Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity

BACKGROUND: Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-alpha induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines. OBJECTIVES: To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing. METHODS: In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Mood questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed an implicit emotional face perception task during functional magnetic resonance imaging. Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression. RESULTS: Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6. CONCLUSIONS: Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokine

The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer.

The advent of neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), has significantly advanced our understanding of the neurophysiological processes supporting a wide spectrum of mind-body approaches to treat pain. A promising self-regulatory practice, mindfulness meditation, reliably alleviates experimentally induced and clinical pain. Yet, the neural mechanisms supporting mindfulness-based pain relief remain poorly characterized. The present review delineates evidence from a spectrum of fMRI studies showing that the neural mechanisms supporting mindfulness-induced pain attenuation differ across varying levels of meditative experience. After brief mindfulness-based mental training (ie, less than 10 hours of practice), mindfulness-based pain relief is associated with higher order (orbitofrontal cortex and rostral anterior cingulate cortex) regulation of low-level nociceptive neural targets (thalamus and primary somatosensory cortex), suggesting an engagement of unique, reappraisal mechanisms. By contrast, mindfulness-based pain relief after extensive training (greater than 1000 hours of practice) is associated with deactivation of prefrontal and greater activation of somatosensory cortical regions, demonstrating an ability to reduce appraisals of arising sensory events. We also describe recent findings showing that higher levels of dispositional mindfulness, in meditation-naïve individuals, are associated with lower pain and greater deactivation of the posterior cingulate cortex, a neural mechanism implicated in self-referential processes. A brief fMRI primer is presented describing appropriate steps and considerations to conduct studies combining mindfulness, pain, and fMRI. We postulate that the identification of the active analgesic neural substrates involved in mindfulness can be used to inform the development and optimization of behavioral therapies to specifically target pain, an important consideration for the ongoing opioid and chronic pain epidemic

Viewing the personality traits through a cerebellar lens. A focus on the constructs of novelty seeking, harm avoidance, and alexithymia

The variance in the range of personality trait expression appears to be linked to structural variance in specific brain regions. In evidencing associations between personality factors and neurobiological measures, it seems evident that the cerebellum has not been up to now thought as having a key role in personality. This paper will review the most recent structural and functional neuroimaging literature that engages the cerebellum in personality traits, as novelty seeking and harm avoidance, and it will discuss the findings in the context of contemporary theories of affective and cognitive cerebellar function. By using region of interest (ROI)- and voxel-based approaches, we recently evidenced that the cerebellar volumes correlate positively with novelty seeking scores and negatively with harm avoidance scores. Subjects who search for new situations as a novelty seeker does (and a harm avoiding does not do) show a different engagement of their cerebellar circuitries in order to rapidly adapt to changing environments. The emerging model of cerebellar functionality may explain how the cerebellar abilities in planning, controlling, and putting into action the behavior are associated to normal or abnormal personality constructs. In this framework, it is worth reporting that increased cerebellar volumes are even associated with high scores in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. On such a basis, it seems necessary to go over the traditional cortico-centric view of personality constructs and to address the function of the cerebellar system in sustaining aspects of motivational network that characterizes the different temperamental trait

Glutamatergic and Resting-State Functional Connectivity Correlates of Severity in Major Depression – The Role of Pregenual Anterior Cingulate Cortex and Anterior Insula

Glutamatergic mechanisms and resting-state functional connectivity alterations have been recently described as factors contributing to major depressive disorder (MDD). Furthermore, the pregenual anterior cingulate cortex (pgACC) seems to play an important role for major depressive symptoms such as anhedonia and impaired emotion processing. We investigated 22 MDD patients and 22 healthy subjects using a combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) approach. Severity of depression was rated using the 21-item Hamilton depression scale (HAMD) and patients were divided into severely and mildly depressed subgroups according to HAMD scores. Because of their hypothesized role in depression we investigated the functional connectivity between pgACC and left anterior insular cortex (AI). The sum of Glutamate and Glutamine (Glx) in the pgACC, but not in left AI, predicted the resting-state functional connectivity between the two regions exclusively in depressed patients. Furthermore, functional connectivity between these regions was significantly altered in the subgroup of severely depressed patients (HAMD > 15) compared to healthy subjects and mildly depressed patients. Similarly the Glx ratios, relative to Creatine, in the pgACC were lowest in severely depressed patients. These findings support the involvement of glutamatergic mechanisms in severe MDD which are related to the functional connectivity between pgACC and AI and depression severity

Capacity and tendency: A neuroscientific framework for the study of emotion regulation.

It is widely accepted that the ability to effectively regulate one's emotions is a cornerstone of physical and mental health. As such, it should come as no surprise that the number of neuroimaging studies focused on emotion regulation and associated processes has increased exponentially in the past decade. To date, neuroimaging research on this topic has examined two distinct but complementary features of emotion regulation - the capacity to effectively utilize a strategy to regulate emotion and to a lesser extent, the tendency to choose to regulate. However, theoretical accounts of emotion regulation have only recently begun to distinguish capacity from tendency. In the present review, we provide a novel framework for conceptualizing these two intertwined, yet distinct, facets of emotion regulation. First we characterize brain regions that support emotion generation and are thus targeted by emotion regulation. Next, we synthesize findings from the dozens of neuroimaging studies that have examined emotion regulation capacity, focusing in particular on the most commonly studied emotion regulation strategy - reappraisal. Finally, we discuss emerging neuroimaging research examining state and trait regulatory tendencies. We conclude by integrating findings from neuroimaging research on emotion regulation capacity and tendency and suggest ways that this integrated model can inform basic and translational neuroscientific research on emotion regulation

Brain circuitry of compulsivity.

Compulsivity is associated with alterations in the structure and the function of parallel and interacting brain circuits involved in emotional processing (involving both the reward and the fear circuits), cognitive control, and motor functioning. These brain circuits develop during the pre-natal period and early childhood under strong genetic and environmental influences. In this review we bring together literature on cognitive, emotional, and behavioral processes in compulsivity, based mainly on studies in patients with obsessive-compulsive disorder and addiction. Disease symptoms normally change over time. Goal-directed behaviors, in response to reward or anxiety, often become more habitual over time. During the course of compulsive disorders the mental processes and repetitive behaviors themselves contribute to the neuroplastic changes in the involved circuits, mainly in case of chronicity. On the other hand, successful treatment is able to normalize altered circuit functioning or to induce compensatory mechanisms. We conclude that insight in the neurobiological characteristics of the individual symptom profile and disease course, including the potential targets for neuroplasticity is an unmet need to advance the field.Dr. Soriano-Mas is funded by a ׳Miguel Servet׳ contract from the Carlos III Health Institute (CP10/00604). Dr. Goudriaan is supported by a VIDI Innovative Research Grant (Grant no. 91713354) funded by the Dutch Scientific Research Association (NWO-ZonMW). Dr. Alonso was funded by the Instituto de Salut Carlos III-FISPI14/00413. Dr. Nakamae received Grant support from MEXT KAKENHI (Nos. 24791223 and 26461753).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.euroneuro.2015.12.00

Magnetoencephalography as a tool in psychiatric research: current status and perspective

The application of neuroimaging to provide mechanistic insights into circuit dysfunctions in major psychiatric conditions and the development of biomarkers are core challenges in current psychiatric research. In this review, we propose that recent technological and analytic advances in Magnetoencephalography (MEG), a technique which allows the measurement of neuronal events directly and non-invasively with millisecond resolution, provides novel opportunities to address these fundamental questions. Because of its potential in delineating normal and abnormal brain dynamics, we propose that MEG provides a crucial tool to advance our understanding of pathophysiological mechanisms of major neuropsychiatric conditions, such as Schizophrenia, Autism Spectrum Disorders, and the dementias. In our paper, we summarize the mechanisms underlying the generation of MEG signals and the tools available to reconstruct generators and underlying networks using advanced source-reconstruction techniques. We then survey recent studies that have utilized MEG to examine aberrant rhythmic activity in neuropsychiatric disorders. This is followed by links with preclinical research, which have highlighted possible neurobiological mechanisms, such as disturbances in excitation/inhibition parameters, which could account for measured changes in neural oscillations. In the final section of the paper, challenges as well as novel methodological developments are discussed which could pave the way for a widespread application of MEG in translational research with the aim of developing biomarkers for early detection and diagnosis

Disrupted Brain Circuitry for Pain‐Related Reward/Punishment in Fibromyalgia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102040/1/art38191.pd