Neural synchrony indexes disordered perception and cognition in schizophrenia

Department of Psychiatry, Veterans Affairs Boston Healthcare System, Harvard Medical School, Psychiatry 116A, 940 Belmont Street, Brockton, MA 02301, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/2005; 101(49):17288-93. DOI: 10.1073/pnas.0406074101
Source: PubMed

ABSTRACT Current views of schizophrenia suggest that it results from abnormalities in neural circuitry, but empirical evidence in the millisecond range of neural activity has been difficult to obtain. In pursuit of relevant evidence, we previously demonstrated that schizophrenia is associated with abnormal patterns of stimulus-evoked phaselocking of the electroencephalogram in the gamma band (30-100 Hz). These patterns may reflect impairments in neural assemblies, which have been proposed to use gamma-band oscillations as a mechanism for synchronization. Here, we report the unique finding that, in both healthy controls and schizophrenia patients, visual Gestalt stimuli elicit a gamma-band oscillation that is phase-locked to reaction time and hence may reflect processes leading to conscious perception of the stimuli. However, the frequency of this oscillation is lower in schizophrenics than in healthy individuals. This finding suggests that, although synchronization must occur for perception of the Gestalt, it occurs at a lower frequency because of a reduced capability of neural networks to support high-frequency synchronization in the brain of schizophrenics. Furthermore, the degree of phase locking of this oscillation is correlated with visual hallucinations, thought disorder, and disorganization in the schizophrenia patients. These data provide support for linking dysfunctional neural circuitry and the core symptoms of schizophrenia.

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Available from: Martha E Shenton, Aug 31, 2015
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    • "| to optimize learning . Conversely , our interface - controlled non - theta state may be a drug - free , non - lesion model of psychiatric / cognitive disorders such as schizophrenia , autism and age - related memory impairments , thought to result from desynchronization of critical brain systems ( Behrendt and Young , 2004 ; Spencer et al . , 2004 ; Asaka et al . , 2005 ; Donkers et al . , 2011 ; Doesburg et al . , 2013 ) . Continuation of this approach will enhance our knowledge of the roles of LFPs as well as their relation to signals in other bandwidths and time frames ( Bullock , 1997 ) , with the goal of a comprehensive description of electrophysiological mechanisms of infor"
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    ABSTRACT: Neurobiological oscillations are regarded as essential to normal information processing, including coordination and timing of cells and assemblies within structures as well as in long feedback loops of distributed neural systems. The hippocampal theta rhythm is a 3-12 Hz oscillatory potential observed during cognitive processes ranging from spatial navigation to associative learning. The lower range, 3-7 Hz, can occur during immobility and depends upon the integrity of cholinergic forebrain systems. Several studies have shown that the amount of pre-training theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning. Our lab has used a brain-computer interface that delivers eyeblink conditioning trials contingent upon the explicit presence or absence of hippocampal theta. A behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to four-fold increase in learning speed. This behavioral effect is accompanied by enhanced amplitude and synchrony of hippocampal local field potentials, multiple-unit excitation, and single-unit response patterns that depend on theta state. Additionally, training in the presence of hippocampal theta has led to increases in the salience of tone-induced unit firing patterns in the medial prefrontal cortex, followed by persistent multi-unit activity during the trace interval. In cerebellum, rhythmicity and precise synchrony of stimulus time-locked local field potentials with those of hippocampus occur preferentially under the theta condition. Here we review these findings, integrate them into current models of hippocampal-dependent learning and suggest how improvement in our understanding of neurobiological oscillations is critical for theories of medial temporal lobe processes underlying intact and pathological learning.
    Frontiers in Systems Neuroscience 04/2015; DOI:10.3389/fnsys.2015.00050
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    • "Positive, negative, and general symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987). We specifically probed the relationship between conceptual disorganization (PANSS item P2) and perceptual organization, since many prior studies have uncovered relations between the two (Keane et al., 2014; Silverstein et al., 2013; Spencer et al., 2004; Uhlhaas et al., 2006). The Premorbid Adjustment Scale (PAS; Cannon-Spoor et al., 1982) was administered to assess social isolation, peer relationships, scholastic performance, school adaptation, and socialsexual aspects of life prior to illness onset. "
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    ABSTRACT: Schizophrenia patients poorly perceive Kanizsa figures and integrate co-aligned contour elements (Gabors). They also poorly process low spatial frequencies (SFs), which presumably reflects dysfunction along the dorsal pathway. Can contour grouping deficits be explained in terms of the spatial frequency content of the display elements? To address the question, we tested patients and matched controls on three contour grouping paradigms in which the SF composition was modulated. In the Kanizsa task, subjects discriminated quartets of sectored circles (“pac-men”) that either formed or did not form Kanizsa shapes (illusory and fragmented conditions, respectively). In contour integration, subjects identified the screen quadrant thought to contain a closed chain of co-circular Gabors. In collinear facilitation, subjects attempted to detect a central low-contrast element flanked by collinear or orthogonal high-contrast elements, and facilitation corresponded to the amount by which collinear flankers reduced contrast thresholds. We varied SF by modifying the element features in the Kanizsa task and by scaling the entire stimulus display in the remaining tasks (SFs ranging from 4 to 12 cycles/deg). Irrespective of SF, patients were worse at discriminating illusory, but not fragmented shapes. Contrary to our hypothesis, collinear facilitation and contour integration were abnormal in the clinical group only for the higher SF (>=10 c/deg). Grouping performance correlated with clinical variables, such as conceptual disorganization, general symptoms, and levels of functioning. In schizophrenia, three forms of contour grouping impairments prominently arise and cannot be attributed to poor low SF processing. Neurobiological and clinical implications are discussed.
    Neuropsychologia 11/2014; 65. DOI:10.1016/j.neuropsychologia.2014.10.031 · 3.45 Impact Factor
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    • "Most of the studies failed to find correlation between P1 amplitude measures and clinical symptoms (Butler et al., 2005; Schechter et al., 2005). However relationships were seen when the visual evoked response was assessed through brain oscillation analysis (Spencer et al., 2004). Despite the progress in localizing neural dysfunctions within the visual system and related areas, there is an urgent need for a more consistent definition of the frequency of basic visual deficits, their reliability and the association with clinical variables. "
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    ABSTRACT: Basic visual dysfunctions are commonly reported in schizophrenia; however their value as diagnostic tools remains uncertain. This study reports a novel electrophysiological approach using checkerboard visual evoked potentials (VEP). Sources of spectral resolution VEP-components C1, P1 and N1 were estimated by LORETA, and the band-effects (BSE) on these estimated sources were explored in each subject. BSEs were Z-transformed for each component and relationships with clinical variables were assessed. Clinical effects were evaluated by ROC-curves and predictive values. Forty-eight patients with schizophrenia (SZ) and 55 healthy controls participated in the study. For each of the 48 patients, the three VEP components were localized to both dorsal and ventral brain areas and also deviated from a normal distribution. P1 and N1 deviations were independent of treatment, illness chronicity or gender. Results from LORETA also suggest that deficits in thalamus, posterior cingulum, precuneus, superior parietal and medial occipitotemporal areas were associated with symptom severity. While positive symptoms were more strongly related to sensory processing deficits (P1), negative symptoms were more strongly related to perceptual processing dysfunction (N1). Clinical validation revealed positive and negative predictive values for correctly classifying SZ of 100% and 77%, respectively. Classification in an additional independent sample of 30 SZ corroborated these results. In summary, this novel approach revealed basic visual dysfunctions in all patients with schizophrenia, suggesting these visual dysfunctions represent a promising candidate as a biomarker for schizophrenia.
    Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.052 · 4.43 Impact Factor
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