Machine learning identification of EEG features predicting working memory performance in schizophrenia and healthy adults

BackgroundWith millisecond-level resolution, electroencephalographic (EEG) recording provides a sensitive tool to assay neural dynamics of human cognition. However, selection of EEG features used to answer experimental questions is typically determined a priori. The utility of machine learning was investigated as a computational framework for extracting the most relevant features from EEG data empirically.MethodsSchizophrenia (SZ; n = 40) and healthy community (HC; n = 12) subjects completed a Sternberg Working Memory Task (SWMT) during EEG recording. EEG was analyzed to extract 5 frequency components (theta1, theta2, alpha, beta, gamma) at 4 processing stages (baseline, encoding, retention, retrieval) and 3 scalp sites (frontal-Fz, central-Cz, occipital-Oz) separately for correctly and incorrectly answered trials. The 1-norm support vector machine (SVM) method was used to build EEG classifiers of SWMT trial accuracy (correct vs. incorrect; Model 1) and diagnosis (HC vs. SZ; Model 2). External validity of SVM models was examined in relation to neuropsychological test performance and diagnostic classification using conventional regression-based analyses.ResultsSWMT performance was significantly reduced in SZ (p < .001). Model 1 correctly classified trial accuracy at 84 % in HC, and at 74 % when cross-validated in SZ data. Frontal gamma at encoding and central theta at retention provided highest weightings, accounting for 76 % of variance in SWMT scores and 42 % variance in neuropsychological test performance across samples. Model 2 identified frontal theta at baseline and frontal alpha during retrieval as primary classifiers of diagnosis, providing 87 % classification accuracy as a discriminant function.ConclusionsEEG features derived by SVM are consistent with literature reports of gamma’s role in memory encoding, engagement of theta during memory retention, and elevated resting low-frequency activity in schizophrenia. Tests of model performance and cross-validation support the stability and generalizability of results, and utility of SVM as an analytic approach for EEG feature selection.

[1]  Valerie Kirsch,et al.  Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: A standardized low resolution tomography (sLORETA) study , 2011, NeuroImage.

[2]  Michael Breakspear,et al.  Effects of mnemonic load on cortical activity during visual working memory: linking ongoing brain activity with evoked responses. , 2013, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[3]  Miguel Castelo-Branco,et al.  Event-related potential responses to perceptual reversals are modulated by working memory load , 2014, Neuropsychologia.

[4]  David A. Lewis,et al.  Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia , 2012, Trends in Neurosciences.

[5]  J. Marrero,et al.  Machine Learning Algorithms Outperform Conventional Regression Models in Predicting Development of Hepatocellular Carcinoma , 2013, The American Journal of Gastroenterology.

[6]  P. O’Donnell,et al.  A shared low-frequency oscillatory rhythm abnormality in resting and sensory gating in schizophrenia , 2012, Clinical Neurophysiology.

[7]  S. Makeig,et al.  Mining event-related brain dynamics , 2004, Trends in Cognitive Sciences.

[8]  A M McIntosh,et al.  Working memory in schizophrenia: a meta-analysis , 2008, Psychological Medicine.

[9]  Jed A. Meltzer,et al.  Effects of Working Memory Load on Oscillatory Power in Human Intracranial EEG , 2007, Cerebral cortex.

[10]  C. Basar-Eroglu,et al.  Event-related theta oscillations during working memory tasks in patients with schizophrenia and healthy controls. , 2005, Brain research. Cognitive brain research.

[11]  R. McCarley,et al.  Abnormal Neural Synchrony in Schizophrenia , 2003, The Journal of Neuroscience.

[12]  P. Uhlhaas,et al.  Working memory and neural oscillations: alpha–gamma versus theta–gamma codes for distinct WM information? , 2014, Trends in Cognitive Sciences.

[13]  J. Karhu,et al.  Theta oscillations index human hippocampal activation during a working memory task. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[14]  O. Paulsen,et al.  Spike Timing of Distinct Types of GABAergic Interneuron during Hippocampal Gamma Oscillations In Vitro , 2004, The Journal of Neuroscience.

[15]  D. Mathalon,et al.  Event-related EEG time-frequency analysis: an overview of measures and an analysis of early gamma band phase locking in schizophrenia. , 2008, Schizophrenia bulletin.

[16]  Daniel Senkowski,et al.  Phase-locking and amplitude modulations of EEG alpha: Two measures reflect different cognitive processes in a working memory task. , 2004, Experimental psychology.

[17]  Arne D. Ekstrom,et al.  Neural Oscillations Associated with Item and Temporal Order Maintenance in Working Memory , 2011, The Journal of Neuroscience.

[18]  Junghee Lee,et al.  Working memory impairments in schizophrenia: a meta-analysis. , 2005, Journal of abnormal psychology.

[19]  Rikkert Hindriks,et al.  Thalamo-cortical mechanisms underlying changes in amplitude and frequency of human alpha oscillations , 2013, NeuroImage.

[20]  W. Klimesch EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis , 1999, Brain Research Reviews.

[21]  Cuntai Guan,et al.  Design of an online EEG based neurofeedback game for enhancing attention and memory , 2013, 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[22]  Miles A Whittington,et al.  Interneuron Diversity series: Inhibitory interneurons and network oscillations in vitro , 2003, Trends in Neurosciences.

[23]  Hung-Chi Wu,et al.  Do resting brain dynamics predict oddball evoked-potential? , 2011, BMC Neuroscience.

[24]  D. Lewis,et al.  Neuroplasticity of Neocortical Circuits in Schizophrenia , 2008, Neuropsychopharmacology.

[25]  W. Klimesch EEG-alpha rhythms and memory processes. , 1997, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[26]  P. Fitzgerald,et al.  Evaluating the Relationship between Long Interval Cortical Inhibition, Working Memory and Gamma Band Activity in the Dorsolateral Prefrontal Cortex , 2008, Clinical EEG and neuroscience.

[27]  A. Gazzaley,et al.  Harnessing the neuroplastic potential of the human brain & the future of cognitive rehabilitation , 2014, Front. Hum. Neurosci..

[28]  Kenji Kirihara,et al.  Hierarchical Organization of Gamma and Theta Oscillatory Dynamics in Schizophrenia , 2012, Biological Psychiatry.

[29]  Marc W Howard,et al.  Gamma oscillations correlate with working memory load in humans. , 2003, Cerebral cortex.

[30]  Yu Cao,et al.  An integrated machine learning approach to stroke prediction , 2010, KDD.

[31]  Xiao-Jing Wang Neurophysiological and computational principles of cortical rhythms in cognition. , 2010, Physiological reviews.

[32]  E Donchin,et al.  A new method for off-line removal of ocular artifact. , 1983, Electroencephalography and clinical neurophysiology.

[33]  Sarah H. Lisanby,et al.  Neuroimage: Clinical Gaba Level, Gamma Oscillation, and Working Memory Performance in Schizophrenia , 2022 .

[34]  Jinbo Bi,et al.  Dimensionality Reduction via Sparse Support Vector Machines , 2003, J. Mach. Learn. Res..

[35]  Isabelle Guyon,et al.  An Introduction to Variable and Feature Selection , 2003, J. Mach. Learn. Res..

[36]  Michael F. Green,et al.  The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. , 2008, The American journal of psychiatry.

[37]  A. Mechelli,et al.  Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: A critical review , 2012, Neuroscience & Biobehavioral Reviews.

[38]  Ron Kohavi,et al.  Wrappers for Feature Subset Selection , 1997, Artif. Intell..

[39]  B. O’Donnell,et al.  Diagnostic specificity of neurophysiological endophenotypes in schizophrenia and bipolar disorder. , 2013, Schizophrenia bulletin.

[40]  F. Benes,et al.  Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. , 1991, Archives of general psychiatry.

[41]  Vladimir Vapnik,et al.  Statistical learning theory , 1998 .

[42]  P. Somogyi,et al.  Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo , 2003, Nature.

[43]  C. Basar-Eroglu,et al.  Working memory related gamma oscillations in schizophrenia patients. , 2007, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[44]  S. Raghavachari,et al.  Gating of Human Theta Oscillations by a Working Memory Task , 2001, The Journal of Neuroscience.

[45]  B. Christensen,et al.  Measuring premorbid IQ in traumatic brain injury: An examination of the validity of the Wechsler Test of Adult Reading (WTAR) , 2008, Journal of clinical and experimental neuropsychology.

[46]  N Kopell,et al.  Gap Junctions between Interneuron Dendrites Can Enhance Synchrony of Gamma Oscillations in Distributed Networks , 2001, The Journal of Neuroscience.

[47]  Chris J. McBain,et al.  Interneurons unbound , 2001, Nature Reviews Neuroscience.

[48]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[49]  Jorne Laton,et al.  Single-subject classification of schizophrenia patients based on a combination of oddball and mismatch evoked potential paradigms , 2014, Journal of the Neurological Sciences.