Meisenzahl_EAPCN_06.ent

  1. Citation
  2. Submitter
  3. Prose Description
  4. Subjects
  5. Conditions
  6. Sessions
  7. Analysis
  8. Experiments
  9. Results Synopsis

Citation

Paper ID: 7020060
Title: Effects of treatment with the atypical neuroleptic quetiapine on working memory function: A functional MRI follow-up investigation
Authors: Meisenzahl E M, Scheuerecker J, Zipse M, Ufer S, Wiesmann M, Frodl T, Koutsouleris N, Zetzsche T, Schmitt G, Riedel M, Spellmann I, Dehning S, Linn J, Bruckmann H, Moller H J
Journal: European Archives of Psychiatry and Clinical Neuroscience
Volume: 256
Pages: 522-531
Date: Dec 2006
Medline Number: 17151834
Citation Keywords: working memory, schizophrenia, neuroleptic treatment, quetiapine, functional magnetic resonance imaging
Laboratory: University of Munich
City: Munich
Country: Germany

Submitter

Submitter Name: Sarah Thelen
Submitter Type: Research Assistant
Email: thelens@uthscsa.edu
Phone: 210.567.8175
Address: The University of Texas Health Science Center San Antonio, Research Imaging Institute M/C 6240, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900

Prose Description

Schizophrenic patients and normal subjects underwent 2 sessions and 5 conditions. Session 1: Before Quetiapine. Session 2: After Quetiapine. Condition 1: 0-Back: subjects viewed letters on a black background and responded with a button press for the letter "X". Condition 2: 0-Back Degraded: subjects viewed letters on a blurred background and responded with a button press for the letter "X". Condition 3: 2-Back: subjects viewed letters on a black background and responded with a button press when the presented letter was the same as the one presented 2 letters back. Condition 4: 2-Back Degraded: subjects viewed letters on a blurry background and responded with a button press when the presented letter was the same as the one presented 2 letters back. Condition 5: Fixation. Experiment 1: 2-Back vs. Fixation, Normals. Experiment 2: 2-Back Degraded vs. Fixation, Normals. Experiment 3: 2-Back vs. Fixation, Normals vs. Schizophrenics, Before Treatment. Experiment 4: 2-Back Degraded vs. Fixation, Normals vs. Schizophrenics, Before Treatment. Experiment 5: 2-Back Degraded vs. Fixation, Schizophrenics vs. Normals, Before Treatment. Experiment 6: 2-Back vs. Fixation, Schizophrenics, After Treatment vs. Before Treatment. Experiment 7: 2-Back Degraded vs. Fixation, Schizophrenics, After Treatment vs. Before Treatment.

Subject Groups

Schizophrenic Patients
Diagnosis: Schizophrenia
Short Description: 11 Males, 1 Female. 9 patients were drug-naive and 3 had been washed out over a period of 3 days, ending 2 days before the beginning of the trial.
Total Subjects: 12
Gender: Mixed
Handedness: Right
Minimum Age: 20
Maximum Age: 48
Mean Age: 34
Native Language: Unknown
External Assessment: Accuracy, Reaction Time

Normals
Diagnosis: Normals
Short Description: 11 Males, 1 Female
Total Subjects: 12
Gender: Mixed
Handedness: Right
Minimum Age: 22
Maximum Age: 48
Mean Age: 34
Native Language: Unknown
External Assessment: Accuracy, Reaction Time

Conditions

  1. 0-Back
    Stimulus: Visual, Letters, subjects viewed letters on a black background
    Response: Hand, Button Press
    Instruction: Discriminate, subjects responded with a button press for the letter "X"
    External Variable: Accuracy, Response Time

  2. 0-Back Degraded
    Stimulus: Visual, Letters, subjects viewed letters on a blurry background
    Response: Hand, Button Press
    Instruction: Discriminate, subjects responded with a button press for the letter "X"
    External Variable: Accuracy, Response Time

  3. 2-Back
    Stimulus: Visual, Letters, subjects viewed letters on a black background
    Response: Hand, Button Press
    Instruction: Recall, subjects responded with a button press when the presented letter was the same as the one presented 2 letters back
    External Variable: Accuracy, Response Time

  4. 2-Back Degraded
    Stimulus: Visual, Letters, subjects viewed letters on a blurry background
    Response: Hand, Button Press
    Instruction: Recall, subjects esponded with a button press when the presented letter was the same as the one presented 2 letters back
    External Variable: Accuracy, Response Time

  5. Fixation
    Stimulus: Visual, Fixation Point, cross
    Response: None, None
    Instruction: Fixate
    External Variable: None

Sessions

  1. Before Quetiapine
    Description: Subjects were scanned prior to receiving any medication.

  2. After Quetiapine
    Description: Subjects were scanned after 12 weeks of steady state treatment with quetiapine. On Day 1 of treatment they received 50 mg, on Day 2 they received 100 mg, followed by daily increases of 100 mg/day to 600 mg/day on Day 7. After Day 7 the dose of medication was adjusted according to the investigators' clinical judgement.

Analysis

Software Package: SPM99
Template Brain: Unknown
Transform: Brett Transform
Reference Space: Talairach

Experiments

  1. 2-Back vs. Fixation, Normals
    Context: Normal Mapping
    Functional Imaging Modality: fMRI
    Subject Groups: Normals
    Conditions: Fixation, 2-Back
    Sessions: Before Quetiapine
    Contrast: Stimulus Type, Response Modality, Response Type, Instruction
    Paradigm Class: n-back
    Behavioral Domain: Cognition.Memory.Working

    Locations

    IDX (mm)Y (mm)Z (mm)SPI ValueSPI Unit
    1-49.021.0-9.06.02t
    2-46.0-42.038.08.98t
    3-42.0-44.048.05.65t
    448.011.023.08.34t
    551.022.015.04.09t
    6-12.0-11.010.08.15t
    7-10.02.09.07.52t
    86.0-19.03.06.91t
    9-40.01.029.07.74t
    1034.021.0-16.07.20t
    11-46.023.026.07.00t
    1246.0-41.041.05.96t
    13-63.0-40.024.05.67t
    1432.0-60.049.05.63t
    15-36.047.07.05.54t
    16-34.042.015.05.09t
    17-42.010.040.04.58t
    18-2.036.018.04.50t
    19-26.021.0-6.014.19t
    202.032.028.07.89t

  2. 2-Back Degraded vs. Fixation, Normals
    Context: Normal Mapping
    Functional Imaging Modality: fMRI
    Subject Groups: Normals
    Conditions: Fixation, 2-Back Degraded
    Sessions: Before Quetiapine
    Contrast: Stimulus Type, Response Modality, Response Type, Instruction
    Paradigm Class: n-back
    Behavioral Domain: Cognition.Memory.Working

    Locations

    IDX (mm)Y (mm)Z (mm)SPI ValueSPI Unit
    1-34.0-52.049.014.49t
    2-46.0-42.046.010.45t
    3-30.025.0-6.012.37t
    4-48.023.0-11.06.92t
    5-28.016.043.011.10t
    6-42.010.036.08.52t
    746.022.021.09.52t
    830.0-58.042.09.16t
    938.0-52.039.05.49t
    10-6.032.019.07.69t
    11-4.020.021.04.98t
    126.0-28.025.07.23t
    1336.019.0-9.07.08t
    148.027.028.06.61t
    15-12.0-5.08.06.44t
    166.0-13.04.05.19t
    17-42.016.05.05.72t
    1830.046.0-9.05.58t
    19-4.014.049.05.50t
    20-12.0-68.044.05.26t
    2153.016.01.05.08t
    22-53.016.07.04.95t
    23-4.023.039.04.87t

  3. 2-Back vs. Fixation, Normals vs. Schizophrenics, Before Treatment
    Context: Disease Effects
    Functional Imaging Modality: fMRI
    Subject Groups: Schizophrenic Patients, Normals
    Conditions: 2-Back, Fixation
    Sessions: Before Quetiapine
    Contrast: Stimulus Type, Response Modality, Response Type, Instruction, Group
    Paradigm Class: n-back
    Behavioral Domain: Cognition.Memory.Working

    Locations

    IDX (mm)Y (mm)Z (mm)SPI ValueSPI Unit
    1-10.0-12.02.05.94t
    222.010.01.05.53t
    328.023.0-6.05.97t
    4-30.025.0-8.04.65t
    524.00.09.04.27t
    646.015.031.04.13t
    7-30.049.012.03.98t
    8-26.013.0-4.05.86t

  4. 2-Back Degraded vs. Fixation, Normals vs. Schizophrenics, Before Treatment
    Context: Disease Effects
    Functional Imaging Modality: fMRI
    Subject Groups: Schizophrenic Patients, Normals
    Conditions: Fixation, 2-Back Degraded
    Sessions: Before Quetiapine
    Contrast: Stimulus Type, Response Modality, Response Type, Instruction, Group
    Paradigm Class: n-back
    Behavioral Domain: Cognition.Memory.Working

    Locations

    IDX (mm)Y (mm)Z (mm)SPI ValueSPI Unit
    140.0-37.041.04.78t
    244.017.029.04.63t
    351.018.012.04.47t
    444.0-38.020.04.07t
    536.015.0-11.03.98t
    612.0-26.023.03.77t

  5. 2-Back Degraded vs. Fixation, Schizophrenics vs. Normals, Before Treatment
    Context: Disease Effects
    Functional Imaging Modality: fMRI
    Subject Groups: Schizophrenic Patients, Normals
    Conditions: Fixation, 2-Back Degraded
    Sessions: Before Quetiapine
    Contrast: Stimulus Type, Response Modality, Response Type, Instruction, Group
    Paradigm Class: n-back
    Behavioral Domain: Cognition.Memory.Working

    Locations

    IDX (mm)Y (mm)Z (mm)SPI ValueSPI Unit
    1-59.0-7.06.06.05t
    2-61.0-21.016.04.10t
    3-51.0-25.012.04.01t
    451.0-11.04.03.83t

  6. 2-Back vs. Fixation, Schizophrenics, After Treatment vs. Before Treatment
    Context: Disease Effects, Drug Effects
    Pharmacology: Pharmacology.Psychiatric Medications.Antipsychotics
    Functional Imaging Modality: fMRI
    Subject Groups: Schizophrenic Patients
    Conditions: 2-Back, Fixation
    Sessions: Before Quetiapine, After Quetiapine
    Contrast: Stimulus Type, Response Modality, Response Type, Instruction, Session
    Paradigm Class: n-back
    Behavioral Domain: Cognition.Memory.Working

    Locations

    IDX (mm)Y (mm)Z (mm)SPI ValueSPI Unit
    1-28.029.02.04.48t

  7. 2-Back Degraded vs. Fixation, Schizophrenics, After Treatment vs. Before Treatment
    Context: Disease Effects, Drug Effects
    Pharmacology: Pharmacology.Psychiatric Medications.Antipsychotics
    Functional Imaging Modality: fMRI
    Subject Groups: Schizophrenic Patients
    Conditions: Fixation, 2-Back Degraded
    Sessions: Before Quetiapine, After Quetiapine
    Contrast: Stimulus Type, Response Modality, Response Type, Instruction, Session
    Paradigm Class: n-back
    Behavioral Domain: Cognition.Memory.Working

    Locations

    IDX (mm)Y (mm)Z (mm)SPI ValueSPI Unit
    1-12.0-56.03.05.55t
    216.0-58.01.05.52t
    330.0-44.045.04.76t

Results Synopsis

RESULTS: At baseline, healthy controls revealed increased activity in the frontal lobe, especially in regions of the prefrontal cortex. Compared to HC, SZ showed hypoactivation in the right dorsolateral prefrontal cortex (DLPFC) and the ventrolateral prefrontal cortex (VLPFC) bilaterally for the 2-back condition. In the 2-back degraded condition there was a hypoactivation in both, the right DLPFC and the VLPFC. Additionally, patients showed bilaterally decreased activation in the basalganglia in the 2-back and in the right caudatus in the 2-back degraded condition compared to healthy controls. After treatment with quetiapine, patients activations patterns were increased. The pre-post comparison of the 2-back condition revealed a significant increase of activation in the left VLPFC at a significance level of 0.001 (uncorrected). The 2-back degraded condition led to a significant activation pattern in the lingual gyrus and the right precuneus. In both wm conditions, at baseline there were no differences in reaction time but only a worse performance in SZ. After treatment, behavioural measurement of responses, including reaction time and performance, showed slight improvements in SZ, although these did not reach statistical significance. CONCLUSIONS: The neuronal networks underlying working memory are clearly altered in schizophrenia. After 12 weeks of treatment with quetiapine monotherapy, patients showed significant clinical improvement and revealed increased BOLD activity in the VLPFC during a working memory task, although there was no improvement of cognitive performance.

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