Limits...
Human fear conditioning and extinction in neuroimaging: a systematic review.

Sehlmeyer C, Schöning S, Zwitserlood P, Pfleiderer B, Kircher T, Arolt V, Konrad C - PLoS ONE (2009)

Bottom Line: On closer inspection, there is considerable variation in methodology and results between studies.However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities.Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany.

ABSTRACT
Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas. Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.

Show MeSH

Related in: MedlinePlus

Brain areas involved in aversive conditioning and/or extinction.Different brain areas (with at least unilateral activation during aversive conditioning and/or extinction) are plotted against the x-axis. The number of studies out of 46 studies per brain region is plotted against the y-axis, taking into account the conditioning design which is delay conditioning in 40, trace conditioning in two, delay and trace conditioning in four, and extinction in seven studies.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2692002&req=5

pone-0005865-g002: Brain areas involved in aversive conditioning and/or extinction.Different brain areas (with at least unilateral activation during aversive conditioning and/or extinction) are plotted against the x-axis. The number of studies out of 46 studies per brain region is plotted against the y-axis, taking into account the conditioning design which is delay conditioning in 40, trace conditioning in two, delay and trace conditioning in four, and extinction in seven studies.

Mentions: As a major and stable result, the amygdala, the ACC and the insular cortex turned out to be crucial structures in the acquisition of aversive delay conditioning, independent of general design characteristics. Twenty-five of the 44 delay conditioning studies reported amygdala activation, with results varying with respect to the laterality of activation. While nine studies reported bilateral amygdala activation (e.g.[31], [49], [64]), eight studies detected left-lateralized (e.g. [27], [61], [65]), and eight right-lateralized activations (e.g.[53], [62]). Methodologically, nineteen of the 25 studies additionally tested for temporal interactions of amygdala activation or split up the acquisition phase into an early and late phase, in order to assess the temporal gradation in the signal intensity of the amygdala. Seventeen of these studies reported learning-related responses of the amygdala (e.g. [45], [48], [57], [66]): fourteen studies found initial increase and rapid decrease of activation during repeated exposure to unpleasant stimuli (e.g. [33], [44]), whereas three studies only reported increases of amygdala activation during the acquisition phase [40], [51], [58]. The remaining 19 delay conditioning studies did not report activation of the amygdala. Seventeen of them did not test for temporal aspects of amygdala activation (e.g. [39]). Sixteen delay conditioning studies found activation of the ACC (e.g. [25], [26]), five of the posterior cingulate cortex (PCC) (e.g. [30]), and two reported activation of the cingulate cortex [33], [57]. Sixteen studies detected insular activities (e.g [39], [54], [65]). These areas are all part of the classical key fear network as described previously [22], [23]. Activation of brain areas such as the hippocampus, the cerebellum, the thalamus, the striatum or the sensory cortices has been reported by fewer delay conditioning studies, underlining the considerable variability in neuroimaging findings. Hippocampal activity, mostly lateralized, was found for example by ten studies (e.g. [34]). Twelve studies showed activation of the striatum (including putamen, accumbens nucleus, caudate nucleus) (e.g. [39], [61]), whereas thalamic activity (including pulvinar, geniculate nucleus) was reported by twelve delay conditioning studies (e.g. [48]) (for details, see Figure 2). As argued below, we believe such differences in results to be methodological in origin [14].


Human fear conditioning and extinction in neuroimaging: a systematic review.

Sehlmeyer C, Schöning S, Zwitserlood P, Pfleiderer B, Kircher T, Arolt V, Konrad C - PLoS ONE (2009)

Brain areas involved in aversive conditioning and/or extinction.Different brain areas (with at least unilateral activation during aversive conditioning and/or extinction) are plotted against the x-axis. The number of studies out of 46 studies per brain region is plotted against the y-axis, taking into account the conditioning design which is delay conditioning in 40, trace conditioning in two, delay and trace conditioning in four, and extinction in seven studies.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2692002&req=5

pone-0005865-g002: Brain areas involved in aversive conditioning and/or extinction.Different brain areas (with at least unilateral activation during aversive conditioning and/or extinction) are plotted against the x-axis. The number of studies out of 46 studies per brain region is plotted against the y-axis, taking into account the conditioning design which is delay conditioning in 40, trace conditioning in two, delay and trace conditioning in four, and extinction in seven studies.
Mentions: As a major and stable result, the amygdala, the ACC and the insular cortex turned out to be crucial structures in the acquisition of aversive delay conditioning, independent of general design characteristics. Twenty-five of the 44 delay conditioning studies reported amygdala activation, with results varying with respect to the laterality of activation. While nine studies reported bilateral amygdala activation (e.g.[31], [49], [64]), eight studies detected left-lateralized (e.g. [27], [61], [65]), and eight right-lateralized activations (e.g.[53], [62]). Methodologically, nineteen of the 25 studies additionally tested for temporal interactions of amygdala activation or split up the acquisition phase into an early and late phase, in order to assess the temporal gradation in the signal intensity of the amygdala. Seventeen of these studies reported learning-related responses of the amygdala (e.g. [45], [48], [57], [66]): fourteen studies found initial increase and rapid decrease of activation during repeated exposure to unpleasant stimuli (e.g. [33], [44]), whereas three studies only reported increases of amygdala activation during the acquisition phase [40], [51], [58]. The remaining 19 delay conditioning studies did not report activation of the amygdala. Seventeen of them did not test for temporal aspects of amygdala activation (e.g. [39]). Sixteen delay conditioning studies found activation of the ACC (e.g. [25], [26]), five of the posterior cingulate cortex (PCC) (e.g. [30]), and two reported activation of the cingulate cortex [33], [57]. Sixteen studies detected insular activities (e.g [39], [54], [65]). These areas are all part of the classical key fear network as described previously [22], [23]. Activation of brain areas such as the hippocampus, the cerebellum, the thalamus, the striatum or the sensory cortices has been reported by fewer delay conditioning studies, underlining the considerable variability in neuroimaging findings. Hippocampal activity, mostly lateralized, was found for example by ten studies (e.g. [34]). Twelve studies showed activation of the striatum (including putamen, accumbens nucleus, caudate nucleus) (e.g. [39], [61]), whereas thalamic activity (including pulvinar, geniculate nucleus) was reported by twelve delay conditioning studies (e.g. [48]) (for details, see Figure 2). As argued below, we believe such differences in results to be methodological in origin [14].

Bottom Line: On closer inspection, there is considerable variation in methodology and results between studies.However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities.Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany.

ABSTRACT
Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas. Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.

Show MeSH
Related in: MedlinePlus