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

Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression

We studied cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced electrical silence of the electroencephalogram (EEG) in 10 patients. Anaesthesia was induced with propofol 2.5 mg kg−1, fentanyl 3 μg kg−1 and vecuronium 0.1 mg kg−1, and a propofol infusion of 250-300 μg kg−1 min−1 was used to induce EEG silence. Cerebral pressure autoregulation was tested by increasing mean arterial pressure (MAP) by 24 (SEM 5) mm Hg from baseline with an infusion of phenylephrine and simultaneously recording middle cerebral artery blood flow velocity (vmca) using transcranial Doppler. Carbon dioxide reactivity was tested by varying Paco2 between 4.0 and 7.0 kPa and recording vmca simultaneously. Although absolute carbon dioxide reactivity was reduced, relative carbon dioxide reactivity was within normal limits for all patients studied (mean 8.5 (SEM 0.8) cm s−1 kPa−1 and 22 (2)% kPa−1, respectively). No significant change in vmca (34 (2) and 35 (2) cm s−1) was observed with the increase in MAP (77 (4) to 101 (4) mm Hg) during autoregulation testing. We conclude that cerebral carbon dioxide reactivity and pressure autoregulation remain intact during propofol-induced isoelectric EE

A Symmetry-Based Method to Infer Structural Brain Networks from Probabilistic Tractography Data

Recent progress in diffusion MRI and tractography algorithms as well as the launch of the Human Connectome Project (HCP) have provided brain research with an abundance of structural connectivity data. In this work, we describe and evaluate a method that can infer the structural brain network that interconnects a given set of Regions of Interest (ROIs) from probabilistic tractography data. The proposed method, referred to as Minimum Asymmetry Network Inference Algorithm (MANIA), does not determine the connectivity between two ROIs based on an arbitrary connectivity threshold. Instead, we exploit a basic limitation of the tractography process: the observed streamlines from a source to a target do not provide any information about the polarity of the underlying white matter, and so if there are some fibers connecting two voxels (or two ROIs) X and Y, tractography should be able in principle to follow this connection in both directions, from X to Y and from Y to X. We leverage this limitation to formulate the network inference process as an optimization problem that minimizes the (appropriately normalized) asymmetry of the observed network. We evaluate the proposed method using both the FiberCup dataset and based on a noise model that randomly corrupts the observed connectivity of synthetic networks. As a case-study, we apply MANIA on diffusion MRI data from 28 healthy subjects to infer the structural network between 18 corticolimbic ROIs that are associated with various neuropsychiatric conditions including depression, anxiety and addiction

The lateral and ventromedial prefrontal cortex work as a dynamic integrated system:evidence from FMRI connectivity analysis

Recent functional magnetic resonance imaging (fMRI) investigations of the interaction between cognition and reward processing have found that the lateral prefrontal cortex (PFC) areas are preferentially activated to both increasing cognitive demand and reward level. Conversely, ventromedial PFC (VMPFC) areas show decreased activation to the same conditions, indicating a possible reciprocal relationship between cognitive and emotional processing regions. We report an fMRI study of a rewarded working memory task, in which we further explore how the relationship between reward and cognitive processing is mediated. We not only assess the integrity of reciprocal neural connections between the lateral PFC and VMPFC brain regions in different experimental contexts but also test whether additional cortical and subcortical regions influence this relationship. Psychophysiological interaction analyses were used as a measure of functional connectivity in order to characterize the influence of both cognitive and motivational variables on connectivity between the lateral PFC and the VMPFC. Psychophysiological interactions revealed negative functional connectivity between the lateral PFC and the VMPFC in the context of high memory load, and high memory load in tandem with a highly motivating context, but not in the context of reward alone. Physiophysiological interactions further indicated that the dorsal anterior cingulate and the caudate nucleus modulate this pathway. These findings provide evidence for a dynamic interplay between lateral PFC and VMPFC regions and are consistent with an emotional gating role for the VMPFC during cognitively demanding tasks. Our findings also support neuropsychological theories of mood disorders, which have long emphasized a dysfunctional relationship between emotion/motivational and cognitive processes in depression

Effects of Subcallosal Cingulate Deep Brain Stimulation on Negative Self-bias in Patients With Treatment-resistant Depression

Background: The cognitive neuropsychological model states that antidepressant treatment alters emotional biases early in treatment, and after this initial change in emotional processing, environmental and social interactions allow for long-term/sustained changes in mood and behavior. Objective: Changes in negative self-bias after chronic subcallosal cingulate (SCC) deep brain stimulation (DBS) were investigated with the hypothesis that treatment would lead to changes in emotional biases followed by changes in symptom severity. Methods: Patients (N = 7) with treatment-resistant depression were assessed at three time points: pretreatment; after one month stimulation; and after six months stimulation. The P1, P2, P3, and LPP (late positive potential) components of the event-related potential elicited by positive and negative trait adjectives were recorded in both a self-referential task and a general emotion recognition task. Results: Results indicate that DBS reduced automatic attentional bias toward negative words early in treatment, as indexed by the P1 component, and controlled processing of negative words later in treatment, as indexed by the P3 component. Reduction in negative words endorsed as self-descriptive after six months DBS was associated with reduced depression severity after six months DBS. Change in emotional processing may be restricted to the self-referential task. Conclusions: Together, these results suggest that the cognitive neuropsychological model, developed to explain the time-course of monoamine antidepressant treatment, may also be used as a framework to interpret the antidepressant effects of SCC DBS. (C) 2015 Elsevier Inc. All rights reserved

Evaluation of Thiel cadaveric model for MRI-guided stereotactic procedures in neurosurgery

BACKGROUND: Magnetic resonance imaging (MRI)-guided deep brain stimulation (DBS) and high frequency focused ultrasound (FUS) is an emerging modality to treat several neurological disorders of the brain. Developing reliable models to train and assess future neurosurgeons is paramount to ensure safety and adequate training of neurosurgeons of the future. METHODS: We evaluated the use of Thiel cadaveric model to practice MRI-guided DBS implantation and high frequency MRI-guided FUS in the human brain. We performed three training sessions for DBS and five sonications using high frequency MRI-guided FUS in five consecutive cadavers to assess the suitability of this model to use in training for stereotactic functional procedures. RESULTS: We found the brains of these cadavers preserved in an excellent anatomical condition up to 15 months after embalmment and they were excellent model to use, MRI-guided DBS implantation and FUS produced the desired lesions accurately and precisely in these cadaveric brains. CONCLUSION: Thiel cadavers provided a very good model to perform these procedures and a potential model to train and assess neurosurgeons of the future

The organizational social context of mental health services and clinician attitudes toward evidence-based practice: a United States national study.

UnlabelledABSTBACKGROUND: Evidence-based practices have not been routinely adopted in community mental health organizations despite the support of scientific evidence and in some cases even legislative or regulatory action. We examined the association of clinician attitudes toward evidence-based practice with organizational culture, climate, and other characteristics in a nationally representative sample of mental health organizations in the United States.MethodsIn-person, group-administered surveys were conducted with a sample of 1,112 mental health service providers in a nationwide sample of 100 mental health service institutions in 26 states in the United States. The study examines these associations with a two-level Hierarchical Linear Modeling (HLM) analysis of responses to the Evidence-Based Practice Attitude Scale (EBPAS) at the individual clinician level as a function of the Organizational Social Context (OSC) measure at the organizational level, controlling for other organization and clinician characteristics.ResultsWe found that more proficient organizational cultures and more engaged and less stressful organizational climates were associated with positive clinician attitudes toward adopting evidence-based practice.ConclusionsThe findings suggest that organizational intervention strategies for improving the organizational social context of mental health services may contribute to the success of evidence-based practice dissemination and implementation efforts by influencing clinician attitudes