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Cerebral Blood Flow in Immediate and Sustained Anxiety
Open accessAbstract
The goal of this study was to compare cerebral blood flow (CBF) changes associated with phasic cued fear versus those associated with sustained contextual anxiety. Positron emission tomography images of CBF were acquired using [O-15]H2O in 17 healthy human subjects as they anticipated unpleasant electric shocks that were administered predictably (signaled by a visual cue) or unpredictably (threatened by the context). Presentation of the cue in either threat condition was associated with increased CBF in the left amygdala. A cue that specifically predicted the shock was associated with CBF increases in the ventral prefrontal cortex (PFC), hypothalamus, anterior cingulate cortex, left insula, and bilateral putamen. The sustained threat context increased CBF in the right hippocampus, mid-cingulate gyrus, subgenual PFC, midbrain periaqueductal gray, thalamus, bilateral ventral striatum, and parieto-occipital cortex. This study showed distinct neuronal networks involved in cued fear and contextual anxiety underlying the importance of this distinction for studies on the pathophysiology of anxiety disorders.
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“Hasler et al. (2007) found that a visual threat cue increased cerebral blood flow in the left amygdala relative to a comparable safe cue.”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Hasler et al. (2007)
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“Previous studies of instructed fear using simple threat cues (e.g., colored squares) have associated phasic fear responses with a left hemisphere bias (Phelps et al., 2001; Funayama et al., 2001; Hasler et al., 2007).”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Hasler et al., 2007
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“The finding that unpredictable threat induced sustained activity of frontoparietal areas involved in sustained attention (Pardo et al., 1991), is consistent with previous neuroimaging studies linking unpredictable threat to hypervigilance (Carlsson et al., 2006; Hasler et al., 2007).”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Hasler et al., 2007
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The contextual brain: implications for fear conditioning, extinction and psychopathology
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Self-citationStress reduction correlates with structural changes in the amygdala
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BackgroundSelf-citationPhasic and sustained fear in humans elicits distinct patterns of brain activity
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“, 1991), is consistent with previous neuroimaging studies linking unpredictable threat to hypervigilance (Carlsson et al., 2006; Hasler et al., 2007).”
InfluentialSelf-citationDiscovering imaging endophenotypes for major depression
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Self-citationUncertainty during anticipation modulates neural responses to aversion in human insula and amygdala
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“Consistently, brain imaging studies in humans and rhesus monkeys have also found that elevated activity in the anterior hippocampus (equivalent to the vHPC in rodents) is associated with sustained anxiety (Hasler et al, 2007; Oler et al, 2010).”
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“…amygdala: x 27, y 2, z 29; left anterior insula: x 33, y 28, z 13; right anterior insula: x 52, y 26, z 9; left ACC/mPFC: x 3, y 14, z 37; right ACC/mPFC: x 6, y 29, z 47, all from Büchel et al.(1998), transformed into MNI coordinates; left hippocampus: x 36, y 28, z 7, from Hasler et al. (2007)].”
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TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies
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“This fMRI study utilized a mixed block-event-related emotional provocation paradigm in 55 healthy participants to simultaneously measure brief and persistent anxious emotional responses, testing the specificity of, and interactions between, these potentially distinct systems.”
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“Preliminary evidence also links BNST function to anxiety in nonhuman primates (Fox et al., 2008; Kalin et al., 2005) and humans (Alvarez et al., 2011; Grupe et al., 2013; Hasler et al., 2007; Somerville et al., 2010, 2013).”
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“In a positron emission tomography study, Hasler et al. (2007) used a cue and context to induce predictable fear or unpredictable anxiety.”
Maciąg, D., Hughes, J., O'Dwyer, G., Pride, Y., Stockmeier, C. A., Sanacora, G., & Rajkowska, G. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.10.027 · Cited by 175
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“Indeed, several studies have identified elevated activity in a subgenual region (including area 25) associated with sustained and unpredictable threat (Alvarez et al., 2011; Hasler et al., 2007).”
BackgroundDynamic activation of the anterior cingulate cortex during anticipatory anxiety
Straube, T., Schmidt, S. N. L., Weiß, T., Mentzel, H., & Miltner, W. H. R. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.10.022 · Cited by 132
“Activation of the hippocampus seems to be associated with those forms of anxiety, which are induced in more sustained anxiety provoking paradigms [in contrast to the amygdala, which is activated during brief anxietyrelated cues (Hasler et al., 2007; Straube et al., 2006, 2007a,b)].”
ResultCan the neuroeconomics revolution revolutionize psychiatry?
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“More specifically, anxiety, depression, and inhibited temperament have been associated with greater levels of activity in the ventral PFC, both in adolescents and in adults (Bush et al., 2000; Drevets et al., 1992, 1997; Hasler et al., 2007; Monk et al., 2006; Steele, Currie, Laurie, & Reid, 2007).”
Neural correlates of altered general emotion processing in social anxiety disorder
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Self-citationHyper-connectivity of subcortical resting state networks in social anxiety disorder
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“Further, PET studies have reported cerebral blood flow (CBF) changes, specific to the striatum, during anticipatory anxiety to electrical shock (Hasler et al., 2007).”
The interplay of hypoxic and mental stress: Implications for anxiety and depressive disorders
Burtscher, J., Niedermeier, M., Hüfner, K., van den Burg, E. H., Kopp, M., Stoop, R., Burtscher, M., Gatterer, H., & Millet, G. P. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104718 · Cited by 110
“, 2021) and blood brain barrier integrity (Halder and Milner, 2019), both of which may be impaired by stress and in anxiety (Hasler et al., 2007) and depressive disorders”
Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models
Chen, G., Carlson, V. C. C., Wang, J., Beck, A., Heinz, A., Dorit Ron, A., Lovinger, D. M., & Buck, K. J. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01520.x · Cited by 98
“…nonhuman primates show that the striatal ventral putamen, the primate counterpart of the rvCP, is associated with depression, anxiety, apathy, stereotypy, and hypoactivity (Hasler et al., 2007; Mah et al., 2007; Worbe et al., 2009), which are frequently observed in the alcohol-withdrawn subjects.”
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Human anterior and posterior hippocampus respond distinctly to state and trait anxiety.
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“…in activity to threat (Butler, Pan, Tuescher, & Engelien, 2007), and still others studying contextual fear conditioning showing increases in hippocampal activity (Alvarez, Biggs, Chen, Pine, & Grillon, 2008; Hasler et al., 2007; also see Ploghaus et al., 2000, for an expectancy violation model).”
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“Moreover, vigilance is heightened, but attention is less focused on specific stimuli during anxiety than fear (Cornwell, Echiverri, Covington, & Grillon, 2008; Hasler et al., 2007).”
Lonsdorf, T. B., Haaker, J., & Kalisch, R. (2014) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu018 · Cited by 89
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“50 These sites help to mediate emotional behaviors such as fear (amygdala, hippocampus) and dyspnea (insula, cingulate cortex).”
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“However, recent imaging studies in humans have shown that the ventral striatum is also responsive to aversive stimuli, such as in anticipation of unpleasant electrical stimulation (Hasler et al., 2007; Jensen et al., 2003) or thermal pain (Becerra et al.”
BackgroundUncertainty is associated with increased selective attention and sustained stimulus processing
Dieterich, R., Endrass, T., & Kathmann, N. (2016) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-016-0405-8 · Cited by 76
“For example, the startle reflex—a somatic marker of defensive motivation (Lang, Bradley, & Cuthbert, 1992)—is enhanced during the anticipation of unpredictable as compared to predictable shocks (Bradford, Shapiro, & Curtin, 2013; Grillon, Baas, Lissek, Smith, & Milstein, 2004; Hefner & Curtin, 2012; Nelson & Shankman,…”
BackgroundMcHugh, S. B., Fillenz, M., Lowry, J. P., Rawlins, J. N. P., & Bannerman, D. M. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07497.x · Cited by 86
“In humans, sustained anxiety evokes significant activation of anterior HPC (Hasler et al., 2007), and in rats reduced anxiety is a consequence of vHPC (but not dHPC) lesions in a variety of tests, including those used in the present study (Bannerman et al., 2002; Kjelstrup et al., 2002; McHugh et…”
BackgroundMethodResultRegional patterns and clinical correlates of basal ganglia morphology in non-medicated schizophrenia
Ballmaier, M., Schlagenhauf, F., Toga, A. W., Gallinat, J., Koslowski, M., Zoli, M., Hojatkashani, C., Narr, K. L., & Heinz, A. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.08.025 · Cited by 80
“Studies on healthy subjects found putamen involvement in emotional distress (Sinha et al., 2004), motivational drives (Sewards and Sewards, 2003), and the expression of fear and anxiety (Hasler et al., 2007).”
BackgroundOler, J. A., Tromp, D., Fox, A. S., Kovner, R., Davidson, R. J., Alexander, A. L., McFarlin, D. R., Birn, R. M., Berg, B. E., deCampo, D. M., et al. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1198-9 · Cited by 82
“2013), as well as from humans (Alvarez et al. 2011; Boll et al. 2013; Hasler et al. 2007; LaBar et al. 1998; Mobbs et al. 2010; Somerville et al. 2010, 2013; Straube et al. 2007), supports the idea that regions of the EAc are involved in maintaining threat-preparedness and initiating physiological and behavioral respo…”
BackgroundAre Essential Trace Elements Effective in Modulation of Mental Disorders? Update and Perspectives
Shayganfard, M. (2021) · Biological Trace Element Research · doi:10.1007/s12011-021-02733-y · Cited by 88
Targeting inflammation: a potential approach for the treatment of depression
Bhatt, S., Devadoss, T., Jha, N. K., Baidya, M., Gupta, G., Chellappan, D. K., Singh, S. K., & Dua, K. (2022) · Metabolic Brain Disease · doi:10.1007/s11011-022-01095-1 · Cited by 83
Neural alterations associated with anxiety symptoms in obstructive sleep apnea syndrome
Kumar, R., Macey, P. M., Cross, R. L., Woo, M. A., Yan‐Go, F. L., & Harper, R. M. (2008) · Depression and Anxiety · doi:10.1002/da.20531 · Cited by 77
“These sites help mediate emotional behaviors such as fear (amygdala, hippocampus)([24,25]) and dyspnea (insula, cingulate cortex).”
BackgroundDistinct contributions of human hippocampal theta to spatial cognition and anxiety
Cornwell, B. R., Arkin, N., Overstreet, C., Carver, F. W., & Grillon, C. (2012) · Hippocampus · doi:10.1002/hipo.22019 · Cited by 73
“, 2008) versus right (Hasler et al., 2007; Alvarez et al., 2008) hippocampal involvement in aversive contexts; animal research rarely addresses questions of lateralized hippocampal function (Klur et al.”
BackgroundInfluentialSelf-citationActivation of the ventral striatum during aversive contextual conditioning in humans
Pohlack, S. T., Nees, F., Ruttorf, M., Schad, L. R., & Flor, H. (2012) · Biological Psychology · doi:10.1016/j.biopsycho.2012.04.004 · Cited by 73
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“…and the PASAT-3s is that the unexpectedness of the stimulus to be cognitively processed was sufficient to generate stress-induced emotional signals, which may have interfered with cognitive control, as already demonstrated [Fischer et al., 2003; Hasler et al., 2007; Wright et al., 2001].”
BackgroundResultYang, X., Tian, K., Wang, D., Wang, Y., Cheung, E. F. C., Xie, G., & Chan, R. C. K. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.04.053 · Cited by 74
Hippocampal but not amygdalar volume affects contextual fear conditioning in humans
Pohlack, S. T., Nees, F., Liebscher, C., Cacciaglia, R., Diener, S. J., Ridder, S., Woermann, F. G., & Flor, H. (2011) · Human Brain Mapping · doi:10.1002/hbm.21224 · Cited by 75
“Furthermore, imaging studies in humans found hippocampal activations during contextual fear conditioning [Alvarez et al., 2008; Hasler et al. 2007; Lang et al., 2009; Marschner et al., 2008].”
BackgroundResultInfluentialHippocampal N-Acetylaspartate Concentration and Response to Riluzole in Generalized Anxiety Disorder
Mathew, S. J., Price, R. B., Mao, X., Smith, E. L., Coplan, J. D., Charney, D. S., & Shungu, D. C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.09.012 · Cited by 70
“In a non-clinical sample, NAA concentrations in the orbital frontal cortices were positively related to a composite measure of state and trait anxiety (55), while in social phobics, NAA/Cr in the ACC was found to be elevated and positively related to symptom severity (32).”
BackgroundInfluentialOsuch, E. A., Willis, M. W., Bluhm, R., Ursano, R. J., & Drevets, W. C. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.010 · Cited by 67
“The anterior insula has been shown to participate in the modulation of contextual fear (62,63) and lesions there reduce fear reactivity to contextual stimuli, but do not affect conditioned stimulus acquisition or response extinction(63).”
Self-citationSteiger-White, F., Nees, F., Wicking, M., Lang, S., & Flor, H. (2015) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2015.06.009 · Cited by 71
“…Marschner et al., 2008; Lang et al., 2009; Pohlack et al., 2012), specifically when configural associations have to be discriminated (Sutherland and McDonald, 1990; Rudy and Sutherland, 1995; Shin et al., 2006; Alvarez et al., 2008; Lang et al., 2009; Marschner et al., 2008; Hasler et al., 2007).”
BackgroundGlotzbach, E., Ewald, H., Andreatta, M., Pauli, P., & Mühlberger, A. (2012) · Cognition & Emotion · doi:10.1080/02699931.2012.656581 · Cited by 54
“On a neural level, phasic fear reactions are coordinated by the amygdala, whereas sustained anxiety reactions are additionally mediated by the bed nucleus of the stria terminalis in rodents (BNST; Davis, Walker, Miles, & Grillon, 2010) and by the hippocampus in humans (Alvarez, Biggs, Chen, Pine, & Grillon, 2008; Hasl…”
BackgroundThe Elevated Plus-Maze Test: Differential Psychopharmacology of Anxiety-Related Behavior
Pawlak, C. R., Karrenbauer, B. D., Schneider, P., & Ho, Y. (2012) · Emotion Review · doi:10.1177/1754073911421374 · Cited by 57
“These data are supported by Hasler et al. (2007), who found that there are distinct neuronal networks involved in cued fear (e.g., bilateral putamen) and contextual anxiety (bilateral ventral striatum).”
BackgroundRavenelle, R., Santolucito, H. B., Byrnes, E. M., BYRNES, J. J., & Donaldson, S. T. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.03.060 · Cited by 60
“Inbred lines of high anxiety-like behavior (HAB) rats show similar profiles to anxious clinical populations, with increased adrenocortical response (Landgraf et al., 1999) and greater activation in brain areas implicated in anxiety (Salomé et al., 2004; Hasler et al., 2007).”
Shih, Y.-W., Tsai, H.-Y., Lin, F.-S., Lin, Y., Chiang, C.-Y., Lu, Z., & Tseng, M. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.2154-18.2018 · Cited by 61
“…certainty (and thus lowered anxiety) about positive expectations downregulates the functional interaction between the aIC and hippocampus, thereby generating an anxiolytic effect and thus dampening the amplification of pain signaling in hippocampus (Gray and McNaughton, 2000; Hasler et al., 2007).”
BackgroundEnhanced discrimination between threatening and safe contexts in high-anxious individuals
Glotzbach-Schoon, E., Tadda, R., Andreatta, M., Tröger, C., Ewald, H., Grillon, C., Pauli, P., & Mühlberger, A. (2013) · Biological Psychology · doi:10.1016/j.biopsycho.2013.01.011 · Cited by 57
“…to unpredictable stressors have been found to be additionally mediated by the bed nucleus of the stria terminalis (BNST; Alvarez et al., 2011; Luyten et al., 2011; Zimmerman and Maren, 2011) and the hippocampus (Alvarez et al., 2008; Hasler et al., 2007; Lang et al., 2009; Marschner et al., 2008).”
BackgroundSelf-citationAlcohol stress response dampening: selective reduction of anxiety in the face of uncertain threat
Hefner, K. R., & Curtin, J. J. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881111416691 · Cited by 74
Schoenfeld, T. J., Kloth, A. D., Hsueh, B., Runkle, M. B., Kane, G. A., Wang, S. S.-H., & Gould, E. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3234-13.2014 · Cited by 49
“…in the medial frontal cortex of humans that correspond to the mPFC in rodents have not been examined for a potential relationship between theta rhythm and anxiety, studies using fMRI have verified increased blood flow in such areas during anxious states (Kalisch et al., 2005; Hasler et al., 2007).”
BackgroundGrillon, C., O’Connell, K., Lieberman, L., Alvarez, G., Geraci, M. F., Pine, D. S., & Monique Ernst, D. (2016) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2016.08.005 · Cited by 44
Self-citationKastner, A. K., Andreatta, M., Pauli, P., & Wieser, M. J. (2018) · Cortex · doi:10.1016/j.cortex.2018.05.008 · Cited by 50
Wieser, M. J., Reicherts, P., Juravle, G., & von Leupoldt, A. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.06.026 · Cited by 42
“In addition, a broad network of brain areas is reported to be activated in unpredictable compared to predictable threat (Alvarez et al., 2011; Carlson et al., 2011; Hasler et al., 2007; Somerville et al., 2013) including the hippocampus, the insula, and the fronto-parietal attention network.”
Additive Effects of Threat-of-Shock and Picture Valence on Startle Reflex Modulation
Bublatzky, F., Guerra, P. M., Pastor, M. C., Schupp, H. T., & Vila, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054003 · Cited by 42
“humans [35,36].”
Affect and the Brain's Functional Organization: A Resting-State Connectivity Approach
Rohr, C. S., Okon‐Singer, H., Craddock, R. C., Villringer, A., & Margulies, D. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068015 · Cited by 42
“Several examples for similar cases exist: for instance, the amygdala was not detected in studies on sustained mood states [77,78].”
Avoidance of learnt fear: Models, potential mechanisms, and future directions
Wong, A. H. K., Wirth, F. M., & Pittig, A. (2022) · Behaviour Research and Therapy · doi:10.1016/j.brat.2022.104056 · Cited by 43
Brain-Wide Mendelian Randomization Study of Anxiety Disorders and Symptoms
Zanoaga, M. D., Friligkou, E., He, J., Pathak, G. A., Koller, D., Cabrera‐Mendoza, B., Stein, M. B., & Polimanti, R. A. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.11.006 · Cited by 41
Ravenelle, R., Neugebauer, N. M., Niedzielak, T. R., & Donaldson, S. T. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.04.048 · Cited by 41
“Becker 1999), an area that has been implicated in anxiety states in both clinical and animal models (Hasler et al., 2007; Favilla et al., 2008).”
BackgroundFear‐learning deficits in subjects with fibromyalgia syndrome?
Jenewein, J., Moergeli, H., Sprott, H., Honegger, D., Brunner, L. M., Ettlin, D. A., Grillon, C., Bloch, K. E., Brügger, M., Schwegler, K., et al. (2013) · European Journal of Pain · doi:10.1002/j.1532-2149.2013.00300.x · Cited by 39
“In healthy volunteers, the anticipation of unpredictably administered electric shocks induces sustained anxiety along with an increase in blood flow in the hippocampus (Hasler et al., 2007).”
BackgroundSelf-citationReducing chronic anxiety by making the threatening event predictable: An experimental approach
Fonteyne, R., Vervliet, B., Hermans, D., Baeyens, F., & Vansteenwegen, D. (2009) · Behaviour Research and Therapy · doi:10.1016/j.brat.2009.06.011 · Cited by 40
Maren, S. (2007) · Science · doi:10.1126/science.1147797 · Cited by 41
Parsing the Role of the Hippocampus in Approach–Avoidance Conflict
Loh, E., Kurth-Nelson, Z. L., Berron, D., Dayan, P., Düzel, E., Dolan, R. J., & Guitart‐Masip, M. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw378 · Cited by 38
“…(Barrós-Loscertales et al. 2006; Levita et al. 2014), most functional studies of approach–avoidance conflict have hitherto employed experimental paradigms with significant spatiotemporal components (e.g., Bach et al. 2014, Hasler et al., 2007; though note a recent exception in O’Neil et al. 2015).”
BackgroundAngiotensin Regulation of Amygdala Response to Threat in High-Trait-Anxiety Individuals
Reinecke, A., Browning, M. D., Breteler, J. K., Kappelmann, N., Ressler, K. J., Harmer, C. J., & Craske, M. G. (2018) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2018.05.007 · Cited by 35
“Similarly, putamen response has been associated with enhanced threat processing (62-64),”
BackgroundStraube, B., Lueken, U., Jansen, A., Konrad, C., Gloster, A. T., Gerlach, A. L., Ströhle, A., Wittmann, A., Pfleiderer, B., Gauggel, S., et al. (2014) · Psychotherapy and Psychosomatics · doi:10.1159/000359955 · Cited by 40
Baas, J. M. P., & Heitland, I. (2014) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2014.10.016 · Cited by 37
Straube, T., Preißler, S., Lipka, J., Hewig, J. S., Mentzel, H., & Miltner, W. H. R. (2009) · Human Brain Mapping · doi:10.1002/hbm.20843 · Cited by 36
“As discussed elsewhere, the amygdala is strongly activated during automatic evaluation and implicit processing of threat signals and seems to be more important for cue-induced, immediate fear, rather than for sustained anxiety [Hasler et al., 2007; Straube et al., 2004, 2006a,b, 2007a,b].”
BackgroundResultAltered Pain Perception and Fear-Learning Deficits in Subjects With Posttraumatic Stress Disorder
Jenewein, J., Erni, J., Moergeli, H., Grillon, C., Schumacher, S., Mueller‐Pfeiffer, C., Hassanpour, K., Seiler, A., Wittmann, L., Schnyder, U., et al. (2016) · Journal of Pain · doi:10.1016/j.jpain.2016.09.002 · Cited by 33
“Deficits in fear learning contribute to perceived unpredictability, a crucial contributor to contextual fear, sustained anxiety and hypervigilance (12).”
BackgroundSelf-citationThe relationship between dlPFC activity during unpredictable threat and CO2-induced panic symptoms
Balderston, N. L., Liu, J., Roberson‐Nay, R., Monique Ernst, D., & Grillon, C. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0006-5 · Cited by 33
Self-citationDissociable roles for hippocampal and amygdalar volume in human fear conditioning
Cacciaglia, R., Pohlack, S. T., Flor, H., & Nees, F. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0807-8 · Cited by 37
“The role of the hippocampus in both rodents and humans has been largely related to more complex forms of aversive learning, such as contextual fear (e.g., Phillips and LeDoux 1992; Hasler et al. 2007; Pohlack et al. 2012b) or trace conditioning (e.”
BackgroundBrain activation and heart rate during script-driven traumatic imagery in PTSD: Preliminary findings
Barkay, G., Freedman, N., Lester, H., Louzoun, Y., Sapoznikov, D., Luckenbaugh, D. A., Shalev, A. Y., Chisin, R., & Bonne, O. B. (2012) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2012.08.007 · Cited by 30
“On the whole, the occipital cortex is increasingly found to be involved in the neurocircuitry of anxiety symptoms and disorders (Hasler et al., 2007).”
BackgroundSelf-citationAcute restraint differently alters defensive responses and fos immunoreactivity in the rat brain
de Andrade, J. S., Abrão, R. O., Céspedes, I. C., Garcia, M. C., Nascimento, J. O. G., Spadari-Bratfisch, R. C., Melo, L. L., da Silva, R. C. B., & Viana, M. D. B. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.03.034 · Cited by 29
Inoue, A., Akiyoshi, J., Muronaga, M., Masuda, K., Aizawa, S., Hirakawa, H., Ishitobi, Y., Higuma, H., Maruyama, Y., Ninomiya, T., et al. (2015) · International Journal of Psychiatry in Clinical Practice · doi:10.3109/13651501.2015.1043133 · Cited by 29
“…changes in the anterior cingulate cortex of humans in fearful states or in pathological anxiety, including phobic fear, PD, generalized anxiety disorder, social anxiety disorder, and posttraumatic stress disorder (Straube et al. 2007; Hasler et al. 2007; Etkin and Wager, 2007; Mobbs et al. 2007).”
BackgroundOxytocin modulates hippocampal perfusion in people at clinical high risk for psychosis
Davies, C., Paloyelis, Y., Rutigliano, G., Cappucciati, M., Micheli, A. D., Ramella‐Cravaro, V., Provenzani, U., Antoniades, M., Modinos, G., Oliver, D., et al. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-018-0311-6 · Cited by 28
An orphan ionotropic glutamate receptor: The δ2 subunit
Mandolesi, G., Cesa, R., Autuori, E., & Strata, P. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.02.050 · Cited by 27
Brain perfusion alterations in depressed patients with Parkinson’s disease
Kim, Y., Jeong, H. S., Song, I., Chung, Y., Namgung, E., & Kim, Y.-D. (2016) · Annals of Nuclear Medicine · doi:10.1007/s12149-016-1119-2 · Cited by 27
“behavioral experiment study of healthy volunteers revealed that sustained anxiety was associated with increased rCBF in various regions, including the parieto-occipital cortex [18].”
BackgroundRoles for the Dorsal Striatum in Aversive Behavior
Stanley, A. T., Lippiello, P., Sulzer, D. L., & Miniaci, M. C. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.634493 · Cited by 26
Line, S. J., Barkus, C., Rawlings, N. B., Jennings, K. A., McHugh, S. B., Sharp, T., & Bannerman, D. M. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12744 · Cited by 26
“The importance of the amygdala for fear conditioning is well established (Davis, 2004; Phelps & LeDoux, 2005), both from human imaging studies (Buchel et al., 1998; LaBar et al., 1998; Hasler et al., 2007) and from lesion studies in animals (Phillips & LeDoux, 1992; Campeau & Davis, 1995).”
BackgroundNishida, K., Koshikawa, Y., Morishima, Y., Yoshimura, M., Katsura, K., Ueda, S., Ikeda, S., Ishii, R., Pascual-Marqui, R. D., & Kinoshita, T. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00266 · Cited by 25
He, J., Kurita, K., Yoshida, T., Matsumoto, K., Shimizu, E., & Hirano, Y. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.07.020 · Cited by 23
Ambient temperature effects on stress-induced hyperthermia in Svalbard ptarmigan
Nord, A., & Folkow, L. P. (2019) · Biology Open · doi:10.1242/bio.043497 · Cited by 23
Pedersen, W. S., Muftuler, L. T., & Larson, C. L. (2019) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsz095 · Cited by 20
“These studies suggest the BNST preferentially responds to unpredictable stimuli, while evidence for an amygdala response to unpredictable vs predictable threat is mixed (Hasler et al., 2007; Sarinopoulos et al., 2010).”
BackgroundOgunbiyi, O., Hindocha, C., Freeman, T. P., & Bloomfield, M. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109900 · Cited by 23
Sink, K. S., Davis, M., & Walker, D. L. (2013) · Learning & Memory · doi:10.1101/lm.032482.113 · Cited by 23
“, from imaging studies [Hasler et al. 2007; Straube et al. 2007; Somerville et al. 2010, 2013; Alvarez et al. 2011; Yassa et al. 2012]), and compelling evidence that elec-”
BackgroundMethodSex differences in gray matter, white matter, and regional brain perfusion in young, healthy adults
Muer, J. D., Didier, K. D., Wannebo, B. M., Sanchez, S., Motlagh, H. K., Haley, T. L., Carter, K. J., Banks, N. F., Eldridge, M. W., Serlin, R. C., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00341.2024 · Cited by 21
The Benefits of Music Listening for Induced State Anxiety: Behavioral and Physiological Evidence
Huang, B., Hao, X., Long, S., Ding, R., Wang, J., Liu, Y., Guo, S., Lu, J., He, M., & Yao, D. (2021) · Brain Sciences · doi:10.3390/brainsci11101332 · Cited by 21
“Additionally, a sustained threat context that stimulated contextual anxiety increased cerebral blood flow in the right hippocampus, mid-cingulate gyrus, thalamus, bilateral ventral striatum and occipital cortex [20].”
BackgroundSustained attention in context conditioning: Evidence from steady-state VEPs
Kastner, A. K., Pauli, P., & Wieser, M. J. (2015) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2015.03.005 · Cited by 19
Distributed and Multifaceted Effects of Threat and Safety
Morrow, K., Murty, D. V. P. S., Kim, J., Song, S., Hu, K., & Pessoa, L. (2021) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_01807 · Cited by 18
“The present study adds to this literature by showing that this region is transiently engaged when a threat context is initially experienced, and closely replicates a previous finding by our lab ((McMenamin et al., 2014); see also (Hasler et al., 2007; Schlund et al., 2013)).”
BackgroundResultInfluentialA neural oscillatory signature of sustained anxiety
Roxburgh, A. D., White, D., Grillon, C., & Cornwell, B. R. (2023) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-023-01132-1 · Cited by 21
“Threat-of-shock has been used in conjunction with noninvasive neuroimaging to localize sustained changes during anxiety states (Alvarez et al., 2011; Balderston et al., 2017; Hasler et al., 2007; Mac-Namara & Barley, 2018; Vytal et al., 2014).”
MethodSelf-citation
Metadata
- Authors
- Hasler, G., Fromm, S., Alvarez, R. P., Luckenbaugh, D. A., Drevets, W. C., & Grillon, C.
- Affiliations
- University Hospital Zurich (CH)
- National Institutes of Health (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-06-06
- Volume
- 27
- Issue
- 23
- Pages
- 6313-6319
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2713601
- OpenAlex
- W1968966534
- Cited by
- 163
- References
- 43
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 9 · 2017: 5 · 2016: 9 · 2015: 7 · 2014: 13 · 2013: 12 · 2012: 10
- FWCI
- 14.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (Z01MH002798)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cerebral blood flow, anxiety, fear, cued fear, amygdala, ventral prefrontal cortex, hippocampus, periaqueductal gray, threat anticipation, anxiety disorders, brain networks
- MeSH terms
- Adult, Anxiety, Blood Circulation Time, Blood Flow Velocity, Cerebrovascular Circulation, Fear, Female, Humans, Male, Middle Aged, Nerve Net, Time Factors, Positron-Emission Tomography
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