The Insular Cortex, von Economo neurons, and awareness of feelings

September 9, 2013 at 3:36 PM
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The Insular Cortex, von Economo neurons, and awareness of feelings

Ilyssa Monda-Loiacono, Golshan Aghanori QC’13, Jungyo Kim QC’13, and Jim Stellar

Led by Ilyssa, who is a graduate student, Golshan, Jungyo, and Jim have been reading papers on the human Insula Cortex, following up a blog co-written by one of us a short time ago.  In that earlier blog post we characterized the Insula cortex as part of a risk-reward system that is also involved in one’s empathy reactions to the observation of pain in others.  Now we want to revisit this issue with some hard-core neuroscience and tie this brain area to a group of neurons that are almost uniquely found in humans.  Then we will link the whole structure to a larger concept of how we communicate between levels of our brain functioning and tie it back to learning from experience in a college education.

Insula Cortex:

The human insula was first described by the anatomist Johann-Christian Reil and is since known as the Island of Reil (Bouvier, 2007). It is buried within the Sylvian fissure at the border of the frontal, temporal and parietal lobes of the brain (Bernhart & Singer, 2012). The insula is shaped like a triangle with its apex (peak) directed down and forward (Flynn, Benson, & Ardila, 1999). It can only be seen anatomically by pulling back the frontal and temporal lobes. The insula is divided into three cytoarchitectonic areas which are thought to be associated with different functions: (1) the anterior agranular insula (Ia) that is related to olfactory and autonomic functions, (2) middle dysgranular insula (Id) that is associated with gustatory functions, and (3) posterior granular insula (Ig) that is associated with somatosensory, auditory and visual functions (Chikama et al. 1997).

Early in fetal development, the tissue of the insula forms on the lateral surface of the cerebral hemisphere, shifts downward in the anterior direction of the temporal lobe, then pivots around the insula surface. The insula remains smooth until the 15th week of gestation and at about the 20th week, there is a differentiation between the posterior and anterior insula (Flynn, Benson, & Ardila, 1999.) The human insula has bidirectional connections with frontal, parietal and temporal lobes, the cingulate gyrus as well as many subcortical structures. Tract-tracing experiments in nonhuman primates suggest that the anterior insula is densely connected with prefrontal regions, such as orbitofrontal cortex (OFC) and the dorsolateral prefrontal cortex (DLPFC), temporo-limbic regions, parahippocampal cortices, the amygdala, the cingulate cortex, thalamus basal ganglia, and the brain stem (Bernhart & Singer, 2012). The posterior insula and the anterior cingulate cortex, receives differentiated inputs for pain, itch, warmth, cooling, and sensual touch, which are central components of physiological homeostasis (Allman, 2010). The anterior insula is also known to the activated by peripheral autonomic changes.

Critchley 2000, found that the anterior insula was activated using the Galvanic Skin response during a decision making task. The anterior insula and the anterior cingulate cortex are also activated by situations that involve social error, resentment, embarrassment, and guilt.  Most notably, they are also activated by feelings of empathy for the suffering of others. Recent studies on the neural mechanisms of empathy for pain, disgust and unpleasant experiences, indicate that empathy is subserved by a cortical network primarily consisting of the frontoinsular cortex and the anterior cingulate cortex (Gu, Liu, Guise, Naidich, Hof & Fan, 2010).  The frontoinsular cortex is known as the limbic sensory region, responsible for sensory integration, conscious awareness and subjective feelings.  The anterior cintulate cortex is known as the limbic motor cortex that participates in voluntary control, self-initiated behaviors, pain, emotion and personality, learning and value of actions and social interaction. A number of neuroimaging studies on pain processing have demonstrated partial neural overlap between the experience of pain in the self and the observation of pain in others. Different sections within the insula are also highly interconnected, allowing a bidirectional flow of information between both the anterior and posterior sections. The posterior insula is thought to be connected to primary and secondary somatosensory areas and the supplemental motor area which are thought to be involved with sensorimotor tasks in humans.

Von Economo neurons:

Constantine Von Economo lived in the early part of the 1900s and discovered an interesting set of neurons that have been more recently studied by John Allman’s laboratory at Caltech and other laboratories. The neurons are found in the anterior portion of the insula cortex in humans in the highest numbers, by far, of any animal.  They are large, reach out to many brain areas, and seem to connect emotional processing to high level cortical processing.  A distinguishing feature of the anterior insula is that it contains what we call today von Economo neurons. They are large bipolar neurons that reside predominantly in layer five of the frontoinsular and anterior cingulate cortices of humans and great apes (Allman, 2010). Their axons are either elongated straight or somewhat crooked resembling a screw-like morphology.   Von Econonomo called these specialized neurons rod and corkscrew cells, referring to the straight and twisted variants of this distinct class of neurons (Allman, 2010).  In his description of these neurons as a rod or corkscrew, he recognized the association between the brain containing them (anterior insula & anterior cingulate) and autonomic function, speculating, “a cerebral representation of the autonomic or sympathetic nervous systems in particular the areas of the insula” (Seeley et al. 2012).

A link to the control of such internal states and associated motivations is also specified by the expression of several neurotransmitter receptors including vasopressin type1a receptors, dopamine type D3 receptors, and serotonin 2b receptors, which have been implicated in social bonding, reward processing and visceral control respectively (Gu, Hof, Fristen, & Fan 2013).  Von Economo neurons also express activating a protein called transcription factor 3 that is involved in stress reactions, and pain sensitivity, interleukin-4 receptor, which is associated which is associated with inflammatory responses, and bombesin peptides such as neuromedin B, as gastrin peptide that participates in gut control (Allman, et. al, 2010).

Von Economo neurons are projection neurons and are substantially larger than the classical pyramid-shaped or pyramidal cells that surround them, however their specific targets are unknown. Their large cell bodies provide for rapid transmission of information to other parts of the brain.  Both in humans and chimpanzees, Von Economo Nuerons appear late in gestation (35 and 45 weeks, respectively) (Fajardo, 2008).  In humans the number of these neurons increases until the ages of four, while in chimpanzees the number decreases in early postnatal life.

The frontoinsula cortex is further distinguished by second large layer five neuron, the fork cells. In 1932, Ngowyang published an article dedicated to the description of these neurons, for which he offered the term “Gabelzellen” (fork cells). The fork cell features a von Economo neuron related, but distinct morphology having a single basal dendrite, but two large divergent apical dendrites (Seeley, 2012). These fork cells are densely populated in the frontoinsula cortex, however they are not located in the anterior cintulate cortex like von Economo neurons.  Based on the location of these neurons, it was proposed that both von Economo neurons and fork cell played a role in both emotional and higher order cognitive behaviors.

Patterns of connectivity in animals have recently been reproduced in humans using diffusion tensor imaging form of brain scan and correlations between the timing of activity patterns in the resting state on an fMRI machine.  Patterns indicate that a central role, especially of the anterior insula, in integrating interoceptive and affective information. (Bernhardt, 2012).

Awareness of Feelings:

Damasio in his recent book, Self Comes to Mind, uses this concept of awareness of feelings to help develop a theory of conscious awareness.  We will leave that to him, but simply note here that these processes of checking with the basic state of well-being, or not, (pleasure and pain) is key to unconscious decision making that underlies much of what we have been writing about in this entire blog.  The idea is simply that the two mechanisms discussed above, or ones much like them, may underlie the communication between what Damaiso calls the “body wellness sense” and the conscious thought processes about which we can talk or have awareness.  We have called this communication between the mammalian brain and the primate brain after the famous triune brain theory of Paul MacLean.  We have also referred to them as conscious vs. unconscious decision making processes after books by Kahneman and Eagleman.  But Blaise Pascal put it best when he said something like “heart has reasons of which reason does not know.”  We have used that quote a lot in this blog.  Maybe some of the neural structures discussed above are part of how “the heart decision processes” may communicate with the “head decision processes” in making such reasons known to reason – to use Pascal’s words.

Experiential education in higher education

By now you hardly need us to state the obvious point…if you made it this far.  The point is that experiential education contains a rich source of information about real-world tasks that students are contemplating, even if that contemplation happens outside consciousness awareness.  Working in an accounting or law firm or for a nongovernmental organization or in a hospital, provides this kind of felt knowledge that allows the student to see if the career is right for them.  They already know some of the facts and theories about the field.  The biology major has been studying the principles of medicine, but it is different when you see them applied to a patient right in front of you who can talk back.  We need a much better understanding of these processes and especially how to integrate these experience with the conscious decision-making processes through which our student must act.  And we need to know how to do that in college so our students graduate just as excellent in their critical thinking ability, but armed with integrated experience so they are work ready and before that are passionate about their education while they are in college.

Additional  references:

Allman, J. M., Tetreault, N. A., Hakeem, H.A., Manye, K.F., Semendeferi, K., Erwin, J.M., Park, S. 2010). The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Structure and Function. 214, 5-6, 495-517.

Augustine, J. (1996). Circuitry and functional aspects of the insular lobe in primate including humans. Brain Research Reviews, 22, 229-244.

Bernhardt, B.C., & Singer. T. (2012) The neural basis of empathy. Annual Review of Neuroscience, 35, 1-23.

Chikama. M., Mchfarland, N.R., Amaral. D.G., & Haber. S.N. Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. (1997). The Journal of Neuroscience, 17, 9686-9705.

Critchley, H., & Seth, A. (2012). Will studies of macaque insula reveal the neural mechanisms of self awareness? Neuron, 74.

Cauda, F., D’Agata. F., Sacco. K., Duca. S., Geminiani, S., & Vercilli, A. (2011) Functional connectivity of the insula in the resting brain. NeuroImage, 55, 8-23.

Flynn, F.G., Benson, D.F., & Ardila, A. (1999). Anatomy of the insula. Journal of Aphasiology, 13, 55-78.

Farjardo, C. Escobar, M.I., Buritica, E., Arteaga. G., Umbarila, J., Casanova. M.F., & Pimienta, H. (2008). Von economo neurons are present in the dorsolateral (dysgranular) prefrontal cortex of humans. Neuroscience Letters, 435, 215-218.

Gu, X., Hof, R. P., Friston, K., Fan, J. (2013) Anterior insula cortex and emotional awareness. J. Comparative Neurology Research in System Neuroscience. 521, 3371-88

Gu, X., Liu, X., Guise, K. G., Hof, P., Naidich, T. P., & Fan, J. (2010). Functional dissociation of the frontoinsular and anterior cingulate cortices in empathy for pain. Journal of Neuroscience, 30(10), 3739-3744.

Seely, W. W., Merkle, F. T. Gaus, S. E., Craig (Baud), A.D., Allman, J.M., & Hof, P.R. (2011). Distinctive neurons of the anterior cingulate and frontoinsular cortex: a historical perspective. Cerebral Cortex, 22, 245-250.

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  1. Women, Decision-Making, and Experiential Education | The Other Lobe of The Brain says:

    […] Where the men and women did differ was in the precise pattern of brain activation including in the anterior insula cortex leaving the authors to conclude that “women are relatively more focused on internal […]

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