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Potentially dangerous stimuli are important contenders for the capture of visual-spatial attention, and it has been suggested that an evolved fear module is preferentially activated by stimuli that are fear relevant in a phylogenetic sense (e.g., snakes, spiders, angry faces). In this study, a visual search task was used to test this hypothesis by directly contrasting phylogenetically (snakes) and ontogenetically (guns) fear-relevant stimuli. Results showed that the modern threat was detected as efficiently as the more ancient threat. Thus, both guns and snakes attracted attention more effectively than neutral stimuli (flowers, mushrooms, and toasters). These results support a threat superiority effect but not one that is preferentially accessed by threat-related stimuli of phylogenetic origin. The results are consistent with the view that faster detection of threat in visual search tasks may be more accurately characterized as relevance superiority effects rather than as threat superiority effects. Keywordsfear; threat detection; basic emotions; visual search; appraisalThe detection of threat-relevant stimuli is controlled by a complex network of neural structures that allow for the rapid perception of potential danger and support a variety of coping strategies such as fighting, freezing, or rapid escape (e.g., Armony & LeDoux, 2000;Calder, Lawrence, & Young, 2001;LeDoux, 1996). The amygdala is a crucial structure within this network and plays an important role in coordinating responses to threatening stimuli (Aggleton, 2000). One theoretical view is that the amygdala operates primarily as a rapid-response "fear module" in the brain that enables both the perception of fear in others and the experience of fear within the individual. Such an evolved fear module is assumed to have been shaped and constrained by evolutionary contingencies so that it is preferentially activated within aversive contexts by stimuli that are relevant in a phylogenetic sense (Öhman, 1993;Öhman & Mineka, 2001). This perspective is compatible with discrete emotions theories (e.g., Ekman, 1984;Tomkins, 1962), in which emotions are considered to be specific response patterns that are elicited most strongly by prototypical eliciting stimuli. Thus, biologically relevant stimuli related to threat would preferentially activate such a system with relatively little computational processing required (LeDoux, 1996). If this view is correct, the fear module should be activated more effectively by phylogenetic threats that are common to all mammals, such as snakes and reptiles.Copyright 2007 by the American Psychological Association Correspondence concerning this article should be addressed to Elaine Fox, Department of Psychology, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ United Kingdom. efox@essex.ac.uk. Several strands of evidence support this view. Specific phobias, for example, are more likely to develop in reaction to situations that posed a threat to the survival of our ancestors, (e.g., predators and heights) than to pote...

Around 30% of patients with schizophrenia show an inadequate response to antipsychotics-ie, treatment resistance. Neuroimaging studies can help to uncover the underlying neurobiological reasons for such resistance and identify these patients earlier. Additionally, studies examining the effect of clozapine on the brain can help to identify aspects of clozapine that make it uniquely effective in patients with treatment resistance. We did a systematic search of PubMed between Jan 1, 1980, and April 13, 2015, to identify all neuroimaging studies that examined treatment-resistant patients or longitudinally assessed the effects of clozapine treatment. We identified 330 articles, of which 61 met the inclusion criteria. Replicated differences between treatment-resistant and treatment-responsive patients include reductions in grey matter and perfusion of frontotemporal regions, and increases in white matter and basal ganglia perfusion, with effect sizes ranging from 0·4 to greater than 1. Clozapine treatment led to reductions in caudate nucleus volume in three separate studies. The available evidence supports the hypothesis that some of the neurobiological changes seen in treatment-resistant schizophrenia lie along a continuum with treatment-responsive schizophrenia, whereas other differences are categorical in nature and have potential to be used as biomarkers. However, further replication is needed, and for neuroimaging findings to be clinically translatable, future studies need to focus on a-priori hypotheses and be adequately powered.

We present an empirical Bayesian scheme for distributed multimodal inversion of electromagnetic forward models of EEG and MEG signals. We used a generative model with common source activity and separate error components for each modality. Under this scheme, the weightings of error for each modality, relative to source components, are estimated automatically from the data, by optimising the model-evidence. This obviates the need for arbitrary user-defined weightings. To evaluate the scheme, we acquired three types of data simultaneously from twelve participants: total magnetic flux (as recorded by 102 magnetometers), orthogonal in-plane gradients of the magnetic field (as recorded by 204 planar gradiometers) and voltage differences in the electrical field (recorded by 70 electrodes). We assessed the relative precision of each sensor-type in terms of signal-to-noise ratio (SNR); using empirical sample variances and optimised estimators from the generative model. We then compared the localisation of face-evoked responses, using each modality separately, with that obtained by their "fusion" under the common generative model. Finally, we quantified the conditional precisions of the source estimates using their posterior covariance, confirming that EEG can improve MEG-based source reconstructions.

Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.OBJECTIVE To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites. DATA SOURCESThe MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.STUDY SELECTION In total, 45 1H-MRS studies contributed data.DATA EXTRACTION AND SYNTHESIS Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor. Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL). MAIN OUTCOMES AND MEASURES RESULTSIn total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F 1,1211.9 = 4.311, P = .04) and Glx (F 1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F 1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F 1,1522.4 = 47.533, P < .001; cerebrospinal fluid-corrected Glu, F 1,1216.7 = 5.610, P = .02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, −0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.CONCLUSIONS AND RELEVANCE F...

Serotonin (5-HT) neurotransmission is implicated in cognitive and emotional processes and a number of neuropsychiatric disorders. The use of positron emission tomography (PET) to measure ligand displacement has allowed estimation of endogenous dopamine release in the human brain; however, applying this methodology to assess central 5-HT release has proved more challenging. The aim of this study was to assess the sensitivity of a highly selective 5-HT(1A) partial agonist radioligand [(11)C]CUMI-101 to changes in endogenous 5-HT levels induced by an intravenous challenge with the selective 5-HT re-uptake inhibitor (SSRI), citalopram, in healthy human participants. We studied 15 healthy participants who underwent PET scanning in conjunction with [(11)C]CUMI-101 after receiving an intravenous infusion of citalopram 10 mg or placebo in a double-blind, crossover, randomized design. Regional estimates of binding potential (BP(ND)) were obtained by calculating total volumes of distribution (V(T)) for presynaptic dorsal raphe nucleus (DRN) and postsynaptic cortical regions. Relative to placebo, citalopram infusion significantly increased [(11)C]CUMI-101 BP(ND) at postsynaptic 5-HT(1A) receptors in several cortical regions, but there was no change in binding at 5-HT(1A) autoreceptors in the DRN. Across the postsynaptic brain regions, citalopram treatment induced a mean 7% in [(11)C]CUMI-101 BP(ND) (placebo 1.3 (0.2); citalopram 1.4 (0.2); paired t-test P=0.003). The observed increase in postsynaptic [(11)C]CUMI-101 availability identified following acute citalopram administration could be attributable to a decrease in endogenous 5-HT availability in cortical terminal regions, consistent with preclinical animal studies, in which acute administration of SSRIs decreases DRN cell firing through activation of 5-HT(1A) autoreceptors to reduce 5-HT levels in postsynaptic regions. We conclude that [(11)C]CUMI-101 may be sensitive to changes in endogenous 5-HT release in humans.

Using a sandwich-masked priming paradigm with faces, we report two ERP effects that appear to reflect different levels of subliminal face processing. These two ERP repetition effects dissociate in their onset, scalp topography, and sensitivity to face familiarity. The “early” effect occurred between 100 and 150 ms, was maximally negative-going over lateral temporoparietal channels, and was found for both familiar and unfamiliar faces. The “late” effect occurred between 300 and 500 ms, was maximally positive-going over centroparietal channels, and was found only for familiar faces. The early effect resembled our previous fMRI data from the same paradigm; the late effect resembled the behavioural priming found, in the form of faster reaction times to make fame judgments about primed relative to unprimed familiar faces. None of the ERP or behavioural effects appeared explicable by a measure of participants’ ability to see the primes. The ERP and behavioural effects showed some sensitivity to whether the same or a different photograph of a face was repeated, but could remain reliable across different photographs, and did not appear attributable to a low-level measure of pixelwise overlap between prime and probe photograph. The functional significance of these ERP effects is discussed in relation to unconscious perception and face processing.

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