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Mark Vangel

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13 papers

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YNIMG Journal 2021 Journal Article

Perturbing fMRI brain dynamics using transcranial direct current stimulation

Yiheng Tu
Jin Cao
Seyhmus Guler
Thalia Chai-Zhang
Joan A. Camprodon
Mark Vangel
Randy L. Gollub
Darin D. Dougherty

The dynamic nature of resting-state functional magnetic resonance imaging (fMRI) brain activity and connectivity has drawn great interest in the past decade. Specific temporal properties of fMRI brain dynamics, including metrics such as occurrence rate and transitions, have been associated with cognition and behaviors, indicating the existence of mechanism distruption in neuropsychiatric disorders. The development of new methods to manipulate fMRI brain dynamics will advance our understanding of these pathophysiological mechanisms from native observation to experimental mechanistic manipulation. In the present study, we applied repeated transcranial direct current stimulation (tDCS) to the right dorsolateral prefrontal cortex (rDLPFC) and the left orbitofrontal cortex (lOFC), during multiple simultaneous tDCS-fMRI sessions from 81 healthy participants to assess the modulatory effects of stimulating target brain regions on fMRI brain dynamics. Using the rDLPFC and the lOFC as seeds, respectively, we first identified two reoccurring co-activation patterns (CAPs) and calculated their temporal properties (e.g., occurrence rate and transitions) before administering tDCS. The spatial maps of CAPs were associated with different cognitive and disease domains using meta-analytical decoding analysis. We then investigated how active tDCS compared to sham tDCS in the modulation of the occurrence rates of these different CAPs and perturbations of transitions between CAPs. We found that by enhancing neuronal excitability of the rDLPFC and the lOFC, the occurrence rate of one CAP was significantly decreased while that of another CAP was significantly increased during the first 6 min of stimulation. Furthermore, these tDCS-associated changes persisted over subsequent testing sessions (both during and before/after tDCS) across three consecutive days. Active tDCS could perturb transitions between CAPs and a non-CAP state (when the rDLPFC and the lOFC were not activated), but not the transitions within CAPs. These results demonstrate the feasibility of modulating fMRI brain dynamics, and open new possibilities for discovering stimulation targets and dynamic connectivity patterns that can ensure the propagation of tDCS-induced neuronal excitability, which may facilitate the development of new treatments for disorders with altered dynamics.

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YNIMG Journal 2019 Journal Article

The relationship of perceptual discrimination to neural mechanisms of fear generalization

Lauri Tuominen
Emily Boeke
Stephanie DeCross
Rick PF. Wolthusen
Shahin Nasr
Mohammed Milad
Mark Vangel
Roger Tootell

The generalization of conditioned fear responses has been shown to decrease as a function of perceptual similarity. However, generalization may also extend beyond the perceptual discrimination threshold, ostensibly due to contributions from processes other than perception. Currently the neural mechanisms that mediate perceptual and non-perceptual aspects of fear generalization are unclear. To investigate this question, we conducted a Pavlovian fear conditioning and generalization experiment, collecting functional magnetic resonance imaging (fMRI), skin conductance and explicit shock likelihood ratings, in 37 healthy subjects. Face stimuli were initially paired (CS+) or not paired (CS) with an electrical shock. During the generalization phase, responses were measured to the CS+, CS and a range of CS + -toCS morphs (generalization stimuli), selected for each participant based on that participant's discrimination ability. Across multiple measurements, we found that fear generalization responses were limited to stimuli that could not be distinguished from the CS + stimulus, thus following a gradient closely linked to perceptual discriminability. These measurements, which were correlated with one another, included skin conductance responses, behavioral ratings, and fMRI responses of anterior insula and superior frontal gyrus. In contrast, responses in areas of the default network, including the posterior cingulate gyrus, angular gyrus and hippocampus, showed a negative generalization function extending to stimuli that were more likely to be distinguished from the CS+. In addition, the generalization gradients of the anterior insula and the behavioral ratings showed some evidence for extension beyond perceptual limits. Taken together, these results suggest that distinct brain areas are involved in perceptual and non-perceptual components of fear generalization.

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YNICL Journal 2018 Journal Article

Diffusion-weighted imaging evidence of altered white matter development from late childhood to early adulthood in Autism Spectrum Disorder

Fikret Işık Karahanoğlu
Bengi Baran
Quynh Trang Huong Nguyen
Djalel-Eddine Meskaldji
Anastasia Yendiki
Mark Vangel
Susan L. Santangelo
Dara S. Manoach

Autism Spectrum Disorder (ASD) is thought to reflect disrupted development of brain connectivity characterized by white matter abnormalities and dyscoordination of activity across brain regions that give rise to core features. But there is little consensus about the nature, timing and location of white matter abnormalities as quantified with diffusion-weighted MRI. Inconsistent findings likely reflect small sample sizes, motion confounds and sample heterogeneity, particularly different age ranges across studies. We examined the microstructural integrity of major white matter tracts in relation to age in 38 high functioning ASD and 35 typically developing (TD) participants, aged 8-25, whose diffusion-weighted scans met strict data-quality criteria and survived group matching for motion. While there were no overall group differences in diffusion measures, the groups showed different relations with age. Only the TD group showed the expected positive correlations of fractional anisotropy with age. In parallel, axial diffusivity was unrelated to age in TD, but showed inverse correlations with age in ASD. Younger participants with ASD tended to have higher fractional anisotropy and axial diffusivity than their TD peers, while the opposite was true for older participants. Most of the affected tracts - cingulum bundle, inferior and superior longitudinal fasciculi - are association bundles related to cognitive, social and emotional functions that are abnormal in ASD. The manifestations of abnormal white matter development in ASD as measured by diffusion-weighted MRI depend on age and this may contribute to inconsistent findings across studies. We conclude that ASD is characterized by altered white matter development from childhood to early adulthood that may underlie abnormal brain function and contribute to core features.

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YNIMG Journal 2014 Journal Article

Resting state connectivity immediately following learning correlates with subsequent sleep-dependent enhancement of motor task performance

Michael D. Gregory
Yigal Agam
Chindhuri Selvadurai
Amanda Nagy
Mark Vangel
Matthew Tucker
Edwin M. Robertson
Robert Stickgold

There is ongoing debate concerning the functions of resting-state brain activity. Prior work demonstrates that memory encoding enhances subsequent resting-state functional connectivity within task-relevant networks and that these changes predict better recognition. Here, we used functional connectivity MRI (fcMRI) to examine whether task-induced changes in resting-state connectivity correlate with performance improvement after sleep. In two separate sessions, resting-state scans were acquired before and after participants performed a motor task. In one session participants trained on the motor sequence task (MST), a well-established probe of sleep-dependent memory consolidation, and were tested the next day, after a night of sleep. In the other session they performed a motor control task (MCT) that minimized learning. In an accompanying behavioral control study, participants trained on the MST and were tested after either a night of sleep or an equivalent interval of daytime wake. Both the fcMRI and the sleep control groups showed significant improvement of MST performance, while the wake control group did not. In the fcMRI group, increased connectivity in bilateral motor cortex following MST training correlated with this next-day improvement. This increased connectivity did not appear to reflect initial learning since it did not correlate with learning during training and was not greater after MST training than MCT performance. Instead, we hypothesize that this increased connectivity processed the new memories for sleep-dependent consolidation. Our findings demonstrate that physiological processes immediately after learning correlate with sleep-dependent performance improvement and suggest that the wakeful resting brain prepares memories of recent experiences for later consolidation during sleep.

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YNIMG Journal 2010 Journal Article

Altered white matter microstructure in the corpus callosum in Huntington's disease: Implications for cortical “disconnection”

H. Diana Rosas
Stephanie Y. Lee
Alexander C. Bender
Alexandra K. Zaleta
Mark Vangel
Peng Yu
Bruce Fischl
Vasanth Pappu

The corpus callosum (CC) is the major conduit for information transfer between the cerebral hemispheres and plays an integral role in relaying sensory, motor and cognitive information between homologous cortical regions. The majority of fibers that make up the CC arise from large pyramidal neurons in layers III and V, which project contra-laterally. These neurons degenerate in Huntington's disease (HD) in a topographically and temporally selective way. Since any focus of cortical degeneration could be expected to secondarily de-afferent homologous regions of cortex, we hypothesized that regionally selective cortical degeneration would be reflected in regionally selective degeneration of the CC. We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified corpus callosum segmentation scheme to examine the CC in healthy controls, huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal callosal cross-sectional thickness and several DTI parameters, including fractional anisotropy (FA), which reflects the degree of white matter organization, radial diffusivity, a suggested index of myelin integrity, and axial diffusivity, a suggested index of axonal damage of the CC. We found a topologically selective pattern of alterations in these measures in pre-manifest subjects that were more extensive in early symptomatic HD subjects and that correlated with performance on distinct cognitive measures, suggesting an important role for disrupted inter-hemispheric transfer in the clinical symptoms of HD. Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing.

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YNIMG Journal 2010 Journal Article

Multi-site characterization of an fMRI working memory paradigm: Reliability of activation indices

Anastasia Yendiki
Douglas N. Greve
Stuart Wallace
Mark Vangel
Jeremy Bockholt
Bryon A. Mueller
Vince Magnotta
Nancy Andreasen

Neuroimaging studies are facilitated significantly when it is possible to recruit subjects and acquire data at multiple sites. However, the use of different scanners and acquisition protocols is a potential source of variability in multi-site data. In this work we present a multi-site study of the reliability of fMRI activation indices, where 10 healthy volunteers were scanned at 4 different sites while performing a working memory paradigm. Our results indicate that, even with different scanner manufacturers and field strengths, activation variability due to site differences is small compared to variability due to subject differences in this cognitive task, provided we choose an appropriate activation measure.

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YNIMG Journal 2009 Journal Article

An fMRI study on the interaction and dissociation between expectation of pain relief and acupuncture treatment

Jian Kong
Ted J. Kaptchuk
Ginger Polich
Irving Kirsch
Mark Vangel
Carolyn Zyloney
Bruce Rosen
Randy L. Gollub

It is well established that expectation can significantly modulate pain perception. In this study, we combined an expectancy manipulation model and fMRI to investigate how expectation can modulate acupuncture treatment. Forty-eight subjects completed the study. The analysis on two verum acupuncture groups with different expectancy levels indicates that expectancy can significantly influence acupuncture analgesia for experimental pain. Conditioning positive expectation can amplify acupuncture analgesia as detected by subjective pain sensory rating changes and objective fMRI signal changes in response to calibrated noxious stimuli. Diminished positive expectation appeared to inhibit acupuncture analgesia. This modulation effect is spatially specific, inducing analgesia exclusively in regions of the body where expectation is focused. Thus, expectation should be used as an important covariate in future studies evaluating acupuncture efficacy. In addition, we also observed dissociation between subjective reported analgesia and objective fMRI signal changes to calibrated pain in the analysis across all four groups. We hypothesize that as a peripheral-central modulation, acupuncture needle stimulation may inhibit incoming noxious stimuli; while as a top-down modulation, expectancy (placebo) may work through the emotional circuit.

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YNIMG Journal 2009 Journal Article

Brain encoding of acupuncture sensation — Coupling on-line rating with fMRI

Vitaly Napadow
Rupali P. Dhond
Jieun Kim
Lauren LaCount
Mark Vangel
Richard E Harris
Norman Kettner
Kyungmo Park

Acupuncture-induced sensations have historically been associated with clinical efficacy. These sensations are atypical, arising from sub-dermal receptors, and their neural encoding is not well known. In this fMRI study, subjects were stimulated at acupoint PC-6, while rating sensation with a custom-built, MR-compatible potentiometer. Separate runs included real (ACUP) and sham (SHAM) acupuncture, the latter characterized by non-insertive, cutaneous stimulation. FMRI data analysis was guided by the on-line rating timeseries, thereby localizing brain correlates of acupuncture sensation. Sensation ratings correlated with stimulation more (p <0. 001) for SHAM (r =0. 63) than for ACUP (r =0. 32). ACUP induced stronger and more varied sensations with significant persistence into no-stimulation blocks, leading to more run-time spent rating low and moderate sensations compared to SHAM. ACUP sensation correlated with activation in regions associated with sensorimotor (SII, insula) and cognitive (dorsomedial prefrontal cortex (dmPFC)) processing, and deactivation in default-mode network (DMN) regions (posterior cingulate, precuneus). Compared to SHAM, ACUP yielded greater activity in both anterior and posterior dmPFC and dlPFC. In contrast, SHAM produced greater activation in sensorimotor (SI, SII, insula) and greater deactivation in DMN regions. Thus, brain encoding of ACUP sensation (more persistent and varied, leading to increased cognitive load) demonstrated greater activity in both cognitive/evaluative (posterior dmPFC) and emotional/interoceptive (anterior dmPFC) cortical regions. Increased cognitive load and dmPFC activity may be a salient component of acupuncture analgesia — sensations focus attention and accentuate bodily awareness, contributing to enhanced top-down modulation of any nociceptive afference and central pain networks. Hence, acupuncture may function as a somatosensory-guided mind–body therapy.

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YNIMG Journal 2009 Journal Article

Expectancy and treatment interactions: A dissociation between acupuncture analgesia and expectancy evoked placebo analgesia

Jian Kong
Ted J. Kaptchuk
Ginger Polich
Irving Kirsch
Mark Vangel
Carolyn Zyloney
Bruce Rosen
Randy Gollub

Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects — including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) — interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture+high expectation and sham acupuncture+high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment).

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YNIMG Journal 2007 Journal Article

Reduced microstructural integrity of the white matter underlying anterior cingulate cortex is associated with increased saccadic latency in schizophrenia

Dara S. Manoach
G. Avinash Ketwaroo
Frida E. Polli
Katharine N. Thakkar
Jason J.S. Barton
Donald C. Goff
Bruce Fischl
Mark Vangel

The anterior cingulate cortex (ACC) is a key component of a network that directs both spatial attention and saccadic eye movements, which are tightly linked. Diffusion tensor imaging (DTI) has demonstrated reduced microstructural integrity of the anterior cingulum bundle as indexed by fractional anisotropy (FA) in schizophrenia, but the functional significance of these abnormalities is unclear. Using DTI, we examined the white matter underlying anterior cingulate cortex in schizophrenia to determine whether reduced FA is associated with prolonged latencies of volitional saccades. Seventeen chronic, medicated schizophrenia outpatients and nineteen healthy controls had high-resolution DTI scans. FA maps were registered to structural scans and mapped across participants using a surface-based coordinate system. Cingulate white matter was divided into rostral and dorsal anterior regions and a posterior region. Patients showed reduced FA in cingulate white matter of the right hemisphere. Reduced FA in the white matter underlying anterior cingulate cortex, frontal eye field, and posterior parietal cortex of the right hemisphere was associated with longer saccadic latencies in schizophrenia, though given the relatively small sample size, these relations warrant replication. These findings demonstrate that in schizophrenia, increased latency of volitional saccades is associated with reduced microstructural integrity of the white matter underlying key cortical components of a right-hemisphere dominant network for visuospatial attention and ocular motor control. Moreover, they suggest that anterior cingulate white matter abnormalities contribute to slower performance of volitional saccades and to inter-individual variability of saccadic latency in chronic, medicated schizophrenia.

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YNIMG Journal 2007 Journal Article

Where left becomes right: A magnetoencephalographic study of sensorimotor transformation for antisaccades

So Young Moon
Jason J.S. Barton
Szymon Mikulski
Frida E. Polli
Matthew S. Cain
Mark Vangel
Matti S. Hämäläinen
Dara S. Manoach

To perform a saccadic response to a visual stimulus, a ‘sensorimotor transformation’ is required (i. e. , transforming stimulus location into a motor command). Where in the brain is this accomplished? While previous monkey neurophysiology and human fMRI studies examined either parietal cortex or frontal eye field, we studied both of these regions simultaneously using magnetoencephalography (MEG). Nineteen healthy participants performed a pseudorandom series of prosaccades and antisaccades during MEG. Antisaccades require a saccade in the direction opposite a suddenly appearing stimulus. We exploited this dissociation between stimulus and saccadic direction to identify cortical regions that show early activity for a contralateral stimulus and late activity for a contralateral saccade. We found that in the left hemisphere both the intraparietal sulcus and the frontal eye field showed a pattern of activity consistent with sensorimotor transformation — a transition from activity reflecting the direction of the stimulus to that representing the saccadic goal. These findings suggest that sensorimotor transformation is the product of coordinated activity across the intraparietal sulcus and frontal eye field, key components of a cortical network for saccadic generation.

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YNIMG Journal 2006 Journal Article

Detailed semiautomated MRI based morphometry of the neonatal brain: Preliminary results

Mitsuhiro Nishida
Nikolaos Makris
David N. Kennedy
Mark Vangel
Bruce Fischl
Kalpathy S. Krishnamoorthy
Verne S. Caviness
P. Ellen Grant

In the neonate, regional growth trajectories provide information about the coordinated development of cerebral substructures and help identify regional vulnerability by identifying times of faster growth. Segmentation of magnetic resonance images (MRI) has provided detailed information for the myelinated brain but few reports of regional neonatal brain growth exist. We report the method and preliminary results of detailed semiautomated segmentation of 12 normative neonatal brains (gestational age 31. 1–42. 6 weeks at time of MRI) using volumetric T1-weighted images. Accuracy was confirmed by expert review of every segmented image. In 5 brains, repeat segmentation resulted in intraclass correlation coefficients >0. 9 (except for the right amygdala) and an average percent voxel overlap of 90. 0%. Artifacts or image quality limited the number of regions segmented in 9/12 data sets and 1/12 was excluded from volumetric analysis due to ventriculomegaly. Brains were segmented into cerebral exterior (N = 8), cerebral lobes (N = 5), lateral ventricles (N = 8), cerebral cortex (N = 6), white matter (N = 6), corpus callosum (N = 7), deep central gray (N = 8), hippocampi (N = 8), amygdalae (N = 8), cerebellar hemispheres (N = 8), vermis (N = 8), midbrain (N = 8), pons (N = 8) and medulla (N = 8). Linear growth (P < 0. 05) was identified in all regions except the cerebral white matter, medulla and ventricles. Striking differences in regional growth rates were noted. These preliminary results are consistent with the heterochronous nature of cerebral development and provide initial estimates of regional brain growth and therefore regional vulnerability in the perinatal time period.

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YNIMG Journal 2004 Journal Article

Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces

Nouchine Hadjikhani
Robert M Joseph
Josh Snyder
Christopher F Chabris
Jill Clark
Shelly Steele
Lauren McGrath
Mark Vangel

Prior imaging studies have failed to show activation of the fusiform gyrus in response to emotionally neutral faces in individuals with autism spectrum disorder (ASD) [Critchley et al. , Brain 124 (2001) 2059; Schultz et al. , Arch. Gen. Psychiatry 57 (2000) 331]. However, individuals with ASD do not typically exhibit the striking behavioral deficits that might be expected to result from fusiform gyrus damage, such as those seen in prosopagnosia, and their deficits appear to extend well beyond face identification to include a wide range of impairments in social perceptual processing. In this study, our goal was to further assess the question of whether individuals with ASD have abnormal fusiform gyrus activation to faces. We used high-field (3 T) functional magnetic resonance imaging to study face perception in 11 adult individuals with autism spectrum disorder (ASD) and 10 normal controls. We used face stimuli, object stimuli, and sensory control stimuli (Fourier scrambled versions of the face and object stimuli) containing a fixation point in the center to ensure that participants were looking at and attending to the images as they were presented. We found that individuals with ASD activated the fusiform face area and other brain areas normally involved in face processing when they viewed faces as compared to non-face stimuli. These data indicate that the face-processing deficits encountered in ASD are not due to a simple dysfunction of the fusiform area, but to more complex anomalies in the distributed network of brain areas involved in social perception and cognition.

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