A Rose by Any Other Name: PTSD and the Olfactory System

In this post, I review and discuss an article on aggression and impulsivity in combat veterans with PTSD tied to Olfactory Identification Dysfunction (OID) (see also Dileo, Brewer, Hopwood, Anderson, & Creamer, 2007). While the human olfactory system has the second highest number of sensory receptor cells – after the visual system (Carlson, 2010, p. 256), is the oldest sensory system evolutionarily speaking (Zillmer, Spiers, & Culbertson, 2008, p. 186), and is the least understood (p. 186), it also has axons (in the olfactory tract of the olfactory bulbs, where the glomeruli synaptically connect to the mitral cells) that project directly to the amygdala and to two other limbic structures called the piriform cortex and the entorhinal cortex (Carlson, 2010, pp. 256-7). This is important for a couple of reasons. First, because the olfactory system does not pass through the thalamus before reaching the cortical (conscious) regions (i.e., Orbitofrontal cortex, OFC, PFC, etc.), rather it links directly to the subcortical limbic system (Zillmer, et al., 2008, p. 189). Second, the olfactorily enervated limbic system, a system largely preconscious, has a direct and practically immediate effect on emotion, mood, and even memory (see also Zillmer, et al., 2008, p. 189). When these systems are disordered, things like Anosmia (think: a-NOSE-mia, loss of smell), dysosmia (distorted smell sensation), phantosmia (experience of a phantom/hallucinatory smell), and hyposmia (diminished taste sensation) are prevalent (Zillmer, et al., 2008, p. 189).

Even Freud was interested in the role of smell and psychological disorders, yet the idea was mostly abandoned until much more recently when scientists began exploring the olfactory correlates of Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and even schizophrenia (i.e., hyposmia and dysosmia as early markers of AD and PD; phantosmia in schizophrenia) (p. 189). Fortunately, the neuropsychological community now has a method of testing for some of these early symptoms, by way of the Pennsylvania Smell Identification Test (UPSIT) – a scratch and sniff test – (Doty, Shaman, & Dann as cited in Zillmer, et al., 2008, p. 189), which Dileo and colleagues also used in their PTSD research (2007).

The deep connectivity to the “smell brain” (or “reptilian brain,” as it is sometimes called) enjoys a burgeoning evidence base and has been found to augment PTSD research and treatment. Dileo and colleagues (2007) add to this research by taking the thinking one step further with the combat veteran population (Vietnam era, outpatient, n=31, with community controls) (p. 523). The authors reasoned that since the complex functioning of the Obitoprefrontal Cortex (OFC) is often impaired in those suffering from PTSD, and since this area of the brain executively applies inhibitory responses, and the OFC is highly enervated to the basolateral amygdala, the OFC is very involved in emotional modulation (2007, pp. 523-4). Aggressiveness and impulsivity is thought to occur due to a failure of medial prefrontal structures to assert executive control over subcortical, limbic, amygdalic firing, the natural question, because of the direct link to the olfactory system, was to test these veterans who are often aggressive and impulsive due to their diagnosis, to determine the correlation of OID. As one might expect, and as other research demonstrates (see also Dileo, et al., 2007, p. 524), the OID is now thought to be a useful measure of OFC integrity and thereby a good predictor of PTSD-associated aggressivity and impulsivity (p. 524). In fact, the “OFC mediates odor identification [and refining of smells] as found via lesion and neuroimaging…[and because the OFC is connected with the limbic system and parallels the circuits for smell identification] OID’s have been strongly associated with impaired inhibition of affect, delusions, and maladaptive behavior (Martzke, Kopala, & Good, as cited in Dileo, et al., 2007, p. 524) and are found in combat veterans with PTSD (p. 528). Most importantly, the study concluded that the presence of OIDs are an important diagnostic indicator in predicting aggression and impulsivity, though as of yet, it remains difficult to say how effective OIDs can be in explaining the complexity of the OFC (p. 529).



References

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

Dileo, J. F., Brewer, W. J., Hopwood, M., Anderson, V., & Creamer, M. (2008). Olfactory identification dysfunction, aggression and impulsivity in war veterans with post-traumatic stress disorder. Psychological Medicine, 38(4), 523-531. doi:10.1017/S0033291707001456

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

Happy same-race face familiarity and the right ventral stream

I have often extolled the ideas of polymodality or association, that the brain does not maintain a one-to-one structure-function correlation, and in visual processing this is also the case (see also Zillmer, Spiers, & Culbertson, 2008). While there is not a common visual processor, despite the name “occipital lobe,” there does exist a “seemingly instantaneous… culmination of separate but locally connected visual-perceptual processes” (p. 200). Not only are these seemingly instantaneous processes happening linearly, they also happen in parallel, giving us what is called bottom up percept formation and top-down building, though the latter is a matter of debate (p. 200).

I might like to include a word or two from a previous post in response to another learner about polymodal circuits in the brain.

The “what” pathway is occipital input along the occipital-temporal (associational) pathway to the inferior temporal region, helps us to recognize objects and perceive things (Zillmer, et al., 2008, p. 160; and for a great discussion on autism spectrum disorders and the Fusiform Face Area or FFA which is part of the social-emotional brain/circuit, which includes, amongst other regions, temporal, frontal, and limbic/other subcortical nuclei, see pp. 316-18). The “where” pathway, which, as you might guess, is similar occipital input orients more to the occipital-parietal pathway and to the posterior parietal lobe, processes this way to give us “where,” or spatial recognition. (Brown, post to a colleague on Capella course page, 2009).

In this post, I will cover one article on the neural correlates of same-race face recognition using positive/happy stimuli. The study in question demonstrated that same-race faces showing positive stimuli (in this case, three races where used, Japanese – the participants were all Japanese – other Asian, and Caucasian) positively correlate to greater amygdalic, posterior cingulate cortex (PCC), and superior temporal gyrus (STG) (the STG because these same-race faces where subjectively more familiar than the others) (Iidaka, Nogawa, Kansaku, & Sadato, 2008, p. 91). These results were also corroborated in many other studies that the authors thoughtfully cited and from which they drew a very clear, logical pattern and generated hypotheses.

Additional findings included that “the PCC is the neural correlate that is specifically involved when the Japanese subjects judge the happy expression on a same-race face;” that the amygdala responded to the presentation of both positive and negative emotional content; that the superior temporal sulcus (STS) is more active when greater personal familiarity is present in the stimulus; that “regions adjacent to the posterior STS may play a similar role as the PCC with regard to the same-race face processing;” and lastly, that because the PCC is implicated in memory retrieval, this region is thought to correlate to a sense of familiarity when the subjects viewed a happy face from their own race (pp. 97-8).

So, what goes wrong when lesions to these areas of the brain occur? Typically, these disorders are referred to as apperceptive and associative visual agnosias, such as prosopagnosia or the inability to recognize people by their faces (Zillmer, et al., 2008, p. 207). While prosopagnosia is thought to be a disorder of higher order processing relayed through the thalamus (p. 204), it is clear that the “what”/ventral stream, a stream that helps to connect visual perception with meaning (p. 206), receives impulses from the subregions of the visual association cortex, the V2 area, and the striate cortex (Carlson, 2010, p. 196). The left hemispheric ventral stream is associated with letters and numbers (symbols) whereas the right is more specific to recognition of faces and other objects (Zillmer, et al., 2008, p. 207). Damage to the right side can result in visual agnosia, such as prosopagnosia; whereas left sided damage results in neglect and problems distinguishing between left and right (p. 207). Cognitive neuropsychologists generally classify these agnosias into two groups: apperceptive visual agnosias (problems with object perception – like seeing in bits and pieces) and associative visual agnosias (problems assigning meaning to objects) (p. 207). If both hemispheres are involved, Balint’s syndrome may be involved, which includes visual agnosia with visuospatial difficulties such as mis-reaching and neglect (p. 207).

These ideas are fascinating in their polymodality and association in tandem, often overlapping, parallel streams. I might pose the following questions for thought: how can researchers acknowledge polymodality, while noting the relative unitariness of various constructs such as “problems differentiating left from right” or degree of happy, same-race face familiarity? Does this have some implication for the physico-behavioral mapping of continuous neurophysiology? What are the implications of extra-regional lesion – that is, when the boundaries of a lesion exceed the region’s known, discrete function?
These and other questions will perhaps keep you up tonight. Rest assured, however, there will be another day to explore this wild west of science.


References

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

Iidaka, T., Nogawa, J., Kansaku, K., & Sadato, N. (2008). Neural correlates involved in processing happy affect on same race faces. Journal of Psychophysiology, 22(2), 91-99. doi:10.1027/0269-8803.22.2.91

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

Is PTSD neurotoxic?

In this brief article I will address biopsychological research of Post Traumatic Stress Disorder (PTSD). The study reviewed (Gilbertson, Shenton, Ciszewski, Kasai, Lasko, Orr & Pitman, 2002) utilized a “case-control” monozygotic twin design. This kind of study is used to explore the influence of heredity on a particular trait (in this case hippocampal volume in PTSD discordant twins, one of whom was exposed to combat in Vietnam, see also Gilbertson, et al., 2002) (Carlson, 2010, p. 166).

Briefly, and as temporal background to frame this particular research, structural magnetic resonance imaging (MRI) studies report that hippocampal volume in PTSD patients is noticeable smaller and it is hypothesized that psychological trauma may cause neurological damage due to neurotoxic activation of corticosteroids leading to hippocampal neuronal death (Gilbertson, et al., 2002, p. 1242). (in fact, this was the hypothesis under study). In this monozygotic twin study, the authors tested this neurotoxic hypothesis, by way of examining combat exposed Vietnam veterans and their stay-home twin brothers in order to revealing whether or not smaller hippocampal volume post – combat experience was either a pre-existing condition or a direct result of traumatic experience (p. 1242). Finally, “[b]ecause monozygotic twins are genetically identical, any differences in hippocampal volume between brothers were interpreted as evidence for environmental effects, such as stress-induced neurotoxicity [as a result of combat exposure and not as a result of a exposure to combat with a smaller pre-existing hippocampal volume]” (p. 1242).

While the study also examined several other variables concomitant to a severe PTSD diagnosis, for example, alcohol abuse and depression, the major finding is stated best by the authors themselves: “the key finding here concerns the identical twins of the higher severity PTSD combat veterans who were not themselves exposed to combat; they showed hippocampal volumes that were comparable to their combat-exposed brothers but significantly smaller than those of combat veterans without PTSD and their non-combat–exposed twins” (p. 1245). This clearly indicates that people with genetically (“given”) smaller hippocampal volumes are more likely to develop severe, unremitting PTSD than those with larger volumes (p. 1245), ceteris parabus. In other words – size matters. This effectively refutes the neurotoxicity hypothesis, therefore “reference to hippocampal ‘atrophy’ in PTSD may be a misnomer” (p. 1245).

This seminal study effectively settled a longstanding controversy of biopsychology, that the brain was injured by trauma due to neurotoxicity. While this is not absolutely ruled out by this study, it is clear that even when comorbid alcohol abuse and depression are circumvented via case-control design, that people who have smaller hippocampal volume are at greater risk for developing severe PTSD, especially when exposed to the terror of combat, and even then, independent of combat severity (p. 1245).

It is important to note that the hippocampus is involved in fear processing, memory (especially declarative memory – or, memory that is explicit, factual, and assessable to conscious awareness; this is highly correlated with the hippocampus and the medial temporal lobe, amongst other areas of the prefrontal cortex – the left dlPFC for encoding and the right PFC for retrieval, according to the Hemispheric-Encoding-Retrieval-Asymmetry (HERA) model, Zillmer, Spiers, & Culbertson, 2008, pp. 227-9), and in the important conditioning and extinction mechanism in animals and, likely, humans (having an effect on neuroendocrine regulation of the hypothalamic–pituitary–adrenal axis) (Gilbertson, et al., 2002, pp. 1245-6). Lastly, it is heredity that is likely the responsible etiology of smaller hippocampi observed in this study of twin Vietnam War-era brothers (though with a dizygotic twin study, this might have been further clarified) (p. 1246). Further sealing up the argument is the fact that in the study those veterans who had combat exposure and larger hippocampal volume and did not develop PTSD refutes the neurotoxic and/or shared environment hypotheses (though without a dizygotic study, this remains unclear) and adds strength to the aforementioned findings of this seminal study demonstrating PTSD susceptibility in those with smaller hippocampal volume (p. 1246).

References

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

Gilbertson, M. W., Shenton, M. E., Ciszewski, A., Kasai, K., Lasko, N. B., Orr, S. P., & Pitman, R. K. (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature Neuroscience, 5(11), 1242-1247. doi:10.1038/nn958

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