The un-predictive brain under threat: a neuro-computational account of anxious hypervigilance

Anxious hypervigilance is marked by sensitized sensory-perceptual processes and attentional biases to potential danger cues in the environment. How this is realized at the neurocomputational level is unknown but could clarify the brain mechanisms disrupted in psychiatric conditions such as posttraumatic stress disorder. Predictive coding, instantiated by dynamic causal models, provides a promising framework to ground these state-related changes in the dynamic interactions of reciprocally connected brain areas.Anxiety states were elicited in healthy participants (n\ua0= 19) by exposure to the threat of unpredictable, aversive shocks while undergoing magnetoencephalography. An auditory oddball sequence was presented to measure cortical responses related to deviance detection, and dynamic causal models quantified deviance-related changes in effective connectivity. Participants were also administered alprazolam (double-blinded, placebo-controlled crossover) to determine whether the cortical effects of threat-induced anxiety are reversed by acute anxiolytic treatment.Deviant tones elicited increased auditory cortical responses under threat. Bayesian analyses revealed that hypervigilant responding was best explained by increased postsynaptic gain in primary auditory cortex activity as well as modulation of feedforward, but not feedback, coupling within a temporofrontal cortical network. Increasing inhibitory gamma-aminobutyric acidergic action with alprazolam reduced anxiety and restored feedback modulation within the network.Threat-induced anxiety produced unbalanced feedforward signaling in response to deviations in predicable sensory input. Amplifying ascending sensory prediction error signals may optimize stimulus detection in the face of impending threats. At the same time, diminished descending sensory prediction signals impede perceptual learning and may, therefore, underpin some of the deleterious effects of anxiety on higher-order cognition

Contextual information resolves uncertainty about ambiguous facial emotions: Behavioral and magnetoencephalographic correlates

We are grateful to Karin Wilken for her assistance in data collection.Environmental conditions bias our perception of other peoples’ facial emotions. This becomes quite relevant in potentially threatening situations, when a fellow’s facial expression might indicate potential danger. The present study tested the prediction that a threatening environment biases the recognition of facial emotions. To this end, low- and medium-expressive happy and fearful faces (morphed to 10%, 20%, 30%, or 40% emotional) were presented within a context of instructed threat-of-shock or safety. Self-reported data revealed that instructed threat led to a biased recognition of fearful, but not happy facial expressions. Magnetoencephalographic correlates revealed spatio-temporal clusters of neural network activity associated with emotion recognition and contextual threat/safety in early to mid-latency time intervals in the left parietal cortex, bilateral prefrontal cortex, and the left temporal pole regions. Early parietal activity revealed a double dissociation of face–context information as a function of the expressive level of facial emotions: When facial expressions were difficult to recognize (lowexpressive), contextual threat enhanced fear processing and contextual safety enhanced processing of subtle happy faces. However, for rather easily recognizable faces (medium-expressive) the left hemisphere (parietal cortex, PFC, and temporal pole) showed enhanced activity to happy faces during contextual threat and fearful faces during safety. Thus, contextual settings reduce the salience threshold and boost early face processing of lowexpressive congruent facial emotions, whereas face-context incongruity or mismatch effects drive neural activity of easier recognizable facial emotions. These results elucidate how environmental settings help recognize facial emotions, and the brain mechanisms underlying the recognition of subtle nuances of fear.German Research Foundation (DFG) BU 3255/1-1 Ju2/024/15 SF58C0

Clinical anxiety promotes excessive response inhibition

BACKGROUND: Laboratory tasks to delineate anxiety disorder features are used to refine classification and inform our understanding of etiological mechanisms. The present study examines laboratory measures of response inhibition, specifically the inhibition of a pre-potent motor response, in clinical anxiety. Data on associations between anxiety and response inhibition remain inconsistent, perhaps because of dissociable effects of clinical anxiety and experimentally manipulated state anxiety. Few studies directly assess the independent and interacting effects of these two anxiety types (state v. disorder) on response inhibition. The current study accomplished this goal, by manipulating state anxiety in healthy and clinically anxious individuals while they complete a response inhibition task. METHOD: The study employs the threat-of-shock paradigm, one of the best-established manipulations for robustly increasing state anxiety. Participants included 82 adults (41 healthy; 41 patients with an anxiety disorder). A go/nogo task with highly frequent go trials was administered during alternating periods of safety and shock threat. Signal detection theory was used to quantify response bias and signal-detection sensitivity. RESULTS: There were independent effects of anxiety and clinical anxiety on response inhibition. In both groups, heightened anxiety facilitated response inhibition, leading to reduced nogo commission errors. Compared with the healthy group, clinical anxiety was associated with excessive response inhibition and increased go omission errors in both the safe and threat conditions. CONCLUSIONS: Response inhibition and its impact on go omission errors appear to be a promising behavioral marker of clinical anxiety. These results have implications for a dimensional view of clinical anxiety

Effect of attention control on sustained attention during induced anxiety

Anxiety has wide-reaching and complex effects on cognitive performance. Although it can intrude on cognition and interfere with performance, it can also facilitate information processing and behavioural responses. In a previous study, we showed that anxiety induced by threat of shock facilitates performance on the Sustained Attention to Response Task, a vigilance test, which probes response inhibition to infrequent nogo stimuli. The present study sought to identify factors that may have contributed to such improved performance, including on- and off-task thinking (assessed with thought probes) and individual differences in attention control, as measured with the Attention Control Scale. Replicating our prior finding, we showed that shock threat significantly reduced errors of commission on the nogo trials. However, we extended this finding in demonstrating that this effect was driven by subjects with low attention control. We therefore confirm that anxiety increases inhibitory control of prepotent responses-a mechanism which is adaptive under threat-and show that this effect is greater in those who rely more upon such prepotent responding, i.e., those with low attentional control

Attentional modulations of pain perception: evidence from laser evoked potentials

This thesis aims to provide a contribution to the current neurophysiological and psychophysiological understanding of nociception and pain processing in humans. The introduction of high-power, radiant heat stimulators (lasers) in sensory physiology has revolutionised the study of the nociceptive system. Laser pulses activate Aδ and/or C skin nociceptors selectively, i.e. without coactivating deeper, tactile mechanoreceptors, and elicit brain responses that can be detected using electroencephalography, and are called laser-evoked potentials (LEP). This was the technique applied in the two experimental studies reported in the present thesis work. The doctoral dissertation is organized in five chapters. Chapter 1 – Introduction - defines the concepts of nociception and pain. It also provides an introduction to the event related potential technique (ERP), a description of basic biophysics and neurophysiology related to LEP recording, followed by a literature review of its related cortical generators. In addition, the Chapter attempts to draw an elementary parallel between LEPs and other EPs elicited by stimuli belonging to other sensory modalities. Chapter 2 – Determinants of vertex potentials – describes the determinants of neural processes of pain perception and support their interpretation through a neurocognitive model of attention. The mechanism of attention allows allocating resources for selection and integration of this process with working memory requirements. More in detail, cognitive science suggested that the attention mechanism can be divided into two categories: stimulus-driven (or ‘bottom-up’) and goal-directed (or ‘top-down’). ‘Top-down’ and ‘bottom-up’ are treated as key interpretative categories to explain the findings reported in this thesis. Infact, they are metaphors which are used to represent information processing in a hierarchical fashion, where lower levels of processing would rely on the physical features of the stimulus while higher levels would involve comparisons with information stored in memory, selection of relevant information in competition and response to the stimulus. A review of selected literature in the field or ERP studies of sensory processing is provided and interpreted within this framework. The thesis aims to contribute to the understanding of both ‘bottom-up’ and ‘top-down’ mechanisms of attention during nociceptive processing, with two distinct experiments. Chapter 3 – Contribution to the analysis of ‘bottom-up features: “Dishabituation of laser-evoked EEG responses: dissecting the effect of certain and uncertain changes in stimulus modality” - presents a study where the hypothesis that a change of modality (from auditory to nociceptive and vicerversa, rather than no change at all) can significantly modulate brain responses (no matter the subjects expectation of this change) has been tested. The results of this study bring support for a determinant role of saliency (here modulated by the novelty introduced by a change in the stimulus modality) in affecting brain responses to the sensory input. Chapter 4 - Hypnotic modulation of sensory and affective dimensions of pain: a top-down signature on pain experience - introduces a study where hypnotic suggestions were used to draw subject’s attention either on intensity or on unpleasantness of pain perception. Thus, the study aimed to investigate whether this manipulation could induce a dissociation between this two measure of subjective experience and whether LEP could reflect the role of focused attention and expectation in indexing changes of subjective feeling. The results are discussed according to previous literature and to a neurocognitive model of pain processing as observed during an altered state of consciousness known to heighten the fronto-parietal network of sustained attention. In Chapter 5 - General discussion - the findings related to these two different research lines are integrated and discussed considering the existing theoretical accounts. The critical assumption is that the understanding of pain processing would largely benefit from the application of an attention-driven interpretative framework within which can be included different theoretical-epistemological views concerning (II) the Bayesian inference in perception, (III) the motivational account of pain monitoring and control, (IV) the neuroanatomy of homeostatic feeling of body integrity and self-regulation. As conclusive remark, the work presented in this thesis wish to highlight the importance of a renewed concept of ‘pain matrix’, based on its function of potential threat detector and action planner, in order to preserve the integrity of the body. In addition, the interpretation of pain as homeostatic-motivational force naturally carries us to consider the ‘pain matrix’ not as a sensory-specific cortical network but rather as an action-specific network, representing the activity by which the individual identifies and responds purposefully to a sudden, potential threat inside or outside of the body

Trait and State Anxiety Effects on Mismatch Negativity and Sensory Gating Event-Related Potentials

We used the auditory roving oddball to investigate whether individual differences in self-reported anxiety influence event-related potential (ERP) activity related to sensory gating and mismatch negativity (MMN). The state-trait anxiety inventory (STAI) was used to assess the effects of anxiety on the ERPs for auditory change detection and information filtering in a sample of thirty-six healthy participants. The roving oddball paradigm involves presentation of stimulus trains of auditory tones with certain frequencies followed by trains of tones with different frequencies. Enhanced negative mid-latency response (130–230 ms post-stimulus) was marked at the deviant (first tone) and the standard (six or more repetitions) tone at Fz, indicating successful mismatch negativity (MMN). In turn, the first and second tone in a stimulus train were subject to sensory gating at the Cz electrode site as a response to the second stimulus was suppressed at an earlier latency (40–80 ms). We used partial correlations and analyses of covariance to investigate the influence of state and trait anxiety on these two processes. Higher trait anxiety exhibited enhanced MMN amplitude (more negative) (F(1,33) = 14.259, p = 6.323 × 10−6, ηp2 = 0.302), whereas state anxiety reduced sensory gating (F(1,30) = 13.117, p = 0.001, ηp2 = 0.304). Our findings suggest that high trait-anxious participants demonstrate hypervigilant change detection to deviant tones that appear more salient, whereas increased state anxiety associates with failure to filter out irrelevant stimuli

Prefrontal inhibition of threat processing reduces working memory interference

Bottom-up processes can interrupt ongoing cognitive processing in order to adaptively respond to emotional stimuli of high potential significance, such as those that threaten wellbeing. However it is vital that this interference can be modulated in certain contexts to focus on current tasks. Deficits in the ability to maintain the appropriate balance between cognitive and emotional demands can severely impact on day-to-day activities. This fMRI study examined this interaction between threat processing and cognition; 18 adult participants performed a visuospatial working memory (WM) task with two load conditions, in the presence and absence of anxiety induction by threat of electric shock. Threat of shock interfered with performance in the low cognitive load condition; however interference was eradicated under high load, consistent with engagement of emotion regulation mechanisms. Under low load the amygdala showed significant activation to threat of shock that was modulated by high cognitive load. A directed top-down control contrast identified two regions associated with top-down control; ventrolateral PFC and dorsal ACC. Dynamic causal modeling provided further evidence that under high cognitive load, top-down inhibition is exerted on the amygdala and its outputs to prefrontal regions. Additionally, we hypothesized that individual differences in a separate, non-emotional top-down control task would predict the recruitment of dorsal ACC and ventrolateral PFC during top-down control of threat. Consistent with this, performance on a separate dichotic listening task predicted dorsal ACC and ventrolateral PFC activation during high WM load under threat of shock, though activation in these regions did not directly correlate with WM performance. Together, the findings suggest that under high cognitive load and threat, top-down control is exerted by dACC and vlPFC to inhibit threat processing, thus enabling WM performance without threat-related interference

Interactions between appetitive and aversive processing in the human brain

The brain mechanisms underlying anxiety/stress and motivation have been investigated extensively. However, they were mainly investigated independently of each other. Even though some studies discussed interactions between these two mechanisms, our understanding of the interaction between anxiety/stress and motivation is still limited. Motivation can be divided into two aspects. One is appetitive motivation to win appetitive outcome, and the other is aversive motivation for avoiding aversive outcome. Accordingly, in current functional MRI study, it was investigated how appetitive/aversive motivational processing would be influenced by anxiety/stress. In the first experiment I investigated interactions between threat and reward processing during anticipation of electric shock and monetary reward. Analysis of skin conductance data during a delay phase revealed competitive interaction between threat and reward processing. Analysis of imaging data during a delay phase also revealed the interaction effect in several regions, including midbrain/ventral tegmental area, caudate, putamen, bed nucleus of the stria terminalis, anterior insula, middle frontal gyrus, and dorsal anterior cingulate cortex. In the second experiment, the interaction between threat and reward/punishment processing was investigated. Analysis of imaging data during a delay phase revealed competitive interaction between threat and reward processing in left caudate. However, responses in the same site did show interaction between threat and punishment processing. Taken together, the findings in two studies suggest competitive processes of threat and reward, and independent processes of threat and punishment

Negative affect impairs associative memory but not item memory.

The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine the effects of emotion on memory for items and their associations. By presenting neutral and negative items with background contexts, Experiment 1 demonstrated that item memory was facilitated by emotional affect, whereas memory for an associated context was reduced. In Experiment 2, arousal was manipulated independently of the memoranda, by a threat of shock, whereby encoding trials occurred under conditions of threat or safety. Memory for context was equally impaired by the presence of negative affect, whether induced by threat of shock or a negative item, relative to retrieval of the context of a neutral item in safety. In Experiment 3, participants were presented with neutral and negative items as paired associates, including all combinations of neutral and negative items. The results showed both above effects: compared to a neutral item, memory for the associate of a negative item (a second item here, context in Experiments 1 and 2) is impaired, whereas retrieval of the item itself is enhanced. Our findings suggest that negative affect impairs associative memory while recognition of a negative item is enhanced. They support dual-processing models in which negative affect or stress impairs hippocampal-dependent associative memory while the storage of negative sensory/perceptual representations is spared or even strengthened