Association of plasma tryptophan concentration with periaqueductal gray matter functional connectivity in migraine patients.

Altered periaqueductal gray matter (PAG) functional connectivity contributes to brain hyperexcitability in migraine. Although tryptophan modulates neurotransmission in PAG projections through its metabolic pathways, the effect of plasma tryptophan on PAG functional connectivity (PAG-FC) in migraine has not been investigated yet. In this study, using a matched case-control design PAG-FC was measured during a resting-state functional magnetic resonance imaging session in migraine without aura patients (n = 27) and healthy controls (n = 27), and its relationship with plasma tryptophan concentration (TRP) was assessed. In addition, correlations of PAG-FC with age at migraine onset, migraine frequency, trait-anxiety and depressive symptoms were tested and the effect of TRP on these correlations was explored. Our results demonstrated that migraineurs had higher TRP compared to controls. In addition, altered PAG-FC in regions responsible for fear-cascade and pain modulation correlated with TRP only in migraineurs. There was no significant correlation in controls. It suggests increased sensitivity to TRP in migraine patients compared to controls. Trait-anxiety and depressive symptoms correlated with PAG-FC in migraine patients, and these correlations were modulated by TRP in regions responsible for emotional aspects of pain processing, but TRP did not interfere with processes that contribute to migraine attack generation or attack frequency.

Homocysteine-related alterations of 18F-FDG brain pattern in metabolic diseases.

Since hyperhomocysteinaemia (HHcys) is implicated as a risk factor for the development of neurodegeneration, and is associated with the development of metabolic diseases,we aimed at analysing the effect of homocysteine (Hcys) on regional fluorine-18-fluorodeoxyglucose (18F-FDG) brain metabolismin 51 controlled type 2 diabetic and in 48 non-DM obese participants. Plasma Hcys levels were measured by an immunoassay. Homocysteine-related 18F-FDG regional brain metabolism was evaluated applying 18F-FDG PET/CT using magnetic resonance imaging (MRI)-based brain template for statistical parametric mapping (SPM) analysis. Homocysteine-related decreased 18F-FDG uptake was shown in the right middle temporal gyrus in the whole population. Diabetics with Hcys above the reference limit expressed decreased glucose metabolismin the left calcarine cortex compared to the obese with HHcys. Regional metabolic alterations evoked on the basis of HHcys draw attention to the potential risk of neurodegeneration caused by metabolic disturbances.

Automated procedure assessing the accuracy of HRCT-PET registration applied in functional virtual bronchoscopy.

BACKGROUND: Bronchoscopy serves as direct visualisation of the airway. Virtual bronchoscopy provides similar visual information using a non-invasive imaging procedure(s). Early and accurate image-guided diagnosis requires the possible highest performance, which might be approximated by combining anatomical and functional imaging. This communication describes an advanced functional virtual bronchoscopic (fVB) method based on the registration of PET images to high-resolution diagnostic CT images instead of low-dose CT images of lower resolution obtained from PET/CT scans. PET/CT and diagnostic CT data were collected from 22 oncological patients to develop a computer-aided high-precision fVB. Registration of segmented images was performed using elastix. RESULTS: For virtual bronchoscopy, we used an in-house developed segmentation method. The quality of low- and high-dose CT image registrations was characterised by expert's scoring the spatial distance of manually paired corresponding points and by eight voxel intensity-based (dis)similarity parameters. The distribution of (dis)similarity parameter correlating best with anatomic scoring was bootstrapped, and 95% confidence intervals were calculated separately for acceptable and insufficient registrations. We showed that mutual information (MI) of the eight investigated (dis)similarity parameters displayed the closest correlation with the anatomy-based distance metrics used to characterise the quality of image registrations. The 95% confidence intervals of the bootstrapped MI distribution were [0.15, 0.22] and [0.28, 0.37] for insufficient and acceptable registrations, respectively. In case of any new patient, a calculated MI value of registered low- and high-dose CT image pair within the [0.28, 0.37] or the [0.15, 0.22] interval would suggest acceptance or rejection, respectively, serving as an aid for the radiologist. CONCLUSION: A computer-aided solution was proposed in order to reduce reliance on radiologist's contribution for the approval of acceptable image registrations.

Sex Differences of Periaqueductal Grey Matter Functional Connectivity in Migraine.

The existence of "sex phenotype" in migraine is a long-standing scientific question. Fluctuations of female sex hormones contribute to migraine attacks, and women also have enhanced brain activity during emotional processing and their functional brain networks seem to be more vulnerable to migraine-induced disruption compared to men. Periaqueductal grey matter (PAG) is a core region of pain processing and modulation networks with possible sex-related implications in migraine. In our study, sex differences of PAG functional resting-state connectivity were investigated in the interictal state in 32 episodic migraines without aura patients (16 women and 16 men). A significant main effect of sex was detected in PAG connectivity with postcentral, precentral, and inferior parietal gyri, and further differences were found between right PAG and visual areas (superior occipital gyrus, calcarine, and cuneus), supplementary motor area, and mid-cingulum connectivity. In all cases, PAG functional connectivity was stronger in female migraineurs compared to males. However, higher average pain intensity of migraine attacks correlated with stronger connectivity of PAG and middle temporal, superior occipital, and parietal gyri in male migraineurs compared to females. Migraine-related disability is also associated with PAG connectivity but without sex differences. Our results indicate that sex differences in PAG connectivity with brain regions involved in sensory and emotional aspects of pain might contribute to the "sex-phenotype" in migraine. The stronger functional connectivity between PAG and pain processing areas may be a sign of increased excitability of pain pathways even in resting-state in females compared to male migraineurs, which could contribute to female vulnerability for migraine. However, pain intensity experienced by male migraineurs correlated with increased connectivity between PAG and regions involved in the subjective experience of pain and pain-related unpleasantness. The demonstrated sex differences of PAG functional connectivity may support the notion that the female and male brain is differently affected by migraine.

OAR sparing 3D radiotherapy planning supported by fMRI brain mapping investigations.

The human brain as an organ has numerous functions; some of them can be visualized by functional imaging techniques (e.g., functional MRI [fMRI] or positron emission tomography). The localization of the appropriate activity clusters requires sophisticated instrumentation and complex measuring protocol. As the inclusion of the activation pattern in modern self-tailored 3D based radiotherapy has notable advantages, this method is applied frequently. Unfortunately, no standardized method has been published yet for the integration of the fMRI data into the planning process and the detailed description of the individual applications is usually missing. Thirteen patients with brain tumors, receiving fMRI based RT planning were enrolled in this study. The delivered dose maps were exported from the treatment planning system and processed for further statistical analysis. Two parameters were introduced to measure the geometrical distance Hausdorff Distance (HD), and volumetric overlap Dice Similarity Coefficient (DSC) of fMRI corrected and not corrected dose matrices as calculated by 3D planning to characterize similarity and/or dissimilarity of these dose matrices. Statistical analysis of bootstrapped HD and DSC data was performed to determine confidence intervals of these parameters. The calculated confidence intervals for HD and DSC were (5.04, 7.09), (0.79, 0.86), respectively for the 40 Gy and (5.2, 7.85), (0.74, 0.83), respectively for the 60 Gy dose volumes. These data indicate that in the case of HD < 5.04 and/or DSC > 0.86, the 40 Gy dose volumes obtained with and without fMRI activation pattern do not show a significant difference (5% significance level). The same conditions for the 60 Gy dose volumes were HD < 5.2 and/or DSC > 0.83. At the same time, with HD > 7.09 and/or DSC < 0.79 for 40 Gy and HD > 7.85 and/or DSC < 0.74 for 60 Gy the impact of fMRI utilization in RT planning is excessive. The fMRI activation clusters can be used in daily RT planning routine to spare activation clusters as critical areas in the brain and avoid their high dose irradiation. Parameters HD (as distance) and DSC (as overlap) can be used to characterize the difference and similarity between the radiotherapy planning target volumes and indicate whether the fMRI delivered activation patterns and consequent fMRI corrected planning volumes are reliable or not.

Effective connectivity differences in motor network during passive movement of paretic and non-paretic ankles in subacute stroke patients.

BACKGROUND: A better understanding of the neural changes associated with paresis in stroke patients could have important implications for therapeutic approaches. Dynamic Causal Modeling (DCM) for functional magnetic resonance imaging (fMRI) is commonly used for analyzing effective connectivity patterns of brain networks due to its significant property of modeling neural states behind fMRI signals. We applied this technique to analyze the differences between motor networks (MNW) activated by continuous passive movement (CPM) of paretic and non-paretic ankles in subacute stroke patients. This study aimed to identify CPM induced connectivity characteristics of the primary sensory area (S1) and the differences in extrinsic directed connections of the MNW and to explain the hemodynamic differences of brain regions of MNW. METHODS: For the network analysis, we used ten stroke patients' task fMRI data collected under CPMs of both ankles. Regions for the MNW, the primary motor cortex (M1), the premotor cortex (PM), the supplementary motor area (SMA) and the S1 were defined in a data-driven way, by independent component analysis. For the network analysis of both CPMs, we compared twelve models organized into two model-families, depending on the S1 connections and input stimulus modeling. Using DCM, we evaluated the extrinsic connectivity strengths and hemodynamic parameters of both stimulations of all patients. RESULTS: After a statistical comparison of the extrinsic connections and their modulations of the "best model", we concluded that three contralateral self-inhibitions (cM1, cS1 and cSMA), one contralateral inter-regional connection (cSMA→cM1), and one interhemispheric connection (cM1→iM1) were significantly different. Our research shows that hemodynamic parameters can be estimated with the Balloon model using DCM but the parameters do not change with stroke. CONCLUSIONS: Our results confirm that the DCM-based connectivity analyses combined with Bayesian model selection may be a useful technique for quantifying the alteration or differences in the characteristics of the motor network in subacute stage stroke patients and in determining the degree of MNW changes.

Central sensitization-related changes of effective and functional connectivity in the rat inflammatory trigeminal pain model.

Central sensitization is a key mechanism in the pathology of several neuropathic pain disorders. We aimed to investigate the underlying brain connectivity changes in a rat model of chronic pain. Non-noxious whisker stimulation was used to evoke blood-oxygen-level-dependent (BOLD) responses in a block-design functional Magnetic Resonance Imaging (fMRI) experiment on 9.4T. Measurements were repeated two days and one week after injecting complete Freund's adjuvant into the rats' whisker pad. We found that acute pain reduced activation in the barrel cortex, most probably due to a plateau effect. After one week, increased activation of the anterior cingulate cortex was found. Analyses of effective connectivity driven by stimulus-related activation revealed that chronic pain-related central sensitization manifested as a widespread alteration in the activity of the somatosensory network. Changes were mainly mediated by the anterior cingulate cortex and the striatum and affected the somatosensory and motor cortices and the superior colliculus. Functional connectivity analysis of nested BOLD oscillations justified that the anterior cingular-somatosensory interplay is a key element of network changes. Additionally, a decreased cingulo-motor functional connectivity implies that alterations also involve the output tract of the network. Our results extend the knowledge about the role of the cingulate cortex in the chronification of pain and indicate that integration of multiple connectivity analysis could be fruitful in studying the central sensitization in the pain matrix.

Population-Level Correction of Systematic Motion Artifacts in fMRI in Patients with Ischemic Stroke.

BACKGROUND: The aim of this study was to reveal potential sources of systematic motion artifacts in stroke functional magnetic resonance imaging (fMRI) focusing on those causing stimulus-correlated motion on the individual-level and separate the motion effect on the fMRI signal changing from the activation-induced alteration at population level. METHODS: Eleven ischemic stroke patients were examined by fMRI. The fMRI paradigm was based on passive ankle movement on both the healthy and the paretic leg's side. Three individual-level motion correction strategies were compared and we introduced five measures to characterize each subjects' in-scanner relative head movement. After analyzing the correlation of motion parameters and the subjects' physiological scale scores, we selected a parameter to model the motion-related artifacts in the second-level analysis. RESULTS: At first (individual) level analysis, the noise-component correction-based CompCor method provided the highest -log10(p) value of cluster-level occurrence probability at 12.4/13.6 for healthy and paretic side stimulus, respectively, with a maximal z-value of 15/16.3. Including the motion parameter at second (group) level resulted in lower cluster occurrence values at 10.9/5.55 while retaining the maximal z-value. CONCLUSIONS: We proposed a postprocessing pipeline for ischemic stroke fMRI data that combine the CompCor correction at first level with the modeling of motion effect at second-level analysis by a parameter obtained from fMRI data. Our solution is applicable for any fMRI-based stroke rehabilitation study since it does not require any MRI-compatible motion capture system and is based on commonly used methods.

Voxel-wise motion artifacts in population-level whole-brain connectivity analysis of resting-state FMRI.

Functional Magnetic Resonance Imaging (fMRI) based brain connectivity analysis maps the functional networks of the brain by estimating the degree of synchronous neuronal activity between brain regions. Recent studies have demonstrated that "resting-state" fMRI-based brain connectivity conclusions may be erroneous when motion artifacts have a differential effect on fMRI BOLD signals for between group comparisons. A potential explanation could be that in-scanner displacement, due to rotational components, is not spatially constant in the whole brain. However, this localized nature of motion artifacts is poorly understood and is rarely considered in brain connectivity studies. In this study, we initially demonstrate the local correspondence between head displacement and the changes in the resting-state fMRI BOLD signal. Than, we investigate how connectivity strength is affected by the population-level variation in the spatial pattern of regional displacement. We introduce Regional Displacement Interaction (RDI), a new covariate parameter set for second-level connectivity analysis and demonstrate its effectiveness in reducing motion related confounds in comparisons of groups with different voxel-vise displacement pattern and preprocessed using various nuisance regression methods. The effect of using RDI as second-level covariate is than demonstrated in autism-related group comparisons. The relationship between the proposed method and some of the prevailing subject-level nuisance regression techniques is evaluated. Our results show that, depending on experimental design, treating in-scanner head motion as a global confound may not be appropriate. The degree of displacement is highly variable among various brain regions, both within and between subjects. These regional differences bias correlation-based measures of brain connectivity. The inclusion of the proposed second-level covariate into the analysis successfully reduces artifactual motion-related group differences and preserves real neuronal differences, as demonstrated by the autism-related comparisons.