Element-centric clustering comparison unifies overlaps and hierarchy

Clustering is one of the most universal approaches for understanding complex data. A pivotal aspect of clustering analysis is quantitatively comparing clusterings; clustering comparison is the basis for many tasks such as clustering evaluation, consensus clustering, and tracking the temporal evolution of clusters. In particular, the extrinsic evaluation of clustering methods requires comparing the uncovered clusterings to planted clusterings or known metadata. Yet, as we demonstrate, existing clustering comparison measures have critical biases which undermine their usefulness, and no measure accommodates both overlapping and hierarchical clusterings. Here we unify the comparison of disjoint, overlapping, and hierarchically structured clusterings by proposing a new element-centric framework: elements are compared based on the relationships induced by the cluster structure, as opposed to the traditional cluster-centric philosophy. We demonstrate that, in contrast to standard clustering similarity measures, our framework does not suffer from critical biases and naturally provides unique insights into how the clusterings differ. We illustrate the strengths of our framework by revealing new insights into the organization of clusters in two applications: the improved classification of schizophrenia based on the overlapping and hierarchical community structure of fMRI brain networks, and the disentanglement of various social homophily factors in Facebook social networks. The universality of clustering suggests far-reaching impact of our framework throughout all areas of science

Disturbances of visual motion perception in bipolar disorder

OBJECTIVES: While cognitive deficits have been well documented in patients with bipolar disorder, visual perception has been less well characterized. Such deficits appear in schizophrenia, which shares genetic risk factors with bipolar disorder, and may contribute to disturbances in visual cognition and learning. METHODS: The present study investigated visual perception in bipolar disorder using psychophysical tests of contrast sensitivity, dot motion discrimination, and form discrimination. The relationship of these measures to mood state, medication status, and cognitive function was investigated. Sixty-one patients with type I bipolar disorder and 67 comparison subjects were tested. RESULTS: Results indicated a deficit in dot motion trajectory discrimination in both euthymic and ill individuals with bipolar disorder, as well as a global deficit in moving grating contrast sensitivity. Ill individuals with bipolar disorder were impaired in psychomotor processing, but this finding was not related to visual processing performance. CONCLUSIONS: These findings could be due to disturbances in specific visual pathways involved in the processing of motion properties, or to a more general deficit which impairs processing of temporally modulated stimuli

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

The auditory steady-state response (ASSR): a translational biomarker for schizophrenia

Electrophysiological methods have demonstrated disturbances of neural synchrony and oscillations in schizophrenia which affect a broad range of sensory and cognitive processes. These disturbances may account for a loss of neural integration and effective connectivity in the disorder. The mechanisms responsible for alterations in synchrony are not well delineated, but may reflect disturbed interactions within GABAergic and glutamatergic circuits, particularly in the gamma range. Auditory steady-state responses (ASSRs) provide a non-invasive technique used to assess neural synchrony in schizophrenia and in animal models at specific response frequencies. ASSRs are electrophysiological responses entrained to the frequency and phase of a periodic auditory stimulus generated by auditory pathway and auditory cortex activity. Patients with schizophrenia show reduced ASSR power and phase locking to gamma range stimulation. We review alterations of ASSRs in schizophrenia, schizotypal personality disorder, and first-degree relatives of patients with schizophrenia. In vitro and in vivo approaches have been used to test cellular mechanisms for this pattern of findings. This translational, cross-species approach provides support for the role of N-methyl-D-aspartate and GABAergic dysregulation in the genesis of perturbed ASSRs in schizophrenia and persons at risk

Dissociating Stimulus-Set and Response-Set in the Context of Task-Set Switching

The primary aim of the present research was to determine how stimulus-set and response-set components of task-set contribute to switch costs and conflict processing. Three experiments are described wherein participants completed an explicitly cued task-switching procedure. Experiment 1 established that task switches requiring a reconfiguration of both stimulus- and response-set incurred larger residual switch costs than task switches requiring the reconfiguration of stimulus-set alone. Between-task interference was also drastically reduced for response-set conflict compared with stimulus-set conflict. A second experiment replicated these findings and demonstrated that stimulus- and response-conflict have dissociable effects on the decision time and motor time components of total response time. Finally, a third experiment replicated Experiment 2 and demonstrated that the stimulus- and response- components of task switching and conflict processing elicit dissociable neural activity as evidence by event-related brain potentials

Cognitive manipulation of brain electric microstates

EEG studies of wakeful rest have shown that there are brief periods in which global electrical brain activity on the scalp remains semi-stable (so-called microstates). Topographical analyses of this activity have revealed that much of the variance is explained by four distinct microstates that occur in a repetitive sequence. A recent fMRI study showed that these four microstates correlated with four known functional systems, each of which is activated by specific cognitive functions and sensory inputs. The present study used high density EEG to examine the degree to which spatial and temporal properties of microstates may be altered by manipulating cognitive task (a serial subtraction task vs. wakeful rest) and the availability of visual information (eyes open vs. eyes closed conditions). The hypothesis was that parameters of microstate D would be altered during the serial subtraction task because it is correlated with regions that are part of the dorsal attention functional system. It was also expected that the sequence of microstates would preferentially transition from all other microstates to microstate D during the task as compared to rest. Finally, it was hypothesized that the eyes open condition would significantly increase one or more microstate parameters associated with microstate B, which is associated with the visual system. Topographical analyses indicated that the duration, coverage, and occurrence of microstate D were significantly higher during the cognitive task compared to wakeful rest; in addition, microstate C, which is associated with regions that are part of the default mode and cognitive control systems, was very sensitive to the task manipulation, showing significantly decreased duration, coverage, and occurrence during the task condition compared to rest. Moreover, microstate B was altered by manipulations of visual input, with increased occurrence and coverage in the eyes open condition. In addition, during the eyes open condition microstates A and D had significantly shorter durations, while C had increased occurrence. Microstate D had decreased coverage in the eyes open condition. Finally, at least 15 microstates (identified via k-means clustering) were required to explain a similar amount of variance of EEG activity as previously published values. These results support important aspects of our hypotheses and demonstrate that cognitive manipulation of microstates is possible, but the relationships between microstates and their corresponding functional systems are complex. Moreover, there may be more than four primary microstates

Differential effects of two early life stress paradigms on cerebellar-dependent delay eyeblink conditioning

Early life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2–9, n = 15) and maternal separation (60 min per day during postnatal day 2–14, n = 13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value

Relationships between auditory event-related potentials and mood state, medication, and comorbid psychiatric illness in patients with bipolar disorder

BACKGROUND: Patients with bipolar disorder (BD) exhibit aberrations in auditory event-related potentials (ERPs), although the relationships between these measures and mood state at testing, comorbid psychiatric illness, presence of psychotic features, and medication usage are unclear. The purpose of this study was to investigate the relationships between these factors and auditory ERP measures in BD patients. METHODS: An auditory 'oddball' discrimination task was used to elicit ERPs from 69 patients with type I BD and 52 healthy controls. Patients were placed into subgroups based upon their mood state at testing (euthymic or symptomatic), and ANOVA was used to compare amplitude and peak latency measures from the N100, P200, N200, and P300 ERP components across subgroups. Multiple regression was used to investigate relationships between ERP measures and comorbid psychiatric diagnosis, history of psychotic features, and medication status. RESULTS: Relative to healthy control participants, euthymic and symptomatic BD patients exhibited reduced P300 and P200 amplitude, but ERP measures did not differ among BD patients on the basis of mood status. A history of a comorbid anxiety disorder was associated with reduced N200 peak latency, but prolonged P300 peak latency among BD patients. No other relationships between clinical variables and ERP measures were significant. CONCLUSIONS: The results suggest that disrupted auditory attention may be observed in BD patients regardless of their mood state at testing, medication status, or history of psychosis. These results extend previous findings, and provide further evidence for aberrations in the P300 ERP as an endophenotype for BD

Disturbed resting state EEG synchronization in bipolar disorder: A graph-theoretic analysis

AbstractDisruption of functional connectivity may be a key feature of bipolar disorder (BD) which reflects disturbances of synchronization and oscillations within brain networks. We investigated whether the resting electroencephalogram (EEG) in patients with BD showed altered synchronization or network properties. Resting-state EEG was recorded in 57 BD type-I patients and 87 healthy control subjects. Functional connectivity between pairs of EEG channels was measured using synchronization likelihood (SL) for 5 frequency bands (δ, θ, α, β, and γ). Graph-theoretic analysis was applied to SL over the electrode array to assess network properties. BD patients showed a decrease of mean synchronization in the alpha band, and the decreases were greatest in fronto-central and centro-parietal connections. In addition, the clustering coefficient and global efficiency were decreased in BD patients, whereas the characteristic path length increased. We also found that the normalized characteristic path length and small-worldness were significantly correlated with depression scores in BD patients. These results suggest that BD patients show impaired neural synchronization at rest and a disruption of resting-state functional connectivity