Ms. Melissa
Hilleary
1101 Yale Blvd., NE
MSC11-6040
Albuquerque, NM 87131
Phone: 505-272-2083
Fax: 505-272-8002
E-mail: mhilleary@mrn.org
Number of Human Subjects projects reported: 24
| MIND-04-510H-N1 | "MIND Clinical Imaging Consortium" |
| MIND-04-533-N1 | "National Consortium Project" |
| MIND-04-540-N2 | "Schizophrenia Consortium" |
| MIND-04-561-N1 | "MIND Clinical Imaging Consortium Protocol: A Joint Study of First Episode and Chronic Schizophrenia" |
| MIND-05-540-N1 | "The MIND MEG Consortium - Human Calibration Study " |
| MIND-05-UNM-01 | "Brain Correlates of Cognitive and Personality Functioning in Human Volunteers" |
| MIND-05-UNM-04 | "Assessment of Lateralized Hippocampal Function in Schizophrenia" |
| MIND-06-300H-N1 | "Imaging the Development of Memory Strategies in Aging" |
| MIND-06-301-555 | "Assessment of Infant Brain Functions with Non-invasive Electrophysiological Techniques - Albuquerque" |
| MIND-06-301-556 | "Auditory and Visual Integration in Schizophrenia Examined Using MEG, EEG, and FMR" |
| MIND-06-420-550 | "Effect of Stimulus Rate and Selective Attention on the Blood Oxygen Level Dependent Response in Schizophrenia" |
| MIND-06-420-551 | "An Event-Related Study of Crossmodal Attention" |
| MIND-06-420-552 | "A Mulitmodal Study of Sensory Gating " |
| MIND-06-435-550 | "MRS Measures of Excitatory Neurotransmission in Pain and Fibromyalgia" |
| MIND-06-435-551 | "Activation of the Anterior Cingulate Due to Adverse Stimulus: An MR Study" |
| MIND-06-552H-N1 | "Glutamatergic Metabolism Across Disease Stages in Schizophrenia" |
| MIND-07-6002.07 | "Magnetic Resonance Core" |
| MIND-07-6002.08.a | "Mobile MR Core: Neurocognitive Assessment of "Callous" Conduct Disorder Youth " |
| MIND-07-6002.08.b | "ERP and fMRI of Emotion and Cognition in Psychopathy" |
| MIND-07-6002.08.c | "MIND Mobile MR Core: Neurocognitive Changes Associated With Behavioral Treatment In Cocaine Abusers" |
| MIND-07-6002.24 | "The Effect of Cigarettes on fMRI Studies of Schizophrenia Patients" |
| MIND-07-6002.33 | "Neurodevelopment Research Program: Diagnosis of Epilepsy and Epileptogenesis After Brain Injury in Infants" |
| MIND-07-6002.35MINN | "FIRST Project: A Diagnostic Clinic for Individuals in the Early Stages of Schizophrenia " |
| MIND-07-6002.35UNM | "FIRST Project: A Diagnostic Clinic for Individuals in the Early Stages of Schizophrenia " |
"MIND Clinical Imaging Consortium"
Principal Investigator: Dr. John Lauriello, University of New Mexico
Project started in: 2004
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: 04-010
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 03/14/06
IRB approval number: 04-010
Explanation of IRB approval:
MIND Institute ended support to the project at the close of FY2006.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This project conducts studies of two cohorts of schizophrenia patients, using the collective resources of four sites linked by The MIND Institute, including the University of New Mexico, University of Minnesota, Massachusetts General Hospital (Boston), and University of Iowa. Studies conducted at these sites are part of the MIND Clinical Imaging Consortium (MCIC), which is a multi-site longitudinal study using a common experimental protocol. The four projects involved in this effort are: MIND-04-510H-N1, MIND-04-533-N1, MIND-04-540-N2, and MIND-04-561-N1.
Over the long-term, this network has amassed a large database of information accessible from all participating sites. The database enables the integration and cross validation of clinical, cognitive, morphometric, and functional neuroimaging results gathered from unique samples of schizophrenia patients using a common experimental protocol across all of the sites. By facilitating the integration of data obtained from multiple sites, the exploration of relationships is enabled between variables that would otherwise obscure significant effects by adding to the variability and noise in the data. The primary clinical aims of this multi-site project are to identify the neural substrates of the core cognitive deficits associated with schizophrenia, their links to the clinical features of the disorder, and their alterations with disease progression and treatment. Major changes to the protocol in 2006 include introduction of electroencephalography / magnetoencephalography (EEG/MEG) imaging, with results compared and contrasted with magnetic resonance imaging (MRI).
Objectives:
1. Evaluate first episode (FE) patients (neuroleptic naïve, if possible) comprehensively at intake and follow them longitudinally with regular serial assessments of clinical and psychosocial measures at six-month intervals.
2. Evaluate chronic, and chronically medicated, patients.
3. Make cross-sectional comparisons of FE verses chronic patients to identify initial crude indicators of the course and outcome of schizophrenia, while the longitudinal data accumulate.
Methodology:
1. Two groups of schizophrenia subjects, FE and chronic, will be comprehensively assessed using the following: clinical descriptors, sociodemographic descriptors, a comprehensive cognitive assessment, morphometric magnetic resonance imaging (mMRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), MEG, and collection of blood for genetic studies.
2. Healthy volunteers will be recruited. The comparison and schizophrenia groups will be matched in age, gender composition, handedness, and parental socioeconomic status.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MRI using a 1.5 Tesla research scanner and MEG.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the individual site.
"National Consortium Project"
Principal Investigator: Dr. Charles Schulz, University of Minnesota
Project started in: 2004
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: 0404M59124
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of Minnesota
Most recent approval: 04/05/06
IRB approval number: 0404M59124
Explanation of IRB approval:
MIND Institute ended support to the project at the close of FY2006.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This project conducts studies of two cohorts of schizophrenia patients, using the collective resources of four sites linked by The MIND Institute, including the University of New Mexico, University of Minnesota, Massachusetts General Hospital (Boston), and University of Iowa. Studies conducted at these sites are part of the MIND Clinical Imaging Consortium (MCIC), which is a multi-site longitudinal study using a common experimental protocol. The four projects involved in this effort are: MIND-04-510H-N1, MIND-04-533-N1, MIND-04-540-N2, and MIND-04-561-N1.
Over the long-term, this network has amassed a large database of information accessible from all participating sites. The database enables the integration and cross validation of clinical, cognitive, morphometric, and functional neuroimaging results gathered from unique samples of schizophrenia patients using a common experimental protocol across all of the sites. By facilitating the integration of data obtained from multiple sites, the exploration of relationships is enabled between variables that would otherwise obscure significant effects by adding to the variability and noise in the data. The primary clinical aims of this multi-site project are to identify the neural substrates of the core cognitive deficits associated with schizophrenia, their links to the clinical features of the disorder, and their alterations with disease progression and treatment. Major changes to the protocol in 2006 include introduction of electroencephalography / magnetoencephalography (EEG/MEG) imaging (at the New Mexico site only), with results compared and contrasted with magnetic resonance imaging (MRI).
Objectives:
1. Evaluate first episode (FE) patients (neuroleptic naïve, if possible) comprehensively at intake and follow them longitudinally with regular serial assessments of clinical and psychosocial measures at six-month intervals.
2. Evaluate chronic, and chronically medicated, patients.
3. Make cross-sectional comparisons of FE verses chronic patients to identify initial crude indicators of the course and outcome of schizophrenia, while the longitudinal data accumulate.
Methodology:
1. Two groups of schizophrenia subjects, FE and chronic, will be comprehensively assessed using the following: clinical descriptors, sociodemographic descriptors, a comprehensive cognitive assessment, morphometric magnetic resonance imaging (mMRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), MEG, and collection of blood for genetic studies.
2. Healthy volunteers will be recruited. The comparison and schizophrenia groups will be matched in age, gender composition, handedness, and parental socioeconomic status.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MRI using a 1.5 Tesla research scanner and MEG.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the individual site.
"Schizophrenia Consortium"
Principal Investigator: Dr. Randy Gollub, Massachusetts General Hosptial
Project started in: 2004
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 2
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital
Most recent approval: 01/05/06
IRB approval number: 2004P-000524
Explanation of IRB approval:
MIND Institute ended support to the project at the close of FY2006.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
MIND (Mental Illness and Neuroscience Discovery) Consortium Calibration Study
The purpose of this protocol is to calibrate the magnetic resonance scanners used in the MIND Clinical Imaging Consortium (MCIC). Massachusetts General Hospital (MGH) elected to keep this protocol active, although no subjects were processed through the study during the reporting period.
Specific Aims: The purpose of this initial calibration study is to develop and validate structural and functional magnetic resonance image (fMRI) acquisition and analysis methods to support a planned multi-site longitudinal neuroimaging study of schizophrenia. The clinical imaging study will be submitted as a separate IRB protocol.
1) To identify, measure, and minimize cross-site variability when performing cross-site functional and structural magnetic resonance imaging studies of healthy controls using the MIND consortium protocols.
2) To validate proposed cognitive activation paradigms, imaging acquisition methods, and data analysis strategies for a planned multi-site clinical imaging study in schizophrenic subjects.
Background: The goal of this proposal is to determine within-site and between-site reliability of the anatomical and functional MRI measures proposed by the MIND Consortium. The MIND Consortium includes investigators at Massachusetts General Hospital, University of Minnesota, University of Iowa, and University of New Mexico. Studies conducted at these sites are part of the MIND Clinical Imaging Consortium (MCIC), which is a multi-site longitudinal study using a common experimental protocol. The four projects involved in this effort are: MIND-04-510H-N1, MIND-04-533-N1, MIND-04-540-N2, and MIND-04-561-N1.
The New Mexico site is coordinating the study. The initial step is to establish standardized functional magnetic resonance imaging acquisition protocols, experimental paradigms, and data analysis procedures using phantoms and healthy human subjects. This protocol is to obtain IRB approval to conduct the initial experimental calibration study in a cohort of ten human subjects who will travel to four acquisition sites and participate in scanning sessions to allow the collection of matching data sets. The resulting data will be analyzed to determine reliability and validity of patterns of activation during functional and structural magnetic resonance imaging across the participating sites.
Subjects will be exposed to:
FMRI: There are several sources of risks. For instance, the subject may experience discomfort being in the confined environment of the scanner. Or, the subject may experience discomfort and frustration carrying out the tasks. The MRI scan may indicate a medical problem in a subject's brain. If the study detects an abnormality in the MRI scan, this information may become part of the subject's hospital record. It is possible that a subject could be unnecessarily worried if a problem were suspected but not actually found.
Exposure to a high magnetic field: The primary known hazard associated with exposure to a static high magnetic field is that the magnet exerts a strong force on ferromagnetic objects. Conventional MRI uses 1.5 Tesla (T) magnets. At most research centers for functional MRI, the research systems for human use have field strengths of 3T or 4T. Imaging at these field strengths is not considered a significant risk according to Food and Drug Administration (FDA) guidelines.
Heating from radio frequency (RF) pulses: The RF pulses that are used for creating the MR signal deposit some energy in the body in the form of heat, but no ionizing radiation is used with MRI. Because the pulse sequences to be used are standard, FDA-approved sequences, we do not expect any hazard associated with power deposition.
Peripheral nerve stimulation from rapidly switched magnetic fields (dB/dt). Magnetic field gradients are switched on and off during imaging to encode the spatial distribution of the MR signal. Gradient switching rate depends on the gradient coil used but does not depend on field strength. The FDA guideline states that a significant risk is involved only when "dB/dt sufficient to produce severe discomfort or painful stimulation" is used. Such severe discomfort has not been reported for studies performed at any of the participating institutions' scanners using the standard pulse sequences to be employed in this study.
Acoustic noise: Acoustic noise is always an unwanted side effect of MR imaging. As currents are pulsed through the gradient coils within the magnetic field, the system acts like a loudspeaker, making a repetitive tapping sound.
Social risk: There is no social risk associated with participation in this study. There are no legal risks to the subjects associated with these paradigms.
There is a risk that the subject's confidentiality will not be maintained from sharing the data among multiple sites. It is possible to reconstruct a form of the facial features from the MRI data; this information may be considered individually identifiable data, although its ability to identify the person has not been confirmed.
There are no other known risks from participation in this study.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital
Most recent approval: 07/04/06
IRB approval number: 2004P-001360
Explanation of IRB approval:
MIND Institute ended support to the project at the close of FY2006.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This project conducts studies of two cohorts of schizophrenia patients, using the collective resources of four sites linked by The MIND Institute, including the University of New Mexico, University of Minnesota, Massachusetts General Hospital (Boston), and University of Iowa. Studies conducted at these sites are part of the MIND Clinical Imaging Consortium (MCIC), which is a multi-site longitudinal study using a common experimental protocol. The four projects involved in this effort are: MIND-04-510H-N1, MIND-04-533-N1, MIND-04-540-N2, and MIND-04-561-N1.
Over the long-term, this network has amassed a large database of information accessible from all participating sites. The database enables the integration and cross validation of clinical, cognitive, morphometric, and functional neuroimaging results gathered from unique samples of schizophrenia patients using a common experimental protocol across all of the sites. By facilitating the integration of data obtained from multiple sites, the exploration of relationships is enabled between variables that would otherwise obscure significant effects by adding to the variability and noise in the data. The primary clinical aims of this multi-site project are to identify the neural substrates of the core cognitive deficits associated with schizophrenia, their links to the clinical features of the disorder, and their alterations with disease progression and treatment. Major changes to the protocol in 2006 include introduction of electroencephalography / magnetoencephalography (EEG/MEG) imaging (at the New Mexico site only), with results compared and contrasted with magnetic resonance imaging (MRI).
Objectives:
1. Evaluate first episode (FE) patients (neuroleptic naïve, if possible) comprehensively at intake and follow them longitudinally with regular serial assessments of clinical and psychosocial measures at six-month intervals.
2. Evaluate chronic, and chronically medicated, patients.
3. Make cross-sectional comparisons of FE verses chronic patients to identify initial crude indicators of the course and outcome of schizophrenia, while the longitudinal data accumulate.
Methodology:
1. Two groups of schizophrenia subjects, FE and chronic, will be comprehensively assessed using the following: clinical descriptors, sociodemographic descriptors, a comprehensive cognitive assessment, morphometric magnetic resonance imaging (mMRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), MEG, and collection of blood for genetic studies.
2. Healthy volunteers will be recruited. The comparison and schizophrenia groups will be matched in age, gender composition, handedness, and parental socioeconomic status.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MRI using a 1.5 Tesla research scanner and MEG.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the individual site.
"MIND Clinical Imaging Consortium Protocol: A Joint Study of First Episode and Chronic Schizophrenia"
Principal Investigator: Dr. Nancy C. Andreasen, University of Iowa
Project started in: 2004
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 3
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of Iowa
Most recent approval: 03/14/06
IRB approval number: 8103070
Explanation of IRB approval:
After a reduction in funding in 2006, the study was not picked up by the MIND Institute in 2007. Research personnel at the University of Iowa may continue with non-DOE resources to analyze data and publish results.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This is a multi-site longitudinal study that collected clinical, cognitive, genetic, morphometic, and functional neuroimaging data from schizophrenia patients and matched controls using a common experimental protocol across four participating sites, including the University of New Mexico, University of Minnesota, Massachusetts General Hospital (Boston), and University of Iowa. Studies conducted at these sites are part of the MIND Clinical Imaging Consortium (MCIC). The four projects involved in this effort are: MIND-04-510H-N1, MIND-04-533-N1, MIND-04-540-N2, and MIND-04-561-N1. At the University of Iowa, the project was conducted under three separate IRB protocols: 8103070 was put into place to process first episode schizophrenia patients and their matched controls. First episode schizophrenia patients were of particular interest to the study in order to understand what factors were at play at the time of onset of the disease (typically, at the first psychotic break).
Over the long-term, this network has amassed a large database of information accessible from all participating sites. The database enables the integration and cross validation of clinical, cognitive, morphometric, and functional neuroimaging results gathered from unique samples of schizophrenia patients using a common experimental protocol across all of the sites. By facilitating the integration of data obtained from multiple sites, the exploration of relationships is enabled between variables that would otherwise obscure significant effects by adding to the variability and noise in the data. The primary clinical aims of this multi-site project are to identify the neural substrates of the core cognitive deficits associated with schizophrenia, their links to the clinical features of the disorder, and their alterations with disease progression and treatment. Major changes to the protocol in 2006 include introduction of electroencephalography / magnetoencephalography (EEG/MEG) imaging (at the New Mexico site only), with results compared and contrasted with magnetic resonance imaging (MRI).
Objectives:
1. Evaluate first episode (FE) patients (neuroleptic naïve, if possible) comprehensively at intake and follow them longitudinally with regular serial assessments of clinical and psychosocial measures at six-month intervals.
2. Evaluate chronic, and chronically medicated, patients.
3. Make cross-sectional comparisons of FE verses chronic patients to identify initial crude indicators of the course and outcome of schizophrenia, while the longitudinal data accumulate.
Methodology:
1. Two groups of schizophrenia subjects, FE and chronic, will be comprehensively assessed using the following: clinical descriptors, sociodemographic descriptors, a comprehensive cognitive assessment, morphometric magnetic resonance imaging (mMRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), MEG, and collection of blood for genetic studies.
2. Healthy volunteers will be recruited. The comparison and schizophrenia groups will be matched in age, gender composition, handedness, and parental socioeconomic status.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MRI using a 1.5 Tesla research scanner and MEG.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the individual site.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of Iowa
Most recent approval: 12/05/05
IRB approval number: 1998010017
Explanation of IRB approval:
After a reduction in funding in 2006, the study was not picked up by the MIND Institute in 2007. Research personnel at the University of Iowa may continue with non-DOE resources to analyze data and publish results.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This is a multi-site longitudinal study that collected clinical, cognitive, genetic, morphometic, and functional neuroimaging data from schizophrenia patients and matched controls using a common experimental protocol across four participating sites, including the University of New Mexico, University of Minnesota, Massachusetts General Hospital (Boston), and University of Iowa. Studies conducted at these sites are part of the MIND Clinical Imaging Consortium (MCIC). The four projects involved in this effort are: MIND-04-510H-N1, MIND-04-533-N1, MIND-04-540-N2, and MIND-04-561-N1. At the University of Iowa, the project was conducted under three separate IRB protocols: 1998010017 was put into place to process chronic schizophrenia patients and their matched controls. Chronic schizophrenia patients were included in the study to provide data about the long-term course of the disease and its effect on brain anatomy and function.
Over the long-term, this network has amassed a large database of information accessible from all participating sites. The database enables the integration and cross validation of clinical, cognitive, morphometric, and functional neuroimaging results gathered from unique samples of schizophrenia patients using a common experimental protocol across all of the sites. By facilitating the integration of data obtained from multiple sites, the exploration of relationships is enabled between variables that would otherwise obscure significant effects by adding to the variability and noise in the data. The primary clinical aims of this multi-site project are to identify the neural substrates of the core cognitive deficits associated with schizophrenia, their links to the clinical features of the disorder, and their alterations with disease progression and treatment. Major changes to the protocol in 2006 include introduction of electroencephalography / magnetoencephalography (EEG/MEG) imaging (at the New Mexico site only), with results compared and contrasted with magnetic resonance imaging (MRI).
Objectives:
1. Evaluate first episode (FE) patients (neuroleptic naïve, if possible) comprehensively at intake and follow them longitudinally with regular serial assessments of clinical and psychosocial measures at six-month intervals.
2. Evaluate chronic, and chronically medicated, patients.
3. Make cross-sectional comparisons of FE verses chronic patients to identify initial crude indicators of the course and outcome of schizophrenia, while the longitudinal data accumulate.
Methodology:
1. Two groups of schizophrenia subjects, FE and chronic, will be comprehensively assessed using the following: clinical descriptors, sociodemographic descriptors, a comprehensive cognitive assessment, morphometric magnetic resonance imaging (mMRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), MEG, and collection of blood for genetic studies.
2. Healthy volunteers will be recruited. The comparison and schizophrenia groups will be matched in age, gender composition, handedness, and parental socioeconomic status.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MRI using a 1.5 Tesla research scanner and MEG.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the individual site.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of Iowa
Most recent approval: 09/06/06
IRB approval number: 199701024
Explanation of IRB approval:
After a reduction in funding in 2006, the study was not picked up by the MIND Institute in 2007. Research personnel at the University of Iowa may continue with non-DOE resources to analyze data and publish results.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This is a multi-site longitudinal study that collected clinical, cognitive, genetic, morphometic, and functional neuroimaging data from schizophrenia patients and matched controls using a common experimental protocol across four participating sites, including the University of New Mexico, University of Minnesota, Massachusetts General Hospital (Boston), and University of Iowa. Studies conducted at these sites are part of the MIND Clinical Imaging Consortium (MCIC). The four projects involved in this effort are: MIND-04-510H-N1, MIND-04-533-N1, MIND-04-540-N2, and MIND-04-561-N1. At the University of Iowa, the project was conducted under three separate IRB protocols: 199701024 was put into place to draw blood from subjects for the project. The blood lines were immortalized and genetic material made available to investigators to search for the genomic variation that may constitute a significant proportion of the heritable factors in persons with schizophrenia.
Over the long-term, this network has amassed a large database of information accessible from all participating sites. The database enables the integration and cross validation of clinical, cognitive, morphometric, and functional neuroimaging results gathered from unique samples of schizophrenia patients using a common experimental protocol across all of the sites. By facilitating the integration of data obtained from multiple sites, the exploration of relationships is enabled between variables that would otherwise obscure significant effects by adding to the variability and noise in the data. The primary clinical aims of this multi-site project are to identify the neural substrates of the core cognitive deficits associated with schizophrenia, their links to the clinical features of the disorder, and their alterations with disease progression and treatment. Major changes to the protocol in 2006 include introduction of electroencephalography / magnetoencephalography (EEG/MEG) imaging (at the New Mexico site only), with results compared and contrasted with magnetic resonance imaging (MRI).
Objectives:
1. Evaluate first episode (FE) patients (neuroleptic naïve, if possible) comprehensively at intake and follow them longitudinally with regular serial assessments of clinical and psychosocial measures at six-month intervals.
2. Evaluate chronic, and chronically medicated, patients.
3. Make cross-sectional comparisons of FE verses chronic patients to identify initial crude indicators of the course and outcome of schizophrenia, while the longitudinal data accumulate.
Methodology:
1. Two groups of schizophrenia subjects, FE and chronic, will be comprehensively assessed using the following: clinical descriptors, sociodemographic descriptors, a comprehensive cognitive assessment, morphometric magnetic resonance imaging (mMRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), MEG, and collection of blood for genetic studies.
2. Healthy volunteers will be recruited. The comparison and schizophrenia groups will be matched in age, gender composition, handedness, and parental socioeconomic status.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MRI using a 1.5 Tesla research scanner and MEG.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the individual site.
"The MIND MEG Consortium - Human Calibration Study"
Principal Investigator: Dr. Matti Hamalainen, Anthinoula A. Martinos Center / Massachusetts General Hospital
Project started in: 2005
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital
Most recent approval: 06/20/06
IRB approval number: 2005-P-001179/3
Explanation of IRB approval:
MIND Institute ended support to the project at the close of FY2006.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
Commercial magnetoencephalography (MEG) arrays are presumably calibrated as they leave the manufacturer. However, the calibration methods employed by manufacturers do not necessarily allow precise determination of sensor array geometry, accurate amplitude calibration for each channel, and crosstalk between channels. Furthermore, comprehensive information about the frequency response characteristics of the systems generally is not available. In order to obtain consistent MEG data and pool results, the MIND Institute MEG sites need reliable, easy-to-use, and fast verification and calibration methods for MEG hardware and software. Our MEG consortium project will address this need by conducting a series of experiments in three phases: (1) calibration of sensor arrays using a dry phantom, (2) verification of hardware and software performance using a realistic human skull phantom, and (3) comparison of human data.
We have completed a calibration study with dry phantoms and human subjects. For the human calibration, we acquired spontaneous, auditory, somatosensory, and visual MEG data with the Elekta-Neuromag Vectorview (Massachusetts General Hospital, MGH), 4D Neuroimaging Magnes (University of Mew Nexico, UNM), and VSM MedTech Omega (MIC) MEG systems from seven subjects. For data analysis, we have employed both in-house software (MNE, BrainStorm, CSST), system specific proprietary software, and third-party commercial packages (CURRY). The possibility to analyze all data in the in-house software packages has been largely due to the efforts of the MGH and Los Alamos members of the consortium. We have created conversion utilities to bring all data to a common file format, to provide access to the various noise compensation methods employed, and to create generally applicable parametrization of the sensor geometries for forward field modeling.
Our initial results, published at the Biomag 2006 Conference in Vancouver, are encouraging. We found that the source modeling results collected from the three sensory modalities are very similar across systems and repetitions of the experiment on a single site. Furthermore, we were able to compare two totally independent implementations of the cortically constrained L2 minimum-norm solutions (MNE and BrainStorm) across the data sets and found excellent agreement. We have also developed software to interpolate and extrapolate data from one sensor array configuration to another and found that in many cases the extrapolation results are virtually indistinguishable.
Our plan is to continue the source analyses and assess the differences between the results using quantitative measures. Furthermore, we are planning to publish the human phantom data sets for use by other laboratories as benchmarks of new source modeling approaches and academic software packages being developed. During the next year, we will also publish our comparison results and associated analytic techniques as full journal papers to serve as a basis for technical and neuroscience grant applications.
"Brain Correlates of Cognitive and Personality Functioning in Human Volunteers"
Principal Investigator: Dr. Rex Jung, The MIND Institute
Project started in: 2005
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 01/31/07
IRB approval number: 05-096
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 68
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
The primary goal of this study is to investigate the contribution of white matter integrity to broad measures of cognition and personality in normal subjects and schizophrenia subjects utilizing diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and voxel based morphometry (VBM).
Objectives:
1. Relate DTI measures of structural integrity (e.g., diffusion anisotropy) within longitudinal white matter fiber tracts (e.g., arcuate fasciculus) to broad measures of cognition.
2. Relate MRS measures of biochemical integrity (e.g., N-acetylaspartate) within white matter underlying association cortices (e.g., angular gyrus) to broad measures of cognition.
3. Relate VBM measures of white matter volumes underlying association cortices (e.g., angular gyrus) and within longitudinal fiber tracts (e.g., arcuate fasciculus) to cognition, accounting for strongly predicted association of structure to biochemical integrity. VBM measures of gray matter volumes, particularly within association cortices (e.g., Brodmann Areas 44, 45, 46, and 39) are hypothesized to be related to broad measures of cognition.
4. The relationship between brain measures and personality measures is exploratory as very little research has been conducted in this area; however, a positive relationship between measures of personality and measures of neuronal metabolic integrity (e.g., MRS) and axonal integrity (DTI) is anticipated.
Methodology:
1. Schizophrenic subjects will be recruited from the University of New Mexico Department of Psychiatry Research. Their mental stability will be determined by their physician. Normal human volunteers will be selected to coordinate an equal number of men (N = 35) and women (N = 35) in the final sample. Groups will be matched for age, handedness, and current intellectual status (Full Scale Intelligence Quotient), as determined by the Wechsler Abbreviated Scale of Intelligence (WASI). Age for all experimental subjects will range from 18 to 65 years to control for developmental changes that may affect white matter integrity (Bartzokis et al., 2003) in older subjects. Potential subjects will be administered a screening estimate of intellectual status (Shipley Institute of Living Scale) to stratify equally across average (90 to 109), high average (110 to 119), and superior (120+) ranges of intelligence.
2. Subjects will undergo magnetic resonance imaging (MRI) and spectroscopy imaging sequences including: 1) structural imaging (T1 morphological images), 2) water supressed and water unsupressed single voxel 1H-MRS within left occipito-parietal white matter and the anterior cingulate cortex (8 cm cubic voxels), 3) water supressed and water unsupressed multivoxel 1H-MRSI slab overlapping brain regions sampled by the single voxel studies , and 4) whole brain DTI, using either a 4 Tesla research scanner or 1.5 Tesla scanner.
3. A cognitive and personality evaluation will be undertaken with the Raven's Advanced Progressive Matrices, a non-verbal measure of reasoning (Raven, 1931). The Raven's was developed to assess, as accurately as possible, the main component of Spearman's general reasoning factor ("g"). It is quick, easy to administer, attractive to those taking it, and displays high construct validity. A clinical measure of intellectual performance, the Wechsler Adult Intelligence Scale-3 (WAIS-3), will also be administered. The WAIS-3 is a reliable, valid, and standardized test consisting of thirteen subtests, eleven of which will be administered to experimental subjects: picture completion, vocabulary, digit symbol-coding, similarities, block design, arithmetic, matrix reasoning, digit span, information, symbol search, and letter-number sequencing. Personality measurement will consist of the NEO Personality Inventory - Revised (NEO-PI-R) which produces summary scores on five personality domains: neuroticism, extraversion, openness, agreeableness, and conscientiousness. These cognitive and personality measures are widely used in psychological research and clinical practice, providing the industry standards against which other tests are evaluated.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MRI and spectroscopy imaging sequences using either a 3 or 1.5 Tesla scanner.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the University of New Mexico Human Subjects Review Committee.
"Assessment of Lateralized Hippocampal Function in Schizophrenia"
Principal Investigator: Dr. Faith Hanlon, The MIND Institute
Project started in: 2005
Status of the Research this Fiscal Year:
Study is not currently enrolling subjects or enrollment of participants is currently suspended, but may resume in the future.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 01/17/07
IRB approval number: 05-067
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Objectives:
This project ties hippocampal-dependent behavioral performance directly to neural mechanisms: whether task-specific right and left hippocampal activity during the nonverbal and verbal transverse patterning (TP) task can be measured directly using magnetoencephalography (MEG). Controls are hypothesized to show lateralized hippocampal activation in verbal versus nonverbal TP. Based on our small pilot study of controls, MEG should show right hippocampus activating for nonverbal stimuli, and left hippocampus should activate for verbal stimuli, both occurring around 400 ms after stimuli onset. In addition, this project characterizes the hippocampal dysfunction in patients with schizophrenia. Based on prior research showing right hippocampal dysfunction in schizophrenia and others suggesting a left hippocampal deficit, a bilateral hippocampal deficit is hypothesized. Finally, this project compares traditional neuropsychological tests of hippocampal function to TP.
Methodology:
Schizophrenia patients will be recruited from the New Mexico Veteran's Administration Health Care System. Their mental stability will be determined by the Structural Clinical Interview for DSM-IV-Patient Edition (SCID) criteria. Normal human controls are selected to match on age, gender, and parental education for the total sample.
Subjects will be trained on four tasks, including verbal and nonverbal versions of transverse patterning and elemental criteria before being tested. Subjects must reach the performance criterion for each of the four tasks.
Subjects will undergo an MEG scan, perform each of the mentioned tasks, as well as a contextual conditioning task (which is also hippocampal dependent). Sessions will continue until 100 artifact-free trials are obtained. Reaction times and percent correct will be recorded for training and MEG performance.
Subjects will undergo a magnetic resonance imaging (MRI) scan to acquire T1-weighted, 3-D anatomic images will be for equivalent current dipole (ECD) co-registration.
Subjects will be administered a neuropsychological battery of tests including: 1) the Shipley Institute of Living Scale, which has verbal and analytical subscales and provides an estimated Wechsler Adult Intelligence Scale-Revised (WAIS-R) full-scale IQ; 2) the logical memory, visual reproduction, and paired associate learning subtests of the Wechsler Memory Scale-Third Edition (WMS-III), which assess the ability to reproduce stories and a series of line figures from memory, and to learn the pairings of words, all traditional tests of hippocampal function; 3) the Autobiographical Memory Interview, which assesses episodic memory and is a traditional test of hippocampal function; 4) the Faces subtests of the WMS-III, which will test for facial recognition/recall deficits; 5) the Connors version of the Continuous Performance Test (CPT), which tests the subject's ability to attend and respond to intermittent visual stimuli; 6) the Digit Span Forward, which requires subjects to repeat increasingly long lists of numbers, and Digit Span Backward, in which subjects are asked to reverse the order of presented numbers (a test of working memory); and 7) the Auditory Consonant Trigrams, a test on which subjects are asked to remember three letters under a varying distracter task load (counting backwards) to assess working memory. Schizophrenia Symptom Ratings (will take approximately one hour to complete): MEG data will be analyzed with CURRY V5 software. This software allows for localization of multiple sources of brain activity from MEG scans, allowing for statistical estimation of the location, timing, and strength of brain activation for each epoch of interest (50 to 250 ms, 200 to 400 ms, and 350 to 550 ms) and for correlated sources.
Once data analysis has localized the sources identified by MEG in each time period, the resulting dipoles will be overlaid onto the subject's MRI scan.
Drugs/Devices/Pharmaceuticals:
MEG images will be acquired on a CTF 275-channel system; MR images will be acquired on a Siemens 1.5 or 3 Tesla MRI scanner.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Volunteers will usually be adult students and/or employees of the University of New Mexico. Exclusion criteria will be: 1) pregnancy, 2) presence of a potentially dangerous device, implanted or otherwise, 3) age less than 18, 4) presence of a medical condition that makes MR scanning dangerous, 5) claustrophobia, 6) weight greater than 300 pounds, and 7) uncontrolled incontinence. Informed consent will be obtained from subjects according to institutional guidelines established by the individual site.
"Imaging the Development of Memory Strategies in Aging"
Principal Investigator: Dr. Cheryl Aine, University of New Mexico
Project started in: 2006
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Study is not currently enrolling subjects or enrollment of participants is currently suspended, but may resume in the future.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 08/08/06
IRB approval number: 06-267
Explanation of IRB approval:
The MIND Institute ended support for the project at the close of FY2006.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This project uses magnetoencephalography (MEG) to examine episodic memory function, along with measures of white matter integrity (i.e., magnetic resonance (MR) morphometry, classification of white matter hyperintensities, and fractional anisotropy, FA), and cognitive integrity (i.e., neuropsychological tests) to demonstrate that healthy "successful" aging is quite different from "normal" aging, since the latter may include pathological processes such as hypertension and diabetes which can increase the risk for dementia. The importance of this distinction is that some pathological processes contributing to cognitive decline can be controlled or prevented. In 2006, a pilot study is being conducted to verify that the memory tests used in the experiments are appropriate before beginning the larger formal study.
Objectives:
1. The use of a spatial/verbal working memory task, where the stimuli are physically identical, will reveal different neural circuitry associated with spatial and verbal processing.
2. Age-related changes in the anatomy and physiology of the brain are linked to the maturation of cognitive abilities, as suggested by developmental cognitive neuroscience (Casey et al., 2005).
3. Although aging is typically associated with prefrontal lobe deficits, this may be due to undiagnosed or uncontrolled pathological processes such as hypertension and diabetes, which predominantly affect frontal lobes as well.
Methodology:
MEG will be used to examine brain function during a memory task and magnetic resonance imaging (MRI) to examine brain structure. The memory tasks will entail the following:
Task 1. Matrices consisting of a red digit among 15 green digits are presented sequentially to the central visual field. Previous pilot data suggests that Memory Set Sizes of 1 and 2 (the number of items to be remembered) should be used and that these set sizes should be blocked. The task is to remember either 1) the red digit presented in the memory sets or 2) the location of the red digit in the memory sets and to respond accordingly to the target stimulus if it was or was not one of the preceding memory set stimuli (right index finger for "no" versus right middle finger for "yes"). The stimuli are 250 ms duration and are presented at a fixed interval of 1.2 per second with a 2 second delay period. This type of design permits clear delineation of encoding, retention during the delay interval, and delayed recognition memory.
Task 2. The primary goals of Task 2 are to verify that subjects were using verbal and spatial strategies in Task 1 and to examine effects associated with distractor stimuli in general (i.e., interference effects). Memory Set Size 2 will be used in this task. The same overall timing will be used in this study but distractors and facilitators will be embedded in the delay interval.
Drugs/Devices/Pharmaceuticals:
MEG data will be acquired on a CTF 275-channel system. Four MR sequences will be acquired on a 1.5T Siemens Sonata MR scanner, including T1-weighted GRE and T2 weighted Turbo Spin Echo, a sequence to identify white matter tracts using diffusion tensor imaging, and a sequence to identify white matter lesions typically found in elderly brains using a Fast Fluid-Attenuated Inversion Recovery (FLAIR) sequence. Generally, MEG and MRI examinations are not painful; no long-term adverse effects from these procedures are known.
Type of Human Subject Involvement:
Subjects will participate in a screening neurological examination, an MEG study encompassing two memory tests, and an MRI scan. The neurological examination will include testing of hearing/vision, coordination of movements, strength, walking, balance, perception of sensations, and reflexes. Informed consent will be obtained from subjects according to institutional guidelines established by the University of New Mexico Human Subjects Review Committee.
"Assessment of Infant Brain Functions with Non-invasive Electrophysiological Techniques - Albuquerque"
Principal Investigator: Dr. Yoshio Okada , University of New Mexico
Project started in: 2006
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 08/08/07
IRB approval number: 03-013
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 24
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Dr. Yoshio Okada, assisted by Tristan Technologies, Inc., designed and built a prototype biomagnetometer system , the baby superconducting quantum interference device (babySQUID), under a grant from the National Institutes of Health (NIH). It is used to collect magnetoencephalographic (MEG) measurements from infants and toddlers. The instrument is comprised of 76 densely packed MEG sensors in a hemispherical arrangement configured to account for the smaller head size of infants. The design allows the baby to sleep during data collection. The babySQUID provides superior spatial resolution, compared to that currently available adult MEG systems. Preliminary results with the prototype reveals that the babySQUID system provides good quality data and offers an exciting opportunity to conduct examinations that identify the locations and timing of stimulus responses in babies from birth to 12 months of age. These efforts are important for helping to understand the basis from which higher cognitive functioning develops in children. A companion to this study is being conducted in Finland under IRB # 03-069; however, the MIND Institute does not allocate funding to this other effort.
Objectives:
1. Measure and analyze MEG signals produced by the brain of normal babies in response to tactile and auditory stimulations. Results to date show that it is possible to collect spontaneous MEG signals with a signal-to-noise ratio (SNR) of approximately 5 to 1. Evoked responses to tactile stimulation of the finger and hand have also been obtained. Evoked responses were seen after averaging signals over approximately 50 to 100 epochs. However, data indicate that the signal quality must be improved and the signal bandwidth must be limited to about 2 to 35 Hz due to presence of strong noise outside of this bandwidth.
2. Obtain spontaneous and evoked responses in conditions with little environmental noise and determine the SNR as a function of bandwidth and number of epochs averaged.
Methodology:
1. Subjects will be newborns, infants, and children up to 14 years of age.
2. External stimuli, either tactile or auditory, will be applied to the subjects. Tactile stimuli will be either puffs of air applied via a plastic tube to the skin of the hand or other parts of the body or mechanical vibration provided by movements of a membrane actuated by a piezo-electric device. The stimuli will be applied at a rate of 10 to 0.1 times per second. Auditory stimuli will be sound (<80 dB) applied via a speaker or ear phone to the subject.
3. When external stimuli are applied, the evoked MEG responses will be collected with the babySQUID, possibly in combination with standard electroencephalography (EEG). Each average will be over a varying number of stimulus epochs between 1 and 400. Stimuli of different amplitudes will be used. A range of interstimulus intervals (10 to 0.1 Hz) will be used. Spontaneous data will be also collected with and without the subject's head over the MEG sensor array.
4. For each evoked response trial, the stimulus will be applied in block and the MEG and or EEG signals will be collected until the desired number of epochs is collected. The trials continue until all the stimulus parameters of interest are tested. The study continues until the baby wakes up, which may be between 10 minutes and one hour. The parent(s) are encouraged to observe every phase of the test. The stimulus to be used is first applied to the parent and the consent for the use of the stimulus is obtained before it is applied to the baby.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo MEG imaging using the Baby SQUID research scanner.
Type of Human Subject Involvement:
Subjects in this protocol will be normal newborns, infants, and children up to 14 years of age. Each study requires that the child skips a nap and one feeding before coming to the testing site. Once the child arrives at the testing site and the parent consents to the study, the parent feeds the baby or makes the baby go to sleep. If the child can understand the parent's instructions, the parent helps the child calm down to lie still for the duration of the study. This cooperation requires several hours of time, even for a measurement lasting 10 to 20 minutes. Informed consent will be obtained from subject's parents according to institutional guidelines established by the University of New Mexico Human Subjects Review Committee.
"Auditory and Visual Integration in Schizophrenia Examined Using MEG, EEG, and FMR"
Principal Investigator: Dr. Julia M. Stephen, The MIND Institute
Project started in: 2006
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 08/07/07
IRB approval number: 06-289
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 9
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
The goals of this project are to examine the functioning of sensory integration responses in healthy normal controls and patients with schizophrenia using magnetoencephalography (MEG), electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) in hopes of identifying differences between the normal and patient populations to better understand this disorder. A number of studies suggest that schizophrenia may be a network disorder in the brain in the sense that it is the interconnections between cortical areas and the communication between these areas that are causing the symptoms of the disease. Multisensory integration has been studied in humans and animals and has been shown to involve a network of cortical and subcortical areas to provide the facilitation found with multisensory versus unisensory stimulation. Many studies have used more complicated cognitive paradigms to identify differences between healthy normal volunteers (HNV) and patients with schizophrenia (SP). However, these paradigms can show variation from subject to subject due to differences in strategy. A multisensory integration paradigm is designed to tap into the network that is hypothesized to be deficient in patients with schizophrenia without introducing the complications of a more complicated cognitive paradigm. A few behavioral studies have suggested that patients with schizophrenia have decreased facilitation in multisensory integration paradigms. These studies have not involved neuroimaging in order to elucidate the neural underpinnings of this deficit. The rationale for using a multisensory integration paradigm is that it provides a bridge between simple sensory and cognitive paradigms. It is important to use neuroimaging tools to better understand the disease of schizophrenia with the long term goal of allowing for targeted treatment of the disease to increase success in managing the disease while hopefully decreasing the side effects that are associated with the current pharmaceutical interventions.
Objectives:
1. To determine the amplitude and timing differences obtained with simultaneous MEG/EEG and independently recorded amplitude differences in fMR in response to auditory and visual integration of near and far stimuli in healthy normal volunteers and schizophrenia patients.
2. To determine the amplitude and timing differences obtained with MEG/EEG and amplitude differences obtained with fMR in response to an auditory and visual integration motion paradigm between healthy normal volunteers and schizophrenia patients.
Methodology:
1. Subjects will participate in two paradigms and be tested both using combined MEG/EEG and in a separate data collection using fMRI.
2. The paradigms consist of individual auditory (simple tones presented binaurally through earplugs), visual [simple soccer ball stimuli presented on a screen placed in front of the subject (MEG/EEG) or projected onto a mirror placed in front of the subject (fMRI)], and simultaneously presented auditory and visual stimuli.
3. The first paradigm presents static stimuli in a perspective drawing, and the subject must decide whether the stimulus is "near" or "far" with a button press.
4. The second paradigm presents moving stimuli, and the subject must decide whether the stimulus is moving toward or away from them.
5. Due to subject fatigue, data from only one paradigm will be collected during a single visit. Therefore, the data for the two paradigms will be collected during two visits for MEG/EEG and two visits for fMRI scans. The visits will be scheduled based on machine availability with an attempt to schedule all visits within a three-week period.
6. MEG/EEG data will be collected using a fully integrated 275-channel CTF biomagnetometer and a 128-channel EEG system, respectively.
7. Functional MRI data will be collected separately on a 4 Tesla MR scanner. Turbo Fire will be used to provide an online data quality monitor.
8. MEG data will be analyzed in both separate and combined data sets from the EEG data.
9. The fMRI data will be analyzed using standard image analysis/statistical methods to determine the areas of activation that are significantly different in the two subject groups.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo and MEG, using a fully integrated 275-channel CTF biomagnetometer, an EEG using a 128-channel EEG system, and functional MR using a 4 Tesla MR scanner.
Type of Human Subject Involvement:
Subjects will participate in a MEG/EEG experimental session for up to one hour. They must hold still during that time, except for several short rest breaks. Subjects will also participate in two separate functional MR scans that may take up to two hours per session (four hour total over two sessions). Informed consent will be obtained from subject's parents according to institutional guidelines established by the University of New Mexico Human Subjects Review Committee.
"Effect of Stimulus Rate and Selective Attention on the Blood Oxygen Level Dependent Response in Schizophrenia"
Principal Investigator: Dr. Andrew R. Mayer, The MIND Institute
Project started in: 2006
Status of the Research this Fiscal Year:
Study protocol is inactive.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 04/10/07
IRB approval number: 04-197
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
One of the core deficits in schizophrenia is a deficit in selective attention, or the ability to focus attention on relevant stimuli and to ignore distractors. Functional magnetic resonance imaging (fMRI) studies examining motor and sensory functioning in schizophrenia have produced mixed indications, with some studies suggesting that schizophrenia may be associated with a decreased neuronal response in primary and tertiary motor cortices as measured by blood oxygenation level dependent (BOLD) techniques, while others suggest an increased BOLD response, and still others suggest that differential circuitry mediates motor functioning in schizophrenics. This project proposes to expand initial work on basic motor and sensory systems in schizophrenia through the investigation of the effects of stimulus rate on the BOLD response, to compare this to the role of selective attention on the BOLD response, and to correlate the BOLD response to morphometric and functional data in the subjects. The results of this project are expected to provide valuable knowledge about the basic characteristics of the BOLD response in schizophrenia, assess the effects of higher order cognitions (i.e., selective attention), and examine whether there is a relationship between structural and functional anomalies.
Objectives:
1. Investigate whether schizophrenia patients will demonstrate a linear increase in the BOLD response in primary visual, auditory, and motor cortex based on increases in the rate of stimulus presentation.
2. Investigate the effects of selective attention on the BOLD response in patients with stable schizophrenia.
3. Correlate structural pathology with changes in the magnitude of the BOLD response.
Methodology:
1. Subjects will undergo fMRI imaging sequences.
2. Subjects will simultaneously be presented with visual (a flashing checkerboard) and auditory stimuli (a pure 1,000 Hz tone) occurring at 0.5, 1, or 2 Hz. In the control condition, participants will be asked to tap one finger in time with the presentation of the visual and auditory stimuli. In the selective attention conditions, participants will also be presented with either a visual (a picture of an eye) or auditory (a picture of an ear) icon, indicating the modality for focused attention while tapping.
3. Each trial will last for 6 seconds and will be followed by a rest period in which participants will be required to maintain central visual fixation.
4. Behavioral data (response time) will be analyzed using mixed-model repeated measures analysis of variance (ANOVA) techniques.
5. The BOLD response will be convolved on a voxel-wise basis, estimating the magnitude of the fMRI signal due to (a) the rate of stimulus presentation and (b) the effect of selective attention to the attended modality during the attention condition. Resultant impulse response functions will then be used as dependent variables in subsequent mixed-model repeated-measures ANOVAs to test for group differences.
6. Morphometric data will be segmented according to the four primary cortical lobes (frontal, temporal, parietal, and occipital) as well as overall grey/white tissue volume. Morphometric data will then be correlated with the magnitude of the BOLD response to assess any relationships between structural and functional pathology.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo fMRI imaging using the 1.5T scanner.
Type of Human Subject Involvement:
Subjects in this protocol will be normal volunteers and schizophrenia patients. Men and women of all racial and ethnic backgrounds will be included. Schizophrenia inclusion criteria are: a) 18 to 40 years of age, b) primary diagnosis of schizophrenia, c) right-handed, d) stable psychotropic medication regimen for at least 3 months, e) stable clinical history as denoted by no psychiatric hospitalizations within the last 3 months, and f) previously established deficit in sensory gating (Huang et al., 2003). Control inclusion criteria are: a) 18 to 40 years of age, b) no current or past history of psychiatric disorder, c) no history of schizophrenia spectrum disorder in a first-degree relative, and d) right handed. Exclusion criteria for both groups are: a) history of severe head injury resulting in loss of consciousness, b) any co-morbid neurological disorders, and c) active substance dependence or abuse (except nicotine in patient sample) within the previous six months. Informed consent will be obtained from subject's parents according to institutional guidelines established by the University of New Mexico Human Subjects Review Committee.
"An Event-Related Study of Crossmodal Attention"
Principal Investigator: Dr. Andrew R. Mayer, The MIND Institute
Project started in: 2006
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 05/09/06
IRB approval number: HRRC#05-100
Explanation of IRB approval:
Protocol approval allowed to expire 03/14/2007. Study is concluded.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 5
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This project will use event-related, functional magnetic resonance imaging (fMRI) neuroimaging technology to examine the cross-modal orienting of spatial attention to visual and aural locations in healthy controls. Shifts of attention can occur specifically in one modality (i.e., an arrow sign directing one to look left), but often occur across two modalities (i.e., one being told to look left) requiring the integration of multisensory information. There are also competing demands for the control of attention from stimuli in the outside (exogenous) world, such as flashing signs or loud noises, as well as from internally-driven goals (endogeneous) or cognitions, such as a desire to look left or to listen more attentively to conversation that is occurring at the adjacent table. The endogenous versus exogenous orienting of attentional focus has reliably produced dissociable behavioral effects within the visual and auditory modalities. However, the behavioral effects associated with cross-modal orienting are less robust and may be more dependent on task parameters.
Objectives:
1. Examine the activation patterns associated with exogenous and endogenous orienting to cross-modal stimuli using a whole-brain, event-related fMRI paradigm. Specifically, the neural substrates of crossmodal orienting will be examined with auditory cues and visual targets (ACVT) as well as visual cues and auditory targets (VCAT).
Methodology:
1. Subjects will undergo anatomical and fMRI imaging sequences.
2. In both ACVT and VCAT, the general stimuli and methods of presentation will be identical. Auditory stimuli will be delivered through an Avotech auditory stimulus delivery system. Visual stimuli will be rear-projected onto a screen located 200 cm from the bore of the magnet.
3. A non-ferrous key press device made from force-sensing resistors will be used to record response times and accuracy. Foam padding will be used to minimize movement of the head within the coil.
4. In both conditions, the visual display will consist of a black background with two white boxes located on either side of a central box. Subjects will be required to respond to the appearance of the target by depressing a button corresponding to the location of the target in space (right versus left). Response time shorter than 100 ms or longer than remainder of the trial length will be considered an anticipatory or missed response and will be discarded from future analyses. The inter-trial interval, or amount of time that elapses between the end of one trial and the beginning of the next trial, will be randomly varied to allow for the best sampling of the hemodynamic response and for the establishment of the baseline resting state with a minimal inter-trial interval of 3 seconds.
5. A total of five imaging series will be collected. Each imaging series will consist of 104 pseudo-randomly presented active trials and 126 baseline trials. The first two imaging series collected will consist of exogenous trials to prevent the establishment of a validity bias. Cue characteristics, the validity ratio, and length of the stimulus-onset asynchrony determine whether attention is summoned through endogenous or exogenous means. Cues will correctly indicate the location of the target in 50 percent of the trials (40 valid trials, 40 invalid trials, 24 catch trials per imaging series) in the exogenous condition and in 75 percent of the trials (60 valid trials, 20 invalid trials, 24 catch trials per imaging series) in the endogenous condition. Because of the low ratio of invalid trials, an extra endogenous imaging series will be collected to obtain a more reliable estimate of neural activation occurring during the invalid trials.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo fMRI imaging using a 1.5 Tesla scanner.
Type of Human Subject Involvement:
The first phase of the study will primarily involve pilot work to ensure that the behavioral effects reported in the literature during crossmodal orienting also exist in the presence of ambient scanner noise. In the second phase of the study, healthy, right-handed volunteers (equal numbers of male and female), between the ages 18 to 40, will complete a fMRI session examining crossmodal orienting (ACVT and VCAT). The fMRI session will occur two to four weeks after behavioral testing. Handedness will be determined using the Edinburgh Handedness Inventory (Buckner, 1998; D'Esposito et al., 1999; Oldfield, 1971). Informed consent will be obtained from subjects according to institutional guidelines established by the University of New Mexico Human Subjects Review Committee.
"A Mulitmodal Study of Sensory Gating"
Principal Investigator: Dr. Andrew R. Mayer, The MIND Institute
Project started in: 2006
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 09/10/07
IRB approval number: HRRC#06-313
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 27
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
This project uses electroencephalography (EEG), magnetoencephalography (MEG), functional magnetic resonanace(fMR), and morphometric analyses to investigate the neuronal network underlying sensory gating in individuals with schizophrenia and matched normal controls. To the knowledge of the invesitigator, this will be the first study to examine the electrophysiological response to distinct and repeated information within the sensory gating paradigm using MEG and fMR. Moreover, this study will also represent one of the first attempts to use MEG and fMR to study a single cognitive process in schizophrenia using nearly identical paradigms. These results should provide a double dissociation in pre-attentional and attention functioning for normal controls and schizophrenics, which will be important for understanding the anomalous processing of sensory data in schizophrenia that often leads to social and cognitive dysfunction. The electrophysiological, hemodynamic, and structural information that these multiple neuroimaging techniques provide will also provide a more complete understanding of the pathophysiology underlying schizophrenia and its relationship to cognition.
Objectives:
1. Examine sensory gating, using the paired click paradigm (Adler et al., 1982) and a variant tone paradigm (Boutros et al., 1999) in schizophrenia using several neuroimaging modalities, including MEG, EEG, and fMR with the objective of comparing and correlating structural and functional pathology. It is hoped findings will lead to a more complete understanding of the complex neuronal pathology underlying this disease and its cognitive manifestations.
Methodology:
1. In the EEG/MEG study, participants will perform three different tasks in which they will passively listen to three different pairs of stimuli consisting of identical clicks, identical tones, and non-identical tones. Also, they will be presented with a visual fixation cross throughout the course of the experiment, in an attempt to minimize eye movements. Trials with excessive electro-oculogram activity (EOG) or other artifacts will be monitored in real time and rejected from the averaging process. A total of 100 non-contaminated trials will be collected for all conditions.
2. The second part of the study will examine sensory gating using fMR, using the same stimuli as above, as well as introducing a single tone condition. The single tone condition will serve as an internal control to ensure that the MR system's high radio frequency is similar for basic auditory stimuli in both schizophrenic and normal control subjects. There will be a total of 80 trials in each condition. To reduce the variability secondary to such factors as medication, symptom severity, and other potential confounds, the fMR data will be collected within two weeks of the MEG data.
3. The MEG/EEG data will be collected using a fully integrated 275-channel CTF biomagnetometer and a 128-channel EEG system, respectively.
4. Functional MRI data will be collected separately on a 1.5 T MR scanner.
5. The MEG data will be analyzed separately from the EEG data. In addition, a combined MEG/EEG analysis will be performed. The sources and timing that generate the MEG/EEG waveforms will be found using the Cortical Start Spatio-Temporal (CSST) inverse modeling approach. The time interval of 20 to 300 ms will be analyzed.
6. The individual subject fMRI analysis will be performed using Analysis of Functional NeuroImaging (AFNI) motion correction algorithm based software and the identified regions of interest will be traced. Once the sources and timecourses are identified using MEG/EEG, the timecourses will be characterized to identify the onset time of activity, as well as the peak latencies, peak durations, and peak amplitudes identified in the timecourses. The timecourses will further be analyzed to determine the functional and effective connectivity between different cortical areas.
7. The MEG data will be interpreted by using statistical methods to determine significant differences in source timing and locations between the normal controls and the patients with schizophrenia. In addition, the fMRI data will be interpreted by using standard image analysis/statistical methods to determine areas of activation that are significantly different between the two subject groups. Any significant differences associated with the stated hypotheses will be reported and interpreted based on the current understanding of the normal and abnormal functioning of the brain in schizophrenia.
Drugs/Devices/Pharmaceuticals:
Subjects will undergo EEG/MEG and fMRI scans.
Type of Human Subject Involvement:
Schizophrenic subjects will be medically stable as defined by no hospitalizations or changes in medical regimen within the last three months. Normal controls that have a history of mental illness, substance abuse, or substance dependence will be excluded. Informed consent will be obtained from subjects according to institutional guidelines established by the University of New Mexico Human Subjects Review Committee.
"MRS Measures of Excitatory Neurotransmission in Pain and Fibromyalgia"
Principal Investigator: Dr. Paul G. Mullins, The MIND Institute
Project started in: 2006
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: The University of New Mexico
Most recent approval: 05/04/07
IRB approval number: HRRC#06-123
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: The University of New Mexico
Most recent approval: 04/05/07
IRB approval number: HRRC#06-094
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 12
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Fibromyalgia (FM) is a chronic pain illness characterized by widespread musculoskeletal aches, pain and stiffness, soft tissue tenderness, general fatigue and sleep disturbances, which is estimated to affect 2 to 4 percent of the population. This project will investigate the neurochemistry in FM using proton magnetic resonance spectroscopy (1H-MRS). In particular, the project will study changes in glutamate (Glu) and glutamine (Gln) levels, which may be reflective of excitatory activity, neurotransmission, and neural activation in response to acute pain in vivo in both normal controls and in patients suffering FM. In addition, this study will use N-acetylaspartate (NAA) levels as a surrogate marker for cognitive function. The project design calls for subjects to undergo 1H-MRS before, during, and after an induced episode of painful stimuli, and a short functional magnetic resonance imaging (fMRI) study of brain response to acute painful stimuli.
Objectives:
1. Determine whether subjects with FM have altered levels of the main neurometabolites (e.g., Glu, Gln, NAA), at rest (i.e., without any applied external stimulus).
2. Determine Glu/Gln responses to painful stimuli in multiple brain regions in FM and control subjects.
3. Correlate changes seen at baseline and during stimulus with fMRI responses to an identical stimulus and to results from neuropsychological testing.
Methodology:
1. FM and normal controls will undergo a neuropsychological assessment and 1H-MRS/fMRI scanning over three sessions (one screening and two experimental) on three separate days.
2. Normal subjects will be verified to be in good physical and mental health through interview, health history, and standard checklists.
3. FM patients will be referred by Wilmer Sibbitt, M.D., a rheumatologist with an extensive population of FM patients. FM patients will be screened for the same contraindications as normal controls, in addtion to being classified using the American College of Rheumatology (ACR) 1990 criteria, including a) widespread pain in combination with b) tenderness at 11 or more of the 18 specific tender point sites (Wolfe, F. 1990). In addition, there will be exclusions for c) the presence of concomitant radiographic abnormalities, d) laboratory abno