Investigation into the mechanisms of depressive illness

Functional and structural brain abnormalities have been reported in many imaging studies of depressive illness. However, the mechanisms by which these abnormalities give rise to symptoms remain unknown. The work described in this thesis focuses on such mechanisms, particularly with regard to neural predictive error signals. Recently, these signals have been reported to be present in many studies on animals and healthy humans. The central hypothesis explored in this thesis is that depressive illness comprises a disorder of associative learning. Chapter 2 reviews the brain regions frequently reported as abnormal in imaging studies of depressive illness, and the normal function of these particular brain regions. It is concluded that such regions comprise the neural substrate for associative learning and emotion. However, confidence in this conclusion is limited by considerable variability in the human imaging literature. Therefore, chapter 3 describes a meta-analysis, which tests the hypothesis that, consistent with the non-imaging literature, the ventromedial prefrontal cortex is most active during emotional experience. The results of the meta-analysis were clearly consistent with this hypothesis. Chapter 4 provides an introduction to neural predictive error signals from the general perspective of homeostatic physiological regulation. Both experimental evidence supporting the error signals, and various formal mathematical theories describing the error signals, are summarised. This provides the background to chapter 5, which describes an original fMRI study which tested the hypothesis that patients with depressive illness would exhibit abnormal predictive error signals in response to unexpected motivationally significant stimuli. Evidence of such abnormality was found. Chapter 6 describes a further original study using transcranial ultrasound and diffusion tensor imaging of the brainstem, which investigated reports of a subtle structural abnormality in depressed patients. If present, it might give rise to abnormal error signals. However, no structural abnormality was found. Finally, chapter 7 discusses the significance of these findings in the context of clinical features of depressive illness and a wide range of treatments, ranging from psychotherapy through antidepressants to physical treatments. A number of potential future studies are identified, which could clarify understanding of depressive illness

When All Else Fails: Management of an Irreparable Rotator Cuff with Capsular Reconstruction and Physical Therapy Targeting Accommodative Musculature

The purpose of this case report is to describe the rehabilitative outcomes on a superior capsular reconstruction surgery following the re-injury of a surgically repaired rotator cuff (RTC) and glenoid labrum that was deemed irreparable.https://soar.usa.edu/flsaspring2018/1005/thumbnail.jp

Opposing patterns of abnormal D1 and D2 receptor dependent cortico-striatal plasticity explain increased risk taking in patients with DYT1 dystonia

Patients with DYT1 dystonia caused by the mutated TOR1A gene exhibit risk neutral behaviour compared to controls who are risk averse in the same reinforcement learning task. It is unclear whether this behaviour can be linked to changes in cortico-striatal plasticity demonstrated in animal models which share the same TOR1A mutation. We hypothesised that we could reproduce the experimental risk taking behaviour using a model of the basal ganglia under conditions where cortico-striatal plasticity was abnormal. As dopamine exerts opposing effects on cortico-striatal plasticity via different receptors expressed on medium spiny neurons (MSN) of the direct (D1R dominant, dMSNs) and indirect (D2R dominant, iMSNs) pathways, we tested whether abnormalities in cortico-striatal plasticity in one or both of these pathways could explain the patient's behaviour. Our model could generate simulated behaviour indistinguishable from patients when cortico-striatal plasticity was abnormal in both dMSNs and iMSNs in opposite directions. The risk neutral behaviour of the patients was replicated when increased cortico-striatal long term potentiation in dMSN's was in combination with increased long term depression in iMSN's. This result is consistent with previous observations in rodent models of increased cortico-striatal plasticity at in dMSNs, but contrasts with the pattern reported in vitro of dopamine D2 receptor dependant increases in cortico-striatal LTP and loss of LTD at iMSNs. These results suggest that additional factors in patients who manifest motor symptoms may lead to divergent effects on D2 receptor dependant cortico-striatal plasticity that are not apparent in rodent models of this disease

Modeling trait anxiety:from computational processes to personality

Computational methods are increasingly being applied to the study of psychiatric disorders. Often, this involves fitting models to the behavior of individuals with subclinical character traits that are known vulnerability factors for the development of psychiatric conditions. Anxiety disorders can be examined with reference to the behavior of individuals high in “trait” anxiety, which is a known vulnerability factor for the development of anxiety and mood disorders. However, it is not clear how this self-report measure relates to neural and behavioral processes captured by computational models. This paper reviews emerging computational approaches to the study of trait anxiety, specifying how interacting processes susceptible to analysis using computational models could drive a tendency to experience frequent anxious states and promote vulnerability to the development of clinical disorders. Existing computational studies are described in the light of this perspective and appropriate targets for future studies are discussed

Cooperative Extension: A Century of Innovation

As Cooperative Extension celebrates its 100th anniversary in 2014, the Land-Grant System will be reflecting on the first century of accomplishments and preparing for a second century of education. This commentary is the first in a series of six throughout the year that will analyze the rich history of Cooperative Extension, examine its role in contemporary society, and help us collaboratively envision the future of this unique American educational endeavor

Implementation of a university faculty mentorship program

Objective: To implement a University Faculty mentorship program in the Division of Emergency Medicine.      Methods: A program based on a unique Schulich faculty mentorship policy was implemented with the help of a Provider Value Officer. The process involved creating a training program which defined the roles of the mentors and mentees and established the principles of an effective mentor-mentee relationship. Faculty received training on how to participate effectively in a Schulich faculty mentorship committee. Each committee consisted of a mentee, and two mentors at the associate professor level (one internal and one external) . Thirteen distinct external divisions were represented. They were instructed to meet twice per year, as arranged by the mentee. The mentee created mentor minutes using a template, and then submitted the minutes to the members of the mentorship committee and the Chair/Chief of Emergency medicine.  The Chair/Chief used the minutes during the annual Continuing Professional Development meeting.Results: In less than a year, the division has successfully transformed its mentorship program. Using the above-mentioned process, 31 of 34 (91%) eligible assistant professors have functioning mentorship committees.  Collaboration and participation between the different faculties has increased. Follow-up meetings with the Chair/Chief and the Provider Value Officer revealed the theme that, universally, participants have perceived Schulich Faculty Mentorship committees as beneficial and are happy with the "fit" of their mentorship committees. Conclusion: Through careful planning and training, a successful Faculty Mentorship program can be initiated in an academic division in less than a year with the help of a local champion given protected time

Compulsivity in opioid dependence

This study was part funded by an unrestricted educational grant provided by Schering-Plough and a grant by an Anonymous Trust. Study support was also provided by the Scottish Mental Health Research Network. AB has received educational grants from Schering Plough and he has received research project funding from Schering-Plough, Merck Serono, and Indivior.Objective: This study aimed to investigate the relationship between compulsivity versus impulsivity and structural MRI abnormalities in opioid dependence. Method: We recruited 146 participants: i) patients with a history of opioid dependence due to chronic heroin use (n=24), ii) heroin users stabilised on methadone maintenance treatment (n=48), iii) abstinent participants with ahistory of opioid dependence due to heroin use (n=24) and iv) healthy controls(n=50). Compulsivity was measured using Intra/Extra-Dimensional (IED) Task and impulsivity was measured using the Cambridge Gambling Task (CGT).Structural Magnetic Resonance Imaging (MRI) data were also obtained. Results: As hypothesised, compulsivity was negatively associated with impulsivity (p<0.02). Testing for the neural substrates of compulsivity versus impulsivity, we found a higher compulsivity/impulsivity ratio associated with significantly decreased white matter adjacent to the nucleus accumbens, bed nucleus of stria terminalis and rostral cingulate in the abstinent group,compared to the other opioid dependent groups. In addition, self-reported duration of opioid exposure correlated negatively with bilateral globus pallidus grey matter reductions. Conclusion: Our findings are consistent with Volkow & Koob’s addiction models and underline the important role of compulsivity versus impulsivity inopioid dependence. Our results have implications for the treatment of opioid dependence supporting the assertion of different behavioural and biological phenotypes in the opioid dependence and abstinence syndromes.PostprintPeer reviewe