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      Real-Time fMRI Neurofeedback Training of Amygdala Activity in Patients with Major Depressive Disorder

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          Abstract

          Background

          Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD), and normalize with remission. Real-time functional MRI neurofeedback (rtfMRI-nf) offers a non-invasive method to modulate this regional activity. We examined whether depressed participants can use rtfMRI-nf to enhance amygdala responses to positive autobiographical memories, and whether this ability alters symptom severity.

          Methods

          Unmedicated MDD subjects were assigned to receive rtfMRI-nf from either left amygdala (LA; experimental group, n = 14) or the horizontal segment of the intraparietal sulcus (HIPS; control group, n = 7) and instructed to contemplate happy autobiographical memories (AMs) to raise the level of a bar representing the hemodynamic signal from the target region to a target level. This 40s Happy condition alternated with 40s blocks of rest and counting backwards. A final Transfer run without neurofeedback information was included.

          Results

          Participants in the experimental group upregulated their amygdala responses during positive AM recall. Significant pre-post scan decreases in anxiety ratings and increases in happiness ratings were evident in the experimental versus control group. A whole brain analysis showed that during the transfer run, participants in the experimental group had increased activity compared to the control group in left superior temporal gyrus and temporal polar cortex, and right thalamus.

          Conclusions

          Using rtfMRI-nf from the left amygdala during recall of positive AMs, depressed subjects were able to self-regulate their amygdala response, resulting in improved mood. Results from this proof-of-concept study suggest that rtfMRI-nf training with positive AM recall holds potential as a novel therapeutic approach in the treatment of depression.

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          Most cited references51

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          Cognitive and emotional influences in anterior cingulate cortex.

          Bush, Luu, Posner (2000)
          Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.
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            Subcortical and cortical brain activity during the feeling of self-generated emotions.

            In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.
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              The functional neuroanatomy of autobiographical memory: a meta-analysis.

              Autobiographical memory (AM) entails a complex set of operations, including episodic memory, self-reflection, emotion, visual imagery, attention, executive functions, and semantic processes. The heterogeneous nature of AM poses significant challenges in capturing its behavioral and neuroanatomical correlates. Investigators have recently turned their attention to the functional neuroanatomy of AM. We used the effect-location method of meta-analysis to analyze data from 24 functional imaging studies of AM. The results indicated a core neural network of left-lateralized regions, including the medial and ventrolateral prefrontal, medial and lateral temporal and retrosplenial/posterior cingulate cortices, the temporoparietal junction and the cerebellum. Secondary and tertiary regions, less frequently reported in imaging studies of AM, are also identified. We examined the neural correlates of putative component processes in AM, including, executive functions, self-reflection, episodic remembering and visuospatial processing. We also separately analyzed the effect of select variables on the AM network across individual studies, including memory age, qualitative factors (personal significance, level of detail and vividness), semantic and emotional content, and the effect of reference conditions. We found that memory age effects on medial temporal lobe structures may be modulated by qualitative aspects of memory. Studies using rest as a control task masked process-specific components of the AM neural network. Our findings support a neural distinction between episodic and semantic memory in AM. Finally, emotional events produced a shift in lateralization of the AM network with activation observed in emotion-centered regions and deactivation (or lack of activation) observed in regions associated with cognitive processes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                11 February 2014
                : 9
                : 2
                : e88785
                Affiliations
                [1 ]Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
                [2 ]Janssen Pharmaceuticals, LCC, of Johnson & Johnson, Inc., Titusville, New Jersey, United States of America
                [3 ]Center for Biomedical Engineering, The University of Oklahoma, Norman, Oklahoma, United States of America
                [4 ]College of Engineering, The University of Oklahoma, Norman, Oklahoma, United States of America
                Bellvitge Biomedical Research Institute-IDIBELL, Spain
                Author notes

                Competing Interests: The authors have read the journal's policy and have the following conflicts. Wayne Drevets, M.D., is an employee of Johnson & Johnson, Inc., and has consulted for Myriad/Rules Based Medicine and for Eisai, Inc. The other authors have declared that no competing interests exist. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: JB VZ KDY WCD. Performed the experiments: KDY RP VZ HY MM JB. Analyzed the data: KDY VZ JB RP. Contributed reagents/materials/analysis tools: JB VZ RP MM KDY. Wrote the paper: KDY JB WCD VZ RP MM HY. Substantially contributed during the whole research project: KDY VZ RP MM HY WCD JB. Discussed research concept and design, data acquisition and data analysis strategies: KDY VZ RP MM HY WCD JB. Helped with writing the paper: KDY VZ RP MM HY WCD JB.

                Article
                PONE-D-13-38101
                10.1371/journal.pone.0088785
                3921228
                24523939
                ecf9afc8-b429-458b-8f11-9b3b54748a81
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 September 2013
                : 12 January 2014
                Page count
                Pages: 13
                Funding
                This research was supported by the Laureate Institute for Brain Research and the William K. Warren Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biotechnology
                Bioengineering
                Biomedical Engineering
                Neuroscience
                Cognitive Neuroscience
                Inhibitions
                Developmental Neuroscience
                Synaptic Plasticity
                Neuroimaging
                fMRI
                Learning and Memory
                Neuropsychology
                Medicine
                Mental Health
                Psychiatry
                Mood Disorders
                Neuropsychiatric Disorders
                Therapies
                Psychotherapy

                Uncategorized
                Uncategorized

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