Nithin Krishna
University of Maryland School of Medicine, USA
Title: Impaired temporal, parietal and frontal/prefrontal coupling and glutamate during auditory working memory in Schizophrenia.
Biography
Biography: Nithin Krishna
Abstract
Working memory (WM) deficit is a core cognitive dysfunction in schizophrenia (SCZ), though its underlying mechanism remains unclear. Long-range synchronization of neuronal oscillations is presumed to mark cognitive processing and facilitate information transfer among broadly separated brain regions. Theta, alpha, and gamma range phase synchronization (PS) is thought to contribute during encoding, maintenance and retrieval phases of WM. Using a novel auditory WM paradigm, we used combined EEG and MRS measures to investigate the putative functional connectivity and neurochemistry in mediating the accuracy and performance during a modified N-Back test (MNB). SCZ patients (n=57) and matched healthy controls (HC, n=51) participated in the study. The MNB task requires rapid comparisons of subtly discrete tones held in memory while resisting the interference of previous tones. EEG recording during the MNB task was used to obtain phase synchronization (PS) values from time frequency data. To examine the contribution of synchronization by neurochemistry, GABA & glutamate were measured using standard techniques at the medial frontal/anterior cingulate. Behaviorally, HC performed considerably better compared to SCZ [F=18.94, p=.000]; SCZ made more errors [F=21.27, p = 0.000] compared to HC. Reaction time (RT) was not significantly different between groups during correct trials (F=000, p=0.985). In contrast, HC had a shorter RT during incorrect trials (F=12.49, p=0.001) compared to SCZ. Neuro-physiologically in HC, correct trials marked by an increased right fronto-temporal, central and left parieto-frontal PS in the alpha frequency; on the contrary, a trend for an increased interhemispheric fronto-frontal, and tempro-occipital PS in the delta frequency band was noted in SZ during the same time. Additionally a significant tempro-frontal and parieto-frontal PS in the theta frequency band did not survive multiple corrections. Neuro-chemically a higher level of GABA (r=.34, p=0.01) was correlated with accuracy in SCZ. In addition, lower levels of glutamate (r=-.33, p=0.05) and glyco-phosphatidylcholine (r=-.31, p=0.05) were correlated with the increased fronto-temporal and fronto-parietal PS respectively. Studies are suggestive that alpha-theta frequency are important for phonological loop during WM tasks, however delta frequencies are more implicated in attention selection specifically inhibiting all interferences that may affect the performance of the task. Our finding are suggesting that SCZ rely heavily on attention and concentration for auditory working memory, and SCZ may utilize parieto-occipital PS rather than a frontal temporal synchronization for auditory working memory implicating cerebellum in auditory working memory, Our finding highlights the role of neurochemistry along with impaired fronto-temporal and parieto-frontal PS abnormality in SCZ.