Spatio-Temporal Correlation Tensors Reveal Functional Structure in Human Brain

Resting state functional magnetic resonance imaging (fMRI) has been commonly used to measure functional connectivity between cortical regions, while diffusion tensor imaging (DTI) can be used to characterize structural connectivity of white matter tracts. In principle combining resting state fMRI and DTI data could allow characterization of structure-function relations of distributed neural networks. However, due to differences in the biophysical origins of their signals and in the tissues to which they apply, there has been no direct integration of these techniques to date. We demonstrate that MRI signal variations and power spectra in a resting state are largely comparable between gray matter and white matter, that there are temporal correlations of fMRI signals that persist over long distances within distinct white matter structures, and that neighboring intervoxel correlations of low frequency resting state signals showed distinct anisotropy in many regions. These observations suggest that MRI signal variations from within white matter in a resting state may convey similar information as their corresponding fluctuations of MRI signals in gray matter. We thus derive a local spatio-temporal correlation tensor which captures directional variations of resting-state correlations and which reveals distinct structures in both white and gray matter. This novel concept is illustrated with in vivo experiments in a resting state, which demonstrate the potential of the technique for mapping the functional structure of neural networks and for direct integration of structure-function relations in the human brain.     

Altered Glutamatergic Metabolism Associated with Punctate White Matter Lesions in Preterm Infants

Preterm infants (∼10% of all births) are at high-risk for long-term neurodevelopmental disabilities, most often resulting from white matter injury sustained during the neonatal period. Glutamate excitotoxicity is hypothesized to be a key mechanism in the pathogenesis of white matter injury; however, there has been no in vivo demonstration of glutamate excitotoxicity in preterm infants. Using magnetic resonance spectroscopy (MRS), we tested the hypothesis that glutamate and glutamine, i.e., markers of glutamatergic metabolism, are altered in association with punctate white matter lesions and “diffuse excessive high signal intensity” (DEHSI), the predominant patterns of preterm white matter injury. We reviewed all clinically-indicated MRS studies conducted on preterm infants at a single institution during a six-year period and determined the absolute concentration of glutamate, glutamine, and four other key metabolites in the parietal white matter in 108 of those infants after two investigators independently evaluated the studies for punctate white matter lesions and DEHSI. Punctate white matter lesions were associated with a 29% increase in glutamine concentration (p = 0.002). In contrast, there were no differences in glutamatergic metabolism in association with DEHSI. Severe DEHSI, however, was associated with increased lactate concentration (p = 0.001), a marker of tissue acidosis. Findings from this study support glutamate excitotoxicity in the pathogenesis of punctate white matter lesions, but not necessarily in DEHSI, and suggest that MRS provides a useful biomarker for determining the pathogenesis of white matter injury in preterm infants during a period when neuroprotective agents may be especially effective.     

Intrinsic Functional Brain Architecture Derived from Graph Theoretical Analysis in the Human Fetus

The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA≥31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.     

Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents

Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood.     

White Matter Hyperintensities among Older Adults Are Associated with Futile Increase in Frontal Activation and Functional Connectivity during Spatial Search

The mechanisms by which aging and other processes can affect the structure and function of brain networks are important to understanding normal age-related cognitive decline. Advancing age is known to be associated with various disease processes, including clinically asymptomatic vascular and inflammation processes that contribute to white matter structural alteration and potential injury. The effects of these processes on the function of distributed cognitive networks, however, are poorly understood. We hypothesized that the extent of magnetic resonance imaging white matter hyperintensities would be associated with visual attentional control in healthy aging, measured using a functional magnetic resonance imaging search task. We assessed cognitively healthy older adults with search tasks indexing processing speed and attentional control. Expanding upon previous research, older adults demonstrate activation across a frontal-parietal attentional control network. Further, greater white matter hyperintensity volume was associated with increased activation of a frontal network node independent of chronological age. Also consistent with previous research, greater white matter hyperintensity volume was associated with anatomically specific reductions in functional magnetic resonance imaging functional connectivity during search among attentional control regions. White matter hyperintensities may lead to subtle attentional network dysfunction, potentially through impaired frontal-parietal and frontal interhemispheric connectivity, suggesting that clinically silent white matter biomarkers of vascular and inflammatory injury can contribute to differences in search performance and brain function in aging, and likely contribute to advanced age-related impairments in cognitive control.     

Structural integrity of the uncinate fasciculus and resting state functional connectivity of the ventral prefrontal cortex in late life depression

Background

Neuroimaging studies in late life depression have reported decreased structural integrity of white matter tracts in the prefrontal cortex. Functional studies have identified changes in functional connectivity among several key areas involved in mood regulation. Few studies have combined structural and functional imaging. In this study we sought to examine the relationship between the uncinate fasciculus, a key fronto-temporal tract and resting state functional connectivity between the ventral prefrontal cortex ((PFC) and limbic and striatal areas.

Methods

The sample consisted of 24 older patients remitted from unipolar major depression. Each participant had a magnetic resonance imaging brain scan using standardized protocols to obtain both diffusion tensor imaging and resting state functional connectivity data. Our statistical approach compared structural integrity of the uncinate fasciculus and functional connectivity data.

Results

We found positive correlations between left uncinate fasciculus (UF) fractional anisotropy (FA) and resting state functional connectivity (rsFC) between the left ventrolateral PFC and left amygdala and between the left ventrolateral PFC and the left hippocampus. In addition, we found a significant negative correlation between left ventromedial PFC-caudate rsFC and left UF FA. The right UF FA did not correlate with any of the seed region based connectivity.

Conclusions

These results support the notion that resting state functional connectivity reflects structural integrity, since the ventral PFC is structurally connected to temporal regions by the UF. Future studies should include larger samples of patients and healthy comparison subjects in which both resting state and task-based functional connectivity are examined.     

Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study

Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.     

Diffusion MRI of complex neural architecture

While functional brain imaging methods can locate the cortical regions subserving particular cognitive functions, the connectivity between the functional areas of the human brain remains poorly understood. Recently, investigators have proposed a method to image neural connectivity noninvasively using a magnetic resonance imaging method called diffusion tensor imaging (DTI). DTI measures the molecular diffusion of water along neural pathways. Accurate reconstruction of neural connectivity patterns from DTI has been hindered, however, by the inability of DTI to resolve more than a single axon direction within each imaging voxel. Here, we present a novel magnetic resonance imaging technique that can resolve multiple axon directions within a single voxel. The technique, called q-ball imaging, can resolve intravoxel white matter fiber crossing as well as white matter insertions into cortex. The ability of q-ball imaging to resolve complex intravoxel fiber architecture eliminates a key obstacle to mapping neural connectivity in the human brain noninvasively.     

Neonatal brain injury and neuroanatomy of memory processing following very preterm birth in adulthood: an fMRI study

Altered functional neuroanatomy of high-order cognitive processing has been described in very preterm individuals (born before 33 weeks of gestation; VPT) compared to controls in childhood and adolescence. However, VPT birth may be accompanied by different types of adverse neonatal events and associated brain injury, the severity of which may have differential effects on brain development and subsequent neurodevelopmental outcome. We conducted a functional magnetic resonance imaging (fMRI) study to investigate how differing degrees of neonatal brain injury, detected by neonatal ultrasounds, affect the functional neuroanatomy of memory processing in VPT young adults. We used a verbal paired associates learning task, consisting of four encoding, four cued-recall and four baseline condition blocks. To further investigate whether differences in neural activation between the groups were modulated by structural brain changes, structural MRI data were also collected. We studied 12 VPT young adults with a history of periventricular haemorrhage with associated ventricular dilatation, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage, 12 individuals with normal ultrasonographic findings, and 17 controls. Results of a linear trend analysis demonstrated that during completion of the paired associates learning task right frontal and right parietal brain activation decreased as the severity of neonatal brain injury increased. There were no statistically significant between-group differences in on-line task performance and participants' intelligence quotient (IQ) at assessment. This pattern of differential activation across the groups was observed particularly in the right middle frontal gyrus during encoding and in the right posterior cingulate gyrus during recall. Structural MRI data analysis revealed that grey matter volume in the right superior temporal gyrus, right cerebellum, left middle temporal gyrus, right globus pallidus and right medial frontal gyrus decreased with increasing severity of neonatal brain injury. However, the significant between-group functional neuroanatomical differences were not directly attributable to the detected structural regional differences.     

When Structure Affects Function – The Need for Partial Volume Effect Correction in Functional and Resting State Magnetic Resonance Imaging Studies

Both functional and also more recently resting state magnetic resonance imaging have become established tools to investigate functional brain networks. Most studies use these tools to compare different populations without controlling for potential differences in underlying brain structure which might affect the functional measurements of interest. Here, we adapt a simulation approach combined with evaluation of real resting state magnetic resonance imaging data to investigate the potential impact of partial volume effects on established functional and resting state magnetic resonance imaging analyses. We demonstrate that differences in the underlying structure lead to a significant increase in detected functional differences in both types of analyses. Largest increases in functional differences are observed for highest signal-to-noise ratios and when signal with the lowest amount of partial volume effects is compared to any other partial volume effect constellation. In real data, structural information explains about 25% of within-subject variance observed in degree centrality – an established resting state connectivity measurement. Controlling this measurement for structural information can substantially alter correlational maps obtained in group analyses. Our results question current approaches of evaluating these measurements in diseased population with known structural changes without controlling for potential differences in these measurements.     

Relating connectional architecture to grey matter function using diffusion imaging

Understanding brain function in terms of connectional architecture is a major goal of neuroimaging. However, direct investigation of the influence of brain circuitry on function has been hindered by the lack of a technique for exploring anatomical connectivity in the in vivo brain. Recent advances in magnetic resonance diffusion imaging have given scientists access to data relating to local white matter architecture and, for the first time, have raised the possibility of in vivo investigations into brain circuitry. This review investigates whether diffusion imaging may be used to identify regions of grey matter that are distinct in their connectional architecture, and whether these connectional differences are reflected either in local cytoarchitecture or in local grey matter function.Establishing a direct relationship between regional boundaries based on diffusion imaging and borders between regions that perform different functions would not only be of great significance when interpreting functional results, but would also provide a first step towards the validation of diffusion-based anatomical connectivity studies.     

White matter injury following systemic endotoxemia or asphyxia in the fetal sheep

White matter injury is the most frequently observed brain lesion in preterm infants. The etiology remains unclear, however, both cerebral hypoperfusion and intrauterine infections have been suggested as risk factors. We compared the neuropathological outcome, including the effect on oligodendrocytes, astrocytes, and microglia, following either systemic asphyxia or endotoxemia in fetal sheep at midgestation. Fetal sheep were subjected to either 25 minutes of umbilical cord occlusion or systemic endotoxemia by administration of Escherichia coli lipopolysaccharide (LPS O111:B4, 100 ng/kg, IV). Periventricular white matter lesions were observed in 2 of 6 asphyxiated fetuses, whereas the remaining animals showed diffuse injury throughout the subcortical white matter and neuronal necrosis in subcortical regions, including the striatum and hippocampus. LPS-treatment resulted in focal inflammatory infiltrates and cystic lesions in periventricular white matter in 2 of 5 animals, but with no neuron specific injury. Both experimental paradigms resulted in microglia activation in the white matter, damaged astrocytes, and loss of oligodendrocytes. These results show that the white matter at midgestation is sensitive to injury following both systemic asphyxia and endotoxemia. Asphyxia induced lesions in both white and subcortical grey matter in association with microglia activation, and endotoxemia resulted in selective white matter damage and inflammation.     

Decreased Resting Functional Connectivity after Traumatic Brain Injury in the Rat

Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.     

West syndrome with periventricular leukomalacia: ten-year clinical study

The aim of the study was to evaluate magnetic resonance imaging (MRI) findings in infants with periventricular leukomalacia (PVL) and West syndrome (WS) and determine the neurodevelopmental outcome in children with West syndrome and PVL. Ultrasound and brain MRI were performed in 37 infants with recognized PVL. PVL was categorized according to De Vries, whereas West syndrome was categorized according to International League Against Epilepsy 1989. West syndrome in our patients developed during the first 2 years of life. The most common interictal abnormality was hypsarrhythmia. All, except two patients had delayed development and various degrees of mental retardation. The most characteristic neuroimaging findings were major reduction in cerebral cortical gray matter volume, reduction in the volume of brain myelin, and delayed myelination. These findings may explain the anatomical association between the West syndrome onset and PVL and intellectual and cognitive deficit in premature infants with PVL.     

Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children

Background

Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain.

Objective

Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years.

Design/Methods

The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998–2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning.

Results

At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk.

Conclusions

Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years.     

Perinatal Clinical Antecedents of White Matter Microstructural Abnormalities on Diffusion Tensor Imaging in Extremely Preterm Infants

Objective

To identify perinatal clinical antecedents of white matter microstructural abnormalities in extremely preterm infants.

Methods

A prospective cohort of extremely preterm infants (N = 86) and healthy term controls (N = 16) underwent diffusion tensor imaging (DTI) at term equivalent age. Region of interest-based measures of white matter microstructure - fractional anisotropy and mean diffusivity - were quantified in seven vulnerable cerebral regions and group differences assessed. In the preterm cohort, multivariable linear regression analyses were conducted to identify independent clinical factors associated with microstructural abnormalities.

Results

Preterm infants had a mean (standard deviation) gestational age of 26.1 (1.7) weeks and birth weight of 824 (182) grams. Compared to term controls, the preterm cohort exhibited widespread microstructural abnormalities in 9 of 14 regional measures. Chorioamnionitis, necrotizing enterocolitis, white matter injury on cranial ultrasound, and increasing duration of mechanical ventilation were adversely correlated with regional microstructure. Conversely, antenatal steroids, female sex, longer duration of caffeine therapy, and greater duration of human milk use were independent favorable factors. White matter injury on cranial ultrasound was associated with a five weeks or greater delayed maturation of the corpus callosum; every additional 10 days of human milk use were associated with a three weeks or greater advanced maturation of the corpus callosum.

Conclusions

Diffusion tensor imaging is sensitive in detecting the widespread cerebral delayed maturation and/or damage increasingly observed in extremely preterm infants. In our cohort, it also aided identification of several previously known or suspected perinatal clinical antecedents of brain injury, aberrant development, and neurodevelopmental impairments.     

Changes of the corpus callosum in children who suffered perinatal injury of the periventricular crossroads of pathways

There is a high incidence of periventricular leukomalacia, caused by hypoxia-ischemia, in preterm infants. These lesions damage the periventricular crossroads of commissural, projection and associative pathways, which are in a close topographical relationship with the lateral ventricles. We explored to what extent abnormalities of echogenicity of the periventricular crossroads correlate with changes in size of the corpus callosum. Our study included nine infants (gestation from 26-41 weeks; birth weight between 938-4450 grams) with perinatal brain injury. Periventricular areas, which topographically correspond to the frontal, main and occipital crossroad, were readily visualized by cranial ultrasound scans, performed during the first two weeks after birth. Corpus callosum mediosagittal area measurements were performed using magnetic resonance images, acquired between the first and sixth postnatal month (postmenstrual age 40-49 weeks). We found a statistically significant correlation between the increased echogenicity in the crossroad areas and the decrease of the corpus callosum midsagittal area (p < 0.05). This supports the hypothesis that callosal fibers can be damaged, during growth through the periventricular crossroads of pathways.     

颞叶癫痫脑“默认模式”的fMRI研究

功能磁共振成像(functional magnetic resonance imaging,fMRI)被用于检测静息时脑功能神经网络.作者运用静息fMRI检测海马硬化颞叶癫痫(temporal lobe epilepsy,TLE)脑"默认模式",采用感兴趣区域功能连接分析检测16例TLE患者和16名正常对照静息时脑的"默认模式",并进行组内和组间分析.研究发现,与正常对照相比,TLE静息时海马、颞极、额叶、颞叶、壳核及楔前叶等脑区与后扣带回的功能连接增强.研究结果表明TLE患者的固有脑功能组织模式有可能出现紊乱.这一研究将有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助.     

Iterative Cross-Correlation Analysis of Resting State Functional Magnetic Resonance Imaging Data

Seed-based cross-correlation analysis (sCCA) and independent component analysis have been widely employed to extract functional networks from the resting state functional magnetic resonance imaging data. However, the results of sCCA, in terms of both connectivity strength and network topology, can be sensitive to seed selection variations. ICA avoids the potential problems due to seed selection, but choosing which component(s) to represent the network of interest could be subjective and problematic. In this study, we proposed a seed-based iterative cross-correlation analysis (siCCA) method for resting state brain network analysis. The method was applied to extract default mode network (DMN) and stable task control network (STCN) in two independent datasets acquired from normal adults. Compared with the networks obtained by traditional sCCA and ICA, the resting state networks produced by siCCA were found to be highly stable and independent on seed selection. siCCA was used to analyze DMN in first-episode major depressive disorder (MDD) patients. It was found that, in the MDD patients, the volume of DMN negatively correlated with the patients'' social disability screening schedule scores.     

Altered Hypothalamic Functional Connectivity with Autonomic Circuits and the Locus Coeruleus in Migraine

The hypothalamus has been implicated in migraine based on the manifestation of autonomic symptoms with the disease, as well as neuroimaging evidence of hypothalamic activation during attacks. Our objective was to determine functional connectivity (FC) changes between the hypothalamus and the rest of the brain in migraine patients vs. control subjects. This study uses fMRI (functional magnetic resonance imaging) to acquire resting state scans in 12 interictal migraine patients and 12 healthy matched controls. Hypothalamic connectivity seeds were anatomically defined based on high-resolution structural scans, and FC was assessed in the resting state scans. Migraine patients had increased hypothalamic FC with a number of brain regions involved in regulation of autonomic functions, including the locus coeruleus, caudate, parahippocampal gyrus, cerebellum, and the temporal pole. Stronger functional connections between the hypothalamus and brain areas that regulate sympathetic and parasympathetic functions may explain some of the hypothalamic-mediated autonomic symptoms that accompany or precede migraine attacks.