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Temporal dynamics play a central role in models of emotion: "fear" is widely conceptualized as a phasic response to certain-and-imminent danger, whereas "anxiety" is a sustained response to uncertain-or-distal harm. Yet the underlying human neurobiology remains contentious. Leveraging an ethnoracially diverse sample, translationally relevant paradigm, and theory-driven modeling approach, we demonstrate that certain and uncertain threat recruit a shared threat-anticipation circuit. This cortico-subcortical circuit exhibits persistently elevated activation when anticipating uncertain-threat encounters and a transient burst of activation in the moments before certain encounters. For many scientists and clinicians, feelings are the defining feature of human fear and anxiety. Here we used an independently validated brain signature to covertly decode the momentary dynamics of anticipatory distress for the first time. Results mirrored the dynamics of neural activation. These observations provide fresh insights into the neurobiology of threat-elicited emotions and set the stage for more ambitious clinical and mechanistic research.
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BACKGROUND: Anxiety is a sustained response to uncertain threats; yet few studies have explored sustained neurobiological activities underlying anxious states, particularly spontaneous neural oscillations. To address this gap, we reanalysed magnetoencephalographic (MEG) data recorded during induced anxiety to identify differences in sustained oscillatory activity between high- and low-anxiety states. METHODS: We combined data from three previous MEG studies in which healthy adults (total N = 51) were exposed to alternating periods of threat of unpredictable shock and safety while performing a range of cognitive tasks (passive oddball, mixed-saccade or stop-signal tasks). Spontaneous, band-limited, oscillatory activity was extracted from middle and late intervals of the threat and safe periods, and regional power distributions were reconstructed with adaptive beamforming. Conjunction analyses were used to identify regions showing overlapping spectral power differences between threat and safe periods across the three task paradigms. RESULTS: MEG source analyses revealed a robust and widespread reduction in beta (14-30 Hz) power during threat periods in bilateral sensorimotor cortices extending into right prefrontal regions. Alpha (8-13 Hz) power reductions during threat were more circumscribed, with notable peaks in left intraparietal sulcus and thalamus. CONCLUSIONS: Threat-induced anxiety is underpinned by a sustained reduction in spontaneous beta- and alpha-band activity in sensorimotor and parietal cortical regions. This general oscillatory pattern likely reflects a state of heightened action readiness and vigilance to cope with uncertain threats. Our findings provide a critical reference for which to identify abnormalities in cortical oscillatory activities in clinically anxious patients as well as evaluating the efficacy of anxiolytic treatments.
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Ansiedad , Magnetoencefalografía , Adulto , Humanos , Corteza Prefrontal , Trastornos de Ansiedad , Lóbulo ParietalRESUMEN
While it has been argued that impulsivity and inhibition are unrelated, previous evidence suggests that the relationship between the two can only be seen when their characteristics are closely matched. The negative urgency subscale of the UPPS-P describes impulsive action during negative affect. This was predicted to correlate more strongly with stop-signal reaction-time (SSRT) during threatening conditions than non-threatening conditions. Healthy participants (N = 68) completed the stop-signal task in threatening (induced by threat-of-shock) and non-threatening conditions after completing the UPPS-P and Spielberg State Trait Anxiety Inventory (STAI) scales. Negative urgency correlated with the difference in SSRT (threat - safe) after controlling for other variables. Conversely, similar correlations were not observed for positive urgency, suggesting threat increases the poorer inhibition seen in those high on negative urgency but not for those high on positive urgency. Additionally, sensation seeking correlated with the difference in SSRT (threat - safe) in the opposite direction, suggesting sensation seeking was related to a reduction in the effect of threat. The findings suggest the relationship between negative urgency and inhibition is facilitated by threatening conditions and that high sensation seekers experience threatening stimuli differently.
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Conducta Impulsiva , Inhibición Psicológica , Humanos , Conducta Impulsiva/fisiología , Tiempo de ReacciónRESUMEN
Anxiety heightens vigilance and stimulus-driven attention to the environment, which may in turn disrupt cognitive control processes such as response inhibition. How this unfolds at the neural level is unclear. Previous evidence implicates the right inferior frontal gyrus (IFG) as an important cortical node in both stimulus-driven attention and inhibitory control. Here we used magnetoencephalography (MEG) to investigate the neural mechanisms involved in the relationship between threat-induced anxiety and stopping during a stop-signal task, where a visual go signal was occasionally followed by an auditory stop signal. Healthy individuals (N = 18) performed the task during the threat of unpredictable shocks and safety to modulate anxious arousal. Behaviorally, we observed that stopping was impaired during threat (i.e. slower estimated stop-signal reaction times), indicating that anxious arousal weakens inhibitory control. MEG source analyses revealed that bilateral IFG and right dorsal prefrontal cortex showed increased beta-band activity (14-30 Hz) to the stop signal that varied as a function of successful stopping during nonanxious (safe) conditions only. Moreover, peak beta-band responses from right IFG were inversely correlated with stopping efficiency during nonanxious conditions. These findings support theoretical claims that beta oscillations function to maintain the current sensorimotor state, and that the lack of differential beta-band activity in prefrontal cortices underlies anxiety-related deficits in inhibitory control. We specifically argue that altered right IFG functioning might directly link impaired cognitive control to heightened stimulus-driven responding in anxiety states.
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Inhibición Psicológica , Imagen por Resonancia Magnética , Ansiedad , Nivel de Alerta/fisiología , Humanos , Corteza Prefrontal/fisiologíaRESUMEN
Hippocampal rhythms are important for spatial navigation. This study examined whether gender differences in human navigation performance are associated with differences in hippocampal rhythms. We measured brain activities in males and females with whole-head magnetoencephalography (MEG), while they performed a virtual Morris water maze task. Behavioural results showed clear gender differences: males were significantly faster than females; unlike males, females did not show improved navigation performance in a familiar vs. new environment. MEG results showed that the magnitudes of right hippocampal/parahippocampal theta rhythm were similar between the two groups during navigation in a new environment; however, unlike males who exhibited a significant decrease in right hippocampal/parahippocampal theta power in the familiar environment shown before, females showed no change. This result may suggest faster environmental learning in males vs. females. After navigating in the new environment during the inter-trial (ITI) rest periods, males showed significantly higher right hippocampal/parahippocampal high-gamma power than females, suggesting greater consolidation in males. Moreover, right hippocampal/parahippocampal theta power during navigation correlated with navigation performance in both genders; high-gamma power during the ITI was correlated with navigation performance only in males. These associations may provide further support for the functional importance of theta and high-gamma rhythms in navigation. Overall, this study provides new insights into the neurophysiological mechanisms underlying gender differences in spatial navigation.
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Ritmo Gamma/fisiología , Navegación Espacial/fisiología , Ritmo Teta/fisiología , Adulto , Encéfalo/fisiología , Femenino , Hipocampo/fisiología , Humanos , Magnetoencefalografía/métodos , Masculino , Giro Parahipocampal/fisiología , Caracteres Sexuales , Factores SexualesRESUMEN
The hippocampus features structurally and functionally distinct anterior and posterior segments. Relatively few studies have examined how these change during aging or in response to pharmacological interventions. Alterations in hippocampal connectivity and changes in glucose regulation have each been associated with cognitive decline in aging. A distinct line of research suggests that administration of glucose can lead to a transient improvement in hippocampus-dependent memory. Here, we probe age, glucose and human cognition with a special emphasis on resting-state functional connectivity (rsFC) of the hippocampus along its longitudinal axis to the rest of the brain. Using a randomized, placebo-controlled, double-blind, crossover design 32 healthy adults (16 young and 16 older) ingested a drink containing 25 g glucose or placebo across two counter balanced sessions. They then underwent resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive testing. There was a clear dissociation in the effects of glucose by age. Magnitude change in rsFC from posterior hippocampus (pHPC) to medial frontal cortex (mPFC) was correlated with individual glucose regulation and gains in performance on a spatial navigation task. Our results demonstrate that glucose administration can attenuate cognitive performance deficits in older adults with impaired glucose regulation and suggest that increases in pHPC-mPFC rsFC are beneficial for navigation task performance in older participants.
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Growing evidence indicates that anxiety impairs cognitive control processes, including inhibitory functioning. However, there are reports of anxiety state-related improvements in response inhibition performance in a go/nogo (GNG) task. Here we employed the stop-signal task (SST) to examine in complementary fashion the link between anticipatory anxiety and inhibitory control. Participants (N = 45) completed the SST under threat of unpredictable shocks and safe conditions while physiological activity (skin conductance and heart rate) was monitored. In addition to increased physiological activity, we found that stop-signal reaction time (SSRT), a robust measure of stopping efficiency, was prolonged during threat compared to safe without any difference in choice reaction times to go stimuli. This finding supports the claim of impaired inhibitory control in anxiety, and by consideration of differences between the SST and GNG tasks, can be reconciled with evidence of improved response inhibition on the latter under similar threat conditions.
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Ansiedad/fisiopatología , Ansiedad/psicología , Inhibición Psicológica , Tiempo de Reacción/fisiología , Análisis y Desempeño de Tareas , Adulto , Cognición , Femenino , Respuesta Galvánica de la Piel/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Adulto JovenRESUMEN
Hippocampal rhythms are believed to support crucial cognitive processes including memory, navigation, and language. Due to the location of the hippocampus deep in the brain, studying hippocampal rhythms using non-invasive magnetoencephalography (MEG) recordings has generally been assumed to be methodologically challenging. However, with the advent of whole-head MEG systems in the 1990s and development of advanced source localization techniques, simulation and empirical studies have provided evidence that human hippocampal signals can be sensed by MEG and reliably reconstructed by source localization algorithms. This paper systematically reviews simulation studies and empirical evidence of the current capacities and limitations of MEG "deep source imaging" of the human hippocampus. Overall, these studies confirm that MEG provides a unique avenue to investigate human hippocampal rhythms in cognition, and can bridge the gap between animal studies and human hippocampal research, as well as elucidate the functional role and the behavioral correlates of human hippocampal oscillations.
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In rodents, hippocampal cell assemblies formed during learning of a navigation task are observed to re-emerge during resting (offline) periods, accompanied by high-frequency oscillations (HFOs). This phenomenon is believed to reflect mechanisms for strengthening newly-formed memory traces. Using magnetoencephalography recordings and a beamforming source location algorithm (synthetic aperture magnetometry), we investigated high-gamma (80-140â¯Hz) oscillations in the hippocampal region in 18 human participants during inter-trial rest periods in a virtual navigation task. We found right hippocampal gamma oscillations mirrored the pattern of theta power in the same region during navigation, varying as a function of environmental novelty. Gamma power during inter-trial rest periods was positively correlated with theta power during navigation in the first task set when the environment was new and predicted greater performance improvement in the subsequent task set two where the environment became familiar. These findings provide evidence for human hippocampal reactivation accompanied by high-gamma activities immediately after learning and establish a link between hippocampal high-gamma activities and subsequent memory performance.
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Ritmo Gamma/fisiología , Hipocampo/fisiología , Magnetoencefalografía/métodos , Aprendizaje por Laberinto/fisiología , Consolidación de la Memoria/fisiología , Giro Parahipocampal/fisiología , Navegación Espacial/fisiología , Adolescente , Adulto , Humanos , Masculino , Descanso , Ritmo Teta , Realidad Virtual , Adulto JovenRESUMEN
BACKGROUND: 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. METHODS: Anxiety states were elicited in healthy participants (n = 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. RESULTS: 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. CONCLUSIONS: 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.
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Ansiedad/fisiopatología , Percepción Auditiva/fisiología , Encéfalo/fisiopatología , Miedo/fisiología , Adulto , Alprazolam/farmacología , Ansiolíticos/farmacología , Ansiedad/tratamiento farmacológico , Percepción Auditiva/efectos de los fármacos , Teorema de Bayes , Encéfalo/efectos de los fármacos , Miedo/efectos de los fármacos , Femenino , Moduladores del GABA/farmacología , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía , Masculino , Modelos Neurológicos , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Procesamiento de Señales Asistido por Computador , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Low frequency theta band oscillations (4-8 Hz) are thought to provide a timing mechanism for hippocampal place cell firing and to mediate the formation of spatial memory. In rodents, hippocampal theta has been shown to play an important role in encoding a new environment during spatial navigation, but a similar functional role of hippocampal theta in humans has not been firmly established. To investigate this question, we recorded healthy participants' brain responses with a 160-channel whole-head MEG system as they performed two training sets of a virtual Morris water maze task. Environment layouts (except for platform locations) of the two sets were kept constant to measure theta activity during spatial learning in new and familiar environments. In line with previous findings, left hippocampal/parahippocampal theta showed more activation navigating to a hidden platform relative to random swimming. Consistent with our hypothesis, right hippocampal/parahippocampal theta was stronger during the first training set compared to the second one. Notably, theta in this region during the first training set correlated with spatial navigation performance across individuals in both training sets. These results strongly argue for the functional importance of right hippocampal theta in initial encoding of configural properties of an environment during spatial navigation. Our findings provide important evidence that right hippocampal/parahippocampal theta activity is associated with environmental encoding in the human brain. Hum Brain Mapp 38:1347-1361, 2017. © 2016 Wiley Periodicals, Inc.
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Ambiente , Lateralidad Funcional/fisiología , Hipocampo/fisiología , Giro Parahipocampal/fisiología , Navegación Espacial/fisiología , Ritmo Teta/fisiología , Adolescente , Adulto , Análisis de Varianza , Mapeo Encefálico , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía , Masculino , Aprendizaje por Laberinto/fisiología , Factores de Tiempo , Interfaz Usuario-Computador , Adulto JovenRESUMEN
Although the monoamine oxidase-A (MAOA) gene has been linked to spatial learning and memory in animal models, convincing evidence in humans is lacking. Performance on an ecologically-valid, virtual computer-based equivalent of the Morris Water Maze task was compared between 28 healthy males with the low MAOA transcriptional activity and 41 healthy age- and IQ-matched males with the high MAOA transcriptional activity. The results revealed consistently better performance (reduced heading error, shorter path length, and reduced failed trials) for the high MAOA activity individuals relative to the low activity individuals. By comparison, groups did not differ on pre-task variables or strategic measures such as first-move latency. The results provide novel evidence of MAOA gene involvement in human spatial navigation using a virtual analogue of the Morris Water Maze task.
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Aprendizaje por Laberinto/fisiología , Monoaminooxidasa/genética , Monoaminooxidasa/metabolismo , Navegación Espacial/fisiología , Adolescente , Genotipo , Técnicas de Genotipaje , Humanos , Masculino , Análisis y Desempeño de Tareas , Transcripción Genética , Interfaz Usuario-Computador , Adulto JovenRESUMEN
Anxiety disorders constitute a sizeable worldwide health burden with profound social and economic consequences. The symptoms are wide-ranging; from hyperarousal to difficulties with concentrating. This latter effect falls under the broad category of altered cognitive performance which is the focus of this review. Specifically, we examine the interaction between anxiety and cognition focusing on the translational threat of unpredictable shock paradigm; a method previously used to characterize emotional responses and defensive mechanisms that is now emerging as valuable tool for examining the interaction between anxiety and cognition. In particular, we compare the impact of threat of shock on cognition in humans to that of pathological anxiety disorders. We highlight that both threat of shock and anxiety disorders promote mechanisms associated with harm avoidance across multiple levels of cognition (from perception to attention to learning and executive function)-a "hot" cognitive function which can be both adaptive and maladaptive depending upon the circumstances. This mechanism comes at a cost to other functions such as working memory, but leaves some functions, such as planning, unperturbed. We also highlight a number of cognitive effects that differ across anxiety disorders and threat of shock. These discrepant effects are largely seen in "cold" cognitive functions involving control mechanisms and may reveal boundaries between adaptive (e.g., response to threat) and maladaptive (e.g., pathological) anxiety. We conclude by raising a number of unresolved questions regarding the role of anxiety in cognition that may provide fruitful avenues for future research.
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Anxiety can be distracting, disruptive, and incapacitating. Despite problems with empirical replication of this phenomenon, one fruitful avenue of study has emerged from working memory (WM) experiments where a translational method of anxiety induction (risk of shock) has been shown to disrupt spatial and verbal WM performance. Performance declines when resources (e.g., spatial attention, executive function) devoted to goal-directed behaviors are consumed by anxiety. Importantly, it has been shown that anxiety-related impairments in verbal WM depend on task difficulty, suggesting that cognitive load may be an important consideration in the interaction between anxiety and cognition. Here we use both spatial and verbal WM paradigms to probe the effect of cognitive load on anxiety-induced WM impairment across task modality. Subjects performed a series of spatial and verbal n-back tasks of increasing difficulty (1, 2, and 3-back) while they were safe or at risk for shock. Startle reflex was used to probe anxiety. Results demonstrate that induced-anxiety differentially impacts verbal and spatial WM, such that low and medium-load verbal WM is more susceptible to anxiety-related disruption relative to high-load, and spatial WM is disrupted regardless of task difficulty. Anxiety impacts both verbal and spatial processes, as described by correlations between anxiety and performance impairment, albeit the effect on spatial WM is consistent across load. Demanding WM tasks may exert top-down control over higher-order cortical resources engaged by anxious apprehension, however high-load spatial WM may continue to experience additional competition from anxiety-related changes in spatial attention, resulting in impaired performance. By describing this disruption across task modalities, these findings inform current theories of emotion-cognition interactions and may facilitate development of clinical interventions that seek to target cognitive impairments associated with anxiety.
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Conventional wisdom dictates we must face our fears to conquer them. This idea is embodied in exposure-based treatments for anxiety disorders, where the intent of exposure is to reverse a history of avoidant behavior that is thought to fuel a patient's irrational fears. We tested in humans the relationship between fear and avoidance by combining Pavlovian differential fear conditioning with a novel task for quantifying spontaneous passive avoidant behavior. During self-guided navigation in virtual reality following de novo fear conditioning, we observed participants keeping their distance from the feared object. At the individual level, passive avoidant behavior was highly associated with maladaptive fear expression (fear-potentiated startle) during late extinction training, indicating that extinction learning was impaired following a brief episode of avoidance. Avoidant behavior, however, was not related to initial acquired fear, raising doubt about a straightforward link between physiological fear and behavioral avoidance. We conclude that a deeper understanding of what motivates avoidance may offer a target for early intervention, before fears transition from the rational to the irrational.
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Reacción de Prevención/fisiología , Extinción Psicológica/fisiología , Miedo/psicología , Adulto , Análisis de Varianza , Concienciación/fisiología , Condicionamiento Clásico , Interpretación Estadística de Datos , Discriminación en Psicología/fisiología , Electromiografía , Femenino , Humanos , Masculino , Músculos Oculomotores/fisiología , Orientación , Reflejo de Sobresalto , Análisis de Regresión , Interfaz Usuario-Computador , Adulto JovenRESUMEN
BACKGROUND: Clinical evidence that ketamine, a nonselective N-methyl-D-aspartate receptor (NMDAR) antagonist, has therapeutic effects within hours in people suffering from depression suggests that modulating glutamatergic neurotransmission is a fundamental step in alleviating the debilitating symptoms of mood disorders. Acutely, ketamine increases extracellular glutamate levels, neuronal excitability, and spontaneous γ oscillations, but it is unknown whether these effects are key to the mechanism of antidepressant action of ketamine. METHODS: Twenty drug-free major depressive disorder patients received a single, open-label intravenous infusion of ketamine hydrochloride (.5 mg/kg). Magnetoencephalographic recordings were made approximately 3 days before and approximately 6.5 hours after the infusion, whereas patients passively received tactile stimulation to the right and left index fingers and also while they rested (eyes-closed). Antidepressant response was assessed by percentage change in Montgomery-Åsberg Depression Rating Scale scores. RESULTS: Patients with robust improvements in depressive symptoms 230 min after infusion (responders) exhibited increased cortical excitability within this antidepressant response window. Specifically, we found that stimulus-evoked somatosensory cortical responses increase after infusion, relative to pretreatment responses in responders but not in treatment nonresponders. Spontaneous somatosensory cortical γ-band activity during rest did not change within the same timeframe after ketamine in either responders or nonresponders. CONCLUSIONS: These findings suggest NMDAR antagonism does not lead directly to increased cortical excitability hours later and thus might not be sufficient for therapeutic effects of ketamine to take hold. Rather, increased cortical excitability as depressive symptoms improve is consistent with the hypothesis that enhanced non-NMDAR-mediated glutamatergic neurotransmission via synaptic potentiation is central to the antidepressant effect of ketamine.
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Antidepresivos/administración & dosificación , Corteza Cerebral/efectos de los fármacos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/patología , Ketamina/administración & dosificación , Potenciales Sinápticos/efectos de los fármacos , Adulto , Análisis de Varianza , Antidepresivos/sangre , Antidepresivos/farmacología , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/patología , Estimulación Eléctrica , Femenino , Dedos/inervación , Lateralidad Funcional , Humanos , Ketamina/análogos & derivados , Ketamina/sangre , Ketamina/farmacología , Magnetoencefalografía , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Tiempo de Reacción/efectos de los fármacos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Current views of the hippocampus assign this structure, and its prominent theta rhythms, a key role in both cognition and affect. We studied this duality of function in humans, where no direct evidence exists. Whole-head magnetoencephalographic (MEG) data were recorded to measure theta activity while healthy participants (N = 25) navigated two virtual Morris water mazes, one in which they risked receiving aversive shocks without warning to induce anxiety and one in which they were safe from shocks. Results showed that threat of shock elevated anxiety level and enhanced navigation performance as compared to the safe condition. MEG source analyses revealed that improved navigation performance during threat was preferentially associated with increased left septal (posterior) hippocampal theta (specifically 4-8 Hz activity), replicating previous research that emphasizes a predominant role of the septal third of the hippocampus in spatial cognition. Moreover, increased self-reported anxiety during threat was preferentially associated with increased left temporal (anterior) hippocampal theta (specifically 2-6 Hz activity), consistent with this region's involvement in mediating conditioned and innate fear. Supporting contemporary theory, these findings highlight simultaneous involvement of the human hippocampus in spatial cognition and anxiety, and clarify their distinct correlates.
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Ansiedad/fisiopatología , Cognición/fisiología , Hipocampo/fisiología , Ritmo Teta/fisiología , Adulto , Afecto/fisiología , Algoritmos , Femenino , Hipocampo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía , Masculino , Aprendizaje por Laberinto/fisiología , Modelos Neurológicos , Modelos Psicológicos , Análisis de Regresión , Análisis y Desempeño de Tareas , Interfaz Usuario-Computador , Adulto JovenRESUMEN
Anxiety is typically considered an impediment to cognition. We propose anxiety-related impairments in cognitive-behavioral performance are the consequences of enhanced stimulus-driven attention. Accordingly, reflexive, habitual behaviors that rely on stimulus-driven mechanisms should be facilitated in an anxious state, while novel, flexible behaviors that compete with the former should be impaired. To test these predictions, healthy adults (N=17) performed a mixed-saccade task, which pits habitual actions (pro-saccades) against atypical ones (anti-saccades), under anxiety-inducing threat of shock and safe conditions. Whole-head magnetoencephalography (MEG) captured oscillatory responses in the preparatory interval preceding target onset and saccade execution. Results showed threat-induced anxiety differentially impacted response times based on the type of saccade initiated, slowing anti-saccades but facilitating erroneous pro-saccades on anti-saccade trials. MEG source analyses revealed that successful suppression of reflexive pro-saccades and correct initiation of anti-saccades during threat was marked by increased theta power in right ventrolateral prefrontal cortical and midbrain regions (superior colliculi) implicated in stimulus-driven attention. Theta activity may delay stimulus-driven processes to enable generation of an anti-saccade. Moreover, compared to safety, threat reduced beta desynchronization in inferior parietal cortices during anti-saccade preparation but increased it during pro-saccade preparation. Differential effects in inferior parietal cortices indicate a greater readiness to execute anti-saccades during safety and to execute pro-saccades during threat. These findings suggest that, in an anxiety state, reduced cognitive-behavioral flexibility may stem from enhanced stimulus-driven attention, which may serve the adaptive function of optimizing threat detection.
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Ansiedad/fisiopatología , Atención/fisiología , Encéfalo/fisiopatología , Cognición/fisiología , Movimientos Sacádicos/fisiología , Adulto , Ansiedad/psicología , Nivel de Alerta/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía , Masculino , Pruebas Neuropsicológicas , Tiempo de Reacción/fisiologíaRESUMEN
Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyper-arousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8-17. Magnetoencephalography (MEG) examined neuronal activity (4-50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability.
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Afecto , Trastorno Bipolar/fisiopatología , Trastorno Bipolar/psicología , Retroalimentación Psicológica , Magnetoencefalografía , Vías Nerviosas/fisiopatología , Adolescente , Mapeo Encefálico/métodos , Niño , Femenino , Lóbulo Frontal/fisiopatología , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Pruebas Neuropsicológicas , Tiempo de Reacción , Índice de Severidad de la EnfermedadRESUMEN
Amygdala reactivity to threat-related distractor stimuli can be abolished in perceptually demanding contexts. Premised on the biological imperative to respond swiftly to threat, we demonstrate, however, that when participants are threatened by shock, greater amygdala responses to fearful compared to neutral distractor faces is preserved under conditions of high attentional demand. Lateral prefrontal cortices also showed selective responding to fearful distractor faces under these conditions, suggesting that threat-related distractor stimuli engaged attentional control mechanisms. We conclude that anxiety elicited by looming threat promotes neurocognitive processes that broaden attention and enhance sensitivity to potential danger cues, even when perceptual systems are taxed.