Cognitive Event-Related Brain Potentials and MRI in Psychosis Dean - PowerPoint PPT Presentation

Cognitive Event-Related Brain Potentials and MRI in Psychosis Dean F Salisbury, PhD Cognitive Neuroscience Laboratory, McLean Hospital Harvard Medical School, Boston, Massachusetts, USA

High-Resolution Measures of Brain Function and Brain Structure Two techniques to examine the physiology of attention in schizophrenia EEG – Millisecond temporal resolution of brain activity at the speed of thought. Poor localization of generator sources in isolation. MRI – Millimeter spatial resolution of anatomy. Pure anatomy. Allows for measurement of the volume of gray and white matter in areas identified as EEG generator sites through invasive depth-recordings.

Temporal Lobe - STG Auditory Processing • Heschl’s gyrus ( HG ) Contains primary auditory cortex. Analysis of simple acoustic features (e.g., pitch) • Moderate bilateral gray matter volume reduction in First- Episode Schizophrenia vs. Mania and Controls • Planum Temporale ( PT ) Secondary and tertiary auditory L. HG cortex. Analysis of complex acoustic features (e.g., speech) L. PT • Marked left hemisphere gray matter volume reduction in First- Episode Schizophrenia vs. Mania and Controls. Hirayasu et al., Arch Gen Psych , 2000; 57: 692 -699

15 Fz ) ERP Waveforms V 10 Con [n=14] µ ( e FIRST EPISODE d 5 FE Sz [n=14] u t i PSYCHOSIS STUDY l p m 0 FE AFF [n=14] A -5 -100 0 100 200 300 400 500 600 700 800 Time (ms) 15 15 15 T3 Cz T4 Amplitude (µV) Amplitude (µV) Amplitude (µV) 10 10 10 5 5 5 0 0 0 -5 -5 -5 -100 0 100 200 300 400 500 600 700 800 -100 0 100 200 300 400 500 600 700 800 -100 0 100 200 300 400 500 600 700 800 Time (ms) Time (ms) Time (ms) 15 Pz Amplitude (µV) 10 5 0 -5 -100 0 100 200 300 400 500 600 700 800 Time (ms)

Temporal Electrode Sites Con (n=14) FIRST EPISODE PSYCHOSIS STUDY FE Sz (n=14) FE AFF (n=14) 10 10 Amplitude (µV) Amplitude (µV) 5 5 0 0 -5 -5 -100 0 100 200 300 400 500 600 700 800 -100 0 100 200 300 400 500 600 700 800 Time (ms) Time (ms) DF Salisbury, ME Shenton, AR Sherwood, IA Fischer, DA Yurgelun-Todd, M Tohen, RW McCarley. (1998). First episode schizophrenic psychosis differs from first episode affective psychosis and controls in P300 amplitude over left temporal lobe. Archives of General Psychiatry, 55: 173-180.

Fz Raw Data Raw Data [µV] Fz 12 10 Time 1 P300 Sz (N= 54) 8 6 Aff (N= 59) expanded samples 4 Con (N= 55) 2 0 -2 -4 -6 -8 0 100 200 300 400 500 600 700 [m s] T 3 Raw Data Raw Data Cz Raw Data Raw Data T 4 Raw Data Raw Data [µV ] [µV] [µV ] Cz T4 T3 12 12 1 2 10 10 1 0 8 8 8 6 6 6 4 4 4 2 2 2 0 0 0 -2 -2 -2 -4 -4 -4 -6 -6 -6 -8 -8 -8 0 100 200 300 400 500 600 700 [m s] 0 100 200 300 400 500 600 700 [m s] 0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 [m s] Pz Raw Data Raw Data [µV] 12 Pz 10 Omnibus midline sites test Omnibus lateral sites test 8 6 Group: F(2,165) = 5.3, p =.006 Group: F(2,165) = 6.1, p =.003 4 Site: F(2,165) = 236.7, p <.0001 Hemisphere: F(1,165) =2.5, p =.12 2 Group x Site: F(4,165) = 4.2, p <.01 Group x Hemisphere: F(2,165) = 6.8, p =.001 0 -2 -4 -6 -8 0 100 200 300 400 500 600 700 [m s]

STG Volume & P3 are Related First Episode Schizophrenia at First Episode (n = 15) P e a k P 300 A m p litu d e 10 8 a t T 3 (µV ) 6 4 r = 0.52 2 p =.047 0 4 6 8 Left Posterior STG Volume (ml) McCarley et al., Archives of General Psychiatry , 2002, 59: 321-331

Left posterior STG gray matter volume change over time Relative volume of left posterior STG 0.60 12/13 decrease (mean ~ 9%) 0.50 0.40 0.30 SCZ (N=13) AFF (N=15) NCL (N=14) Kasai et al., Am J Psychiatry, 2003

P3 is not reduced further in the first few years after first hospitalization Time1 Time2 10.0 10.0 10.0 5.0 5.0 5.0 0.0 0.0 0.0 -5.0 -5.0 -5.0 Schizophrenia Affective (Manic) Controls (n = 21) Psychosis (n = 38) (n = 36) Salisbury et al., Unpublished Data

0 Pitch Deviant First Episode Schizophrenia (n=21) -2 Mismatch Controls (n=27) -4 Fz -6 0 0 0 -2 -2 -2 -4 -4 -4 T3 Cz T4 -6 -6 -6 0 -2 -4 Pz -6 Salisbury et al., Archives of General Psychiatry , 2002, 59: 686-694

MMN Amplitude Correlates with Left Heschl’s Gyrus Volume in First-Episode Schizophrenia Mismatch Negativity Amplitude 0.0 0.0 0.0 -5.0 -5.0 -5.0 r = -.52 r = .02 r = -.12 p = .02 p = .94 p = .51 -10.0 -10.0 -10.0 0.5 1.5 2.5 0.5 1.5 2.5 0.5 1.5 2.5 Left HG Left HG Left HG Volume Volume Volume Affective (Manic) Schizophrenia Controls Psychosis (n = 20) (n = 32) (n = 21) Salisbury et al., Archives of General Psychiatry , In Press

Follow-up MMN Pitch Deviant Mismatch Fz Grand Average Fz Grand Average Fz Grand Average [µV] [µV] [µV] Schizophrenia Controls Affective (Manic) Psychosis 1.5 1.5 1.5 1.0 1.0 1.0 (n = 16) (n = 20) (n = 17) 0.5 0.5 0.5 0.0 0.0 0.0 -0.5 -0.5 -0.5 -1.0 -1.0 -1.0 -1.5 -1.5 -1.5 -2.0 -2.0 -2.0 -2.5 -2.5 -2.5 -3.0 -3.0 -3.0 -3.5 -3.5 -3.5 -4.0 -4.0 -4.0 Time 1 -4.5 -4.5 -4.5 -5.0 -5.0 -5.0 Time 2 MMN -5.5 -5.5 -5.5 0 50 100 150 200 250 [m s] 0 50 100 150 200 250 [m s] 0 50 100 150 200 250 [m s] Salisbury et al., Archives of General Psychiatry , In Press

10 10 %Change in Gray Matter Volume 5 5 % Change in Heschl’s Gyrus 0 0 and Planum -5 -5 Temporale gray matter volume -10 -10 over 1.5 years -15 -15 Right Heschl's Gyrus Left Heschl's Gyrus -20 -20 10 10 %Change in Gray Matter Volume 5 5 0 0 -5 -5 -10 -10 -15 -15 Left Planum Temporale Right Planum Temporale Kasai K et al., Archives Gen -20 -20 Psychiatry. 2003; 60:766-775 Schizophrenia Affective Controls Schizophrenia Affective Controls (n = 13) (n = 15) (n = 22) (n = 13) (n = 15) (n = 22)

Reductions in MMN Amplitude Correlate with Reductions in Left Heschl’s Gyrus Gray Matter Volume at 1.5 Year Retest 3.0 3.0 3.0 MMN Amplitude Change 1.0 1.0 1.0 -1.0 -1.0 -1.0 -3.0 -3.0 -3.0 r = .62 r = -.01 r = .33 p = .04 p > .98 p > .27 -5.0 -5.0 -5.0 -0.4 -0.2 0 0.2 -0.4 -0.2 0 0.2 -0.4 -0.2 0 0.2 Left HG Volume Left HG Volume Left HG Volume Change Change Change Affective (Manic) Schizophrenia Controls Psychosis (n = 11) (n = 13) (n = 13) Salisbury et al., Archives of General Psychiatry , In Press

Combined High Temporal Resolution and High Structural Resolution Brain Measures Combined ERP & MRI measures allow one to target generator sites of physiological activity related to cognitive activation and their pathology In this example, abnormal physiology associated with structural brain changes during the early stages of schizophrenia. This finding, in turn, may identify new therapeutic targets ERPs associated with specific processing activity can be measured in other domains, such as facial affect identification, or lexical and semantic priming, gamma driving (20, 30, 40 Hz input) as a probe of local circuit integrity