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      Real-time fMRI neurofeedback training of the amygdala activity with simultaneous EEG in veterans with combat-related PTSD

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          Abstract

          Posttraumatic stress disorder (PTSD) is a chronic and disabling neuropsychiatric disorder characterized by insufficient top-down modulation of the amygdala activity by the prefrontal cortex. Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging method with potential for modifying the amygdala-prefrontal interactions. We report the first controlled emotion self-regulation study in veterans with combat-related PTSD utilizing rtfMRI-nf of the amygdala activity. PTSD patients in the experimental group (EG, n=20) learned to upregulate BOLD activity of the left amygdala (LA) using rtfMRI-nf during a happy emotion induction task. PTSD patients in the control group (CG, n=11) were provided with a sham rtfMRI-nf. The study included three rtfMRI-nf training sessions, and EEG recordings were performed simultaneously with fMRI. PTSD severity was assessed using the Clinician-Administered PTSD Scale (CAPS). The EG participants showed a significant reduction in total CAPS ratings, including significant reductions in avoidance and hyperarousal symptoms. Overall, 80% of the EG participants demonstrated clinically meaningful reductions in CAPS ratings, compared to 38% in the CG. During the first session, fMRI connectivity of the LA with the orbitofrontal cortex and the dorsolateral prefrontal cortex (DLPFC) was progressively enhanced, and this enhancement significantly and positively correlated with initial CAPS ratings. Left-lateralized enhancement in upper alpha EEG coherence also exhibited a significant positive correlation with initial CAPS ratings. Reduction in PTSD severity between the first and last rtfMRI-nf sessions significantly correlated with enhancement in functional connectivity between the LA and the left DLPFC. Our results demonstrate that the rtfMRI-nf of the amygdala activity has the potential to correct the amygdala-prefrontal functional connectivity deficiencies specific to PTSD.

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          Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.

          The prefrontal cortex and the amygdala have synergistic roles in regulating purposive behavior, effected through bidirectional pathways. Here we investigated the largely unknown extent and laminar relationship of prefrontal input-output zones linked with the amygdala using neural tracers injected in the amygdala in rhesus monkeys. Prefrontal areas varied vastly in their connections with the amygdala, with the densest connections found in posterior orbitofrontal and posterior medial cortices, and the sparsest in anterior lateral prefrontal areas, especially area 10. Prefrontal projection neurons directed to the amygdala originated in layer 5, but significant numbers were also found in layers 2 and 3 in posterior medial and orbitofrontal cortices. Amygdalar axonal terminations in prefrontal cortex were most frequently distributed in bilaminar bands in the superficial and deep layers, by columns spanning the entire cortical depth, and less frequently as small patches centered in the superficial or deep layers. Heavy terminations in layers 1-2 overlapped with calbindin-positive inhibitory neurons. A comparison of the relationship of input to output projections revealed that among the most heavily connected cortices, cingulate areas 25 and 24 issued comparatively more projections to the amygdala than they received, whereas caudal orbitofrontal areas were more receivers than senders. Further, there was a significant relationship between the proportion of 'feedforward' cortical projections from layers 2-3 to 'feedback' terminations innervating the superficial layers of prefrontal cortices. These findings indicate that the connections between prefrontal cortices and the amygdala follow similar patterns as corticocortical connections, and by analogy suggest pathways underlying the sequence of information processing for emotions.
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            The role of the amygdala in emotional processing: a quantitative meta-analysis of functional neuroimaging studies.

            Functional neuroimaging studies have provided strong support for a critical role of the amygdala in emotional processing. However, several controversies remain in terms of whether different factors-such as sex, valence and stimulus type-have an effect on the magnitude and lateralization of amygdala responses. To address these issues, we conducted a meta-analysis of functional neuroimaging studies of visual emotional perception that reported amygdala activation. Critically, unlike previous neuroimaging meta-analyses, we took into account the magnitude (effect size) and reliability (variance) associated with each of the activations. Our results confirm that the amygdala responds to both positive and negative stimuli, with a preference for faces depicting emotional expressions. We did not find evidence for amygdala lateralization as a function of sex or valence. Instead, our findings provide strong support for a functional dissociation between left and right amygdala in terms of temporal dynamics. Taken together, results from this meta-analysis shed new light on several of the models proposed in the literature regarding the neural basis of emotional processing.
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              Estimating sample size in functional MRI (fMRI) neuroimaging studies: statistical power analyses.

              Estimation of statistical power in functional MRI (fMRI) requires knowledge of the expected percent signal change between two conditions as well as estimates of the variability in percent signal change. Variability can be divided into intra-subject variability, reflecting noise within the time series, and inter-subject variability, reflecting subject-to-subject differences in activation. The purpose of this study was to obtain estimates of percent signal change and the two sources of variability from fMRI data, and then use these parameter estimates in simulation experiments in order to generate power curves. Of interest from these simulations were conclusions concerning how many subjects are needed and how many time points within a scan are optimal in an fMRI study of cognitive function. Intra-subject variability was estimated from resting conditions, and inter-subject variability and percent signal change were estimated from verbal working memory data. Simulations derived from these parameters illustrate how percent signal change, intra- and inter-subject variability, and number of time points affect power. An empirical test experiment, using fMRI data acquired during somatosensory stimulation, showed good correspondence between the simulation-based power predictions and the power observed within somatosensory regions of interest. Our analyses suggested that for a liberal threshold of 0.05, about 12 subjects were required to achieve 80% power at the single voxel level for typical activations. At more realistic thresholds, that approach those used after correcting for multiple comparisons, the number of subjects doubled to maintain this level of power. Copyright 2002 Elsevier Science B.V.
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                Author and article information

                Journal
                27 January 2018
                Article
                1801.09165
                adb4b434-bdd1-4430-a821-f13cd8ffbc0d

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

                History
                Custom metadata
                26 pages, 15 figures
                q-bio.NC physics.med-ph

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