CLINICAL NEUROSCIENTIST

The academic department at the University of North Dakota (UND), under the leadership of Richard Stadter, fostered a tradition of inclusion and collaboration between many disciplines of clinical neuroscience. There were, of course, psychiatrists and psychologists, but also neurologists, neurosurgeons, neuroradiologists, neuropsychologists, neuropharmacologists, neurolinguists, as well as representatives of other related disciplines. Dr. Stadter stood out for his curiosity, diversity of interests, and interdisciplinary perspective. He always looked at how research findings could be used in clinical and educational ways. He was a chairman of a thriving department, almost a renaissance man, dedicated to his work, and highly supportive of the residency training program. I came as a psychiatry resident in such a favorable atmosphere which suited my own orientation in the field of health care.

Orientation toward research in schizophrenia

Even though I had significant obligations related to work, training, exams, and everything else, I decided to pursue my passion for research with the support of my training director, Dr. Staton. I could not miss an opportunity to interact and learn from the eminent investigators who buzzed all around me. When I was in my second year relieved that I passed the dreaded licensing exam, and completed the internal medicine training, I joined the team headed by a professor of neuropsychology who was interested in neuropsychological findings in patients diagnosed with schizophrenia and schizoaffective disorder. I participated in the entire process of planning and conducting this ambitious project. Of course, I didn’t perform neuropsychological testing or interpretation of the results because that required specialized training. To sum it up, I was involved in a very innovative, exciting, and intellectually stimulating work that lasted six months.

I was immersed in the subject of the study, examined the available literature, and gained the knowledge necessary to write an original paper in order to enter the Bingham Award competition for scholarships in schizophrenia. At that time in my career, I was keenly interested in learning as much as possible about schizophrenia. I had years of experience as a result of my 8-year employment at a neuropsychiatric hospital in Vršac where I treated many patients with this condition. I was ambitious, driven, and focused. Even now I could visualize sitting on the apartment floor surrounded by about 100 separate papers which I used as references. Luckily, I knew how to fully utilize my organizational skills to produce, in a short period of time, an award-winning manuscript.

Later on, I had a unique opportunity to learn research methodology at the Neuropsychiatric Research Institute in Fargo, North Dakota. This time it was the basic neuroscience research using post-mortem brain tissues of patients with schizophrenia and evaluating an investigational drug that binds to specific sites in the brain. Naturally, in this study, I did not interact with patients, but with their physical brains in the laboratory setting using the autoradiographic methodology. I was invested in the process, and even applied for a grant, which I didn't get, but at the end of the day, I realized that I wasn't cut for that type of research. I was a clinician at the core, so interacting with living patients was important to me.

Misidentification syndromes

Because I was surrounded by clinically oriented neuroscientists studying brain-behavior relations, I decided to join them. In this process, while doing a clinical rotation at the consultation-liaison psychiatric service in the hospital, I encountered a patient who had a massive stroke in the right brain hemisphere. He was referred to me due to the development of depressive symptoms, but I had noticed a rare phenomenon of reduplication syndrome, in which the patient believed that a person (his wife), place (hospital), time (earlier in his life), had been replaced by “doubles” or relocated. This syndrome is typically delusional because the false beliefs are accompanied by a conviction that is not correctable by experience or reason. This patient didn’t have any prior psychiatric history and it was obvious that damage to the brain tissue was responsible for the production of his unusual symptoms. Very few reports in the published literature had described replication misidentification syndromes arising from a single cerebral vascular disease lesion. It is for this reason and thanks to Dr. Staton's encouragement that I decided to draft the paper and submit it for publication. I was helped by many members of the department with the final version of this manuscript. While I was the author and Dr. Staton was cited as the second author, many others were recognized as contributors. This case report was published in the reputable journal Brain and Cognition. *

I was further interested in exploring the literature related to misidentification syndromes in general. The result of my efforts was the review paper that appeared in The Jefferson Journal of Psychiatry. ** I explored different syndromes by their phenomenology, epidemiology, clinical characteristics, associated clinical findings, etiological theories, diagnostic evaluation, and treatment. The best known of these is Capgras syndrome, the belief that a familiar person or object has been replaced by a nearly identical duplicate or an impostor. If you have ever watched the movie Invasion of the Body Snatchers, you understand the basic features of this misidentification syndrome. In this classic science fiction horror movie, the plot is related to the extraterrestrial invasion taking over an entire community by large seed pods that replicated and replaced human beings. In the film, those who claimed that their family members had been replaced by impostors were initially regarded as delusional, as is the case in true Capgras syndrome. I distinctly remember the first time I watched this classic cult film of 1956 and the disturbing emotional state it produced in me. The subject of impostors had been so well portrayed that numerous adaptations and variations on this topic followed. In my clinical practice, I have seen patients with Capgras syndrome and the devastation it has inflicted on them and their families. It is usually associated with known psychiatric disorders such as paranoid schizophrenia, schizoaffective psychosis, and bipolar disorder.

Having reviewed the extensive literature, I was surprised to discover that the explanation for this syndrome was provided by Dr. Staton. He proposed that there is an anatomical and functional disconnection in the deep right temporal parietal occipital region of the brain which causes deficits in memory integration. New memory registration is disconnected from past memory stores and orientation to the present is based solely on a recollection from the past causing the phenomenon of duplication of persons or objects. *** Another member of our team neurolinguist Dr. Van Lancker offered another perspective. She explained that the delusion of misidentification is a disturbance in the experience of familiarity. Feelings of familiarity include affective interaction between subject and object. In the situation of the right hemisphere dysfunction when there is a defective perception and processing of affective information, that could lead to simultaneous intellectual recognition and affective non-recognition (feelings of unfamiliarity) of known persons and/or objects. ****

Other delusional syndromes

As is evident from the above, I was deeply interested in neural correlates of rare delusional syndromes. To further pursue this interest I started collaborating with Dr. E. Ross, the behavioral neurologist, who distinguished himself in the investigation of nonverbal aspects of language and their relations with the right brain hemisphere. We decided to organize neuropsychiatric case conferences using patients with specific brain conditions, such as stroke, epilepsy, tumor, head injury, etc., who presented primarily with psychiatric syndromes. For this purpose, I identified patients with autoscopic hallucinations, delusions of parasitosis, and Cotard’s syndrome. All of them were misdiagnosed and inadequately treated. They were grateful for our interest and diagnostic accuracy which facilitated their treatment. The case conference was a success and Dr. Ross was great to work with, but due to other obligations, we didn’t produce publications based on this work.

I was in particular intrigued by the phenomenon of autoscopic hallucinations, seeing one’s body at a distance. As I teenager I was obsessed with Dostoyevsky, and I read most of his novels. One of them, The Double, described the phenomenon of the doppelgänger, a visual look-alike, or a double, of the main character of the novel. My patient with autoscopic hallucinations saw himself at a distance during the seizure in the temporal lobe region of the brain. He accepted his double as his “real self”, with the feeling of belonging. This reminded me of a similar phenomenon, out-of-body experience (OBE), in which a person reports leaving his physical body and seeing it from an outside perspective, for example from the ceiling looking down at the body lying in bed. My interest in the near-death-experience studies introduced me to the OBE, which prominently features as one of the common elements of that experience. These hallucinatory phenomena reveal that even the most basic things we take for granted, being grounded in a body, identifying with it, and viewing the world from that perspective, can be disrupted by the dysfunction of the brain.

Cotard’s syndrome, “a walking corpse syndrome”, which I encountered the most, in which the person holds a belief that he is dead, that his organs are rotten or gone, that he is condemned, etc. Usually, it is encountered in patients suffering from extremely severe, psychotic depression, and in these cases, is transient. There are other patients where damage to the brain region called the insula is documented. It is becoming increasingly evident that the insula is responsible for the subjective perception of our body states. Thus, a damaged insula probably interferes with the sense of our own body and leads to misperceptions, such as claims of being dead in patients suffering from Cotard's syndrome.

Visit to the NIMH

Following all of these activities, and on Dr. Staton's recommendation, I was selected for a weeklong visit to the National Institute of Mental Health (NIMH) in Bethesda, Maryland. I was one of 12 who received the award in recognition of my research activities. I had the opportunity to meet and greet some of my favorite research psychiatrists such as Daniel Weinberger. I followed closely his work in understanding schizophrenia. Dr. Weinberger advanced the neurodevelopmental theory of schizophrenia. He argued that the “lesion” in schizophrenia occurred early in development and involved distributed neural circuitries. He believed that no single etiology had a monopoly on the underlying pathology and that clinical and biological heterogeneity reflects inter‐individual variation. He highlighted the deterministic role of brain maturation in the clinical expression of schizophrenia. Weinberger pioneered the application of neuroimaging in psychiatry research. He is responsible for the finding that the prefrontal cortex is considered the main region of interest in many imaging and brain tissue studies related to schizophrenia. My previous studying of the literature enabled me to ask him “intelligent” questions about his research design and the ongoing projects he was working on.

Another of my heroes that I interacted with during my visit was Robert Post, the Chief of the Biological Psychiatry Branch at NIMH. He devoted his career to improving our understanding and treatment of refractory unipolar and bipolar illnesses. Dr. Post was instrumental in pioneering the use of carbamazepine, an anticonvulsant, in the treatment of patients with lithium-resistant bipolar disorder. Animal studies had allowed him to re-conceptualize the recurrence and progression of mood disorders at the level of cyclic alterations in gene expression. He suggested the kindling hypothesis which states that initial episodes of a mood disorder are more likely to be influenced by psychosocial stressors than later episodes. The successive mood episodes grow increasingly more autonomous from the outside factors due to established epigenetic, neurophysiological, or structural changes. These views emphasized the importance of early and long-term treatment of mood disorders to prevent increasing susceptibility to the recurrence of episodes, cycle acceleration and treatment resistance. Particularly, the use of anticonvulsant medications such as carbamazepine, divalproex sodium, and lamotrigine has shown anti-kindling effects and good long-term benefits.

Finally, I met Norman Rosenthal, who was the first, almost on his own, to systematically describe seasonal affective disorder ("winter depression"), a few years earlier. ***** He advanced the use of bright light therapy, which compensates for the loss of sunlight and resets the body's inner clock during the winter months. Because of the long and dark winters in North Dakota, I was very interested in learning from the “guru” about this condition, so widespread among the patients that I treated in Fargo. My interaction with him in 1991 and reading his popular book two years later, ****** gave me an insight into chronobiology and chronotherapy, which I have since studied and applied with success as a treatment of choice to numerous patients. I even used it myself because most people are affected to certain degrees by the effect of changing seasons on daily functioning. The crown result of my involvement in this subject came many years later when I gave a presentation on the topic at the conference for mental health professionals in Fargo. *******

“Green card”

When I got back to Fargo, I was excited and determined to apply for a research program after finishing my residency training in psychiatry. The biggest stumbling block in that plan was my status in the U.S. When I arrived in 1988, I was allowed to stay only until I finished the training, and then I had to return to Yugoslavia. The only exception to this was if the U.S. government agency recommended a waiver to the U.S. Information Agency, the issuer of my J-1 visa. The reason for the waiver and my continued stay in the United States must have to do with the fact that my presence is of national interest. This could happen only in two ways. The first path is if the United States government agency wants to employ me directly. Path number two is if the Department of Health and Human Services, which oversees the National Institute of Health, is asking for an exemption because of my participation in research of national interest.

I hired the best immigration attorney in Minneapolis to assist me in this difficult process. Apparently, this was a multistep activity that required significant financial and human support to succeed. After much consideration, I made a pragmatic and rational decision that the Veterans Administration Medical Center (VAMC) in Fargo is my best option for employment. I had the support of the VAMC and UND leaders, who were willing to put in the extra effort. After a grueling and agonizing process that lasted nine months, I was finally approved on November 2, 1992, as a permanent resident of the United States. The last step was a successful interview with Immigration and Naturalization Service at its district office in Bloomington, Minnesota. The approval was based on my employment at the VAMC in Fargo as director of the hospital psychiatric unit and assistant professor of psychiatry at the University of North Dakota. I obviously had to give up my career path as a researcher to be able to stay in this country. So, I did. This is how my new alternative career path was set in motion. I had to become an “expert” in immigration law, to be able to work with my lawyer in developing strategies that led to the achievement of the primary goal, of staying in the country. I have high respect for a lot of people because of the role they played in that process. With this writing, I would like to single out Robert Aronson, an exceptional lawyer and human being, who played a pivotal role among the individuals to whom I am grateful.

* Reduplication after right middle cerebral artery, by Zeljko Jocic and R. Dennis Staton, Brain and Cognition, 23, 222-230, 1993

** Delusional Misidentification Syndromes, by Zeljko Jocic, The Jefferson Journal of Psychiatry, 10 (1), 3-12, 1992

*** Reduplicative paramnesia, by RD Staton et al., Cortex, 18: 23-36, 1982

**** Personal relevance and the human right hemisphere, by D Van Lancker, Brain and Cognition, 17, 64-92, 1991

***** Seasonal affective disorder: A description of the syndrome and preliminary findings with light therapy, by NE Rosenthal at al., Archives of General Psychiatry, 41: 72-80, 1984

****** Winter Blues, by Norman Rosenthal, Guilford Press, 1993

******* Circadian Rhythms & Mood Disorders, by Zelko Leon, University of North Dakota, Fargo, ND (Grand Rounds), 2014