Meisenzahl_EAPCN_06.ent
- Citation
- Submitter
- Prose Description
- Subjects
- Conditions
- Sessions
- Analysis
- Experiments
- 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
- 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 - 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 - 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 - 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 - Fixation
Stimulus: Visual, Fixation Point, cross
Response: None, None
Instruction: Fixate
External Variable: None
Sessions
- Before Quetiapine
Description: Subjects were scanned prior to receiving any medication. - 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
- 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
ID X (mm) Y (mm) Z (mm) SPI Value SPI Unit 1 -49.0 21.0 -9.0 6.02 t 2 -46.0 -42.0 38.0 8.98 t 3 -42.0 -44.0 48.0 5.65 t 4 48.0 11.0 23.0 8.34 t 5 51.0 22.0 15.0 4.09 t 6 -12.0 -11.0 10.0 8.15 t 7 -10.0 2.0 9.0 7.52 t 8 6.0 -19.0 3.0 6.91 t 9 -40.0 1.0 29.0 7.74 t 10 34.0 21.0 -16.0 7.20 t 11 -46.0 23.0 26.0 7.00 t 12 46.0 -41.0 41.0 5.96 t 13 -63.0 -40.0 24.0 5.67 t 14 32.0 -60.0 49.0 5.63 t 15 -36.0 47.0 7.0 5.54 t 16 -34.0 42.0 15.0 5.09 t 17 -42.0 10.0 40.0 4.58 t 18 -2.0 36.0 18.0 4.50 t 19 -26.0 21.0 -6.0 14.19 t 20 2.0 32.0 28.0 7.89 t - 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
ID X (mm) Y (mm) Z (mm) SPI Value SPI Unit 1 -34.0 -52.0 49.0 14.49 t 2 -46.0 -42.0 46.0 10.45 t 3 -30.0 25.0 -6.0 12.37 t 4 -48.0 23.0 -11.0 6.92 t 5 -28.0 16.0 43.0 11.10 t 6 -42.0 10.0 36.0 8.52 t 7 46.0 22.0 21.0 9.52 t 8 30.0 -58.0 42.0 9.16 t 9 38.0 -52.0 39.0 5.49 t 10 -6.0 32.0 19.0 7.69 t 11 -4.0 20.0 21.0 4.98 t 12 6.0 -28.0 25.0 7.23 t 13 36.0 19.0 -9.0 7.08 t 14 8.0 27.0 28.0 6.61 t 15 -12.0 -5.0 8.0 6.44 t 16 6.0 -13.0 4.0 5.19 t 17 -42.0 16.0 5.0 5.72 t 18 30.0 46.0 -9.0 5.58 t 19 -4.0 14.0 49.0 5.50 t 20 -12.0 -68.0 44.0 5.26 t 21 53.0 16.0 1.0 5.08 t 22 -53.0 16.0 7.0 4.95 t 23 -4.0 23.0 39.0 4.87 t - 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
ID X (mm) Y (mm) Z (mm) SPI Value SPI Unit 1 -10.0 -12.0 2.0 5.94 t 2 22.0 10.0 1.0 5.53 t 3 28.0 23.0 -6.0 5.97 t 4 -30.0 25.0 -8.0 4.65 t 5 24.0 0.0 9.0 4.27 t 6 46.0 15.0 31.0 4.13 t 7 -30.0 49.0 12.0 3.98 t 8 -26.0 13.0 -4.0 5.86 t - 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
ID X (mm) Y (mm) Z (mm) SPI Value SPI Unit 1 40.0 -37.0 41.0 4.78 t 2 44.0 17.0 29.0 4.63 t 3 51.0 18.0 12.0 4.47 t 4 44.0 -38.0 20.0 4.07 t 5 36.0 15.0 -11.0 3.98 t 6 12.0 -26.0 23.0 3.77 t - 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
ID X (mm) Y (mm) Z (mm) SPI Value SPI Unit 1 -59.0 -7.0 6.0 6.05 t 2 -61.0 -21.0 16.0 4.10 t 3 -51.0 -25.0 12.0 4.01 t 4 51.0 -11.0 4.0 3.83 t - 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
ID X (mm) Y (mm) Z (mm) SPI Value SPI Unit 1 -28.0 29.0 2.0 4.48 t - 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
ID X (mm) Y (mm) Z (mm) SPI Value SPI Unit 1 -12.0 -56.0 3.0 5.55 t 2 16.0 -58.0 1.0 5.52 t 3 30.0 -44.0 45.0 4.76 t
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.