Faculty Bibliography

We examined the patterns and variability of recovery post-stroke in multiple behavioral domains. A large cohort of first time stroke patients with heterogeneous lesions was studied prospectively and longitudinally at 1-2 weeks, 3 months and one year post-injury with structural MRI to measure lesion anatomy and in-depth neuropsychological assessment. Impairment was described at all timepoints by a few clusters of correlated deficits. The time course and magnitude of recovery was similar across domains, with change scores largely proportional to the initial deficit and most recovery occurring within the first three months. Damage to specific white matter tracts produced poorer recovery over several domains: attention and superior longitudinal fasciculus II/III, language and posterior arcuate fasciculus, motor and corticospinal tract. Finally, after accounting for the severity of the initial deficit, language and visual memory recovery/outcome was worse with lower education, while the occurrence of multiple deficits negatively impacted attention recovery.

While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to represent stimuli and task states, and that information capacity measured through whole brain models is a theory-driven measure of processing capacity that could be used as a biomarker of injury for outcome prediction or target for rehabilitation intervention.

Recent research has demonstrated the importance of global changes to the functional organization of brain network following stroke. Resting functional magnetic resonance imaging (R-fMRI) is a non-invasive tool that enables the measurement of functional connectivity (FC) across the entire brain while placing minimal demands on the subject. For these reasons, it is a uniquely appealing tool for studying the distant effects of stroke. However, R-fMRI studies rely on a number of premises that cannot be assumed without careful validation in the context of stroke. Here, we describe strategies to identify and mitigate confounds specific to R-fMRI research in cerebrovascular disease. Five main topics are discussed: (a) achieving adequate co-registration of lesioned brains, (b) identifying and removing hemodynamic lags in resting BOLD, (c) identifying other vascular disruptions that affect the resting BOLD signal, (d) selecting an appropriate control cohort, and (e) acquiring sufficient fMRI data to reliably identify FC changes. For each topic, we provide guidelines for steps to improve the interpretability and reproducibility of FC-stroke research. We include a table of confounds and approaches to identify and mitigate each. Our recommendations extend to any research using R-fMRI to study diseases that might alter cerebrovascular flow and dynamics or brain anatomy.

Recent randomized controlled trials of psilocybin-assisted psychotherapy for patients with cancer suggest that this treatment results in large-magnitude reductions in anxiety and depression as well as improvements in attitudes toward disease progression and death, quality of life, and spirituality. To better understand these findings, we sought to identify psychological mechanisms of action using qualitative methods to study patient experiences in psilocybin-assisted psychotherapy. Semistructured interviews were conducted with 13 adult participants with clinically elevated anxiety associated with a cancer diagnosis who received a single dose of psilocybin under close clinical supervision. Transcribed interviews were analyzed using interpretative phenomenological analysis, which resulted in 10 themes, focused specifically on cancer, death and dying, and healing narratives. Participants spoke to the anxiety and trauma related to cancer, and perceived lack of available emotional support. Participants described the immersive and distressing effects of the psilocybin session, which led to reconciliations with death, an acknowledgment of cancer's place in life, and emotional uncoupling from cancer. Participants made spiritual or religious interpretations of their experience, and the psilocybin therapy helped facilitate a felt reconnection to life, a reclaiming of presence, and greater confidence in the face of cancer recurrence. Implications for theory and clinical treatment are discussed.

Screening, brief intervention, and referral to treatment (SBIRT) has been widely implemented as a method to address substance use disorders in general medical settings, and some evidence suggests that its use is associated with decreased societal costs. In this paper, we investigated the economic impact of SBIRT using data from Screening, Motivational Assessment, Referral, and Treatment in Emergency Departments (SMART-ED), a multisite, randomized controlled trial. Utilizing self-reported information on medical status, health services utilization, employment, and crime, we conduct a benefit-cost analysis. Findings indicate that neither of the SMART-ED interventions resulted in any significant changes to the main economic outcomes, nor had any significant impact on total economic benefit. Thus, while SBIRT interventions for substance abuse in Emergency Departments may be appealing from a clinical perspective, evidence from this economic study suggests resources could be better utilized supporting other health interventions.

The psychological mechanisms of action involved in psilocybin-assisted psychotherapy are not yet well understood. Despite a resurgence of quantitative research regarding psilocybin, the current study is the first qualitative study of participant experiences in psilocybin-assisted psychotherapy. Semistructured interviews were carried out with 13 adult participants aged 22 to 69 years (M = 50 years) with clinically elevated anxiety associated with a cancer diagnosis. Participants received a moderate dose of psilocybin and adjunctive psychotherapy with an emphasis on the process of meaning-making. Verbatim transcribed interviews were analyzed by a five-member research team using interpretative phenomenological analysis. General themes found in all or nearly all transcripts included relational embeddedness, emotional range, the role of music as conveyor of experience, meaningful visual phenomena, wisdom lessons, revised life priorities, and a desire to repeat the psilocybin experience. Typical themes found in the majority of transcripts included the following: exalted feelings of joy, bliss, and love; embodiment; ineffability; alterations to identity; a movement from feelings of separateness to interconnectedness; experiences of transient psychological distress; the appearance of loved ones as guiding spirits; and sharing the experience with loved ones posttreatment. Variant themes found in a minority of participant transcripts include lasting changes to sense of identity, synesthesia experiences, catharsis of powerful emotion, improved relationships after treatment, surrender or letting go, forgiveness, and a continued struggle to integrate experience. The findings support the conclusion that psilocybin-assisted psychotherapy may provide an effective treatment for psychological distress in cancer patients. Implications for theory and treatment are discussed.

Research activity on the potential clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades, and promises to continue to expand. Experimental study of hallucinogen-assisted treatment, and any future clinical use, requires the development of psychotherapeutic models that are appropriate to the disorder being treated and effectively integrated with the pharmacologic component of the treatment. To provide a framework for thinking about possible treatment models, we provide an overview of the history of psychedelic-assisted treatment, review what is known about the therapeutic mechanisms of these treatments, and consider the various purposes of psychotherapy in the context of both research and clinical use of psychedelic-assisted treatment. We then provide a description of a therapy model we have developed and are currently using in a trial of psilocybin-assisted treatment for alcoholism. Finally, we discuss advantages and disadvantages of a range of alternative models, emphasizing the need for research to determine the most effective treatment models for any indications for which efficacy becomes established.

BACKGROUND AND OBJECTIVES: Psychiatry residents provide care for individuals diagnosed with co-occurring mental illness and substance use disorders (SUDs). Small studies have shown that clinicians in general possess negative attitudes towards these dually diagnosed individuals. This is a serious concern, as clinicians' stigmatizing attitudes towards individuals with mental illnesses may have a particularly potent adverse impact on treatment. The goal of this study was to examine the attitudes of psychiatry residents towards individuals with diagnoses of schizophrenia, multiple SUDs, co-occurring schizophrenia and SUDs, and major depressive disorder. METHODS: A questionnaire was sent to psychiatry residents (N = 159) around the country. It was comprised of two sections: (i) demographic information, which included information about level of training; and (ii) the 11-item Medical Condition Regard Scale (MCRS) for individuals with the four different diagnoses. RESULTS: Psychiatry residents had more stigmatizing attitudes towards individuals with diagnoses of SUDs with and without schizophrenia than towards those individuals with diagnoses of schizophrenia or major depressive disorder alone. Senior residents possessed more negative attitudes towards individuals with SUDs than junior residents. DISCUSSION AND CONCLUSIONS: The attitudes of psychiatry residents' towards individuals with SUDs with and without schizophrenia were negative and were worse among senior residents. There were many potential reasons for these findings, including repeat negative experiences in providing care for these individuals. SCIENTIFIC SIGNIFICANCE: The negative attitudes of psychiatry residents towards individuals with SUDs are worrisome. Future work is needed to better understand these attitudes and to develop interventions to improve them. (Am J Addict 2016;XX:1-5).

OBJECTIVES: This report identifies the institutional barriers to, and benefits of, buprenorphine maintenance treatment (BMT) integration in an established hospital-based opioid treatment program (OTP). METHODS: This case study presents the authors' experiences at the clinic, hospital, and corporation levels during efforts to integrate BMT into a hospital-based OTP in New York City and a descriptive quantitative analysis of the characteristics of hospital outpatients treated with buprenorphine from 2006 to 2013 (N=735). RESULTS: Integration of BMT into an OTP offered patients the flexibility to transition between intensive structured care and primary care or outpatient psychiatry according to need. Main barriers encountered were regulations, clinical logistics of dispensing medications, internal cost and reimbursement issues, and professional and cultural resistance. CONCLUSIONS: Buprenorphine integration offers a model for other OTPs to facilitate partnerships among primary care and mental health clinics to better serve diverse patients with varying clinical needs and with varying levels of social support.