From Freud to Magnets

From Freud to Magnets

There’s a decent chance that you’ve heard of Sigmund Freud, the household name of twentieth century psychiatry. His name is spoken in all kinds of tones – most often, respect, unease, and contempt. In an introduction to psychology course that many of you may have attended here at UCLA, his name was spoken with dismissal and ridicule. Some say this is rightly so, seeing as there is no evidence to support his ideas about human behavior. In fact, his ideas have proven catastrophically unprovable. However, while scientific critique is the way by which science marches on, disrespect of a historical and influential thinker in front of hundreds of eager, impressionable students isn’t. Whether or not we agree with him, Freud is a giant whose shoulders physicians and scientists stand on today. The narrative of psychiatry that he influenced so tremendously is one that is now emerging into the spotlight once again, but with a radically different face. Today, psychiatry comes hand in hand with data science, advanced genetics, and brain stimulation magnets, at UCLA as much as with any other research institution. How did we get here?

Freud’s claim about life was that humans invest libido in activities, people, objects and goals, and that the effects of this are deeply embedded in subconscious processes. He posited crucially important stages at which people particularly invest themselves in others. In a sense, then, it’s natural that Freud produced theories about the effects of childhood interactions on behavior. His therapeutic treatments were designed to help patients unravel knots of repressed feelings, by leading them through conversational therapy until the patients revealed to themselves the root cause of their issues. The problem was that to reach that depth, the physician entered the murky waters of subjectivity – the home of art, not science. Thus, while Freud brought out the idea that the interaction of people with their unique and complex inner lives is profoundly relevant to illness, his approach de-emphasized the sure, rigorous classification of symptoms that is a basis of medicine.

The scoffing tone directed at Freud isn’t all that different from the critique that has traditionally been aimed at psychiatry by other branches of medicine, for being ‘brainless’, in two senses of the term. To understand this, let’s go back to the twentieth-century state of psychiatry. Again, Freud’s approach, which had at first taken psychiatry by storm, was de-emphasizing the observation and classification of symptoms. On the other hand, John Watson, who studied how organisms learn and develop new behaviors, was championing the behaviorism school of thought, which is defined by its concern with what is on the surface of human behavior. In other words, behaviorism is only interested in what is objectively measurable. In the later 20th century, the dominant psychoanalytic methods were under heavy criticism, for their unscientific method and unreliable results. This reached a turning point when a 1973 paper in Science, titled “On Being Sane In Insane Places”, reported secretly admitting 8 pseudopatients who claimed occasional voices saying a few words (Rosenhan, 1973), but then acted completely normal for the entirety of their hospital stay. The finding was that in each case, psychiatrists and hospital staff disregarded completely normal behavior and histories, instead making each patient fit a diagnosis of schizophrenia in remission. The sane couldn’t be distinguished from the insane and since the treatment of patients and the words of physicians hold a power of suggestion, the medical maxim, “First, do no harm” was being profoundly violated. As it turned out, the official manual of psychiatry, or the diagnostic and statistical manual of mental disorders (DSM) was redone in 1980. The new one, six times greater in size, contained a radically rigorous classification of symptoms, with almost nothing remaining from psychoanalytic methods.

The sociologist Christopher Badcock makes an interesting comparison between this shift and mental illness itself. His idea first acknowledges that mentalism, which is the ability to understand other people’s behavior in terms such as intention, emotion, and meaning, can be thought of as a spectrum, with the autism spectrum disorders on the hypomentalist side and psychotic disorders on the hypermentalist side (hypo = below normal, hyper = above normal). In the twentieth-century psychiatry battle, then, one could make the analogy that psychoanalysis was hypermentalist while behaviorism was hypomentalist. In other words, this means that psychoanalysis was trying to dig too deep into patients, similar to how those on the psychotic spectrum often overinterpret the social world around them. On the other hand, behaviorism was staying too far on the surface, similar to how those who are on the autism spectrum have trouble interpreting the social world around them.

Thus, the changes of 1980 were criticized by many clinicians for being hypomentalist and for sacrificing validity for consistency. This means that although the manual of psychiatry, or the diagnostic and statistical manual of mental disorders (DSM), could now produce the same diagnoses across all physicians, it wasn’t necessarily making the right diagnosis in all those cases. The new DSM also helped push psychoanalysis out of the way, considering that digging into a patient’s life story is less relevant to classifying symptoms – and saving time. What slowly took its place was cognitive therapy, a more direct style in which patterns of thought are changed – and coincidentally, more time is saved. Since the eighties, however, psychiatry has moved more and more towards biological factors and neuroscience. The David and Goliath dynamic is that therapies don’t lead to research and drugs that make money- seventy billion dollars of it a year. However, the irony is that these drugs still largely function as crude chemical tuners of the transmitters moving around in our brain. The thirty years after 1980 didn’t reveal any game-changing drugs. However, something new might be on the horizon.

In 2013, the National Institute of Mental Health (NIMH), announced a shift from funding DSM-guided research to funding biomarker-based research. A guiding assumption of the new NIMH system is that, “Mental disorders are biological disorders involving brain circuits that implicate specific domains of cognition, emotion, or behavior.” This complicates the debate, because although the NIMH is acknowledging the shortsightedness of the current system and introducing a paradigm shift, it is moving further away from therapy. In a sense, then, there are still two camps of opinion, a history-centered and biology-centered camp, representing the nurture and nature debate, respectively. Is psychiatric disorder best understood and treated via genetics and brain function?  Or, is it better understood as a social and intensely personal process? The director of UCLA’s Neuropsychiatric Institute, Dr. Peter Whybrow, in his book, ‘A Mood Apart’, makes the case for the moderate position. His case studies, interweaving patient narratives with science, are the testament to his own conclusion, “the evidence is overwhelming that judicious pharmacological intervention plus a program of self-education – which is the core of any psychotherapy – is the best approach to treatment and prevention”. In psychiatric disorder, nature and nurture are probably intimately related, albeit to different degrees in each disorder. Sometimes, genetic makeup causes behavioral dysfunction. Sometimes, it only creates a slight predisposition. In other cases, social stress can cause biological or behavioral change. However, these ideas have only in the last 10 years begun to be properly explored, and it is the gap between genetics, neuroscience, and psychiatry that the NIMH believes can be crossed. In the 2012 special issue of Nature Neuroscience, entitled Focus on Social Neuroscience, Naomi Eisenberger and Steve Cole explain the emergence of a new field called social neuroscience. They introduce the idea, which we will follow, that social connections alter the activity of the brain, but note that this discussion extends to genetic, immunological and other molecular risk factors for disease. Social neuroscience, is a style of experimentation that looks at how different structures and patterns of brain activity predict different behaviors. This means that the property of a particular pathway in the brain can predict a particular behavior, or response to a social stimulus. The jump to medicine lies in the possibility that this pathway might predict a particular disorder. The final jump is that modern tools could be used to treat the disorder by changing this particular pathway, or biomarker. This is potentially a way to respect both the history and biology of a person without assuming that one comes before the other. Might diagnosing patients in this manner allow for both standardization and accuracy?

Dr. Marc Heiser, MD PhD, is a fellow in child psychiatry here at UCLA. During medical school at UCSF, Dr. Heiser came to UCLA and worked on a project, “The Essential Role of Broca’s Area in Imitation” with Dr. Marco Iacoboni at the Brain Mapping Center. He returned to UCSF, undertook a PhD, and now, is treating patients with a combination of therapy and drugs, as most psychiatrists do. As a scientist, however, his mission involves research into better ways to diagnose and treat patients. One of the tools that Dr. Heiser uses is called transcranial magnetic stimulation (TMS), a particularly sci-fi-ish kind of tool. TMS works by way of a focused magnetic pulse, which according to Faraday’s law, induces an electrical current that itself produces an opposing magnetic field. Considering that communication in the brain is initiated by electrical charge, magnetic stimulation excites the brain activity in tissue up to a few centimeters beneath the skull – painlessly. Using a different frequency of pulses, the magnetic field can also inhibit neural communication. When one considers that neuroscience for decades has been building up an atlas of brain regions and the functions they are responsible for, the utility of TMS becomes more clear.

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The TMS clinic that Dr. Heiser helps operate is an example of what is seemingly the first next-generation psychiatric treatment. Major depressive disorder affects about 15 million Americans a year. There are approximately 20-25 different drugs on the market to treat it, with most of them acting as chemical tuners. In 2008, however, TMS was approved to treat drug-resistant depression. Over weeks, daily TMS sessions strengthen circuits in the frontal areas of the brain, which are thought to act as a check on the negative feelings arising from a deeper, anxiety-laden area of the brain called the amygdala.

This development should and is being viewed cautiously, but is nonetheless promising. In other studies, such as an experimental one by a father of TMS, Professor Alvaro Pascual-Leone of Harvard, TMS was tried on people who suffer from Asperger’s Syndrome, a form of autism that renders people unable to pick up on the emotional cues of others. His team targeted a frontal region thought to contain a high proportion of mirror neurons, which relate to our perceptions of movements and emotions in others. One of the subjects, writer John Elder Robison, wrote a book, ‘Switched On’’, about the extraordinary experience of feeling for the first time. He also writes about the unexpected downsides to this kind of treatment. In another study, TMS was used in duo with another method, that of resting state functional connectivity. TMS cannot affect a brain region more than a few centimeters below the skull, but brain imaging can show you where the informational highways that lead to it are. This team first identified surface regions that were strongly connected to the hippocampus, a structure that holds any memory you can explicitly declare. Excitatory TMS was then used to excite these areas (Wang et al., 2014), which to you Angelenos can be thought of as generating a flood of traffic heading south on the 5. Eventually, San Diego gets a little more activity; likewise, the memory centers become excited, which in this case enhanced the subjects’ performance on a memory task. In a non-clinical example, researchers used inhibitory TMS to temporarily knock out superficial, frontal brain regions involved in social judgment. This ‘freed’ subjects, causing them to be more generous in an economic game that gauged altruistic behavior.

The idea here is that while psychiatrists are beginning to think about mental disorder differently, scientists are probing and questioning the brains of animals and humans. TMS has its shortcomings, including imprecision, a short-lasting effect, and unpredictability, but it is itself, like the history of psychiatric treatment, an example of the fact that progress occurs over many small, crude steps. PhD students in electrical- and neuro-engineering will continue to churn out theses and projects on the subject of TMS, at the same time as students of neuroscience understand how specific circuits underlie specific behaviors. Also, TMS is also just one example of where neuroscience and psychiatry are meeting. Another new approach, called optogenetics, is allowing for – get ready for it –  millisecond- and millimeter-scale light-triggered activation of  genetically altered brain cells in animals. Interestingly, one of the pioneers of this approach is Dr. Karl Deisseroth, a psychiatrist who’s revolutionizing of neuroscience research in animals has come full-circle. The studies on motivation, aggression, and addiction that are going on in mice around the world with the tools of optogenetics have already led to new models for TMS-based clinical trials in humans.micestatue

You might note that the tone of the discussion – the discussion that guides lots and lots of grant money – has shifted far from human narrative. That is in fact the complaint of many experienced clinicians, who are being asked to tell patients that they are a product of their brain, and that their brain is defective. The response to that is two-fold. The first defense is that the biomarker approach does not assume that the biology is the cause.  Rather, it aims treatment at the fact that those with mental illness do have altered biology and brain connectivity. The second defense is that the approach does not mean that the patient’s narrative is unimportant. Physicians can tune brain activity at the time as they understand the patient and lead them through therapy. In some cases, this is happening simultaneously, as in neurofeedback, which lets patients themselves see and change a particular brain signal in real-time (Zotev et al., 2014). A second complaint of clinicians is that psychiatry, even in the past 10 years, or the ‘decade of the brain’, hasn’t been able to reduce a mental illness down to any one biological cause, so why continue going down that path? Again, the response is two-fold. The first defense is a gamble and points to the new techniques of molecular biology, genetics, and neuroscience as evidence that something is on the way. The second defense, more of a counter-attack, is that the biomarker approach can potentially couple diagnosis and treatment. Rather than identify a disorder based on behavioral symptoms and treat it chemically, the biomarker approach can potentially diagnose a disorder based on an aberrant pattern of brain connectivity, and target that same pattern for treatment.

Thus, change continues. It is wisely acknowledged by both sides that looking at mental disorders under the microscope of biomarkers might prove harmful at some points. It could rob patients of a feeling of control, encourage pharmaceutical greed, and deflect attention away from the responsibility of public policy to address those in the inner city and in poverty who are suffering. After all, TMS, optogenetics, and other treatments aren’t useful if health care and insurance policies stand in the way. One can only hope, however, that there is some larger march towards achieving the opposite. A correspondence between Albert Einstein and Sigmund Freud, published in 1933 under the title “Why War?” discussed how to rid the world of, ‘the psychosis of hate and destructiveness’. World War II began a decade later. Today, psychiatry continues to heal people from the shrapnel of biology and social life, while science begins to tackle how those two interact. Just maybe, it might work.

 

 

 

References

Christov-Moore, L., Sugiyama, T., Grigaityte, K., & Iacoboni, M. (2016). Increasing generosity by disrupting prefrontal cortex. Social Neuroscience, 1–8. http://doi.org/10.1080/17470919.2016.1154105

Eisenberger, N., Cole, S. (2012). Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health. Nature Neuroscience. 15(5), 669-674.

Rosenhan, D. L. (1973). On being sane in insane places. Science, 179(4070), 250–258.

Wang, J. X., Rogers, L. M., Gross, E. Z., Ryals, A. J., Dokucu, M. E., Brandstatt, K. L., et al.     (2014). Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science, 345(6200), 1054–1057. http://doi.org/10.1126/science.1252900
Zotev, V., Phillips, R., Yuan, H., Misaki, M., & Bodurka, J. (2014). Self-regulation of human brain activity using simultaneous real-time fMRI and EEG neurofeedback. NeuroImage, 85(3), 985–995. http://doi.org/10.1016/j.neuroimage.2013.04.126

 

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