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ICOSR 2017: Hallucinations Researchers Remember "The Missing Ralph"

2 May 2017

As part of our ongoing coverage of the 2017 International Congress on Schizophrenia Research (ICOSR), held March 25-28 in San Diego, we bring you session summaries from some of the participants in the Young Investigator program. We are, as always, grateful for the gracious assistance of YI program directors Laura Rowland and Scott Sponheim, as well as Michelle Tidwell of the ICOSR staff. For this report, we thank Sonia Bansal of the Maryland Psychiatric Research Center.

Earlier this year, the research community lost one of its highly distinguished scientists, Ralph E. Hoffman, to illness. He was a pioneering researcher internationally renowned for his work on the pathophysiology and treatment of auditory hallucinations. This year at ICOSR, a special memorial symposium was held on the morning of Saturday, March 25, to honor his influential work and scholarship. Four prominent researchers who had crossed paths with Hoffman at various phases in his life and career presented collaborative research across different research areas and discussed concepts emanating from Hoffman’s work (see SRF related news).

Phil Corlett of Yale University, and one of Hoffman’s more recent collaborators, opened the session by recounting his delightful sessions spent with Hoffman administering transcranial magnetic stimulation (TMS) to patients who hear voices. He referred to Hoffman as a true Renaissance man whose power of clear thinking on basic phenomenology was reflected in his deep commitment to patients and treatment, just as much as to research ideas. Corlett described Hoffman’s identification of foci of abnormal activity and connectivity in the brains of patients who hear voices. In their collaborative work, using TMS, they sought to rectify these aberrances, thus reducing the frequency of and distress caused by the voices. Bilateral TMS was administered to 15 patients daily for a period of four weeks with changes in voice experiences being assessed using subjective interviews, and brain activity using functional magnetic resonance imaging (fMRI). In this study, the TMS was observed to reduce the frequency and distress of the voices, as well as decrease hyperconnectivity in insula-Wernicke’s coupling, areas of abnormal connectivity between frontal and temporal areas. This work, grounded in circuitry and phenomenology, truly captured Hoffman’s commitment to improving patients’ lives, as evidenced by this quote from a patient: “Never better! Lessened my hallucinations by well over 50 percent and could not be happier with the results.” Inspired by these findings and carrying this work forward, Corlett and colleagues are beginning a new study to manipulate the directional connectivity between insula and Wernicke’s areas using a double cone coil.

In the second talk, Iris Sommer of University Medical Center Utrecht began by outlining some of the work done at the Voices Clinic, which she started. This clinic focuses on improving basic coping skills, reducing fear and anxiety associated with hearing voices, psychoeducation on voices, and group therapy. It therefore comes as no surprise that she derived inspiration from Hoffman’s work and commitment to improving caring for patients with auditory-verbal hallucinations, and at the same time an appreciation of the neurological fundamentals. She posited that in order to understand auditory hallucinations, it is imperative that linguistics, inner speech, and underlying mechanisms are better understood. Based on a 2005 study by Hoffman and his colleagues, where a left temporoparietal TMS intervention selectively altered neurobiological factors determining frequency of hallucinations, Sommer’s team further explored this technique in medication-resistant patients. The researchers administered a series of randomized placebo or TMS-controlled trials in samples of approximately 60 patients, but did not observe a selective improvement in TMS versus sham treatment, although a small percentage (10 percent) responded well to the treatment. Some of the predictors of TMS response were proposed to be age, as well as TMS working better when there is no strong relationship with a delusional explanation. To conclude, she emphasized that despite lack of significant scientific proof, patients have in fact been helped, and that this technique is rife with potential for effective treatment.

Jonathan Cohen, from Princeton University then outlined the state of affairs and challenges in the field of psychiatry in his talk titled “Computational Psychiatry: The Missing Link (and Missing Ralph).” He described cognitive neuroscience and psychiatry as being "parallel universes" and then delineated challenges faced in understanding how the brain functions at a system level and how instabilities in the same give rise to mental illnesses, and further, how to translate this knowledge into effective treatment strategies. In his words, “the odyssey of psychiatry in the past half a century has been something of an Alice in Wonderland.” Cohen said that the majority of research focused on levels of analysis that are too low (e.g., neuromodulation and biochemical) or too high (e.g., symptomatology assessment), and suggested that efforts to span these levels of analysis have not been inclusive of the systems level of analysis. He proposed that, in line with Hoffman’s ability to “move freely across many levels” and his distinctive mathematical conceptualization of phenomena, the field of psychiatry must delve into mathematical and computational analysis in order to overcome the challenges faced.

In all the talks, and in the eulogy delivered by John Krystal, it was evident how influential and inspirational Ralph Hoffman has been to the field. His ability to “form bridges and make intellectual traffic flow in a meaningful way from one side to the other”; to deeply understand his patients’ experience of their illness; and his passion, diligence, and dedication to his work and family are an inspiration for generations to come. All those in attendance, including his wife and children, were moved and stimulated by the research conducted and talks given in his honor, and the torch being carried forward.