A Developmental Perspective on Early and Current Motor Abnormalities and Psychotic-Like Symptoms.

BACKGROUND AND HYPOTHESIS: Psychotic-like experiences (PLEs) are prevalent in the general population and, because they represent a lower end of the psychosis vulnerability spectrum, may be useful in informing mechanistic understanding. Although it is well-understood that motor signs characterize formal psychotic disorders, the developmental trajectory of these features and their relationships with PLEs are less well-understood. STUDY DESIGN: Data from 7559 adolescents and young adults (age 11-21) in the Philadelphia Neurodevelopmental Cohort were used to investigate whether early-life milestone-attainment delays relate to current adolescent sensorimotor functioning and positive and negative PLEs. Current sensorimotor functioning was assessed using the Computerized Finger Tapping task (assessing motor slowing) and Mouse Practice task (assessing sensorimotor planning). STUDY RESULTS: Early developmental abnormalities were related to current adolescent-aged motor slowing (t(7415.3) = -7.74, corrected-P < .001) and impaired sensorimotor planning (t(7502.5) = 5.57, corrected-P < .001). There was a significant interaction between developmental delays and current sensorimotor functioning on positive and negative PLEs (t = 1.67-4.51), such that individuals with early developmental delays had a stronger positive relationship between sensorimotor dysfunction and PLEs. Importantly, interaction models were significantly better at explaining current PLEs than those treating early and current sensorimotor dysfunction independently (χ2 = 4.89-20.34). CONCLUSIONS: These findings suggest a relationship between early developmental delays and current sensorimotor functioning in psychosis proneness and inform an understanding of heterotypic continuity as well as a neurodevelopmental perspective of motor circuits. Furthermore, results indicate that motor signs are a clear factor in the psychosis continuum, suggesting that they may represent a core feature of psychosis vulnerability.

Pre-saccadic shifts of attention in individuals diagnosed with schizophrenia.

INTRODUCTION: Pathophysiological theories of schizophrenia (SZ) symptoms posit an abnormality in using predictions to guide behavior. One such prediction is based on imminent movements, via corollary discharge signals (CD) that relay information about planned movement kinematics to sensory brain regions. Empirical evidence suggests a reduced influence of sensorimotor predictions in individuals with SZ within multiple sensory systems, including in the visual system. One function of CD in the visual system is to selectively enhance visual sensitivity at the location of planned eye movements (pre-saccadic attention), thus enabling a prediction of the to-be-foveated stimulus. We expected pre-saccadic attention shifts to be less pronounced in individuals with SZ than in healthy controls (HC), resulting in unexpected sensory consequences of eye movements, which may relate to symptoms than can be explained in the context of altered allocation of attention. METHODS: We examined this question by testing 30 SZ and 30 HC on a pre-saccadic attention task. On each trial participants made a saccade to a cued location in an array of four stimuli. A discrimination target that was either congruent or incongruent with the cued location was briefly presented after the cue, during saccade preparation. Pre-saccadic attention was quantified by comparing accuracy on congruent trials to incongruent trials within the interval preceding the saccade. RESULTS: Although SZs were less accurate overall, the magnitude of the pre-saccadic attention effect generally did not differ across groups nor show a convincing relationship with symptom severity. We did, however, observe that SZ had reduced pre-saccadic attention effects when the discrimination target (probe) was presented at early stages of saccade planning, when pre-saccadic attention effects first emerged in HC. CONCLUSION: These findings suggest generally intact pre-saccadic shifts of attention in SZ, albeit slightly delayed. Results contribute to our understanding of altered sensory predictions in people with schizophrenia.

Stronger tilt aftereffects in individuals diagnosed with schizophrenia spectrum disorders but not bipolar disorder.

An altered use of context and experience to interpret incoming information has been posited to explain schizophrenia symptoms. The visual system can serve as a model system for examining how context and experience guide perception and the neural mechanisms underlying putative alterations. The influence of prior experience on current perception is evident in visual aftereffects, the perception of the "opposite" of a previously viewed stimulus. Aftereffects are associated with neural adaptation and concomitant change in strength of lateral inhibitory connections in visually responsive neurons. In a previous study, we observed stronger aftereffects related to orientation (tilt aftereffects) but not luminance (negative afterimages) in individuals diagnosed with schizophrenia, which we interpreted as potentially suggesting altered cortical (but not subcortical) adaptability and local changes in excitatory-inhibitory interactions. Here, we tested whether stronger tilt aftereffects were specific to individuals with schizophrenia or extended to individuals with bipolar disorder. We measured tilt aftereffects and negative afterimages in 32 individuals with bipolar disorder, and compared aftereffect strength to a previously reported group of 36 individuals with schizophrenia and 22 healthy controls. We observed stronger tilt aftereffects, but not negative afterimages, in individuals with schizophrenia as compared to both controls and individuals with bipolar disorder, who did not differ from each other. These results mitigate concerns that stronger tilt aftereffects in schizophrenia are a consequence of medication or of the psychosocial consequences of a severe mental illness.

Abnormal Oculomotor Corollary Discharge Signaling as a Trans-diagnostic Mechanism of Psychosis.

BACKGROUND AND HYPOTHESIS: Corollary discharge (CD) signals are "copies" of motor signals sent to sensory areas to predict the corresponding input. They are a posited mechanism enabling one to distinguish actions generated by oneself vs external forces. Consequently, altered CD is a hypothesized mechanism for agency disturbances in psychosis. Previous studies have shown a decreased influence of CD signals on visual perception in individuals with schizophrenia-particularly in those with more severe positive symptoms. We therefore hypothesized that altered CD may be a trans-diagnostic mechanism of psychosis. STUDY DESIGN: We examined oculomotor CD (using the blanking task) in 49 participants with schizophrenia or schizoaffective disorder (SZ), 36 bipolar participants with psychosis (BPP), and 40 healthy controls (HC). Participants made a saccade to a visual target. Upon saccade initiation, the target disappeared and reappeared at a horizontally displaced position. Participants indicated the direction of displacement. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of pre-saccadic target to inform perception. Thus, multi-level modeling was used to examine the influence of target displacement and saccade landing site on displacement judgements. STUDY RESULTS: SZ and BPP were equally less sensitive to target displacement than HC. Moreover, regardless of diagnosis, SZ and BPP with more severe positive symptoms were more likely to rely on saccade landing site. CONCLUSIONS: These results suggest that altered CD may be a trans-diagnostic mechanism of psychosis.

Blunted pupil light reflex is associated with negative symptoms and working memory in individuals with schizophrenia.

Two largely separate lines of research have documented altered pupillary dynamics in individuals diagnosed with schizophrenia. An older set of studies has demonstrated reductions in the pupillary light reflex (PLR) in individuals with schizophrenia; however, clinical and cognitive correlates of this blunted PLR have been relatively unexplored. More recently, a large body of work has demonstrated reductions in pupillary dilation in response to cognitive demands in individuals with schizophrenia, and the degree of this blunted pupil dilation has been related to more severe cognitive deficits and motivational negative symptoms. These clinically relevant alterations in the cognitive modulation of pupil size have been interpreted as reflecting insufficient information processing resources or inappropriate effort allocation. To begin to bridge these two lines of work, we investigated the PLR in 34 individuals with schizophrenia and 30 healthy controls and related the amplitude of the PLR to motivational negative symptoms and cognitive performance. Consistent with prior work, we found that the PLR was reduced in individuals with schizophrenia, and furthermore, that these measurements were highly reliable across individuals. Blunted constriction was associated with more severe motivational negative symptoms and poorer working memory among individuals with schizophrenia. These observed correlates provide a bridge between older literature documenting an altered PLR and more recent work reporting associations between negative symptoms, cognition, and blunted pupillary dilation in response to cognitive demands in individuals with schizophrenia. We provide possible mechanistic interpretations of our data and consider a parsimonious explanation for reduced cognitive- and light-related modulation of pupil size.