Timing is everything: Neural response dynamics during syllable processing and its relation to higher-order cognition in schizophrenia and healthy comparison subjects

Abstract

Successful linguistic processing requires efficient encoding of successively-occurring auditory input in a time-constrained manner, especially under noisy conditions. In this study we examined the early neural response dynamics to rapidly-presented successive syllables in schizophrenia participants and healthy comparison subjects, and investigated the effects of noise on these responses. We used magnetoencephalography (MEG) to reveal the time-course of stimulus-locked activity over bilateral auditory cortices during discrimination of syllable pairs that differed either in voice onset time (VOT) or place of articulation (POA), in the presence or absence of noise. We also examined the association of these early neural response patterns to higher-order cognitive functions.The M100 response, arising from auditory cortex and its immediate environs, showed less attenuation to the second syllable in patients with schizophrenia than healthy comparison subjects during VOTbased discrimination in noise. M100 response amplitudes were similar between groups for the first syllable during all three discrimination conditions, and for the second syllable during VOT-based discrimination in quiet and POA-based discrimination in noise. Across subjects, the lack of M100 attenuation to the second syllable during VOT-based discrimination in noise was associated with poorer task accuracy, lower education and IQ, and lower scores on measures of Verbal Learning and Memory and Global Cognition.Because the neural response to the first syllable was not significantly different between groups, nor was a schizophrenia-related difference obtained in all discrimination tasks, early linguistic processing dysfunction in schizophrenia does not appear to be due to general sensory input problems. Rather, data suggest that faulty temporal integration occurs during successive syllable processing when the signal-to-noise ratio is low. Further, the neural mechanism by which the second syllable is suppressed Corresponding author: Sophia Vinogradov, Associate Chief for Research and Education, Mental Health Service, San Francisco VA Medical Center, Associate Professor, Department of Psychiatry, University of California, San Francisco, Sophia.vinogradov@ucsf.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. during noise-challenged VOT discrimination appears to be important for higher-order cognition and provides a promising target for neuroscience-guided cognitive training approaches to schizophrenia. NIH Public Access

Neural mechanisms regulating different forms of risk-related decision-making: Insights from animal models

“…Note however, that differences in delay duration used in human (hypothetical seconds to months) vs. animal (seconds to minutes) delay discounting tasks may limit cross-species translational validity of such testing (McClure et al, 2007;Schultz, 2010). Nevertheless, another important aspect of such decision-making paradigms concerns temporal perception (Wittmann et al, 2007), in that the ability to perceive time is often altered in patients with schizophrenia, bipolar disorder, and other conditions (McDowell et al, 1996;Dale et al, 2010;Papageorgiou et al, 2013) and can be affected by treatments such as amphetamine (Fowler et al, 2009). Such changes in temporal perception in patients should be taken into account in future studies investigating mechanistic changes underlying decision-making deficits.…”

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“…Indeed, evidence from older adults shows that successful perceptual training induces more efficient and reliable prefrontal cortical operations, allowing for improved working memory performance (Berry et al, 2010;Gazzaley, 2010). Vinogradov et al have shown increases both in the amplitude of the M100 response in A1 and in very early g band oscillatory power in lateral prefrontal cortex after intensive auditory training in schizophrenia, concomitant with improved behavioral performance (Dale et al, 2010;Brown et al, under review). (3) Learning-induced plasticity is critically dependent on the behavioral state of the animal, and is profoundly influenced by neuromodulatory neurotransmitters.…”

“…They applied 50 h of a research version of the software described above in the Mahncke et al study and compared it with 50 h of commercial computer games, examining behavioral outcomes as well as changes in serum biomarkers, MEG indices of early neural processing, and fMRI patterns of activation during untrained memory tasks (Adcock et al, 2009;Fisher et al, 2009Fisher et al, , 2010Dale et al, 2010;Hinckley et al, under review;Subramaniam et al, in press). Schizophrenia participants showed significant improvement in verbal learning and memory and in general cognition in response to training (effect sizes of 0.86 in a per protocol analysis); cognitive improvements were associated with improved quality of life at 6 months; subjects exposed to training showed significant increases in serum BDNF levels, while computer games control subjects did not; medication-induced serum anticholinergic activity was negatively correlated with the cognitive response to training; training increased restingstate a band functional connectivity in cortex; and also increased BOLD activation patterns in medial prefrontal cortex during an untrained memory task and restored the association between level of activation and task performance.…”

“…In healthy subjects, training was associated with activation changes in frontal and parietal cortex, consistent with plasticity in a working memory network (Klingberg, 2010). Vinogradov's group examined intensive computerized auditory training in adults with persistent schizophrenia and showed that participants significantly improved their verbal memory performance as well as early magnetoencephalographic (MEG) responses in auditory and prefrontal cortex; cognitive gains were positively associated with quality of life 6 months later (Adcock et al, 2009;Fisher et al, 2009Fisher et al, , 2010Dale et al, 2010). In a large-scale trial of older adults, subjects who received computerized training in perceptual speed of processing showed significantly improved cognition, lower rates of depression, and lower medical expenditures at 1 year, plus greater self-rated health outcomes at 5 years, compared with those who received therapist coaching in reasoning and memory (Wolinsky et al, 2009a(Wolinsky et al, , b, 2010; electroencephalography (EEG) revealed training-induced modifications in early visual processing that were associated with improvement in working memory (Berry et al, 2010).…”

Cognitive Remediation for Schizophrenia: A Review of Recent Findings

“…The other study concluded there were no gains in neurocognition and no changes in electroencephalogram (EEG) measures following 40 hours of BrainFitness training [36]. Two other studies [37,38] that were published before our publication period showed improved verbal memory and auditory neural responses (M100) after intensive auditory training. The MEG findings contradict Rass et al's study [36], but are in line with the original neuroplasticity-based studies from Fisher and colleagues [34,39], which reported significant improvements in verbal learning and memory and global cognition, and maintenance of treatment gains at 6- month follow-up.…”