Targeting the Connectome for Treatment of Mental Disorders

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Olutola Ebunlomo

Topic: Targeting the Connectome for Treatment of Mental Disorders: “But the brain is naturally endowed with the organisms for connectome change– reweighting, reconnection, rewiring, and regeneration– that are exquisitely controlled. Since genes and other molecules guide the four R's, they could serve as targets for drugs...the idea of the connectome as the target for medications...” (Seung, 2012, 217)

The idea of curing mental disorders holistically, meaning not just relieving the side effects, but truly repairing the source of the problem is a daunting feat. Even more daunting, is the idea of preventing these mental disorders, especially when knowing for sure when and in whom they will arise seems impossible. However, these limitations arise with the train of thought that medication for mental disorders must remain target-specific. If the connectome, the part of the brain suited for change and development, were thoroughly investigated, the potential of finding medications that treat the source and even prevent is much more viable. In focusing on the most adaptable part of the brain, the possibility of correcting mental disorders, even those that cause damage to brain cells, could be increased. The next step would also be equipping the connectome with the safeguards necessary to protect the brain from becoming affected by neurodegenerative disorders. The potential of the connectome, as a dynamic and versatile entity, could revolutionize the relatively archaic approach to mental disorders practiced for the most part today. The goal of connectomics is to map the structural and functional networks through which the brain is interconnected. The brain is studied as a network or set of subnetworks for the purpose of finding the pattern of connectivity between specific regions that specialize in specific functions that pose limitations on brain dynamics. Through such, it can be learned the brain’s processing abilities. Segmenting the brain and studying its parts in isolation, is no longer a very promising option. The span of mental disorders and their effects on the brain are too wide to constrain study to particular sections. It seems that this method, the reductionist approach, may be reaching its limit in terms of providing new and meaningful insight into the treatment of mental disorders.

There has been a recent push to begin conceptualizing mental disorders as “alterations in large-scale functional and structural brain networks.” This new approach has produced a series of studies, for example: the works of scientists Harrison (who showed the relevance of ventral corticostriatal networks in characterizing the symptoms of obsessive compulsive disorder) and Zhang (who showed instrinsic alterations in the architecture of a network supporting cognitive control in OCD patients), that demonstrate how the mapping of the connectome in OCD patients revealed certain aspects or patterns in neural activity in people with these disorders. This is just one example of how examining the connectome can provide beneficial markers for psychiatric disorders, not just in one section of the brain, but throughout it. Connectomics may also play a role in establishing the genetic alterations that eventually induce mental disorders.

In studying the connectome for treatment of mental disorders, neuroimaging technology is at the forefront of any potential breakthrough. The aim of studying the conenctome is to be able to differentiate between what can be categorized as a “regular” connectome versus an “irregular” connectome, which would then fit into a standard predetermined to be specific to particular mental disorders. However, before such definite maps of the connectome are made for the sake of treatment of mental disorders, the primary goal is to develop neuroimaging technologies that will increase the accuracy and efficiency of such endeavors. Recent attempts at neuroimaging include the recently developed method of Diffusion Spectrum Imaging (DSI). DSI revealed the grid structure of neural connections. DSI is described as “the refinement of diffusion tensor imaging that uses fMRI technology to infer the presence of axonal fibers from the motion of surrounding water molecules.” The new DSI scanner is called the Siemens 3T Connectom, which has been able to successfully reveal fiber pathways in detail faster and more accurately than its predecessors.

Apendix 1.jpg (Appendix 1)

However, the issue of this DSI scanner remains finding ways of linking the fiber pathways it reveals to specific functions. Another issue, not with just the scanner, but with all attempts of neuroimaging, is that it is a “snapshot” of a changing structure that reacts differently under certain circumstances. The very thing that the connectome is praised for: adaptability is what is holding back progress on effectively mapping it for the sake of progress in the study of mental disorders. This posits the idea that maybe to use neuroimaging successfully, the focus cannot be on obtaining one inactive image of the connectome, but rather on capturing motion in short video stills of the connectome in different circumstances. This could also resolve the issue of matching the fiber pathways to their specific functions. The video would show which parts of t he connectome are most active in particular situations and from that, it could be deduced which parts of the connectome do what. In finding the ways that a “regular” conenctome moves versus how it looks, there can also be a more accurate perception of what a “normal” connectome is and how to get an “irregular” connectome (meaning one damaged by a mental disorder” to function “regularly” again.

The role of the conenctome in treating mental disorders is already a part of current research. In the study “Exploring the Psychosis Functional Connectome: Aberrant Intrinsic Networks in Schizophrenia and Bipolar Disorder,” scientists are using the knowledge of connectomes that current neuroimaging techniques have provided. They compared patients with schizophrenia and bipolar disorder, disorders that share a lot of symptoms, with normal patients to monitor the intrinsic functional brain networks (regions showing temporal coherence with one another) in all three of the subject types. Their observations showed noticeable differences in the way the connectomes, intrinsic functional brain networks, of bipolar and schizophrenic reacted.

Apendix 2.jpg (image of the differences of the functional network connectivity, Appendix 2)

EApendix 3.jpg (Illustration depicting the key regions that showed differences between the groups tested, Appendix 3)

This shows that even in mental disorders considered somewhat similar, there can still be clear differentiation between them in the mapping of the connectome. This confirms the value of the connectome, and mapping it, in creating standards for connectomes affected by mental disorders, which would eventually serve as the “before” in a “before and after” approach to treating the connectome or in preparing it to prevent mental disorders.

The potential for the connectome in the treatment of mental disorders has not yet been fully explored. With the advancement of neuroimaging technology comes the prospect of more accurate standards upon which to base mental disorders. To meet the growing complexity of the brain and its disorders, there must be a reevaluation of the way mental disorders are looked upon. They can no longer be attributed to section specific-happenings; the expanse of mental disorders must be observed throughout the brain. Mapping the conenctome is a dynamic process and must be regarded as such. The reaction of the connectome to specific circumstances and the way it adapts to change, destruction, and growth can be helpful in treating mental disorders. Once there is a firm enough grasp on the study of the connectome, there comes the opportunity to manipulate it¬– both for the purposes of repair and even prevention.

Appendix: 1. National Institute of Mental Health. “Brain Wiring A No Brainer?” March 29, 2012. 2. Calhoun, V.D., Sui, J., Kiehl, K., Turner, J.A., Allen, E.A., Pearlson, G. Exploring the Psychosis Functional Connectome: Aberrant Intrinsic Networks in Schizophrenia and Bipolar Disorder: Figure 2. Frontiers in Psychiatry. 2012. 3. Calhoun, V.D., Sui, J., Kiehl, K., Turner, J.A., Allen, E.A., Pearlson, G. Exploring the Psychosis Functional Connectome: Aberrant Intrinsic Networks in Schizophrenia and Bipolar Disorder: Figure 4. Frontiers in Psychiatry. 2012.