Extinction & its Role in Consolidation
The previous findings are supported in human neuroimaging research. During an event-related paradigm Phelps and colleagues (2004) observed that fear conditioning learning (i.e. images of blue squares (CS) while being paired with an aversive US, mild shock to the wrist) and extinction (unpairing CS-US) were characterized by temporally sequenced phases suggestive of consolidation processes (Phelps, Delgado, Nearing, & LeDoux, 2004). These phases were associated by activations of different brain regions. Accordingly the acquisition phase (i.e. during the delays after pairing trials) was associated with initial reactive cue dependent autonomic arousal (i.e. SCR-skin conductance response) and significant prefrontal activity in the anterior (rostral) portions of the midcingulate (MCC), the anterior insular cortex (INS) and caudate nucleus (Buchel, Dolan, Armony & Friston, 1999). These structures have previously been associated with autonomic arousal (Augstine, 1996; Critchley, Mathias, Josephs, O’Doherty, Zanini, Dewar et al., 2003; Kuniecki, Urbanic, Sobiecka, Kozub, & Binder, 2003), pain perception (Frot & Mauguiere, 2003; Leone, Proietti Cecchini, Mea, Tullo, Curone, & Bussone, 2006; Rainville, Duncan, Price, Carrier, & Bushnell, 1997), the emotion of fear (Damasio, Grabowski, Bechara, Damasio, Ponto et al., 2000; Vogt, Berger, & Derbyshire, 2003), and event-related fear conditioning (Buchel et al., 1999) in the human.
During the next phase of fear conditioning or extinction (US-CS unpairing) subjects were subjected to the CS in absence to the aversive US (wrist shock). This phase was entitled Day 1 Extinction. Task performance showed enhance fear conditioning effects, as the CS alone was able to elicit autonomic arousal reflected in increased skin conductance response (SCR). Reactive activation values to the CS for previously noted midcingulate and insular cortices decreased. Phase activations in these regions coupled with enhanced and sustained autonomic arousal were probably reflective of amygdala-associated brainstem influences (Liddell, Brown, Kemp, Barton, Das, Peduto et al., 2005).
During the next and last testing session and further CS unpairing (Day 2 Extinction), BOLD signals and activations allowed expression of areas that had initially been associated with initial autonomic arousal during pairing US-CS noted above (i.e. the MCC and anterior insular cortex during reactive response) however with the strength of autonomic arousal decreased dramatically. Extinction-induced regional changes negatively correlated with autonomic arousal (Critchley, Tang, Glaser, Butterworth, & Dolan, 2005).
The previous discussion can be represented in the subsequent bar chart.
For BOLD signals and regional activations involving both hemispheres, the single largest value was selected for this chart’s development. Voxel values are reflected vertically on the y-axis. The phases of fear conditioning are noted horizontally on the x-axis. Each bar in the chart represents a different brain region during each of the three phases. For instance the chart reflects that the MCC and insula engage more voxel activations during pairing and extinction but fewer voxels during the unpairing phase
This point graph depicts the BOLD signal in voxels on the y-axis and brain regions on the x-axis within context of the three different phases, i.e. pairing, unpairing, and extinction. The point chart’s findings correspond to those provided for the bar chart.
These findings suggest that there is a temporal sequencing for consolidating fear conditioning learning and extinction. Consolidation processes seem to begin with fear acquisition learning (Phelps et al., 2004). Accordingly the pairing phase is associated with activations in the anterior cingulate and insular cortices as well as caudate nucleus (Buchel et al., 1999). As noted previously plasticity in anterior regions of the medial (and lateral prefrontal) cortex is probably needed for the expression of the next phase (second unpairing phase) of fear-instilling avoidance conditioning (Gabriel, Kubota, Sparenborg, Straube, & Vogt, 1991). This next phase, the unpairing phase, according to the above findings is characterized by reduced expression in the anterior cingulate and insular cortices.
As noted earlier the animal research has referenced involvement of other brain regions during fear conditioning processes. Their findings suggest that the amygdala mediates CS-US pairing. The posterior cingulate cortex (PCC) (Yonelinas, Otten, Shaw, & Rugg, 2005) and parahippocampus of the hippocampal formation (Maratos, Dolan, Morris, Henson, & Rugg, 2001) in the later phases of single session learning have been shown to support cue-specific recallable recognition. This is an important distinction for understanding of consolidation processes, as “cue dependent” recallable recognition is a precursor for later cue independent recallable retrieval. Interestingly, according to the animal research, initial involvement of the posterior cingulate cortex and hippocampal region signals the organism’s immediate response to removing and unpairing the initial US (Gabriel et al., 1991; Kang & Gabriel, 1998). In another neuroimaging study PCC rCBF activity during the unpairing or second phase of fear conditioning (Doronbekov, Tokunaga, Ikejiri, Kazui, Hatta, Masaki et al., 2005) may be suggestive of either its regional dependent consolidation involvement in CS cue dependent recognition or its initial CS unpairing or both. These findings suggest a shift from one stage of consolidation to another with US removal. Finally, there is an extinction phase that returns neural activity back to anterior structures but without apparent autonomic arousal. These regions also support cue-nonspecific and the hippocampal-independent recallable retrieval of autobiographical memory over time (Maguire, Henson, Mummery, & Frith, 2001). As noted earlier in this web site this supports hippocampal lesioning retrograde amnesia studies, which suggest that an intact prefrontal cortex not an intact hippocampus is needed for remote memory retrieval.
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