The Relationship between Amygdala Activation and Passive Exposure Time to an Aversive Cue during a Continuous Performance Task

The allocation of attention modulates negative emotional processing in the amygdala. However, the role of passive exposure time to emotional signals in the modulation of amygdala activity during active task performance has not been examined. In two functional Magnetic Resonance Imaging (fMRI) experiments conducted in two different groups of healthy human subjects, we examined activation in the amygdala due to cued anticipation of painful stimuli while subjects performed a simple continuous performance task (CPT) with either a fixed or a parametrically varied trial duration. In the first experiment (N = 16), engagement in the CPT during a task with fixed trial duration produced the expected attenuation of amygdala activation, but close analysis suggested that the attenuation occurred during the period of active engagement in CPT, and that amygdala activity increased proportionately during the remainder of each trial, when subjects were passively exposed to the pain cue. In the second experiment (N = 12), the duration of each trial was parametrically varied, and we found that amygdala activation was linearly related to the time of passive exposure to the anticipatory cue. We suggest that amygdala activation during negative anticipatory processing depends directly on the passive exposure time to the negative cue

The Parametric, Psychological, Neuropsychological, and Neuroanatomical Properties of Self and World Evaluation

Background: As an individual moves from adolescence to adulthood, they need to form a new sense of self as their environment changes from a limited to a more expansive structure. During this critical stage in development the last dramatic steps of neural development occur and numerous psychiatric conditions begin to manifest. Currently, there is no measure that aids in the quantification of how the individual is adapting to, and conceptualizing their role in, these new structures. To fill this gap we created the Self and World Evaluation Expressions Test(SWEET). Method: Sixty-five young adults (20.6 years-old), 36 with a history of drug use, completed the SWEET. A factor analysis was performed on the SWEET and the resultant factors were correlated with psychological, neuropsychological, and neuroanatomical battery that included both T1-wieghted and diffusion tensor magnetic resonance imaging scans. Results: We derived four factors: Self, Social-Emotional, Financial-Intellectual, and Spirituality. While showing limited relationships to psychological and neuropsychological measures, both white matter integrity and gray matter density showed significant relationships with SWEET factors. Conclusions: These findings suggest that while individual responses may not be indicative of psychological or cognitive processes they may relate to changes in brain structure. Several of these structures, such as the negative correlation of the affective impact of world with the dorsal anterior corpus callosum white matter integrity have been observed in psychiatri

AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder:COORDINATE-MDD consortium design and rationale

BACKGROUND: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states. METHODS: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants. RESULTS: We are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites. CONCLUSION: We describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project

Dynamical Principles of Emotion-Cognition Interaction: Mathematical Images of Mental Disorders

The key contribution of this work is to introduce a mathematical framework to understand self-organized dynamics in the brain that can explain certain aspects of itinerant behavior. Specifically, we introduce a model based upon the coupling of generalized Lotka-Volterra systems. This coupling is based upon competition for common resources. The system can be regarded as a normal or canonical form for any distributed system that shows self-organized dynamics that entail winnerless competition. Crucially, we will show that some of the fundamental instabilities that arise in these coupled systems are remarkably similar to endogenous activity seen in the brain (using EEG and fMRI). Furthermore, by changing a small subset of the system's parameters we can produce bifurcations and metastable sequential dynamics changing, which bear a remarkable similarity to pathological brain states seen in psychiatry. In what follows, we will consider the coupling of two macroscopic modes of brain activity, which, in a purely descriptive fashion, we will label as cognitive and emotional modes. Our aim is to examine the dynamical structures that emerge when coupling these two modes and relate them tentatively to brain activity in normal and non-normal states

Visceral and cutaneous pain : neural correlates and pharmacological intervention

Our brain is involved in processing pain, whether it is superficial cutaneous pain, caused by a scratch or a burn, or deep internal pain, caused by heartburn or gas in the intestines. Moreover, activation of a common cortical network is suggested during different types of pain in humans, implying that as long as the stimulus is painful it will be processed similarly in the cerebral cortex. However, no one has yet made direct comparison between superficial and deep pain of similar intensity and location; direct comparison is necessary in order to see how superficial pain relates to a more clinically relevant deep pain and to further our understanding of the latter.In three separate studies, the perception of visceral and cutaneous pain in humans was examined using psychophysical, brain imaging and pharmacological approaches, respectively. The first study revealed that for a similar given intensity, duration and location, visceral pain is more unpleasant, more varied qualitatively, more diffuse and more persistent after stimulation has ended, suggesting that there are some significant distinctions in the neural processes of external and internal pain in humans. The second study examined such processes with functional magnetic resonance imaging (fMRI), disclosing substantial differences in cortical processing of sensory information from skin and viscera, including limbic areas associated with the emotional component of pain (anterior cingulate and insular cortices), and sensory areas (primary somatosensory cortex). In addition, several similar cortical areas were activated by both superficial and deep pain, consistent with the existence of a common pain network independent of the nature of pain. The final study examined a possible divergence in pharmacological processes underlying deep and superficial pain, which could arise from differences in neuronal processing. The findings revealed that NMDA-receptors mediate both visceral and cutaneous pain in humans, yet the affect of visceral pain might be more susceptible to their blockers, which may be a potential explanation for different treatments of visceral and cutaneous pains.Together these studies provide direct evidence of the differences and similarities between visceral and cutaneous pain in humans within the perceptual, physiological and pharmacological domains

Interoception, homeostatic emotions and sympathovagal balance

We briefly review the evidence for distinct neuroanatomical substrates that underlie interoception in humans, and we explain how they substantialize feelings from the body (in the insular cortex) that are conjoined with homeostatic motivations that guide adaptive behaviours (in the cingulate cortex). This hierarchical sensorimotor architecture coincides with the limbic cortical architecture that underlies emotions, and thus we regard interoceptive feelings and their conjoint motivations as homeostatic emotions We describe how bivalent feelings, emotions and sympathovagal balance can be organized and regulated efficiently in the bicameral forebrain as asymmetric positive/negative, approach/avoidance and parasympathetic/sympathetic components. We provide original evidence supporting this organization from studies of cardiorespiratory vagal activity in monkeys and functional imaging studies in healthy humans showing activation modulated by paced breathing and passively viewed emotional images. The neuroanatomical architecture of interoception provides deep insight into the functional organization of all emotional feelings and behaviours in humans.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'

Pain and emotion in the insular cortex: evidence for functional reorganization in major depression

Major Depressive Disorder (MDD) is among the top causes of disability worldwide and many patients with depression experience pain symptoms. Little is known regarding what makes depressed persons feel like they are in pain. An increasing number of neuroimaging studies show that both physical pain and depression involve the insular cortex. The present study aimed to investigate whether emotional processing in MDD patients is topologically shifted towards the insular area(s) involved in pain processing in healthy individuals. To achieve this aim, we investigated the functional organization of the insula by conducting meta-analyses of previously published neuroimaging studies on: (1) emotion in patients with MDD, (2) emotion in healthy subjects, and (3) physical pain in healthy subjects. Our results show that the dorsal part of the insula is reproducibly activated during experimental pain in healthy individuals, with multiple separate pain-related areas aligned along its dorsal border. Regions with maximal pain-related activation likelihood estimate (ALE) were located in the posterior (left) and dorsal mid-anterior insula (left and right). Furthermore, emotion-related peaks in healthy subjects were found both in its ventral (as shown in a previous meta-analysis) and dorsal anterior part. Importantly, emotion-related peaks in depressed patients were shifted to the dorsal anterior insula, where regions related to physical pain in healthy subjects are located. This shift was reflected in the observation that median z-coordinates of emotion-related responses in the left hemisphere were significantly larger in depressed patients than in healthy controls. This shift of emotion-related responses to the dorsal insula, i.e., where pain-processing takes place in healthy subjects, may play a role in "emotional allodynia" - a notion that individuals with MDD experience pain in response to stimuli that are normally not painful