Abstract Recent rodent studies suggest that gonadal hormones influence extinction of conditioned fear. Here we investigated sex differences in, and the influence of estradiol and progesterone on, ...fear extinction in healthy humans. Men and women underwent a two-day paradigm in which fear conditioning and extinction learning took place on day 1 and extinction recall was tested on day 2. Visual cues were used as the conditioned stimuli and a mild electric shock was used as the unconditioned stimulus. Skin conductance was recorded throughout the experiment and used to measure conditioned responses (CRs). Blood samples were obtained from all women to measure estradiol and progesterone levels. We found that higher estradiol during extinction learning enhanced subsequent extinction recall but had no effects on fear acquisition or extinction learning itself. Sex differences were only observed during acquisition, with men exhibiting significantly higher CRs. After dividing women into low- and high-estradiol groups, men showed comparable extinction recall to high-estradiol women, and both of these groups showed higher extinction recall than low-estradiol women. Therefore, sex differences in extinction memory emerged only after taking into account women's estradiol levels. Lower estradiol may impair extinction consolidation in women. These findings could have practical applications in the treatment of anxiety disorders through cognitive and behavioral therapies.
Psychiatric neurosurgery, specifically stereotactic ablation, has continued since the 1940s, mainly at a few centers in Europe and the US. Since the late 1990s, the resurgence of interest in this ...field has been remarkable; reports of both lesion procedures and the newer technique of deep brain stimulation (DBS) have increased rapidly. In early 2009, the US FDA granted limited humanitarian approval for DBS for otherwise intractable obsessive-compulsive disorder (OCD), the first such approval for a psychiatric illness. Several factors explain the emergence of DBS and continued small-scale use of refined lesion procedures. DBS and stereotactic ablation have been successful and widely used for movement disorders. There remains an unmet clinical need: current drug and behavioral treatments offer limited benefit to some seriously ill people. Understandings of the neurocircuitry underlying psychopathology and the response to treatment, while still works in progress, are much enhanced. Here, we review modern lesion procedures and DBS for OCD in the context of neurocircuitry. A key issue is that clinical benefit can be obtained after surgeries targeting different brain structures. This fits well with anatomical models, in which circuits connecting orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), basal ganglia, and thalamus are central to OCD pathophysiology and treatment response. As in movement disorders, dedicated interdisciplinary teams, here led by psychiatrists, are required to implement these procedures and maintain care for patients so treated. Available data, although limited, support the promise of stereotactic ablation or DBS in carefully selected patients. Benefit in such cases appears not to be confined to obsessions and compulsions, but includes changes in affective state. Caution is imperative, and key issues in long-term management of psychiatric neurosurgery patients deserve focused attention. DBS and contemporary ablation also present different patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use.
There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three ...processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems.
To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral ...system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for identification of the emotional significance of a stimulus, production of affective states, and automatic regulation of emotional responses; and 2) a dorsal system, including the hippocampus, dorsal anterior cingulate gyrus, and prefrontal cortex, for the effortful regulation of affective states and subsequent behavior. In this critical review, we have examined evidence from studies employing a variety of techniques for distinct patterns of structural and functional abnormalities in these neural systems in schizophrenia, bipolar disorder, and major depressive disorder. In each psychiatric disorder, the pattern of abnormalities may be associated with specific symptoms, including emotional flattening, anhedonia, and persecutory delusions in schizophrenia, prominent mood swings, emotional lability, and distractibility in bipolar disorder during depression and mania, and with depressed mood and anhedonia in major depressive disorder. We suggest that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder.
Context. Both multi-messenger astronomy and new high-throughput wide-field surveys require flexible tools for the selection and analysis of astrophysical transients. Aims. Here we introduce the alert ...management, photometry, and evaluation of light curves (AMPEL) system, an analysis framework designed for high-throughput surveys and suited for streamed data. AMPEL combines the functionality of an alert broker with a generic framework capable of hosting user-contributed code; it encourages provenance and keeps track of the varying information states that a transient displays. The latter concept includes information gathered over time and data policies such as access or calibration levels. Methods. We describe a novel ongoing real-time multi-messenger analysis using AMPEL to combine IceCube neutrino data with the alert streams of the Zwicky Transient Facility (ZTF). We also reprocess the first four months of ZTF public alerts, and compare the yields of more than 200 different transient selection functions to quantify efficiencies for selecting Type Ia supernovae that were reported to the Transient Name Server (TNS). Results. We highlight three channels suitable for (1) the collection of a complete sample of extragalactic transients, (2) immediate follow-up of nearby transients, and (3) follow-up campaigns targeting young, extragalactic transients. We confirm ZTF completeness in that all TNS supernovae positioned on active CCD regions were detected. Conclusions. AMPEL can assist in filtering transients in real time, running alert reaction simulations, the reprocessing of full datasets as well as in the final scientific analysis of transient data. This is made possible by a novel way of capturing transient information through sequences of evolving states, and interfaces that allow new code to be natively applied to a full stream of alerts. This text also introduces a method by which users can design their own channels for inclusion in the AMPEL live instance that parses the ZTF stream and the real-time submission of high-quality extragalactic supernova candidates to the TNS.
Taking advantage of the Cluster satellite mission and especially the observations made by the instrument WHISPER to deduce the electron number density along the orbit of the satellites, we studied ...the relationships between the plasmapause positions (LPP) and the following LPP indicators: (a) solar wind coupling functions Bz (Z component of the interplanetary magnetic field vector, B, in GSM system), BV (related to the interplanetary electric field; B is the magnitude of the interplanetary magnetic field vector, V is solar wind velocity), and dΦmp/dt (which combines different physical processes responsible for the magnetospheric activity) and (b) geomagnetic indices Dst, Ap and AE. The analysis is performed separately for three magnetic local time (MLT) sectors (Sector1 – night sector (01:00–07:00 MLT); Sector2 – day sector (07:00–16:00 MLT); Sector3 – evening sector (16:00–01:00 MLT)) and for all MLTs taken together. All LPP indicators suggest the faster plasmapause response in the postmidnight sector. Delays in the plasmapause responses (hereafter time lags) are approximately 2–27 h, always increasing from Sector1 to Sector3. The obtained fits clearly resolve the MLT structures. The variability in the plasmapause is the largest for low values of LPP indicators, especially in Sector2. At low activity levels,LPP exhibits the largest values on the dayside (in Sector2) and the smallest on the postmidnight side (Sector1). Displacements towards larger values on the evening side (Sector3) and towards lower values on the dayside (Sector2) are identified for enhanced magnetic activity. Our results contribute to constraining the physical mechanisms involved in the plasmapause formation and to further study the still not well understood related issues.
In response to queries about whether brain imaging technology has reached the point where it is useful for making a clinical diagnosis and for helping to guide treatment selection, the American ...Psychiatric Association (APA) has recently written a position paper on the Clinical Application of Brain Imaging in Psychiatry. The following perspective piece is based on our contribution to this APA position paper, which specifically emphasized the application of neuroimaging in mood disorders. We present an introductory overview of the challenges faced by researchers in developing valid and reliable biomarkers for psychiatric disorders, followed by a synopsis of the extant neuroimaging findings in mood disorders, and an evidence-based review of the current research on brain imaging biomarkers in adult mood disorders. Although there are a number of promising results, by the standards proposed below, we argue that there are currently no brain imaging biomarkers that are clinically useful for establishing diagnosis or predicting treatment outcome in mood disorders.
Obsessive-compulsive disorder (OCD) may be characterized by impaired self-regulation and behavioral inhibition. Elevated fear and anxiety are common characteristics of this disorder. The neurobiology ...of fear regulation and consolidation of safety memories have not been examined in this patient population.
To examine the psychophysiological and neurobiological correlates of conditioned fear extinction in patients with OCD.
Cross-sectional, case-control, functional magnetic resonance imaging study.
Academic medical center.
Twenty-one patients with OCD and 21 healthy participants.
Skin conductance responses and blood oxygenation level-dependent responses.
The between-group difference noted in our psychophysiological measure (skin conductance responses) was during extinction recall: patients with OCD showed impaired extinction recall relative to control subjects. Regarding the functional magnetic resonance imaging data, patients with OCD showed significantly reduced activation in the ventromedial prefrontal cortex across training phases. Moreover, reduced activation in the patients with OCD was noted in the caudate and hippocampus during fear conditioning, as well as in the cerebellum, posterior cingulate cortex, and putamen during extinction recall. Contrary to our prediction, OCD symptom severity was positively correlated with the magnitude of extinction memory recall. Also contrary to our prediction, functional responses of the ventromedial prefrontal cortex were positively correlated with symptom severity, and functional responses of the dorsal anterior cingulate cortex were inversely correlated with symptom severity.
As expected, our study showed that fear extinction and its neural substrates are impaired in patients with OCD. However, this study also yielded some surprising and unexpected results regarding the correlates between extinction capacity and its neural substrates and the severity of symptoms expressed in this disorder. Thus, our data report neural correlates of deficient fear extinction in patients with OCD. The negative correlations between fear extinction deficits and Yale-Brown Obsessive-Compulsive Scale symptoms in OCD suggest that there may be other factors, in addition to fear extinction deficiency, that contribute to the psychopathology of OCD.
: Advances in neuroimaging techniques over the past two decades have allowed scientists to investigate the neurocircuitry of anxiety disorders. Such research has implicated the orbitofrontal cortex ...(OFC). Characterizing the role of OFC in anxiety disorders, however, is principally complicated by two factors–differences in underlying pathophysiology across the anxiety disorders and heterogeneity in function across different OFC sub‐territories. Contemporary neurocircuitry models of anxiety disorders have primarily focused on amygdalo‐cortical interactions. The amygdala is implicated in generating fear responses, whereas cortical regions, specifically the medial OFC (mOFC) and the ventromedial prefrontal cortex (vmPFC), are implicated in fear extinction. In contrast to mOFC, anterolateral OFC (lOFC) has been associated with negative affects and obsessions and thus dysfunctional lOFC may underlie different aspects of certain anxiety disorders. Herein, we aim to review the above‐mentioned theories and provide a heuristic model for conceptualizing the respective roles of mOFC and lOFC in the pathophysiology and treatment of anxiety disorders. We will also review the role of the OFC in fear extinction and the implications of this role to the pathophysiology of anxiety disorders.
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