β-adrenergic modulation of oddball responses in humans

Detection of salient or motivationally significant stimuli is of adaptive importance. The neurophysiological correlates of this detection have been extensively studied in 'oddball' paradigms. Much theoretical data supports the role of noradrenergic systems in generating oddball responses. We combine psychopharmacology and functional neuroimaging to demonstrate modulation of neuronal responses to oddball nouns by the β-adrenergic antagonist propranolol. Critically, responses in regions implicated in oddball detection, namely right ventrolateral prefrontal cortex and temporoparietal junction (TPJ), were abolished by propranolol. Thus, oddball responses depend on modulatory adrenergic inputs, mediated via β-adrenergic receptors

Prefrontal-occipitoparietal coupling underlies late latency human neuronal responses to emotion

Enhanced late positive potentials (LPPs) evoked by highly arousing unpleasant and pleasant stimuli have been consistently observed in event-related potential experiments in humans. Although the psychological factors modulating the LPP have been studied in detail, the neurobiological underpinnings of this response remain poorly understood. Current models suggest that the LPP is a product of both an automatic facilitation of perceptual activity, as well as postperceptual processing under cognitive control. Here we applied magnetoencephalography (MEG) and beamformer analysis combined with Granger causality measures to provide a mechanistic account for LPP generation that reconciles these two models. We demonstrate that the magnetic homolog of the LPP, mLPP, is localized within bilateral occipitoparietal and right prefrontal cortex. Critically, directed functional connectivity analysis between these brain regions, indexed by Granger causality, demonstrates stronger bidirectional influences between frontal and occipitoparietal cortex for high arousing emotional relative to low arousing neutral pictures. Thus, both bottom-up and top-down accounts of the late latency response to emotion derived from psychological studies can be explained by a reciprocal codependency between activity in prefrontal and occipitoparietal cortex

Firm level factors that affect returns to real estate investment trusts

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2000.Includes bibliographical references (leaves 72-73).This thesis examines the historical financial data for publicly traded securities issued by Real Estate Investment Trusts (REITS). The inquiry isolates certain quantifiable firm specific financial data and organizes that data into pooled, time-series cross-sections. Annual returns to capital are determined for certain equity REITS from 1990 to 1999 and are used as the dependent variable in a statistical regression analysis. The analysis includes independent variables drawn from a database and includes variables to adjust results for the impact of macroeconomic factors. In addition, indexes for the broader markets are identified and included in the regressions to adjust for the impact of trends in the general market. Following adjustments for macroeconomic factors and general market trends the regression results identify various firm specific variables that display a statistically significant relationship to relative returns to capital in REIT securities over time. Negative impacts on returns are observed for increases in firm size and for certain debt features such as variable rate debt, unsecured debt, and total debt. Positive impacts on returns are associated with higher levels of asset growth as well as relatively higher levels of secured debt and preferred stock. The expected positive correlation of returns with increases in broader stock market indexes and negative correlation with increasing short-term interest rates is not displayed. For the period from 1993 to 1999, the data indicate an inverse correlation of REIT returns to the stock market as represented by the S&P 500 index and a direct relation with short-term interest rates. Interpretations of the results are provided in a form that relates the firm level determinates of returns to capital with the history of REITS and their organizational and tax characteristics. Alternatives for further inquiry are identified and implications for investors and REIT managers are discussed.by William B. Strange, III and Duo Tang.S.M

Bidirectional synaptic plasticity can explain bidirectional retrograde effects of emotion on memory

Emotional events can cither impair or enhance memory for immediately preceding items, '["he GANK model explains this bidirectional effect as a glulamale "priority" signal that modulates nor adrenaline release depending on arousal state. We argue for an alternative explanation: that priority itself evokes phasic nor adrenaline release. Thus, contrasting K-l memory effects are explained by a mechanism based on the Bienensloek-Cooper—Munro theory

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -521Cmayor queT DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region

Orienting to fear under transient focal disruption of the human amygdala

Responding to threat is under strong survival pressure, promoting the evolution of systems highly optimised for the task. Though the amygdala is implicated in detecting threat, its role in the action that immediately follows-orienting-remains unclear. Critical to mounting a targeted response, such early action requires speed, accuracy, and resilience optimally achieved through conserved, parsimonious, dedicated systems, insured against neural loss by a parallelized functional organisation. These characteristics tend to conceal the underlying substrate not only from correlative methods but also from focal disruption over time scales long enough for compensatory adaptation to take place. In a study of six patients with intracranial electrodes temporarily implanted for the clinical evaluation of focal epilepsy, here we investigate gaze orienting to fear during focal, transient, unilateral direct electrical disruption of the amygdala. We show that the amygdala is necessary for rapid gaze shifts towards faces presented in the contralateral hemifield regardless of their emotional expression, establishing its functional lateralisation. Behaviourally dissociating the location of presented fear from the direction of the response, we implicate the amygdala not only in detecting contralateral faces, but also in automatically orienting specifically towards fearful ones. This salience-specific role is demonstrated within a drift-diffusion model of action to manifest as an orientation bias towards the location of potential threat. Pixel-wise analysis of target facial morphology reveals scleral exposure as its primary driver, and induced gamma oscillations-obtained from intracranial local field potentials-as its time-locked electrophysiological correlate. The amygdala is here re-conceptualised as a functionally lateralised instrument of early action, reconciling previous conflicting accounts confined to detection, and revealing a neural organisation analogous to the superior colliculus, with which it is phylogenetically kin. Greater clarity on its role has the potential to guide therapeutic resection, still frequently complicated by impairments of cognition and behaviour related to threat, and inform novel focal stimulation techniques for the management of neuropsychiatric conditions

Neuronal population representation of human emotional memory

Understanding how emotional processing modulates learning and memory is crucial for the treatment of neuropsychiatric disorders characterized by emotional memory dysfunction. We investigate how human medial temporal lobe (MTL) neurons support emotional memory by recording spiking activity from the hippocampus, amygdala, and entorhinal cortex during encoding and recognition sessions of an emotional memory task in patients with pharmaco-resistant epilepsy. Our findings reveal distinct representations for both remembered compared to forgotten and emotional compared to neutral scenes in single units and MTL population spiking activity. Additionally, we demonstrate that a distributed network of human MTL neurons exhibiting mixed selectivity on a single-unit level collectively processes emotion and memory as a network, with a small percentage of neurons responding conjointly to emotion and memory. Analyzing spiking activity enables a detailed understanding of the neurophysiological mechanisms underlying emotional memory and could provide insights into how emotion alters memory during healthy and maladaptive learning

Temporal dynamics of amygdala response to emotion- and action-relevance

It has been proposed that the human amygdala may not only encode the emotional value of sensory events, but more generally mediate the appraisal of their relevance for the individual's goals, including relevance for action or task-based needs. However, emotional and non-emotional/action-relevance might drive amygdala activity through distinct neural signals, and the relative timing of both kinds of responses remains undetermined. Here, we recorded intracranial event-related potentials (iERPs) from nine amygdalae of patients undergoing epilepsy surgery, while they performed variants of a Go/NoGo task with faces and abstract shapes, where emotion- and action-relevance were orthogonally manipulated. Our results revealed early amygdala responses to emotion facial expressions starting ~130ms after stimulus-onset. Importantly, the amygdala responded to action-relevance not only with face stimuli but also with abstract shapes (squares), and these relevance effects consistently occurred in later time-windows (starting ~220ms) for both faces and squares. A similar dissociation was observed in gamma activity. Furthermore, whereas emotional responses habituated over time, the action-relevance effect increased during the course of the experiment, suggesting progressive learning based on the task needs. Our results support the hypothesis that the human amygdala mediates a broader relevance appraisal function, with the processing of emotion-relevance preceding temporally that of action-relevance

A ventromedial prefrontal dysrhythmia in obsessive-compulsive disorder is attenuated by nucleus accumbens deep brain stimulation

Background: Obsessive-compulsive disorder (OCD) has consistently been linked to abnormal frontostriatal activity. The electrophysiological disruption in this circuit, however, remains to be characterized. Objective/hypothesis: The primary goal of this study was to investigate the neuronal synchronization in OCD patients. We predicted aberrant oscillatory activity in frontal regions compared to healthy control subjects, which would be alleviated by deep brain stimulation (DBS) of the nucleus accumbens (NAc). Methods: We compared scalp EEG recordings from nine patients with OCD treated with NAc-DBS with recordings from healthy controls, matched for age and gender. Within the patient group, EEG activity was compared with DBS turned off vs. stimulation at typical clinical settings (3.5 V, frequency of stimulation 130 Hz, pulse width 60 ms). In addition, intracranial EEG was recorded directly from depth macro electrodes in the NAc in four OCD patients. Results: Cross-frequency coupling between the phase of alpha/low beta oscillations and amplitude of high gamma was significantly increased over midline frontal and parietal electrodes in patients when stimulation was turned off, compared to controls. Critically, in patients, beta (16-25 Hz)-gamma (110-166 Hz) phase amplitude coupling source localized to the ventromedial prefrontal cortex, and was reduced when NAc-DBS was active. In contrast, intracranial EEG recordings showed no beta-gamma phase amplitude coupling. The contribution of non-sinusoidal beta waveforms to this coupling are reported. Conclusion: We reveal an increased beta-gamma phase amplitude coupling in fronto-central scalp sensors in patients suffering from OCD, compared to healthy controls, which may derive from ventromedial prefrontal regions implicated in OCD and is normalized by DBS of the nucleus accumbens. This aberrant cross-frequency coupling could represent a biomarker of OCD, as well as a target for novel therapeutic approaches. (C) 2021 The Authors. Published by Elsevier Inc.This work was supported by Project grants SAF2015-65982-R from the Spanish Ministry of Economy and Competitiveness to BS and PSI2014-58654-JIN to JGR, an FPI Predoctoral Fellowship (BES-2016-079470) to ST, and BIAL Foundation Grant 119/12 to BS. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC-2018-COG 819814)

Action boosts episodic memory encoding in humans via engagement of a noradrenergic system

We are constantly interacting with our environment whilst we encode memories. However, how actions influence memory formation remains poorly understood. Goal-directed movement engages the locus coeruleus (LC), the main source of noradrenaline in the brain. Noradrenaline is also known to enhance episodic encoding, suggesting that action could improve memory via LC engagement. Here we demonstrate, across seven experiments, that action (Go-response) enhances episodic encoding for stimuli unrelated to the action itself, compared to action inhibition (NoGo). Functional magnetic resonance imaging, and pupil diameter as a proxy measure for LC-noradrenaline transmission, indicate increased encodingrelated LC activity during action. A final experiment, replicated in two independent samples, confirmed a novel prediction derived from these data that emotionally aversive stimuli, which recruit the noradrenergic system, modulate the mnemonic advantage conferred by Go-responses relative to neutral stimuli. We therefore provide converging evidence that action boosts episodic memory encoding via a noradrenergic mechanism