Resolving the neural circuits of anxiety

Calhoon, Gwendolyn G.; Tye, Kay M.

doi:10.1038/nn.4101

Cited by 522 publications

(496 citation statements)

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“…Similarly, the MEMRI signal measured one week after CSDS could reflect neuronal activation related to long-term physiological and behavioral changes observed in defeated animals 10 . The regions we selected for immunohistochemical analysis have been implicated in the processing of social and emotional behaviour in mice and humans 6,23,24,28 . However, we only observed repeated activation of a subset of these regions during chronic psychosocial stress in mice.…”

Section: Discussionmentioning

confidence: 99%

Brain activation induced by chronic psychosocial stress in mice

Laine

Sokołowska

Dudek

et al. 2017

European Neuropsychopharmacology

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Chronic psychosocial stress is a well-established risk factor for neuropsychiatric diseases. Abnormalities in brain activity have been demonstrated in patients with stress-related disorders. Global brain activation patterns during chronic stress exposure are less well understood but may have strong modifying effects on specific brain circuits and thereby influence development of stress-related pathologies. We determined neural activation induced by chronic social defeat stress, a mouse model of psychosocial stress. To assess chronic activation with an unbiased brain-wide focus we used manganese-enhanced magnetic resonance imaging (MEMRI) and immunohistochemical staining of ∆FOSB, a transcription factor induced by repeated neural activity. One week after 10-day social defeat we observed significantly more activation in several brain regions known to regulate depressive and anxiety-like behaviour, including the prefrontal cortex, bed nucleus of stria terminalis, ventral hippocampus and periaqueductal grey in stressed compared to control mice. We further established that the correlation of ∆FOSB positive cells between specific brain regions was altered following chronic social defeat. Chronic activation of these neural circuits may relate to persistent brain activity changes occurring during chronic psychosocial stress exposure, with potential relevance for the development of anxiety and depression in humans.Psychosocial stress increases the risk for both somatic and psychiatric diseases and worsens their prognosis 1-4 . This term refers to a broad range of experiences, including lack of normative care, abuse, and problems in peer relationships such as bullying 5 . Stress-related mental disorders like major depressive disorder (MDD) and anxiety disorders are associated with altered activation of specific brain regions. For example, neuroimaging has revealed that resting-state activity is reduced in the prefrontal cortex (PFC) 6 and increased in the hippocampus 7 while task-related reactivity is decreased in the hippocampus 8 and nucleus accumbens 9 of MDD patients. Interpretation of the human imaging findings is difficult as activation patterns in tasks carried out during brain imaging may differ from those occurring during naturalistic chronic stress exposure. Because patients enrolled in these studies also tend to have an extensive history of symptoms and medication use, it is challenging to reveal direct consequences of chronic psychosocial stress itself. In contrast, animal models allow investigation of specific stressors in a controlled manner to establish the mechanisms connecting chronic psychosocial stress exposure, brain activation, and subsequent emotional and social behaviour.Chronic social defeat stress (CSDS) is a rodent model of psychosocial stress, which produces many behavioural features similar to the symptoms of human anxiety and mood disorders, such as social aversion, anhedonia (decreased sucrose-preference) and increased self-administration of drugs of abuse 10,11 . These behavioural phenotypes...

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Section: Discussionmentioning

confidence: 99%

Brain activation induced by chronic psychosocial stress in mice

Laine

Sokołowska

Dudek

et al. 2017

European Neuropsychopharmacology

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“…The main input to the amygdala, e.g., from prefrontal cortex pathways, is the lateral and the intercalated cell masses, considered to be the main site of fear acquisition (Hartley & Phelps, 2009). In contrast, the central nucleus is the main output, showing dense connections with the brainstem, suggesting that the central nucleus mediates the expression of fear (Calhoon & Tye, 2015;Janak & Tye, 2015;Kalin, Shelton, & Davidson, 2004). Thus, the amygdala is considered to be a main hub in the fear circuitry (LeDoux, 2003).…”

Section: The Fear Circuitrymentioning

confidence: 99%

Hjärnan formas av psykologisk behandling

Månsson

2016

Linköping Studies in Behavioural Science

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Restructuring the socially anxious brain -using magnetic resonance imaging to advance our understanding of effective cognitive behaviour therapy for social anxiety disorder Printed by Linköping University Print Services (LiU-Tryck) in Linköping, Sweden, 2016 All previously published papers were reproduced with permission from the publishers ACKNOWLEDGEMENTAvhandlingen har genomförts i ett nära samarbete med forskare vid Uppsala universitet och Umeå Centre for Functional Brain Imaging (UFBI). Forskarskolan i klinisk psykiatri vid Karolinska Institutet tillhandhöll en bra forskarutbildning och PRIMA barn-och vuxenpsykiatri gav mig klinisk erfarenhet.Gerhard Andersson har utmanat och sporrat mig genom hela resan. Förutom färdigheter som forskare så kommer jag minnas när Gerhard gömt mina nycklar, häcklat Björn Afzelius-plattorna och burit iväg min cykel och annonserat att den "bortskänkes". Men Gerhards hyss överträffar knappats det brev som jag skickade med internposten för ett par år sedan. Tomas Furmark är en viktig del på min utvecklingskurva som forskare och när ni hör mig säga att "det finns ett par stenar till att vända på" eller att "man skulle ju vilja veta…" så förstår ni nu var det kommer från. Tomas är en av mina förebilder som forskare, men vi har också haft väldigt rolig under konferenserna och karaokekvällarna. C-J Boraxbekk fångade tidigt upp mitt intresse för forskning och det är tack vare C-Js inbjudan som jag fick möjligheten att pyssla med hjärnavbildningsforskning. Per Carlbring kom till Umeå som en vind och tog psykologstudenter med storm. Det hade inte blivit en randomiserad klinisk prövning utan Per. Jag har haft turen att få lära mig av fyra duktiga forskare från olika forskningskulturer och arbetssätt. Denna erfarenhet kommer forma mig som vetenskapsman. Jag har nu flera rollmodeller vars hantverk jag fått se på nära håll. Inte minst har jag haft väldigt kul. Från botten av mitt hjärta -tack Gerhard, Tomas, C-J och Per! Jag har haft ett stort nätverk av kollegor och kompisar som varit betydelsefulla och som jag vill berätta mer om. Andre F Marquand, Steven C R Williams, Alireza Salami, Owe Bodlund, Malin Gren Landell och Carl-Johan Uckelstam bidrog med klinisk kompetens och stöd vid analysarbete. I Umeå hade jag ett stort gäng studenter som hjälpte till vid experimenten, ingen nämnd ingen glömd. Blivande hjärnforskaren Hugo Hesser är inte bara en kul gubbe och en engagerad lärare som jag beundrar han tackade även ja till att vara granskare på mitt slutseminarium. Delar av mina arbeten granskades vid halvtid av Håkan Fischer, en hyvens person som också introducerat mig till ett gäng hyggliga sömnforskare. Helen MacDonald, a dear friend and a fellow EABCT board member, helped me with proof reading. Det var med alla dessa personers hjälp som jag kunde sätta pricken över i:et! Många har bidragit med kunskap genom att jag tagit del av deras forskning, lyssnat på deras presentationer eller att vi diskuterat kniviga frågor. Här vill jag passa på att tacka ett urval av dessa inspiratörer. För e...

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“…The majority of support for such a specialized circuitry comes from rodent research on the acquisition and extinction of fear-responses to conditioned stimuli (see e.g. Apps & Strata, 2015;Bentz & Schiller, 2015;Calhoon & Tye, 2015;Gross & Sabino Canteras, 2012;Karalis et al, 2016;Li et al, 2013;Tovote, Fadok, & Lüthi, 2015;Van Le et al, 2016).…”

Section: Theories Of Prioritized Threat Processingmentioning

confidence: 99%

“…In daily life, such stimulus-driven allocation of attention to threat is not necessarily beneficial and could even endanger survival (Calhoon & Tye, 2015;. If we return to the example of the spider on the dashboard, stimulus-driven attention to this spider likely comes at little to no cost when you are a passenger in the car.…”

Section: Theories Of Prioritized Threat Processingmentioning

confidence: 99%

Top-down influences on the attentional orienting to and disengagement from threat

Vromen¹

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The rapid detection and processing of potential threats enables a fast response to danger and provides a survival benefit (e.g. Tooby & Cosmides, 1990).Theories of threat processing suggest that we have a specialized threat module that enables the automatic (i.e. bottom-up driven) detection and evaluation of stimuli with a high threat value (Bentz & Schiller, 2015;2015;). Such theories suggest that threat processing is (largely) unaffected by top-down cognitive influences, but it remains debated whether attention to threat is contingent on top-down influences.Furthermore, it remains unexplored whether top-down processes can differentially affect the pre-attentive orienting of attention to threat and the subsequent disengagement of focal attention from such a threat. Strong versions of the threat module would predict that both the early (i.e. orienting) and later processing (i.e. disengagement) of threat should be unaffected by top-down influences, whereas more moderate versions would propose only the early stages of threat processing (i.e. orienting) to be unaffected by topdown processes. Theories of attention on the other hand do not explicitly model attention to be contingent on a stimulus' threat value. Such theories propose that only a stimulus its features (e.g. green) can be processed pre-attentively and thus a stimulus' identity and its associated threat value should not drive orienting , Wolfe, Cave, & Franzel, 1989 Wolfe, , 2006. Moreover, such theories propose that both orienting and disengagement should be subject to top-down modulation, albeit perhaps to different degrees (see .In this thesis I assessed whether top-down task goals modulate attention to threat. I assessed specifically how the relevance of a potential threat to the current task-goal affects the orienting and disengagement of attention. To disentangle orienting and disengagement, I developed a novel cueing paradigm that controlled the allocation of attention before the threat presentation. On disengagement trials, attention would be precued to the threat location; on orienting trials attention would be pre-cued to one of the non-threat locations. The goal-relevance of the threat was manipulated by rendering the threat distractor its identity similar or dissimilar to one of the targets.In Chapter 2, I assessed the influence of top-down task goals on the disengagement of focal attention. Specifically, I investigated whether disengagement from a simplistic threat distractor (spider silhouette) is contingent on the threat distractor's relevance to the immediate task-goal. Across two experiments I varied which stimuli were the designated targets (coloured green) that required a response. The results show that iii the threat distractor delayed disengagement when its identity was relevant to the current task-goal (i.e. identify whether the target is a spider or cat), but not when it was irrelevant to the task-goal (i.e. identify whether the target is a bird or fish). Thus, chapter 2 provides initial evidence that disengagement from...

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Resolving the neural circuits of anxiety

Cited by 522 publications

References 146 publications

Brain activation induced by chronic psychosocial stress in mice

Brain activation induced by chronic psychosocial stress in mice

Hjärnan formas av psykologisk behandling

Top-down influences on the attentional orienting to and disengagement from threat

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