27 research outputs found
Eyeblink Conditioning in Schizophrenia: A Critical Review
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
Motor deficits in schizophrenia quantified by nonlinear analysis of postural sway.
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
Cerebellar Activation Deficits in Schizophrenia During an Eyeblink Conditioning Task
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
Eyeblink conditioning in schizophrenia: A critical review
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 paper thoroughly reviews all published studies investigating EBC in schizophrenia, with an emphasis on possible effect 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
The clinical and prognostic value of motor abnormalities in psychosis, and the importance of instrumental assessment
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
Postural control in bipolar disorder: increased sway area and decreased dynamical complexity.
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
New insights into the nature of cerebellar-dependent eyeblink conditioning deficits in schizophrenia: A hierarchical linear modeling approach
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 (ANOVA) 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 3-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
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Instrument-based assessment of motor function yields no evidence of dyskinesia in adult first-degree biological relatives of individuals with schizophrenia and schizoaffective disorder
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