect model (p < 0.05) was performed to investigate the effect of time and ILL on cognition. RESULTS: At 6 months, significant decrease of the following DTI metrics was detected: AD (genu, body, splenium, right parahippocampal cingulum: p ≤ 0.0046); MD (body, both cingulate gyri: p ≤ 0.0050); RD (left cingulate gyrus: p = 0.0021); FA (splenium: p < 0.0001). ANOVA confirmed significant effect of female sex on AD + MD reduction (body, right cingulate gyrus) and AD reduction (left cingulate gyrus) (p ≤ 0.0254). Significant negative effect of ILL on some DTI metric changes was found (AD + MD-body: p ≤ 0.0050; MD-left cingulate gyrus: p = 0.0087). Cognitive performance remained stable with significant negative correlation of ILL and retrograde memory and visual scores (p ≤ 0.0483). CONCLUSION: Significant effect of TAVR on cerebral microstructural integrity was found with reduced diffusivities opposite to the trends reported in various neurodegenerative conditions/ageing, notably in women and lower ILL, and with preserved/improved cognition. TRIAL REGISTRATION NUMBER: NCT02826200 at ClinicalTrials.gov; date of registration: 07. July 2016.

Circadian Variation of Migraine Attack Onset Affects fMRI Brain Response to Fearful Faces.

Background: Previous studies suggested a circadian variation of migraine attack onset, although, with contradictory results - possibly because of the existence of migraine subgroups with different circadian attack onset peaks. Migraine is primarily a brain disorder, and if the diversity in daily distribution of migraine attack onset reflects an important aspect of migraine, it may also associate with interictal brain activity. Our goal was to assess brain activity differences in episodic migraine subgroups who were classified according to their typical circadian peak of attack onset. Methods: Two fMRI studies were conducted with migraine without aura patients (n = 31 in Study 1, n = 48 in Study 2). Among them, three subgroups emerged with typical Morning, Evening, and Varying start of attack onset. Whole brain activity was compared between the groups in an implicit emotional processing fMRI task, comparing fearful, sad, and happy facial stimuli to neutral ones. Results: In both studies, significantly increased neural activation was detected to fearful (but not sad or happy) faces. In Study 1, the Evening start group showed increased activation compared to the Morning start group in regions involved in emotional, self-referential (left posterior cingulate gyrus, right precuneus), pain (including left middle cingulate, left postcentral, left supramarginal gyri, right Rolandic operculum) and sensory (including bilateral superior temporal gyrus, right Heschl's gyrus) processing. While in Study 2, the Morning start group showed increased activation compared to the Varying start group at a nominally significant level in regions with pain (right precentral gyrus, right supplementary motor area) and sensory processing (bilateral paracentral lobule) functions. Conclusion: Our fMRI studies suggest that different circadian attack onset peaks are associated with interictal brain activity differences indicating heterogeneity within migraine patients and alterations in sensitivity to threatening fearful stimuli. Circadian variation of migraine attack onset may be an important characteristic to address in future studies and migraine prophylaxis.

[Correction of the physiological artefacts at pre-surgical clinical functional MR]. / Fiziológiai mutermékek jelentosége az idegsebészeti mutétek elott végzett funkcionális MR-vizsgálatokban.

BACKGROUND AND PURPOSE: Pre-surgical functional MRI (fMRI) is an important modality of examinations before brain surgery. There are several artefacts (e.g. motion, susceptibility) which may hinder the evaluation of fMRI data. Physiological artefacts (breathing, pulsation) also affect the sensitivity and specificity of anatomical localization. The aim of this study is to demonstrate the efficiency of physiological artefact identification and removal methods for presurgical evaluation. METHODS: Siemens Magnetom Verio 3T MRI scanner was used to collect data. The physiological parameters (breathing, pulse) were recorded with the MRI system's built-in devices. Data from fourteen patients - with primary brain tumour - were evaluated with SPM12 utilizing the RETROICOR/RVHR tool to detect and decrease the effect of physiological artefacts. We compared the statistical maps obtained with and without the physiological correction using the Jaccard similarity coefficient, and ROI analyses. RESULTS: Significant differences were found in the mean ROI values (p<0.0016) and the extensions of eloquent activations (p<0.0013), when using the physiological correction (RETORICOR/RVHR) based on convolution method. On the other hand, no significant differences were found between the ROIs' standard deviations (F=0.28). The RETROICOR/ RVHR method helps to define the precise localisation of eloquent areas (p<0.009). The number of irrelevant (non-significant) voxels were increased (p<0.001). . CONCLUSION: Minimising of physiological artefacts in fMRI data calculations, the (RETROICOR/RVHR) method based on convolution has been successfully adapted. This algorithm could be helpful before neurosurgical intervention. The activity pattern became more reliable.

Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study.

BACKGROUND: The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. METHODS: Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. RESULTS: Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8-10 min of citalopram infusion. CONCLUSIONS: Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine.

Association between migraine frequency and neural response to emotional faces: An fMRI study.

Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebral processing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity might reflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonance imaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between 41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed increased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontal pole relative to healthy controls. We also found that higher attack frequency in migraine patients was related to increased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearful expressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences remained significant after controlling for anxiety and depressive symptoms. These findings indicate that enhanced response to emotional stimuli might explain the migraine trigger effect of psychosocial stressors that gradually leads to increased somatosensory response to emotional clues and thus contributes to the progression or chronification of migraine.

Altered neural activity to monetary reward/loss processing in episodic migraine.

The dysfunctions of the mesolimbic cortical reward circuit have been proposed to contribute to migraine pain. Although supporting empirical evidence was mainly found in connection with primary rewards or in chronic migraine where the pain experience is (almost) constant. Our goal however was to investigate the neural correlates of secondary reward/loss anticipation and consumption using the monetary incentive delay task in 29 episodic migraine patients and 41 headache-free controls. Migraine patients showed decreased activation in one cluster covering the right inferior frontal gyrus during reward consumption compared to controls. We also found significant negative correlation between the time of the last migraine attack before the scan and activation of the parahippocampal gyrus and the right hippocampus yielded to loss anticipation. During reward/loss consumption, a relative increase in the activity of the visual areas was observed the more time passed between the last attack and the scan session. Our results suggest intact reward/loss anticipation but altered reward consumption in migraine, indicating a decreased reactivity to monetary rewards. The findings also raise the possibility that neural responses to loss anticipation and reward/loss consumption could be altered by the proximity of the last migraine attack not just during pre-ictal periods, but interictally as well.

Are the Variants of the Circle of Willis Determined by Genetic or Environmental Factors? Results of a Twin Study and Review of the Literature.

BACKGROUND: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. METHODS: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. RESULTS: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. CONCLUSION: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.

Spontaneous migraine attack causes alterations in default mode network connectivity: a resting-state fMRI case report.

BACKGROUND: Although migraine is one of the most investigated neurologic disorders, we do not have a perfect neuroimaging biomarker for its pathophysiology. One option to improve our knowledge is to study resting-state functional connectivity in and out of headache pain. However, our understanding of the functional connectivity changes during spontaneous migraine attack is partial and incomplete. CASE PRESENTATION: Using resting-state functional magnetic resonance imaging we assessed a 24-year old woman affected by migraine without aura at two different times: during a spontaneous migraine attack and in interictal phase. Seed-to-voxel whole brain analysis was carried out using the posterior cingulate cortex as a seed, representing the default mode network (DMN). Our results showed decreased intrinsic connectivity within core regions of the DMN with an exception of a subsystem including the dorsal medial and superior frontal gyri, and the mid-temporal gyrus which is responsible for pain interpretation and control. In addition, increased connectivity between the DMN and pain and specific migraine-related areas, such as the pons and hypothalamus, developed during the spontaneous migraine attack. CONCLUSION: Our preliminary results provide further support for the hypothesis that alterations of the DMN functional connectivity during migraine headache may lead to maladaptive top-down modulation of migraine pain-related areas which might be a specific biomarker for migraine.

Diffusion weighted magnetic resonance imaging demonstrates tumor response following palliative embolization of a recurrent shoulder plasmacytoma.

We report the palliative embolization and functional imaging follow-up of a recurrent shoulder plasmacytoma. The multiple myeloma patient complained of severe pain and discomfort, while he could not tolerate further chemotherapy. The left shoulder lesion had earlier received a high dose of irradiation. Thus, the well-vascularized lesion was embolized via feeding arteries branching off from the left subclavian artery in two sessions. The patient's symptoms rapidly improved post-embolization and the serum free light chain ratio stabilized at a lower level. The follow-up magnetic resonance image showed increased diffusivity in previously restricted tumor foci. This has negatively correlated with the decreased fludeoxyglucose uptake on PET, suggesting post-embolization necrosis.

[Role of the intraoperative electrical brain stimulation in conserving the speech and language function in neurosurgical procedures on conscious patients]. / Az intraoperatív elektromos agyi stimuláció szerepe a nyelvi és beszédfunkciók megorzése céljából éber betegeken végzett idegsebészeti beavatkozások során.

AIM OF THE STUDY: To summarize the results gained with awake craniotomies, which were performed in either low grade glioma patients or epilepsy surgical patients whose tumor or epileptogenic zone, was in the vicinity of eloquent, mostly language, cortices. PATIENT SELECTION AND METHODS: In our retrospective study we selected 16 patients who were operated awake between 1999-2011 at the Neurosurgical Department of MAV Kórház Budapest, or at the National Institute of Neurosciences in Budapest, or at the Neurosurgical Department of the University of Debrecen in Debrecen. In the presurgical evaluation if it was possible we performed functional magnetic resonance imaging, tractography and detailed neuropsychological testing. At the National Institute of Neurosciences all patients were operated with the aid of MR guided neuronavigation. RESULTS: Anesthesia was carried out without complications in all of the 16 cases. Monitoring of sleep deepness has significantly contributed to the safety of anesthesia during the superficial anesthezied states of the operation. The intraoperative neuropsychological tasks used for testing language were sensitive enough to judge the little disturbances in speech during stimulation. Stimulation evoked seizures could be adequately managed during surgery and did not influence the outcome of the procedures. The use of neuronavigation helped significantly by planning the optimal place for the craniotomy and by intraoperative orientation. CONCLUSIONS: Awake craniotomies require well practiced surgical teams, which requires the cooperation of neuro-anesthesiologits, neurosurgeons, neuropsychologist and electrophysiologists. It has two goals, first to reduce the time of surgery to minimize surgical complications, secondly the detailed intraoperative mapping of cognitive and motor functions to avoid any neurological deficit. The intraoperative anatomical data provided by the neuronavigation and the functional data provided by awake intraoperative stimulation of the patient together serve the safety of the patient which is essential in the neurologically minimal invasive neurosurgical approach of the 21st century.

[Surgical treatment of resistant epilepsy, caused by hemispherical dysgenesis--case report]. / Hemisphaerialis dysgenesis okozta rezisztens epilepszia mûtéti kezelése--esetismertetés.

A part of patients with the therapy resistant epilepsy can be cured by surgical interventions. The more concordant the presurgical evaluation data, the better prognosis the patient has postoperatively. In case of discordant examination data, multimodal evaluation or case-specific decision might be successful. We report on a five-year-old boy with bilateral (left-dominated) cortical dysplasia and therapy resistant epilepsy. The ictal EEG did not help to localize the seizure onset zone, semiology had little lateralization value; however, FDG-PET showed left hemispheric hypermetabolism. The child became almost seizure-free and showed improved development after left-sided hemispherotomy.