Forget the excitotoxic tiger: Memory, traumatic stress, and the amygdalae

Stress in both humans and animals has various effects, biopsychologically. One important effect (along with behavioral anxiety, hyperarousal, gastrointestinal motility, food intake changes, increased defecation, sleep disturbances, attentional deficits, and avoidance of novel stimuli, etc.) includes memory deficit (Vermetten, & Bremner, 2002, p. 127). Some of the physiological components of memory include the prefrontal cortex (PFC – especially in working memory), hippocampus (involved in declarative memory formation and sends efferent information to various areas for consolidation; even spatial memory in the right-posterior hippocampus; place/topographic, etc. – see also Carlson, 2010, pp. 471 & 483-4), the neocortex (damage to which causes semantic dementia – loss of facts), and the structure upon which I focus this post, the amygdala – involved in the emotional encoding of memory, and of course the hippocampi – which will not be discussed here in depth, the curious reader might consult any of the sources listed in the references section.

Stress has massive effects on memory processes involving “neurohormonal modulation of the laying down of memory traces” even thought to influence the strength of neuronal connections that influences consolidation (Vermetten, & Bremner, 2002, p. 138). In fact, “[i]ncreased level[s] of norepinephrine released during stress can modulate memory formation through action on the brain. … norepinephrine modulates [the following] aspects of memory: acquisition of new information… attentional component[s] of memory storage … and working memory” (pp. 138-9).

Norepinephrine isn’t the only neurochemical to influence the stressed brain, the glucocorticoids and glutamate also potentiate (especially in long term potentiation, LTP) severe damage to the structures and functions of the brain (Carlson, 2010, pp. 444-5). When stressed (damaged or diseased), synaptic vesicles are triggered to release glutamate that transporters do not remove, rather accumulate, in excess, extracellularly, allowing Ca+ ions to enter NMDA receptors leading to excitotoxicity and cell death (also happens in ischemic cascade in traumatic brain injury [TBI], stroke [cerebral vascular accident, CVA], autism, and Alzheimer’s Disease [AD]) (Carlson, 2010, pp. 446-8; Zillmer, Spiers, & Culbertson, 2008). Two other chemicals, dopamine (DA - especially in the PFC with working memory system, downregulated during stress) and epinephrine are endogenous memory modulators – and are especially active during arousal and stress (upregulated during stress) (see also Vermetten, & Bremner, 2002, p. 139).

The amygdala is involved in emotional memory and in the conditioned fear response (learning) mechanism (Carlson, 2010, pp. 369-71; Vermetten, & Bremner, 2002, p. 139). In fact, studies show that “the degree of activation of the amygdala during the encoding of emotionally arousing material (positive or negative) correlates significantly with subsequent recall of the material (declarative retention increase through enhanced hippocampal consolidation, though, with an upper limit – chronic over-arousal leads to impaired memory due to adrenalcortical upregulation – Zillmer, et al., 2008, p. 260). Lastly, the authors reviewed for this post (Vermetten & Bremner, 2002), provide an excellent (and very technical) synopsis of the major amygdalic connectivities (studied via lesion/damage) involved in stress, quoted here at length:

“Lesions of the central nucleus of the amygdala have been shown to completely block fear conditioning, while electrical stimulation of the central nucleus increases acoustic startle… The central nucleus of the amygdala projects to a variety of brain structures via the stria terminalis and the ventral amygdalofugal pathway. One pathway is from the central nucleus to the brainstem startle reflex circuit (nucleus reticularis pontis caudalis). … Pathways from the amygdala to the lateral hypothalamus effect peripheral sympathetic responses to stress. … Electrical stimulation of the amygdala in human subjects resulted in signs and symptoms of fear and anxiety including an increase in heart rate and blood pressure, increased muscle tension, subjective sensations of fear or anxiety … and increases in peripheral catecholamines. … There are also important connections between cortical association areas, thalamus and amygdala that are important in shaping the emotional valence of the cognitive response to stressful stimuli. In addition to thalamo-cortico-amygdala connections, there are direct pathways from thalamus to amygdala, which could account for fear responses below the level of conscious awareness” (pp. 139-40).

Maybe the most likely candidate for discussion of memory system damage is the boundary-ignoring, progressive dementia (traditionally thought of as a cortical dementia) known as Alzheimer’s Dementia [AD] (Zillmer, et al., 2008, p. 411). AD is a fatal illness, marked by both cortical and subcortical atrophy/degeneration; with postmortem autopsy (the only way the diagnosis is confirmed) revealing most damage to the cortical temporoparietal association areas (as well as the frontal – including subcorticofrontal nucleaus basalis of Meynert and olfactory areas – temporal, and parietal areas generally) and the subcortical limbic cortexes (where the amygdalae and hippocampi live) (p. 411).

In sum, the memory system is a very complex and interconnected one, impacted by experience and genetics, trauma and disease. I hope to incorporate this learning into my specialization with the work of those suffering the sequelae of trauma. Memory is a vast area, perhaps even a subspecialty in traumatology, and comprises many different areas of inquiry ranging from false memory, recovered memory, repression of memory, anterograde amnesia, retrograde amnesia, dissociative disorders, and, really, the entire foundation of traumatology. Were it not for memory, no one would have a problem with trauma, after the bodily reactions had passed – the sympathetic nervous reactions, the shaking, and the discharging. I recall the work of Peter Levine (Waking the Tiger) and his storying of the process an animal in the wild might go through after a brush with death, an attack. The animal might rest, shake and discharge, then get up and rejoin the heard. If only if it were that simple with humans.

Certainly, understanding the biopsychological underpinnings of memory and trauma are vital to my work. It is helpful to gain familiarity with the scientific thinking behind some of the interventions recommended by literature, and begin to see ripples and echoes of dovetailing work fitting nicely together, rounding out the toolkit to best help those who suffer their memories.


References


Carlson, N. (2010). Physiology of behavior, (10th ed.). Boston: Allyn & Bacon.

Vermetten, E., & Bremner, J. (2002). Circuits and systems in stress. I. Preclinical studies. Depression and Anxiety, 15(3), 126-147. doi:10. 1002/da.10016

Zillmer, E., Spiers, M., & Culbertson, W. (2008). Principles of neuropsychology, (2nd ed.). Belmont, CA: Thomson Wadsworth.