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For years, the cerebellum was left out of functional magnetic resonance imaging (fMRI) studies due to technological limitations. The advent of novel data acquisition and reconstruction strategies (e.g., whole-brain simultaneous multi-slice imaging) employing multi-channel array coils has overcome such limitations, ushering unprecedented improvements in temporal signal-to-noise ratio and spatiotemporal resolution. Here, we aim to provide a brief report on the deep cerebellar nuclei, specifically focusing on the dentate nuclei, the primary output nuclei, situated within both cognitive and motor cerebello-cerebral circuits. We highlight the importance of functional parcellation in refining our understanding of broad resting-state functional connectivity (RSFC) in both health and disease. First, we review work relevant to the functional topography of the dentate nuclei, including recent advances in functional parcellation. Next, we review RSFC studies using the dentate nuclei as seed regions of interest in neurological and psychiatric populations and discuss the potential benefits of applying functionally defined subdivisions. Finally, we discuss recent technological advances and underscore ultrahigh-field neuroimaging as a tool to potentiate functionally parcellated RSFC analyses in clinical populations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This special section on theories of psychopathology provides an opportunity to collect the emergent, cross-cutting scholarship that is challenging traditional approaches to understanding mental illness. Here, we appraise the state of theory in the field and emphasize the pitfalls of working in the context of overly flexible, unchallenged, and essentially unchallengeable theoretic models, such as the biopsychosocial model, which we argue has become the de facto theoretic model for our field. We further posit that theoretic shortcomings are contributing to the often-referenced pessimism regarding our progress in understanding and treating mental illness, and introduce the charge of the authors of the papers in this section to articulate novel, falsifiable theories of psychopathology. We briefly touch on the intertwined issue of how to define psychopathology and discuss a key issue raised by the array of papers comprising the section, namely how to conceptualize the spatiotemporal boundaries of complex causal systems. We then use this schematic for understanding how these theories relate to each other and to the vanilla biopsychosocial model they are vying to replace. Ultimately, it is our belief and hope that progress in theoretic thinking will catalyze faster progress in research and improvements to and novel developments in clinical prevention and intervention efforts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Investigations within the Human Connectome Project have expanded to include studies focusing on brain disorders. This paper describes one of the investigations focused on psychotic psychopathology: The psychosis Human Connectome Project (P-HCP). The data collected as part of this project were multimodal and derived from clinical assessments of psychopathology, cognitive assessments, instrument-based motor assessments, blood specimens, and magnetic resonance imaging (MRI) data. The dataset will be made publicly available through the NIMH Data Archive. In this report we provide specific information on how the sample of participants was obtained and characterized and describe the experimental tasks and procedures used to probe neural functions involved in psychotic disorders that may also mark genetic liability for psychotic psychopathology. Our goal in this paper is to outline the data acquisition process so that researchers intending to use these publicly available data can plan their analyses. MRI data described in this paper are limited to data acquired at 3 Tesla. A companion paper describes the study's 7 Tesla image acquisition protocol in detail, which is focused on visual perceptual functions in psychotic psychopathology., (Copyright © 2021. Published by Elsevier Inc.)

The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders ( n = 31) and healthy controls ( n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework., (© The Author(s) 2021. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

There is accruing evidence of cerebellar abnormalities in individuals with schizophrenia as measured by performance on a variety of tasks believed to be dependent on cerebellar integrity, including delay eyeblink conditioning. There is also evidence of cerebellar dysfunction on a neural level in schizophrenia from both task-based and resting state neuroimaging studies, however few studies have examined cerebellar neural function while the cerebellum is directly recruited in individuals with schizophrenia. In the current pilot study, we examined neural activity during an explicitly cerebellar task in individuals with schizophrenia or schizoaffective disorder and non-psychiatric controls. Participants underwent delay eyeblink conditioning during fMRI. Results indicated eyeblink conditioning impairment in patients as evidenced by a group by time interaction for conditioned responses. A significant cluster of cerebellar activation was present in controls but not patients during the first half of conditioning; there were no significant differences in activation between groups. An ROI analysis focused on the cerebellum in patients revealed two significant clusters that were inversely associated with negative symptom severity. These results are broadly consistent with the theory of cognitive dysmetria, wherein cerebellar abnormalities are theorized to contribute to motor as well as cognitive and affective disturbances in schizophrenia., Competing Interests: Declarations of Competing Interests None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: A number of motor abnormalities have been reported in psychotic disorders, including dyskinesia and psychomotor slowing. There is also evidence for many of the same motor abnormalities in biological first-degree relatives and accruing evidence for motor abnormalities in bipolar disorder. In addition to motor dysfunction, there are also shared symptom domains amongst these populations., Objectives: We explored the associations of (1) current and lifetime psychosis and mood symptom domains and (2) domains of psychosis proneness with various domains of motor function in a transdiagnostic sample (n = 149)., Method: Individuals with schizophrenia, schizoaffective disorder, or bipolar disorder, biological first-degree relatives of individuals with a psychotic disorder, and controls completed measures of psychomotor speed and movement fluidity, and neural activity related to motor preparation (stimulus-locked lateralized readiness potential, S-LRP) and execution (response-locked LRP) was assessed using EEG. All participants completed the Brief Psychiatric Rating Scale; patients were additionally assessed for lifetime psychosis and mood episode symptoms, and relatives and controls completed the Chapman psychosis proneness scales., Results: Multiple regression revealed levels of current negative symptoms and mania were significantly positively associated with psychomotor slowing even after accounting for current antipsychotic medication dosage and duration of illness. S-LRP onset latency was significantly positively associated with magical ideation., Conclusion: Domains of motor function are associated with various mood and psychosis symptom domains in a transdiagnostic sample, which may provide insight into brain abnormalities relevant to the expression of symptoms across disorders., (© 2019 S. Karger AG, Basel.)

Deficits in response inhibition have been observed in schizophrenia and bipolar disorder; however, the neural origins of the abnormalities and their relevance to genetic liability for psychosis are unknown. We used a stop-signal task to examine motor inhibition and associated neural processes in schizophrenia patients (n = 57), bipolar disorder patients (n = 21), first-degree biological relatives of patients with schizophrenia (n = 34), and healthy controls (n = 56). Schizophrenia patients demonstrated motor control deficits reflected in longer stop-signal reaction times and elongated reaction times. With the possibility of needing to inhibit a button press, both schizophrenia and bipolar disorder patients showed diminished reductions of the P300 brain response and only the healthy controls demonstrated adjustments in response execution time, as measured by response-locked lateralized readiness potentials. Schizotypal traits in the biological relatives were associated with less P300 modulation consistent with the motor-related anomalies being associated with subtle schizophrenia-spectrum symptomatology in family members. The two patient groups had elongated response selection processes as manifest in the delayed onset of the stimulus-locked lateralized readiness potential. The bipolar disorder group was unique in showing significantly diminished neural responses to the stop-signal to inhibit a response. Antipsychotic medication dosage was related to worse motor inhibition, thus motor inhibition deficits in schizophrenia may be partially explained by the effect of pharmacological agents. Failed modulation of brain processes in relation to response inhibition probability and the lengthening of motor response selection appear to be transdiagnostic abnormalities spanning schizophrenia and bipolar disorder., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

There is accruing evidence of spontaneous dyskinesia in individuals with schizophrenia that is independent of medication exposure. Dyskinetic motor behavior is also present in individuals who are at high risk of schizophrenia and appears to have prognostic value for the development of psychosis. Nonetheless, it remains unclear whether dyskinesia is present in first-degree relatives of individuals with schizophrenia and thus associated with genetic liability for schizophrenia (i.e., an endophenotype), or whether the motor abnormality is a biomarker specific to the disease state spectrum. There is also limited information about links between dyskinesia and clinically relevant phenomena such as symptoms and cognition. Because dyskinesia marking genetic liability is likely to be subtle, we used sensitive instrument-based measurement of handwriting fluency to quantify dyskinesia in medicated individuals with schizophrenia or schizoaffective disorder, unaffected first-degree biological relatives of individuals with schizophrenia and schizoaffective disorder, and control participants. Results indicated that medicated individuals with schizophrenia or schizoaffective disorder exhibited more dyskinesia than both relatives and controls, with no difference between relatives and controls. Dyskinesia in individuals with schizophrenia or schizoaffective disorder was unrelated to current antipsychotic medication dosage, but associated with worse working memory function and greater positive formal thought disorder. These results provide evidence that dyskinesia is not associated with unexpressed genetic liability for schizophrenia., (Published by Elsevier B.V.)

Motor abnormalities comprise several clinical signs intrinsic to psychosis. Critically, these features are of prognostic value in individuals at-risk for psychosis, and for those in early stages of psychotic disorders. Motor abnormalities such as tremor, rigidity, and neurological soft signs often go unrecognized. Currently, advances in this area are limited by a paucity of theoretical conceptions categorizing or linking these behaviours to underlying neurobiology affected in psychosis. However, emerging technological advances have significantly improved the ability to detect and assess motor abnormalities with objective instruments in a timely and reliable manner. Further, converging evidence has laid the groundwork for theoretically and empirically derived categorization and conceptualization. This review summarizes these advances, stressing the importance of motor abnormalities for understanding vulnerability across different stages of psychosis and introducing these innovative instrumental approaches. Patients, researchers and clinicians will benefit from these new developments, as better assessment aids the development of targeted interventions to ultimately improve the care for individuals experiencing psychosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Evidence of cerebellar dysfunction in schizophrenia has mounted over the past several decades, emerging from neuroimaging, neuropathological, and behavioral studies. Consistent with these findings, cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been identified in schizophrenia. While repeated-measures analysis of variance is traditionally used to analyze dEBC data, hierarchical linear modeling (HLM) more reliably describes change over time by accounting for the dependence in repeated-measures data. This analysis approach is well suited to dEBC data analysis because it has less restrictive assumptions and allows unequal variances. The current study examined dEBC measured with electromyography in a single-cue tone paradigm in an age-matched sample of schizophrenia participants and healthy controls (N = 56 per group) using HLM. Subjects participated in 90 trials (10 blocks) of dEBC, during which a 400 ms tone co-terminated with a 50 ms air puff delivered to the left eye. Each block also contained 1 tone-alone trial. The resulting block averages of dEBC data were fitted to a three-parameter logistic model in HLM, revealing significant differences between schizophrenia and control groups on asymptote and inflection point, but not slope. These findings suggest that while the learning rate is not significantly different compared to controls, associative learning begins to level off later and a lower ultimate level of associative learning is achieved in schizophrenia. Given the large sample size in the present study, HLM may provide a more nuanced and definitive analysis of differences between schizophrenia and controls on dEBC.

There is accruing evidence of cerebellar abnormalities in schizophrenia. The theory of cognitive dysmetria considers cerebellar dysfunction a key component of schizophrenia. Delay eyeblink conditioning (EBC), a cerebellar-dependent translational probe, is a behavioral index of cerebellar integrity. The circuitry underlying EBC has been well characterized by non-human animal research, revealing the cerebellum as the essential circuitry for the associative learning instantiated by this task. However, there have been persistent inconsistencies in EBC findings in schizophrenia. This article thoroughly reviews published studies investigating EBC in schizophrenia, with an emphasis on possible effects of antipsychotic medication and stimulus and analysis parameters on reports of EBC performance in schizophrenia. Results indicate a consistent finding of impaired EBC performance in schizophrenia, as measured by decreased rates of conditioning, and that medication or study design confounds do not account for this impairment. Results are discussed within the context of theoretical and neurochemical models of schizophrenia.

White matter abnormalities in schizophrenia have been revealed by many imaging techniques and analysis methods. One of the findings by diffusion tensor imaging is a decrease in fractional anisotropy (FA), which is an indicator of white matter integrity. On the other hand, elevation of metabolic rate in white matter was observed from positron emission tomography (PET) studies. In this report, we aim to compare the two structural and functional effects on the same subjects. Our comparison is based on the hypothesis that signal fluctuation in white matter is associated with white matter functional activity. We examined the variance of the signal in resting state fMRI and found significant differences between individuals with schizophrenia and non-psychiatric controls specifically in white matter tissue. Controls showed higher temporal signal-to-noise ratios clustered in regions including temporal, frontal, and parietal lobes, cerebellum, corpus callosum, superior longitudinal fasciculus, and other major white matter tracts. These regions with higher temporal signal-to-noise ratio agree well with those showing higher metabolic activity reported by studies using PET. The results suggest that individuals with schizophrenia tend to have higher functional activity in white matter in certain brain regions relative to healthy controls. Despite some overlaps, the distinct regions for physiological noise are different from those for FA derived from diffusion tensor imaging, and therefore provide a unique angle to explore potential mechanisms to white matter abnormality.

A disturbance in the integration of information during mental processing has been implicated in schizophrenia, possibly due to faulty communication within and between brain regions. Graph theoretic measures allow quantification of functional brain networks. Functional networks are derived from correlations between time courses of brain regions. Group differences between SZ and control groups have been reported for functional network properties, but the potential of such measures to classify individual cases has been little explored. We tested whether the network measure of betweenness centrality could classify persons with schizophrenia and normal controls. Functional networks were constructed for 19 schizophrenic patients and 29 non-psychiatric controls based on resting state functional MRI scans. The betweenness centrality of each node, or fraction of shortest-paths that pass through it, was calculated in order to characterize the centrality of the different regions. The nodes with high betweenness centrality agreed well with hub nodes reported in previous studies of structural and functional networks. Using a linear support vector machine algorithm, the schizophrenia group was differentiated from non-psychiatric controls using the ten nodes with the highest betweenness centrality. The classification accuracy was around 80%, and stable against connectivity thresholding. Better performance was achieved when using the ranks as feature space as opposed to the actual values of betweenness centrality. Overall, our findings suggest that changes in functional hubs are associated with schizophrenia, reflecting a variation of the underlying functional network and neuronal communications. In addition, a specific network property, betweenness centrality, can classify persons with SZ with a high level of accuracy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Impaired ability to maintain an upright posture may reflect impairment in the cerebellum, a critical structure for the fluid coordination of neural information, thought to be disrupted in psychosis. The current study utilized an instrumental measure of posture in individuals at ultrahigh risk (UHR) for psychosis (n=43) and healthy controls (n=44). Positive and negative symptoms were assessed twice over 12months. Results showed that increased postural sway in the UHR group predicted changes in negative symptoms. This study provides an important prospective view on the relationship between cerebellar-sensitive behavior and integral symptoms, which until now has received limited biomarker research., (Published by Elsevier B.V.)

Recent studies of schizophrenia have revealed cognitive and memory deficits that are accompanied by disruptions of neuronal connectivity in cortical and subcortical brain regions. More recently, alterations of topological organization of structural networks in schizophrenia are also being identified using graph theoretical analysis. However, the role of the cerebellum in this network structure remains largely unknown. In this study, global network measures obtained from diffusion tensor imaging were computed in the cerebella of 25 patients with schizophrenia and 36 healthy volunteers. While cerebellar global network characteristics were slightly altered in schizophrenia patients compared with healthy controls, the patients showed a retained small-world network organization. The modular architecture, however, was changed mainly in crus II. Furthermore, schizophrenia patients had reduced correlations between modularity and microstructural integrity, as measured by fractional anisotropy (FA) in lobules I-IV and X. Finally, FA alterations were significantly correlated with the Positive and Negative Syndrome Scale symptom scores in schizophrenia patients. Taken together, our data suggest that schizophrenia patients have altered network architecture in the cerebellum with reduced local microstructural connectivity and that cerebellar structural abnormalities are associated symptoms of the disorder., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Consistent with reports of cerebellar structural, functional, and neurochemical anomalies in schizophrenia, robust cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been observed in the disorder. Impaired dEBC is also present in schizotypal personality disorder, an intermediate phenotype of schizophrenia. The present work sought to determine whether dEBC deficits exist in nonpsychotic first-degree relatives of individuals with schizophrenia. A single-cue tone dEBC paradigm consisting of 10 blocks with 10 trials each (9 paired and 1 unpaired trials) was used to examine the functional integrity of cerebellar circuitry in schizophrenia participants, individuals with a first-degree relative diagnosed with schizophrenia, and healthy controls with no first-degree relatives diagnosed with schizophrenia. The conditioned stimulus (a 400ms tone) coterminated with the unconditioned stimulus (a 50ms air puff to the left eye) on paired trials. One relative and 2 healthy controls were removed from further analysis due to declining conditioned response rates, leaving 18 schizophrenia participants, 17 first-degree relatives, and 16 healthy controls. Electromyographic data were subsequently analyzed using growth curve models in hierarchical linear regression. Acquisition of dEBC conditioned responses was significantly impaired in schizophrenia and first-degree relative groups compared with controls. This finding that cerebellar-mediated associative learning deficits are present in first-degree relatives of individuals with schizophrenia provides evidence that dEBC abnormalities in schizophrenia may not be due to medication or course of illness effects. Instead, the present results are consistent with models of schizophrenia positing cerebellar-cortical circuit abnormalities and suggest that cerebellar abnormalities represent a risk marker for the disorder., (© The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite known deficits in postural control in patients with schizophrenia, this domain has not been investigated in youth at ultra high-risk (UHR) for psychosis. This is particularly relevant as postural control implicates dysfunction in the cerebellum-a region implicated in cognitive dysmetria conceptions of schizophrenia but poorly understood in the prodrome. Here, we extended our understanding of movement abnormalities in UHR individuals to include postural control, and have linked these deficits to both symptom severity and cerebello-cortical network connectivity. UHR and healthy control participants completed an instrumentally based balance task to quantify postural control along with a resting state brain imaging scan to investigate cerebellar networks. We also quantified positive and negative symptom severity with structured clinical interviews. The UHR group showed overall increased postural sway and decreased cerebello-cortical resting state connectivity, relative to controls. The decreased cerebello-cortical connectivity was seen across multiple networks. Postural sway was also correlated with cerebellar connectivity in this population and uniquely positively correlated with the severity of negative symptoms. Finally, symptom severity was also associated with cerebellar connectivity. Together, our results point to a potential deficit in sensory integration as an underlying contributor to the increased postural sway, and provide evidence of cerebellar abnormalities in UHR individuals. These results extend our understanding of the motor abnormalities of UHR individuals beyond striatum-based dyskinesias to include postural control and sensory integration deficits, and implicate the cerebellum as a distinct neural substrate preceding the onset of psychosis. Taken together, our results extend the cognitive dysmetria framework to UHR populations., (Copyright © 2014 Wiley Periodicals, Inc.)

Research has suggested that many with schizophrenia experience decrements in synthetic metacognition, or the abilities to form integrated representations of oneself and others and then utilize that knowledge to respond to problems. Although such deficits have been linked with functional impairments even after controlling for symptoms and neurocognition, it is unclear to what extent these deficits can distinguish persons with schizophrenia from others experiencing significant life adversity but without psychosis. To explore this issue we conducted logistic regression analysis to determine whether assessment of metacognition could distinguish between 166 participants with schizophrenia and 51 adults with HIV after controlling for social cognition and education. Metacognition was assessed with the Metacognitive Assessment Scale Abbreviated (MAS-A), and social cognition with the Bell Lysaker Emotion Recognition Test. We observed that the MAS-A total score was able to correctly classify 93.4% of the schizophrenia group, with higher levels of metacognition resulting in increased likelihood of accurate categorization. Additional exploratory analyses showed specific domains of metacognition measured by the MAS-A were equally able to predict membership in the schizophrenia group. Results support the assertion that deficits in the abilities to synthesize thoughts about oneself and others into larger representations are a unique feature of schizophrenia., (Published by Elsevier Ltd.)

Purpose: To compare the direct cost of treating glaucoma patients with Trabectome, iStent, and endoscopic cyclophotocoagulation (ECP) versus topical medications in Ontario, Canada. Costs are projected over a 6-year period, and presented on a per-patient level from the perspective of the Ontario Health Insurance Plan (OHIP)., Methods: The per-bottle cost of each medication was obtained from the 2011 Ontario Drug Benefit (ODB) formulary. A wastage adjustment fee was added to the cost, as was a pharmacy markup, and an ODB dispensing fee. Previously published medication prescription rates were used to determine the frequency with which each medication is prescribed. We estimated the overall cost by taking a weighted average of the cost of each class of glaucoma medications.The cost of each glaucoma device was determined by contacting local distributors. We then added the cost of disposables used during surgery (viscoelastic and keratome) to the cost of each procedure. Start-up costs for each device and surgeons' fees were excluded from the overall cost., Results: At 6 years, treatment with the Trabectome offered a cumulative cost savings of $279.23, $1572.55, and $2424.71 per patient versus monodrug, bidrug, and tridrug therapy, respectively. A cumulative cost difference of -$20.77, $1272.55, and $2124.71 per patient were found when comparing iStent versus monodrug, bidrug, and tridrug therapy, respectively. Treatment with ECP yielded a cost savings of $779.23, $2072.55, and $2924.71 per patient versus monodrug, bidrug, and tridrug therapy, respectively., Conclusions: Over a projected period of 6 years, the Trabectome, iStent, and ECP may all offer a modest cost savings to OHIP versus the cost of glaucoma medication. Further analysis of direct and indirect costs to patients as well as quality of life assessments will help further delineate the role of these treatments in the glaucoma treatment paradigm.

Eyeblink conditioning (EBC) is a widely used translational probe of cerebellar function in both humans and non-human animals. Decades of animal research have identified the cerebellum as critical for EBC. While there is evidence for the involvement of the cerebellum in human EBC, the neural circuitry of EBC in healthy humans has yet to be fully elucidated. The purpose of this study was to design and validate a highly customisable system for EBC stimulus presentation and response recording using infrared (IR) reflectance suitable for use in magnetic resonance imaging (MRI) environments; in this way, the neural activity of EBC could be investigated using fMRI in humans. Four participants underwent delay EBC and simultaneous fMRI. The results indicate (1) a high signal-to-noise ratio in the IR reflectance data that effectively quantifies the eyeblink morphology and timing and (2) evidence of conditioning in the fMRI environment. The quality of the data, the feasibility of conducting EBC experiments in the fMRI environment, and the customisability of the current system to fit a variety of EBC experimental design parameters are discussed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Many with schizophrenia have been found to experience difficulties recognizing a range of their own mental states including memories and emotions. While there is some evidence that the self perception of empathy in schizophrenia is often at odds with objective observations, little is known about the correlates of rates of concordance between self and rater assessments of empathy for this group. To explore this issue we gathered self and rater assessments of empathy in addition to assessments of emotion recognition using the Bell Lysaker Emotion Recognition Task, insight using the Scale to Assess Unawareness of Mental Disorder, and symptoms using the Positive and Negative Syndrome Scale from 91 adults diagnosed with schizophrenia spectrum disorders. Results revealed that participants with better emotion recognition, better insight, fewer positive symptoms and fewer depressive symptoms produced self ratings of empathy which were more strongly correlated with assessments of empathy performed by raters than participants with greater deficits in these domains. Results suggest that deficits in emotion recognition along with poor insight and higher levels of positive and depressive symptoms may affect the degree of agreement between self and rater assessments of empathy in schizophrenia., (Published by Elsevier Ireland Ltd.)

Objective: To compare visual acuity and central retinal thickness in patients initially treated with bevacizumab (Avastin) and switched to ranibizumab (Lucentis) for neovascular age-related macular degeneration (AMD)., Design: A retrospective chart review., Participants: This study included 87 eyes from 80 patients over the age of 65 with neovascular AMD., Methods: Patients were initially treated with bevacizumab injections every 6 weeks and then switched to ranibizumab every 4 weeks when it became publicly funded by the Ontario government. Outcomes include comparison of visual acuity and central retinal thickness after bevacizumab treatment, and after switching to ranibizumab., Results: Visual acuity improved significantly versus initial baseline values following a treatment course of 3 or more injections of bevacizumab (0.58 logMar, SD = 0.30 vs 0.73 logMar, SD = 0.41; p = 0.0007). Patients then showed a further significant improvement in visual acuity after switching and receiving a course of ranibizumab (0.51 logMar, SD = 0.32) (p = 0.0122). Mean central retinal thickness as measured by optical coherence tomography significantly decreased after a course of bevacizumab (p = 0.0158), and a further decrease was noted after a subsequent course of ranibizumab (p < 0.0001)., Conclusions: There was a significant improvement in visual acuity and central retinal thickness in patients with neovascular AMD initially treated with bevacizumab. When these patients were uniformly switched to ranibizumab there was a further significant improvement in visual acuity and a reduction of retinal thickness. It appears that ranibizumab can maintain, or improve the effect achieved after an initial course of bevacizumab., (Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Motor dysfunction is a consistently reported but understudied aspect of schizophrenia. Postural sway area was examined in individuals with schizophrenia under four conditions with different amounts of visual and proprioceptive feedback: eyes open or closed and feet together or shoulder width apart. The nonlinear complexity of postural sway was assessed by detrended fluctuation analysis (DFA). The schizophrenia group (n = 27) exhibited greater sway area compared to controls (n = 37). Participants with schizophrenia showed increased sway area following the removal of visual input, while this pattern was absent in controls. Examination of DFA revealed decreased complexity of postural sway and abnormal changes in complexity upon removal of visual input in individuals with schizophrenia. Additionally, less complex postural sway was associated with increased symptom severity in participants with schizophrenia. Given the critical involvement of the cerebellum and related circuits in postural stability and sensorimotor integration, these results are consistent with growing evidence of motor, cerebellar, and sensory integration dysfunction in the disorder, and with theoretical models that implicate cerebellar deficits and more general disconnection of function in schizophrenia.

Objectives: To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables., Design: Observational study., Setting: University-based research facility., Participants: Twenty-five women with BC who had received chemotherapy, 19 women with BC who had not received chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables., Results: Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls. The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other 2 groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. Older age and lower educational level were associated with increased executive function impairment in the chemotherapy group., Conclusions: These findings provide further evidence of neurological impairment associated with primary BC irrespective of treatment history. The left caudal lateral prefrontal region may be particularly vulnerable to the effects of chemotherapy and/or disease severity and may represent a novel biomarker of subjective executive dysfunction in chemotherapy-treated women. Furthermore, negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level.

Objectives: Theoretical and empirical evidence suggests that impaired time perception and the neural circuitry contributing to internal timing mechanisms may contribute to severe psychiatric disorders, including mood disorders. The structures that are involved in subsecond timing, i.e., cerebellum and basal ganglia, have also been implicated in the pathophysiology of bipolar disorder. However, the timing of subsecond intervals has infrequently been studied in this population., Methods: Paced finger-tapping tasks have been used to characterize internal timing processes in neuropsychiatric disorders. A total of 42 bipolar disorder patients (25 euthymic, 17 manic) and 42 age-matched healthy controls completed a finger-tapping task in which they tapped in time with a paced (500-ms intertap interval) auditory stimulus (synchronization), then continued tapping without auditory input while attempting to maintain the same pace (continuation). This procedure was followed using the dominant index finger, then with alternating thumbs., Results: Bipolar disorder participants showed greater timing variability relative to controls regardless of pacing stimulus (synchronization versus continuation) or condition (dominant index finger versus alternating thumbs). Decomposition of timing variance into internal clock versus motor implementation components using the Wing-Kristofferson model showed higher clock variability in the bipolar disorder groups compared to controls, with no differences between groups on motor implementation variability., Conclusions: These findings suggest that internal timing mechanisms are disrupted in bipolar disorder patients, independent of symptom status. Increased clock variability in bipolar disorder may be related to abnormalities in cerebellar function., (© 2011 John Wiley and Sons A/S.)

Structural, neurochemical, and functional abnormalities have been identified in the brains of individuals with bipolar disorder, including in key brain structures implicated in postural control, i.e. the cerebellum, brainstem, and basal ganglia. Given these findings, we tested the hypothesis that postural control deficits are present in individuals with bipolar disorder. Sixteen participants with bipolar disorder (BD) and 16 age-matched non-psychiatric healthy controls were asked to stand as still as possible on a force platform for 2 minutes under 4 conditions: (1) eyes open-open base; (2) eyes closed-open base; (3) eyes open-closed base; and (4) eyes closed-closed base. Postural sway data were submitted to conventional quantitative analyses of the magnitude of sway area using the center of pressure measurement. In addition, data were submitted to detrended fluctuation analysis, a nonlinear dynamical systems analytic technique that measures complexity of a time-series, on both the anterior-posterior and medio-lateral directions. The bipolar disorder group had increased sway area, indicative of reduced postural control. Decreased complexity in the medio-lateral direction was also observed for the bipolar disorder group, suggesting both a reduction in dynamic range available to them for postural control, and that their postural corrections were primarily dominated by longer time-scales. On both of these measures, significant interactions between diagnostic group and visual condition were also observed, suggesting that the BD participants were impaired in their ability to make corrections to their sway pattern when no visual information was available. Greater sway magnitude and reduced complexity suggest that individuals with bipolar disorder have deficits in sensorimotor integration and a reduced range of timescales available on which to make postural corrections.

Purpose: To assess the utility of image-guided transnasal endoscopic surgery for a variety of orbital diseases requiring decompression of at least one orbital wall., Method: A descriptive case series of consecutive orbital procedures requiring decompression of at least one wall. All procedures were performed using a transnasal endoscopic approach and an intraoperative image-guided LandmarX system for anatomical guidance., Results: A 3-year review yielded 17 cases, including 6 cases with compressive mucoceles, 4 neoplasms, 4 patients with proptosis secondary to Graves' Ophthalmopathy, 1 case of an intraorbital abscess, 1 fungal mycetoma, and 1 hemangioma. These cases all had improved postoperative clinical status without any serious complications. The LandmarX system was a valuable intraoperative tool in all 17 cases., Conclusions: The endoscopic transnasal approach to orbital decompression surgery allows for good visualization and is minimally invasive. Using this approach in conjunction with the LandmarX image-guided system allows for improved anatomical localization and provided good results in all cases.

Purpose: To evaluate clinical aspects of patients with the diagnosis of plateau iris (PI) or pseudoplateau iris (PPI) made by ultrasound biomicroscopy (UBM) in order to determine if there are any clinical factors that can help differentiate between these two entities., Method: A retrospective cohort of consecutive UBM patients with the diagnosis of PI or PPI. The diagnosis of PI was based on an anteriorly positioned ciliary body that abutted the peripheral iris, a narrow (<10 degrees) or closed angle for at least 180 degrees, and the anterior portion of the iris positioned anterior to scleral spur. The diagnosis of PPI was similar to plateau except that large or a cluster of small cysts had to be present in the iridociliary sulcus., Results: There were a total of 76 patients (29% male), 21 with PPI and 55 with PI. Patients with PPI were more likely to be male (p = 0.005), slightly younger (51.5 (SD 10.7) vs 57.9 (10.2) p = 0.0190), have a "bumpy" peripheral iris appearance (p = 0.003), have greater trabecular meshwork pigmentation (2.0 (0.7) vs 1.3 (0.6) p = 0.004) and have fewer clock hours of gonioscopic angle closure versus plateau iris patients (5.1 (4.3) vs 9.2 (4.2) p = 0.0009). Spherical equivalent was not significantly different between groups (0.50D (1.69) PPI vs 1.33D (2.42) PI; p = 0.187)., Conclusions: In patients being referred to a UBM clinic for evaluation of angle-closure mechanism, younger males with a bumpy peripheral iris have a higher likelihood of having a diagnosis of pseudoplateau iris. However, clinical factors do not appear to discriminate well between PPI and PI. UBM is extremely helpful in confirming underlying mechanism and guiding therapy.

Background: Our objectives were to present the spectrum of eye injuries caused by indoor soccer, as seen at our institution, and to initiate discussion as to whether eye protection should become mandatory for this indoor sport., Methods: Chart review of patients presenting to our institution with eye injuries from indoor soccer., Results: Five cases were identified from 2001-2005, all occurring during the winter or late fall. Each injury was due to contact with the soccer ball itself. Initially, all 5 patients presented with commotio retinae (1 with a prominent retinal and vitreous hemorrhage and 2 with smaller retinal hemorrhages), 2 with hyphema and traumatic mydriasis, 1 with subconjunctival hemorrhage, and 1 with upper lid edema and ecchymosis. Three resolved uneventfully with 20/20 or better vision; however, in 2 there were findings of choroidal rupture with chorioretinal scarring. One of these had 20/20 vision and a discontinuous choroidal rupture peripherally, and the other had 20/40 vision and extensive chorioretinal scarring. One patient also showed a peculiar persistent iris scar., Interpretation: Soccer-related eye injuries have been recognized as an important ophthalmologic problem in Europe and now increasingly so in North America. With the increasing popularity of indoor soccer in Canada, serious eye injuries have become more prevalent. On the basis of the prevalence and the nature and mechanism of the ocular trauma, we believe there may be a need to make eye protection mandatory for all forms of soccer.

Case Report: Setleis syndrome is a rare ectodermal dysplasia with characteristic ophthalmic findings. We describe the first 2 reported cases in Canadian individuals of Aboriginal descent., Comments: Although most ophthalmic findings are benign, it is important to recognize the clinical significance for management and genetic counselling. We postulate an autosomal dominant inheritance in our cases.

This study examined the relationship between bulimia and family variables. Eight hundred twenty female college students completed a personal history questionnaire, the Bulimia Test, and the Eating Disorders Inventory. Twenty-four subjects who met the DSM-III-R criteria for bulimia were compared with 24 subclinical bulimics and 24 symptom-free subjects on demographic and family variables, including subscales from the Family Environment Scale and the Parental Bonding Instrument. Significant group differences indicated that the families of bulimics differ from other families. However, in contrast to the findings of research done in treatment settings, bulimics in this nonclinical setting did not report more family conflict or less caring from their parents than did symptom-free subjects.

Beagle bitches were treated on days 20-22 of pregnancy with TPT as an aqueous solution administered subcutaneously via a minipump at a rate of 10 micrograms per hour for either 24 (I) or 48 hours (II). Additional animals received a single subcutaneous injection of 200 micrograms of TPT as an aqueous solution (III) or dissolved in polyethylene glycol 400 (IV) or the methyl ester of TPT dissolved in polyethylene glycol 400 (V). The duration of action was assessed by the nadir in circulating progesterone levels. By this criterion the duration of action in the different groups ranked I=III

The performance in vivo of nafarelin acetate, a potent analogue of luteinizing hormone-releasing hormone, microencapsulated in poly(d,l-lactide-co-glycolide), was evaluated. The influence of polymer composition and molecular weight on the estrus-suppressing activity of the microspheres in female rats was determined. Compound release was shown to be effected by polymer erosion rather than by diffusion. A triphasic release of compound was observed, which was adjusted by altering the critical parameters of the polymer. A mechanism for the release of the compound was proposed. The primary release phase was compound loss by diffusion from the surface of the microspheres. The secondary phase of subeffective rates of release occurred concomitantly with polymer hydrolysis and a decrease in its molecular weight, although it remained insoluble. Dissolution of low-molecular weight fragments and erosion of the bulk of the polymer then initiated the tertiary phase of release of compound.

A formulation containing 95% delmadinone acetate was compressed at three different pressures. These pressures resulted in a pellet density difference of 19%. In vivo dissolution profiles were determined for five lots of pellets. The pellets were implanted subcutaneously in rats, removed periodically, and assayed chemically for remaining steroid. The resulting data were fit, using the computer program NONLIN, to a dissolution model. The dissolution rate for the lot with the lowest density made at the lowest compression was statistically (p less than 0.05) different from the four other lots. A possible explanation for this increased dissolution rate could be that channeling occurs within the pellet, thereby increasing the effective dissolving surface. The results also indicate that equivalent dissolution rates between lots are reached at a certain compression and density.

Preliminary studies on use of the synthetic prostaglandin, fenprostalene, as an abortifacient had indicated that maximum effectiveness was dependent upon slow delivery. Because both route of administration and formulation control delivery rates, the influences of intramuscular (im) vs subcutaneous (sc) injections, and aqueous acetate buffer (AAB) vs polyethylene glycol-400 (PEG) vehicles on the plasma concentration and urinary excretion of fenprostalene were compared. Feedlot heifers were administered 1 mg injections of [13,14-3H]-fenprostalene. Blood samples and total urine excretion were collected during the following 96 h. The maximum concentration of tritium in plasma occurred at 2 h for AAB-im (.90 ng eq/ml), PEG-im (.75 ng eq/ml) and AAB-sc (.64 ng eq/ml), and then declined throughout 24 h with t 1/2 values of 6.1, 9.4 and 9.2 h, respectively. The peak concentration from PEG-sc was lower (.37 ng eq/ml, P less than .05), observed later (4h, P less than .05) and declined more slowly following peak concentration (t 1/2 = 15.1 h, P less than .05). Consistent with delayed absorption, a smaller fraction (P less than .05) of the total radioactivity excreted in urine was recovered during the first 24 h after injection for PEG-sc (85%) than for PEG-im (95%), AAB-sc (97%) or AAB-im (99%). In a tissue distribution study, plasma, urine and fecal samples were collected and heifers were slaughtered at various times following sc injection of 1 mg of [3H] fenprostalene in PEG. Peak concentrations of tritium in plasma occurred between 4 and 8 h and declined with a t 1/2 of 15.2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

This study examined the relation of eating attitudes and behaviors to family dynamics and psychological adjustment in a nonclinical group of female university freshmen. Family dynamics variables, which were measured by the Family Environment Scale (FES), included Control, Cohesion, Conflict, Organization, Expressiveness, Independence, Achievement-Orientation, Intellectual-Cultural Orientation, Active-Recreational Orientation, and Moral Religious Emphasis. Psychological adjustment was measured by the Hopkins Symptom Checklist (HSC). Variables on this scale included Anxiety, Depression, Somatization, Obsessive-Compulsive, and Interpersonal Sensitivity. Eating attitudes and behaviors were measured by the Bulimia Test (BULIT), a 32-item self-report inventory. Multivariate analysis of variance indicated that bulimics, subclinical bulimics, and normals could be differentiated on the Hopkins Symptom Checklist. Univariate analyses revealed differences between the groups on all of the HSC measures and the Organization scale of the FES. The results suggest that conclusions about the causal relationships between maladaptive family patterns and bulimia presented in previous research should be viewed with caution.

An automated system for the simultaneous dissolution testing of six samples was developed consisting of four basic units: dissolution vessels and stirring unit, a peristaltic pump, a rotary stream multiport switching valve and programmer, and a UV spectrophotometer with recorder. Among the major advantages of such a system are: (a) paddle or basket stirring with variable speed is used, (b) the tablet or capsule (wire coil required) locates reproducibly at the bottom of a round-bottom reaction flask when utilizing paddle-type stirring, (c) a USP basket for tablet or capsule dissolution testing can be used, (d) continuous or intermittent sampling is possible, (e) the flow system readily adapts to UV-visible detector or fluorescence spectroscopy, (f) the system readily adapts to automated determination of the intrinsic dissolution of a material, and (g) the cost is low because of the multiport switching valve and inexpensive UV monitor required. Studies were performed using this apparatus to demonstrate the response characteristics of the system, its reproducibility, potential problems, and precautions required. This dissolution system was used to determine the dissolution characteristics of a new steroid tablet formulation, including a formulation and lot demonstrated to be bioavailable.