Fear conditioning is associated with dynamic directed functional interactions between and within the human amygdala, hippocampus, and frontal lobe

Abstract

The current model of fear conditioning suggests that it is mediated through modules involving the amygdala (AMY), hippocampus (HIP), and frontal lobe (FL). We now test the hypothesis that habituation and acquisition stages of a fear conditioning protocol are characterized by different event-related causal interactions (ERC) within and between these modules. The protocol employed the painful cutaneous laser as the unconditioned stimulus and ERC was estimated by analysis of local field potentials recorded through electrodes implanted for investigation of epilepsy. During the pre-stimulus interval of the habituation stage FL>AMY ERC interactions were common. For comparison, in the post-stimulus interval of the habituation stage only a subdivision of the FL (dorsal lateral prefrontal cortex, dlPFC) still exerted the FL>AMY ERC interaction (dlFC>AMY). For a further comparison, during the poststimulus interval of the acquisition stage the dlPFC>AMY interaction persisted and an AMY>FL interaction appeared. In addition to these ERC interactions between modules, the results also show ERC interactions within modules. During the post-stimulus interval HIP>HIP ERC interactions were more common during acquisition, and deep hippocampal contacts exerted causal interactions upon superficial contacts, possibly explained by connectivity between the perihippocampal gyrus and the hippocampus. During the prestimulus interval of the habituation stage AMY>AMY ERC interactions were commonly found, while interactions between the deep and superficial amygdala (indirect pathway) were independent of intervals and stages. These results suggest that the network subserving fear includes distributed or widespread modules, some of which are themselves `local networks'. ERC interactions between and within modules can be either static or change dynamically across intervals or stages of fear conditioning.

Painful cutaneous laser stimuli induce event-related gamma-band activity in the lateral thalamus of humans

“…The terms "gamma band (Ͼ30 Hz)" or "40 Hz" have often been used to describe synchronous neuronal signals. However, the actual frequency ranges showing synchronization between neurons in different structures are variable and are mostly in the range of 20 -60 Hz, which includes the activity below the gamma band (Engel (Andres et al 1999;Classen et al 1998;Mima et al 2001;von Stein et al 1999), subdural electrodes (Ohara et al 2001(Ohara et al , 2004, and depth electrodes (Liu et al 2011a;Tallon-Baudry et al 2001). Therefore, synchronous oscillations are not necessarily limited to the gamma band or to particular cortical structures, especially in the case of large-scale synchrony.…”

Gender difference in valproic acid-induced neuroprotective effects on APP/PS1 double transgenic mice modeling Alzheimer's disease

“…Pavlovian classical conditioning is commonly used to study contextual fear learning [39,40]. This test clearly demonstrated that male AD mice had better learning and memory than female mice, and VPA treatment improved the learning and memory of the AD mice with gender differences.…”

EEG analysis reveals widespread directed functional interactions related to a painful cutaneous laser stimulus

“…Here we briefly describe ERC methods that have already been described in detail in previous reports (Boatman-Reich et al 2010; Korzeniewska et al 2003Korzeniewska et al , 2008Liu et al 2011aLiu et al , 2011b). …”

“…We have now tested the hypothesis that attention to the laser stimulus is associated with increased EEG functional interactions involving widespread cortical structures, which are different from the structures associated with attention to a nonpainful electrical stimulus. The widespread functional interactions were quantified by the event-related causality (ERC), an approach that has previously been used to study event-related interactions among brain areas (Boatman-Reich et al 2010;Korzeniewska et al 2003Korzeniewska et al , 2008Liu et al 2011aLiu et al , 2011b. As a corollary of this hypothesis, we tested whether the analysis of the EEG would show evidence of pain-related ERC interactions characteristic of critical sites.…”