The neurophysiology of biological motion perception in schizophrenia.

IntroductionThe ability to recognize human biological motion is a fundamental aspect of social cognition that is impaired in people with schizophrenia. However, little is known about the neural substrates of impaired biological motion perception in schizophrenia. In the current study, we assessed event-related potentials (ERPs) to human and nonhuman movement in schizophrenia.MethodsTwenty-four subjects with schizophrenia and 18 healthy controls completed a biological motion task while their electroencephalography (EEG) was simultaneously recorded. Subjects watched clips of point-light animations containing 100%, 85%, or 70% biological motion, and were asked to decide whether the clip resembled human or nonhuman movement. Three ERPs were examined: P1, N1, and the late positive potential (LPP).ResultsBehaviorally, schizophrenia subjects identified significantly fewer stimuli as human movement compared to healthy controls in the 100% and 85% conditions. At the neural level, P1 was reduced in the schizophrenia group but did not differ among conditions in either group. There were no group differences in N1 but both groups had the largest N1 in the 70% condition. There was a condition × group interaction for the LPP: Healthy controls had a larger LPP to 100% versus 85% and 70% biological motion; there was no difference among conditions in schizophrenia subjects.ConclusionsConsistent with previous findings, schizophrenia subjects were impaired in their ability to recognize biological motion. The EEG results showed that biological motion did not influence the earliest stage of visual processing (P1). Although schizophrenia subjects showed the same pattern of N1 results relative to healthy controls, they were impaired at a later stage (LPP), reflecting a dysfunction in the identification of human form in biological versus nonbiological motion stimuli

Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia

There is a burgeoning need for innovative treatment strategies to improve the cognitive deficits in schizophrenia. Cognitive remediation (CR) is effective at the group level, but the variability in treatment response is large. Given that CR may depend on intact neuroplasticity to produce cognitive gains, it is reasonable to combine it with strategies that harness patients’ neuroplastic potential. In this review, we discuss two non-pharmacological approaches that can enhance neuroplasticity and possibly augment the effects of CR in schizophrenia: physical exercise and transcranial direct current stimulation (tDCS). Substantial body of evidence supports the beneficial effect of physical exercise on cognition, and a handful of studies in schizophrenia have shown that physical exercise in conjunction with CR has a larger impact on cognition than CR alone. Physical exercise is thought to stimulate neuroplasticity through the regulation of central growth factors, and current evidence points to brain-derived neurotrophic factor as the potential underlying mechanism through which physical exercise might enhance the effectiveness of CR. tDCS has emerged as a potential tool for cognitive enhancement and seems to affect the cellular mechanisms involved in long-term potentiation (LTP). A few reports have demonstrated the feasibility of integrating tDCS with CR in schizophrenia, but there are insufficient data to determine if this multimodal approach leads to incremental performance gain in patients. Larger randomized controlled trials are necessary to understand the mechanisms of the combined tDCS–CR intervention. Future research should take advantage of new developments in neuroplasticity paradigms to examine the effects of these interventions on LTP

The neurophysiology of biological motion perception in schizophrenia.

IntroductionThe ability to recognize human biological motion is a fundamental aspect of social cognition that is impaired in people with schizophrenia. However, little is known about the neural substrates of impaired biological motion perception in schizophrenia. In the current study, we assessed event-related potentials (ERPs) to human and nonhuman movement in schizophrenia.MethodsTwenty-four subjects with schizophrenia and 18 healthy controls completed a biological motion task while their electroencephalography (EEG) was simultaneously recorded. Subjects watched clips of point-light animations containing 100%, 85%, or 70% biological motion, and were asked to decide whether the clip resembled human or nonhuman movement. Three ERPs were examined: P1, N1, and the late positive potential (LPP).ResultsBehaviorally, schizophrenia subjects identified significantly fewer stimuli as human movement compared to healthy controls in the 100% and 85% conditions. At the neural level, P1 was reduced in the schizophrenia group but did not differ among conditions in either group. There were no group differences in N1 but both groups had the largest N1 in the 70% condition. There was a condition × group interaction for the LPP: Healthy controls had a larger LPP to 100% versus 85% and 70% biological motion; there was no difference among conditions in schizophrenia subjects.ConclusionsConsistent with previous findings, schizophrenia subjects were impaired in their ability to recognize biological motion. The EEG results showed that biological motion did not influence the earliest stage of visual processing (P1). Although schizophrenia subjects showed the same pattern of N1 results relative to healthy controls, they were impaired at a later stage (LPP), reflecting a dysfunction in the identification of human form in biological versus nonbiological motion stimuli

A randomized controlled trial comparing a "bottom-up" and "top-down" approach to cognitive training in schizophrenia.

The development of effective cognitive training (CT) interventions is critical for improving the daily lives of people with schizophrenia. At this point, it is unclear whether a so-called "bottom-up" or "top-down" CT approach is more beneficial for inducing cognitive gains and generalization in this population. The aims of this randomized controlled trial were to: 1) Compare the effects of these two types of training approaches on performance-based (MATRICS Consensus Cognitive Battery, MCCB) and neurophysiological (mismatch negativity, MMN) measures of cognition, and 2) Evaluate MMN as a potential predictor of treatment response. Ninety-nine patients with persistent schizophrenia (mean age of 51 and illness duration of 30 years) were randomly assigned in a 2:2:1 ratio to a "bottom-up" intervention that selectively targets basic auditory processing and verbal learning (Brain Fitness), a "top-down" intervention that targets a broad range of higher-order cognitive functions (COGPACK), or a control condition consisting of commercial computer games (Sporcle). Participants completed on average 30 h of training over 12 weeks. Despite demonstrated improvement on training tasks, we found no significant treatment effects on measures of neurocognition (MCCB), MMN, or functional capacity from either intervention. Interestingly, there was an association between an enhanced MMN response at 6 weeks and improved reasoning/problem solving at 12 weeks in the COGPACK group. Although this study had several methodological strengths, the results were mainly negative. It suggests that CT trials in schizophrenia should try to better understand mediators and moderators of treatment response to develop more personalized interventions

MEG resting-state oscillations and their relationship to clinical symptoms in schizophrenia

Neuroimaging studies suggest that schizophrenia is characterized by disturbances in oscillatory activity, although at present it remains unclear whether these neural abnormalities are driven by dimensions of symptomatology. Examining different subgroups of patients based on their symptomatology is thus very informative in understanding the role of neural oscillation patterns in schizophrenia. In the present study we examined whether neural oscillations in the delta, theta, alpha, beta and gamma bands correlate with positive and negative symptoms in individuals with schizophrenia (SZ) during rest. Resting-state brain activity of 39 SZ and 25 neurotypical controls was recorded using magnetoencephalography. Patients were categorized based on the severity of their positive and negative symptoms. Spectral analyses of beamformer data revealed that patients high in positive symptoms showed widespread low alpha power, and alpha power was negatively correlated with positive symptoms. In contrast, patients high in negative symptoms showed greater beta power in left hemisphere regions than those low in negative symptoms, and beta power was positively correlated with negative symptoms. We further discuss these findings and suggest that different neural mechanisms may underlie positive and negative symptoms in schizophrenia. Keywords: Schizophrenia, Resting-state, MEG, Neural oscillations, Negative symptoms, Positive symptoms, Alpha band, Beta ban

Predicting response to cognitive training for schizophrenia using results from two studies with different outcomes

BackgroundCollaborative data sharing between research groups provides an opportunity to explore the basis for the heterogeneity in cognitive training outcomes reported in the schizophrenia literature. The current analyses focused on the contribution of site and participant characteristics to these heterogeneous outcomes.MethodsData from two independent studies, from New York (NY) and Los Angeles (LA), were combined to yield a sample of 132 outpatient adults with schizophrenia/schizoaffective disorder. While similar treatment doses, cognitive exercises and outcome measures were used, sites differed in use of coaching, group discussion and compensation. Between-site differences in participant demographic and baseline clinical characteristics were tested. Regression examined predictors of change in cognition (MCCB) and functional capacity (UPSA) which could explain site differences in treatment effects.ResultsMedium to large treatment effect size differences in MCCB and UPSA favored the NY site over LA. When the studies were combined, the effect of site was significant for both outcomes with a medium effect size difference. After controlling for background characteristics, the effect of site was reduced for both outcomes, but remained significant for cognition. Improvement in UPSA was associated with better baseline MCCB (p < 0.001), lower baseline UPSA (p < 0.001) and younger age (p = 0.019). The overall model with site, baseline scores, and participant background characteristics explained about 30% to 40% of the variance in outcomes.DiscussionParticipant and treatment characteristics are both predictive of outcomes, but treatment characteristics may be more consequential to cognitive gain, while participant characteristics may be more consequential to change in functional capacity