This study is funded by NIH (R21 MH090384, R01 EB006494, RO1 EB009666, R01 NS051622). We thank H. Sarofin and C. Lacadie for their technical assistance.

1. Stimulus Development
Extensive stimulus development is needed. Contamination-related and neutral images must be collected and piloted to ensure the anxiety induced by these stimuli is balanced across provocation conditions and significantly greater in the provocation conditions than in the neutral conditions. More specifically, the following four stimulus sets are needed:
<ol>
	<li>Localizer stimuli: 300 contamination-related images and 300 neutral images are used to loca...

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	<li>Mataix-Cols, D., Cullen, S., Lange, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+anxiety+associated+with+obsessive-compulsive+symptom+dimensions+in+normal+volunteers.">Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers.</a> Biol. Psychiatry. 53, 482-493 (2003).</li><li>Mataix-Cols, D., Wooderson, S., Lawrence, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+neural+correlates+of+washing,+checking,+and+hoarding+symptom+dimensions+in+obsessive-compulsive+disorder.">Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder.</a> Arch. Gen. Psychiatry. 61, 564-576 (2004).</li><li>Menzies, L., Chamberlain, S. R., Laird, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Integrating+evidence+from+neuroimaging+and+neuropsychological+studies+of+obsessive-compulsive+disorder:+the+orbitofrontal-striatl+model+revisited.">Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofrontal-striatl model revisited.</a> Neuroscience and Biobehavioral Reviews. 32, 525-549 (2008).</li><li>Whiteside, S. P., Port, J. D., Abramowitz, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+meta-analysis+of+functional+neuroimaging+in+obsessive-compulsive+disorder.">A meta-analysis of functional neuroimaging in obsessive-compulsive disorder.</a> Psychiatry Research. 132, 69-79 (2004).</li><li>Swedo, S. E., Schapiro, M. B., Grady, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+glucose+metabolism+in+childhood-onset+obsessive-compulsive+disorder.">Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder.</a> Archives of General Psychiatry. 46, 518-523 (1989).</li><li>Swedo, S. E., Pietrini, P., Leonard, H. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+glucose+metabolism+in+childhood-onset+obsessive-compulsive+disorder.+Revisualization+during+pharmacotherapy.">Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy.</a> Arch. Gen. Psychiatry. 49, 690-694 (1992).</li><li>deCharms, R. C., Christoff, K., Glover, G. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Learned+regulation+of+spatially+localized+brain+activation+using+real-time+fMRI.">Learned regulation of spatially localized brain activation using real-time fMRI.</a> NeuroImage. 21, 436-443 (2004).</li><li>deCharms, R. C., Maeda, F., Glover, G. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Control+over+brain+activation+and+pain+learned+by+using+real-time+functional+MRI.">Control over brain activation and pain learned by using real-time functional MRI.</a> Proceedings of the National Academy of Sciences. 102, 18626-18631 (2005).</li><li>Rota, G., Sitaram, R., Veit, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-regulation+of+regional+cortical+activity+using+real-time+fMRI:+the+right+inferior+frontal+gyrus+and+linguistic+processing.">Self-regulation of regional cortical activity using real-time fMRI: the right inferior frontal gyrus and linguistic processing.</a> Hum. Brain. Mapp. 30, 1605-1614 (2009).</li><li>Weiskopf, N., Veit, R., Erb, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Physiological+self-regulation+of+regional+brain+activity+using+real-time+functional+magnetic+resonance+imaging+(fMRI):+methodology+and+exemplary+data.">Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.</a> NeuroImage. 19, 577-586 (2003).</li><li>Yoo, S. S., Jolesz, F. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+MRI+for+neurofeedback:+feasibility+study+on+a+hand+motor+task.">Functional MRI for neurofeedback: feasibility study on a hand motor task.</a> Neuroreport. 13, 1377-1381 (2002).</li><li>Yoo, S. S., O'Leary, H. M., Fairneny, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increasing+cortical+activity+in+auditory+areas+through+neurofeedback+functional+magnetic+resonance+imaging.">Increasing cortical activity in auditory areas through neurofeedback functional magnetic resonance imaging.</a> Neuroreport. 17, 1273-1278 (2006).</li><li>Caria, A., Sitaram, R., Veit, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volitional+control+of+anterior+insula+activity+modulates+the+response+to+aversive+stimuli.+A+real-time+functional+magnetic+resonance+imaging+study.">Volitional control of anterior insula activity modulates the response to aversive stimuli. A real-time functional magnetic resonance imaging study.</a> Biological psychiatry. 68, 425-432 (2010).</li><li>Caria, A., Veit, R., Sitaram, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regulation+of+anterior+insular+cortex+activity+using+real-time+fMRI.">Regulation of anterior insular cortex activity using real-time fMRI.</a> Neuroimage. 35, 1238-1246 (2007).</li><li>Hamilton, J. P., Glover, G. H., Hsu, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+subgenual+anterior+cingulate+cortex+activity+with+real-time+neurofeedback.">Modulation of subgenual anterior cingulate cortex activity with real-time neurofeedback.</a> Hum. Brain. Mapp. 32, 22-31 (2011).</li><li>Johnston, S., Linden, D. E., Healy, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Upregulation+of+emotion+areas+through+neurofeedback+with+a+focus+on+positive+mood.">Upregulation of emotion areas through neurofeedback with a focus on positive mood.</a> Cognitive, affective &#38; behavioral neuroscience. 11, 44-51 (2011).</li><li>Johnston, S. J., Boehm, S. G., Healy, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurofeedback:+A+promising+tool+for+the+self-regulation+of+emotion+networks.">Neurofeedback: A promising tool for the self-regulation of emotion networks.</a> NeuroImage. 49, 1066-1072 (2010).</li><li>Zotev, V., Krueger, F., Phillips, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-regulation+of+amygdala+activation+using+real-time+fMRI+neurofeedback.">Self-regulation of amygdala activation using real-time fMRI neurofeedback.</a> PLoS One. 6, e24522-e24522 (2011).</li><li>Haller, S., Birbaumer, N., Veit, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-time+fMRI+feedback+training+may+improve+chronic+tinnitus.">Real-time fMRI feedback training may improve chronic tinnitus.</a> Eur. Radiol. 20, 696-703 (2010).</li><li>Bloch, M. H., Landeros-Weisenberger, A., Kelmendi, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+systematic+review:+antipsychotic+augmentation+with+treatment+refractory+obsessive-compulsive+disorder.">A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.</a> Mol. Psychiatry. 11, 622-632 (2006).</li><li>Jenike, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+practice.+Obsessive-compulsive+disorder.">Clinical practice. Obsessive-compulsive disorder.</a> N. Engl. J. Med. 350, 259-265 (2004).</li><li>Pallanti, S., Quercioli, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment-refractory+obsessive-compulsive+disorder:+methodological+issues,+operational+definitions+and+therapeutic+lines.">Treatment-refractory obsessive-compulsive disorder: methodological issues, operational definitions and therapeutic lines.</a> Prog. Neuropsychopharmacol. Biol. Psychiatry. 30, 400-412 (2006).</li><li>Mataix-Cols, D., Lawrence, N. S., Wooderson, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Maudsley+Obsessive-Compulsive+Stimuli+Set:+validation+of+a+standardized+paradigm+for+symptom-specific+provocation+in+obsessive-compulsive+disorder.">The Maudsley Obsessive-Compulsive Stimuli Set: validation of a standardized paradigm for symptom-specific provocation in obsessive-compulsive disorder.</a> Psychiatry. Res. 168, 238-241 (2009).</li><li>Lang, P. J., Bradley, M. M., Cuthbert, B. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=International+affective+picture+system+(IAPS):+Affective+ratings+of+pictures+and+instruction+manual.">International affective picture system (IAPS): Affective ratings of pictures and instruction manual.</a> Technical Report A-82008. , (2008).</li><li>Burns, G. L., Keortge, S. G., Formea, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Revision+of+the+Padua+Inventory+of+obsessive+compulsive+disorder+symptoms:+distinctions+between+worry,+obsessions,+and+compulsions.">Revision of the Padua Inventory of obsessive compulsive disorder symptoms: distinctions between worry, obsessions, and compulsions.</a> Behaviour research and therapy. 34, 163-173 (1996).</li><li>Scheinost, D., Hampson, M., Bhawnani, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+GPU+accelerated+motion+correction+algorithm+for+real-time+fMRI.">A GPU accelerated motion correction algorithm for real-time fMRI.</a> Human Brain Mapping. , 639 (2011).</li><li>Hampson, M., Scheinost, D., Qiu, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Biofeedback+from+the+supplementary+motor+area+reduces+functional+connectivity+to+subcortical+regions.">Biofeedback from the supplementary motor area reduces functional connectivity to subcortical regions.</a> Brain Connectivity. 1, 91-98 (2011).</li><li>Johnson, K. A., Hartwell, K., Lematty, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intermittent+"Real-time"+fMRI+Feedback+Is+Superior+to+Continuous+Presentation+for+a+Motor+Imagery+Task:+A+Pilot+Study.">Intermittent "Real-time" fMRI Feedback Is Superior to Continuous Presentation for a Motor Imagery Task: A Pilot Study.</a> J. Neuroimaging. , (2011).</li><li>Yoo, S. S., Lee, J. H., O'Leary, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+magnetic+resonance+imaging-mediated+learning+of+increased+activity+in+auditory+areas.">Functional magnetic resonance imaging-mediated learning of increased activity in auditory areas.</a> Neuroreport. 18, 1915-1920 (2007).</li></ol>

Biofeedback of real-time fMRI data is a new technique and more work is needed to optimize this method so as to maximize learning in subjects. Recent studies have explored how learning changes with different numbers of runs or scanning sessions,14, 18, 27 how the feedback paradigm affects learning28, and whether the learning induced by a given biofeedback protocol results in changes in brain function that persist beyond the end of the biofeedback training period.15, 18, 27, 29 However, a ...

real-time fmri biofeedback targeting the orbitofrontal cortex for contamination anxiety

We present a method for training subjects to control activity in a region of their orbitofrontal cortex associated with contamination anxiety using biofeedback of real-time functional magnetic resonance imaging (rt-fMRI) data. Increased activity of this region is seen in relationship with contamination anxiety both in control subjects1 and in individuals with obsessive-compulsive disorder (OCD),2 a relatively common and often debilitating psychiatric disorder involving contamination anxiety. Although many brain regions have been implicated in OCD, abnormality in the orbitofrontal cortex (OFC) is one of the most consistent findings.3, 4 Furthermore, hyperactivity in the OFC has been found to correlate with OCD symptom severity5 and decreases in hyperactivity in this region have been reported to correlate with decreased symptom severity.6 Therefore, the ability to control this brain area may translate into clinical improvements in obsessive-compulsive symptoms including contamination anxiety. Biofeedback of rt-fMRI data is a new technique in which the temporal pattern of activity in a specific region (or associated with a specific distributed pattern of brain activity) in a subject's brain is provided as a feedback signal to the subject. Recent reports indicate that people are able to develop control over the activity of specific brain areas when provided with rt-fMRI biofeedback.7-12 In particular, several studies using this technique to target brain areas involved in emotion processing have reported success in training subjects to control these regions.13-18 In several cases, rt-fMRI biofeedback training has been reported to induce cognitive, emotional, or clinical changes in subjects.8, 9, 13, 19 Here we illustrate this technique as applied to the treatment of contamination anxiety in healthy subjects. This biofeedback intervention will be a valuable basic research tool: it allows researchers to perturb brain function, measure the resulting changes in brain dynamics and relate those to changes in contamination anxiety or other behavioral measures. In addition, the establishment of this method serves as a first step towards the investigation of fMRI-based biofeedback as a therapeutic intervention for OCD. Given that approximately a quarter of patients with OCD receive little benefit from the currently available forms of treatment,20-22 and that those who do benefit rarely recover completely, new approaches for treating this population are urgently needed.

Watch this Scientific Journal Video about Real-time fMRI Biofeedback Targeting the Orbitofrontal Cortex for Contamination Anxiety at JoVE.com

Real-time fMRI Biofeedback Targeting the Orbitofrontal Cortex for Contamination Anxiety

Here we present a method for training people to control a brain area involved in contamination anxiety and for probing the relationship between contamination anxiety and brain connectivity patterns.

We present a method for training subjects to control activity in a region of their orbitofrontal cortex associated with contamination anxiety using ...

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20.7K visualizações.  Yale University School of Medicine. Aqui apresentamos um método para a formação de pessoas para controlar uma área do cérebro envolvida na ansiedade de contaminação e para sondar a relação entre a ansiedade de contaminação e os padrões de conectividade do cérebro.