Measurements of sensory gating and cognition in patients with schizophrenia and auditory verbal hallucinations (AVH)

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Topographic changes of P50 and P300 ERP assessed with high-density EEG

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Experimental set-up and preliminary data

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Sara Marcu, Ovidiu C. Banea, Eric Wassermann, Aron D. Jónasson, Eysteinn Ívarsson, Sigurjón Stefansson, Paolo Gargiulo

Schizophrenia

• Complex neuropsychiatric disorder → affects how a person thinks, feels and behave

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• Origins → Multifactorial: It is thought that an interaction between genes, a range of environmental and probably psychosocial factors.

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• SYMPTOMS:
• Positive: Delusion, hallucinations, paranoia, agitations
• Negative: Apathy, social withdrawal, anhedonia (reduced feelings of pleasure)
• Cognitive: poor “executive functioning”, sensory gating dysfunction, problems with “working memory”

Sensory gating & brain ecology

Sensory gating describes neurological processes of filtering out redundant or unnecessary stimuli in the brain from all possible environmental stimuli.

Deficits in sensory gating are an important endophenotype for schizophrenia (Toyomaki et al 2015) .

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Schizophrenia

Auditory Verbal Hallucinations (AVH)

Most common positive symptom of schizophrenia

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Treatments

• Pharmacological treatment → does not ameliorate AVH in 20-30% of patients and is often associated with side effects.
• Cognitive-behavioral therapy (CBT) → as an augmentation to antipsychotic medication
• rTMS

Transcranial Magnetic Stimulation TMS

In 1999, Hoffman and colleagues started to explore rTMS

for the treatment of AVH. When the coil was directed at the

left temporoparietal cortex, they were able to ameliorate

medication - resistant AVH.

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Slotema et al 2014

AVH-TMS Icelandic clinical trial

AIM

Main objectives are to identify changes in psychometric scales and neurophysiological measurements between baseline (T1), 10 days after the treatment with rTMS (T2) at one month (T3) and at three months (T4).

Ethics committee of the National University Hospital was obtained in April 2018

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Topographic changes of P50 and P300 ERP assessed with high-density EEG

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Research Hypotheses (within AVH-TMS study)

Neurophysiological hypotheses are that rTMS treatment:

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1) Decreases the P50 second response (sensory gating improvement)

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2) Increases the amplitude and reduces the latency of P300

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For this work, we looked to both P50 and P300 cortical topography. We want to analyse these components before and after the treatment.

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We obtained data from 8 HS and 4 patients.

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Here we present data on 1 HS and 1 patient recorded before the treatment.

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EEG recording

• We analyzed P50 and P300 topography in baseline condition (this research) and they will be further investigated after receiving 10 sessions rTMS treatment.

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• The ERP signals were obtained from 256-channel EEG waveguard cap using eego mylab system (ANT Neuro, Netherlands).

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• Electrodes impedance was set less than 10 kΩ and EEG data was collected at a sampling rate of 1024 Hz.

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P50

P 50 is a component as the most positive peak between 30 and 70 ms post-stimulus (auditory) onset. In a double auditory stimulus paradigm, the P50 response amplitude of the second (S2) or test stimulus [to that of the first (S1) or conditioned stimulus] demonstrates sensory gating.

It seems that the P50 is the most powerful and reliable neuroscience biomarker in schizophrenia (Heinrichs et al 2004).

P50

EEG recording

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• Paired-click paradigm
• Pure tone (1500 Hz, 6-ms duration, 80 dB SPL) used as the click sound and presented during a 500-ms interval through headphones.

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• 150 paired stimuli in 5 blocks with interstimulus interval of 10 seconds, which provided 25 minutes of EEG measurement.
• we instructed participants to watch a silent film.

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Analysis

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• The signals were digitized for an epoch of 300 ms starting 100 ms prior to the presentation of each auditory stimulus (-100 ms to +200 ms)
• Referenced to the average of left and right mastoid electrodes

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P50

P300

The auditory P300 is a time-locked ERP component indexing attentional resources allocated to the target stimuli and/or the context updating. The P300 peak is defined as the largest positive deflection in the time range from 270 to 470 msec.

The reduced amplitudes of the auditory P300 have been among the most consistent biological findings in schizophrenic patients.

The schizophrenic patients showed a specific P300 amplitude reduction over left temporal electrode sites when the simple paradigm was used (Weisbrod et al 1997).

P300

EEG recording

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• Auditory oddball paradigm attention task
• Recordings between 11AM and 14 PM
• The frequent (F) and the rare (R) auditory stimuli were presented binaurally through headphones at an ISI between tones of 1.1 sec
• 1 trial of 160 tones, randomly with a probability of 0.2 (Stefánsson and Jónsdóttir 1996)
• We instruct participants to be attent at the rare stimuli without counting or moving a finger.

Analysis

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• The signals were digitized for an epoch of 1000 ms starting 100 ms prior to the presentation of each auditory stimulus (-100 ms to +900 ms)
• Referenced to the average

P50 patient (S1 signal)

P 300

Rare

patient

ROI for P300 and P50 topographic analysis 105 or 35 electrodes

1) Left Anterior�89 90 91 92 93 80 81 82 83 84 72 73 74 75 76�L1E-L5E, L1D-L5D, L1C-L5C�

2) Left Posterior�103 104 105 106 94 95 96 97 98 85 86 87 88 77 78�L5F-L8F, L6E-L10E, L6D-L9D, L6B-L7B�

3) Medial Anterior�42 43 44 45 46 121 122 123 124 125 170 171 172 173 174�L3L-L7L, Z3Z-Z7Z, R3R-R7R�

4) Medial Central�47 48 49 50 51 126 127 128 247 248 175 176 177 178 179�L8L-L12L, Z8Z-Z12Z, R8R-R12R�

5) Medial Posterior�52 53 54 55 56 249 250 251 252 253 180 181 182 183 184�L13L-L17L, Z13Z-Z17Z, R13R-R17R�

6) Right Anterior�217 218 219 220 221 208 209 210 211 212 200 201 202 203 204�R1E-R5E, R1D-R5D, R1C-R5C�

7) Right Posterior�231 232 233 234 222 223 224 225 226 213 214 215 216 198 199�R5F-R8F, R6E-R10E, R6D-R9D, R6B-R7B�

PRELIMINARY RESULTS

P50 Healthy participant S1 (blue) vs S2 (red)

P50 (49 ms)

Patient P50 S1 (blue) VS S2 (red)

PRELIMINARY RESULTS

P300, patient

Frequent

Rare

P300 (rare stimulus) average reference HS. ERPs plot with scalp map

P300 (rare stimulus) average reference PATIENT. ERPs plot with scalp map

Latency series HS vs patient - different components topography

z-score shows amplitude

Conclusions

• The topographical representation of P50 and P300 recorded with HD EEG helps to identify cortical regions with better signal.

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• It seems that in the patient group there are differences of P300 topographic representation in comparison with healthy subjects with cortical signal delayed and apparently disorganized.

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• The preprocessing and data analysis is in progress and we want to improve them.

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Thank you

A fertile ground for inspiration !

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