From the Cell to the Brain –Fear and Anxiety across the Levels of Neuroscience
The four studies presented in this thesis independently provided support for a dynamic multilevel account for anxiety-related phenomena (see Table 2). Study 1 showed how medial prefrontal cortex activity (i.e., Structure Level) measured with EEG was related to heart rate (PNS Level) and provided som...
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|Summary:||The four studies presented in this thesis independently provided support for a dynamic multilevel account for anxiety-related phenomena (see Table 2). Study 1 showed how medial prefrontal cortex activity (i.e., Structure Level) measured with EEG was related to heart rate (PNS Level) and provided some evidence that this association was dynamically linked to trait anxiety: in conditions of negative but not positive feedback did trait anxiety increase the link between cortical and cardiac activity. This modulation is consistent with the functional definition of anxiety given that negative but not positive feedback is normally associated with increased danger in the future.
Study 2 showed how dopaminergic genes (Molecule Level) and manipulations of dopamine (Synapse Level) presumably affected network states (Network Level), which then influenced brain activity at the AMC (Structure Level) and error-related behavior (Whole System Level). The unexpected finding that trait-anxiety was not related to error monitoring in that study can be explained post hoc by task characteristics (Olvet & Hajcak, 2009), again suggesting that some patterns of multilevel interactions are dynamically linked to anxiety.
Study 3 tested individuals with GAD (manifest at the Whole System Level) using a
neuropsychological test designed to measure future-orientation in patients with damage of the ventromedial prefrontal cortex (Structure Level) and resulting impairments in neurovisceral connectivity (Bechara et al., 1997) thus affecting the CNS and PNS-Levels. Consistent with (a) the assumed future-orientation of anxiety and (b) increased neurovisceral connectivity in anxiety (Study 1) individuals with GAD performed better in the IGT than non-anxious control participants.
Finally, Study 4 manipulated intracellular signalling cascades (Molecule Level),
thereby modulating synaptic learning and extinction learning (Synapse Level), which then affected fear-related reflex potentiation (CNS-Level and Whole Systems Level). In contrast to prior studies that found improved extinction learning of hippocampus-dependent fear memory (e.g., fear conditioned to a place), Study 4 found that rolipram disturbed extinction learning of presumably hippocampus independent fear-memory (e.g., fear conditioned to a sound). Together with these other studies, Study 4 thus provides further evidence that situational characteristics (place vs. sound as cue for present danger) may influence various levels (including the Molecule Level) with regard to fear processing.
As can be seen in Table 2, some studies covered different levels than others. Of
course, the herein proposed subdivision into eight levels of organization should be seen as a flexible framework used for illustrating the multilevel perspective rather than as a rigid model. Future research may uncover that much more levels of organization are needed to explain certain phenomena, and there may also be cases when good predictions can be made based on fewer than eight levels. However, Table 2 also shows that guesses for most empty cells can be made based on existing theories and research findings. A critical exception may be the network level, and it has been noted by others that this level is underrepresented in cognitive neuroscience research. However, the network level may be particularly critical for linking what we know about substances, cells, synapses and neurons (mostly based on in vitro work) to what we know about anxiety relevant structures (based on neuroimaging, EEG and lesion studies). From this perspective, future studies that include the neural network levels when investigating danger-reduction phenomena may be indispensable stations for achieving a wholistic understanding of fear and anxiety.|