Self-Regulation of Amygdala Activation Using Real-Time fMRI Neurofeedback

Real-time functional magnetic resonance imaging (rtfMRI) with neurofeedback allows investigation of human brain neuroplastic changes that arise as subjects learn to modulate neurophysiological function using real-time feedback regarding their own hemodynamic responses to stimuli. We investigated the feasibility of training healthy humans to self-regulate the hemodynamic activity of the amygdala, which plays major roles in emotional processing. Participants in the experimental group were provided with ongoing information about the blood oxygen level dependent (BOLD) activity in the left amygdala (LA) and were instructed to raise the BOLD rtfMRI signal by contemplating positive autobiographical memories. A control group was assigned the same task but was instead provided with sham feedback from the left horizontal segment of the intraparietal sulcus (HIPS) region. In the LA, we found a significant BOLD signal increase due to rtfMRI neurofeedback training in the experimental group versus the control group. This effect persisted during the Transfer run without neurofeedback. For the individual subjects in the experimental group the training effect on the LA BOLD activity correlated inversely with scores on the Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale. The whole brain data analysis revealed significant differences for Happy Memories versus Rest condition between the experimental and control groups. Functional connectivity analysis of the amygdala network revealed significant widespread correlations in a fronto-temporo-limbic network. Additionally, we identified six regions — right medial frontal polar cortex, bilateral dorsomedial prefrontal cortex, left anterior cingulate cortex, and bilateral superior frontal gyrus — where the functional connectivity with the LA increased significantly across the rtfMRI neurofeedback runs and the Transfer run. The findings demonstrate that healthy subjects can learn to regulate their amygdala activation using rtfMRI neurofeedback, suggesting possible applications of rtfMRI neurofeedback training in the treatment of patients with neuropsychiatric disorders

The Selectivity and Functional Connectivity of the Anterior Temporal Lobes

One influential account asserts that the anterior temporal lobe (ATL) is a domain-general hub for semantic memory. Other evidence indicates it is part of a domain-specific social cognition system. Arbitrating these accounts using functional magnetic resonance imaging has previously been difficult because of magnetic susceptibility artifacts in the region. The present study used parameters optimized for imaging the ATL, and had subjects encode facts about unfamiliar people, buildings, and hammers. Using both conjunction and region of interest analyses, person-selective responses were observed in both the left and right ATL. Neither building-selective, hammer-selective nor domain-general responses were observed in the ATLs, although they were observed in other brain regions. These findings were supported by “resting-state” functional connectivity analyses using independent datasets from the same subjects. Person-selective ATL clusters were functionally connected with the brain's wider social cognition network. Rather than serving as a domain-general semantic hub, the ATLs work in unison with the social cognition system to support learning facts about others

Functional Neuroimaging Correlates of Autobiographical Memory Deficits in Subjects at Risk for Depression

Overgeneral autobiographical memory (AM) manifests in individuals with major depressive disorder (MDD) tested during depressed (dMDD) or remitted phases (rMDD), and healthy individuals at high-risk (HR) for developing MDD. The current study aimed to elucidate differences in hemodynamic correlates of AM recall between rMDDs, HRs, and controls (HCs) to identify neural changes following previous depressive episodes without the confound of current depressed mood. HCs, HRs, and unmedicated rMDDs (n = 20/group) underwent fMRI while recalling AMs in response to emotionally valenced cue words. HRs and rMDDs recalled fewer specific and more categorical AMs relative to HCs. During specific AM recall, HRs had increased activity relative to rMDDs and HCs in left ventrolateral prefrontal cortex (VLPFC) and lateral orbitofrontal cortex. During positive specific AM recall, HRs and HCs had increased activity relative to rMDDs in bilateral dorsomedial prefrontal cortex (DMPFC) and left precuneus. During negative specific AM recall HRs and HCs had increased activity in left VLPFC and right DMPFC, while rMDDs had increased activity relative to HRs and HCs in right DLPFC and precuneus. Differential recruitment of medial prefrontal regions implicated in emotional control suggests experiencing a depressive episode may consequently reduce one’s ability to regulate emotional responses during AM recall

Regional differences in the BOLD response to masked-sad faces versus masked-neutral faces (SN-NN) and masked-happy versus masked-neutral faces (HN-NN) in patients with major depressive disorder and healthy controls.

<p>Abbreviations: L = left; R = right; MDD = major depressive disorder; HC = healthy control; SN = masked-sad faces; HN = masked-happy faces; NN = masked-neutral faces; SN-NN = masked-sad versus masked-neutral faces; HN-NN = masked-happy versus masked-neutral faces; STG = superior temporal gyrus; OFC = orbitofrontal cortex; C = cortex; ACC = anterior cingulate cortex; G = gyrus; PFC = prefrontal cortex.</p>*<p>The cluster size was significant after applying a cluster threshold of k = 23 voxels using Monte Carlo simulations implemented in AFNI's AlphaSim program to correct for multiple comparisons.</p>#<p>The statistical t-values for these regions are reported in the text, while corresponding z-values are reported in the table.</p

The Extended Functional Neuroanatomy of Emotional Processing Biases for Masked Faces in Major Depressive Disorder

<div><h3>Background</h3><p>Major depressive disorder (MDD) is associated with a mood-congruent processing bias in the amygdala toward face stimuli portraying sad expressions that is evident even when such stimuli are presented below the level of conscious awareness. The extended functional anatomical network that maintains this response bias has not been established, however.</p> <h3>Aims</h3><p>To identify neural network differences in the hemodynamic response to implicitly presented facial expressions between depressed and healthy control participants.</p> <h3>Method</h3><p>Unmedicated-depressed participants with MDD (n = 22) and healthy controls (HC; n = 25) underwent functional MRI as they viewed face stimuli showing sad, happy or neutral face expressions, presented using a backward masking design. The blood-oxygen-level dependent (BOLD) signal was measured to identify regions where the hemodynamic response to the emotionally valenced stimuli differed between groups.</p> <h3>Results</h3><p>The MDD subjects showed greater BOLD responses than the controls to masked-sad versus masked-happy faces in the hippocampus, amygdala and anterior inferotemporal cortex. While viewing both masked-sad and masked-happy faces relative to masked-neutral faces, the depressed subjects showed greater hemodynamic responses than the controls in a network that included the medial and orbital prefrontal cortices and anterior temporal cortex.</p> <h3>Conclusions</h3><p>Depressed and healthy participants showed distinct hemodynamic responses to masked-sad and masked-happy faces in neural circuits known to support the processing of emotionally valenced stimuli and to integrate the sensory and visceromotor aspects of emotional behavior. Altered function within these networks in MDD may establish and maintain illness-associated differences in the salience of sensory/social stimuli, such that attention is biased toward negative and away from positive stimuli.</p> </div

Neuroimaging results for masked-sad versus masked-neutral faces (SN-NN) and masked-happy versus masked-neutral faces (HN-NN).

<p>(a–b) Voxels showing differences in the hemodynamic response to SN-NN between MDD and HC subjects in the (a) left rostral superior temporal gyrus and (b) right anterior orbitofrontal cortex. (c–e) Voxels showing differences in the hemodynamic response to HN-NN between MDD and HC subjects in the (c) left orbitofrontal cortex, (d) left anterior insula, and (e) left pregenual anterior cingulate cortex. Bar graphs of the contrast eigenvariates with standard error bars are shown to the right of the corresponding statistical parametric map images in MDD versus HC subjects for the loci identified within the ANOVA (a–e). Abbreviations: L = left; R = right; MDD = major depressive disorder; HC = healthy control, SN = masked-sad faces; HN = masked-happy faces; NN = masked-neutral faces; SN-NN = masked-sad versus masked-neutral faces; HN-NN = masked-happy versus masked-neutral faces; rSTG = rostral superior temporal gyrus; OFC = orbitofrontal cortex; Ins = insula; latOFC = lateral orbitofrontal cortex; Thal = thalamus; pgACC = pregenual anterior cingulate cortex.</p

Regional differences in the BOLD response to masked-sad faces versus masked-happy faces (SN-HN) in patients with major depressive disorder and healthy controls.

<p>Abbreviations: L = left; R = right; MDD = major depressive disorder; HC = healthy control; SN = masked-sad faces; HN = masked-happy faces; SN-HN = masked-sad versus masked-happy faces; C = cortex.</p>*<p>The cluster size was significant after applying a cluster threshold of k = 23 voxels using Monte Carlo simulations implemented in AFNI's AlphaSim program to correct for multiple comparisons.</p>#<p>The statistical t-values for these regions are reported in the text, while corresponding z-values are reported in the table.</p>∧<p>The peak amygdala coordinate varies slightly from those reported in our previous paper <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046439#pone.0046439-Victor1" target="_blank">[8]</a> because here we report results for SN-HN based on a different statistical approach (2×3 ANOVA).</p

Mean and standard deviation results for subject demographic characteristics and clinical symptom rating scales.

a<p>MDD>HC, p<0.001.</p><p>Abbreviations: HC = healthy control; MDD = current major depressive disorder; WASI = Weschler Abbreviated Scale of Intelligence; HAM-D = Hamilton Depression Rating Scale; ATQ = Automatic Thoughts Questionnaire; IDS-SR = Inventory of Depressive Symptoms- Self-Rating; STAI-S = State-Trait Anxiety Inventory- State; STAI-T = State-Trait Anxiety Inventory- Trait; TCQ-D = Thought Control Questionnaire- distraction subscale; TCQ-W = Thought Control Questionnaire- worry subscale; TCQ-P = Thought Control Questionnaire- punishment subscale.</p