Ms. Melissa
Hilleary
1101 Yale Blvd., NE
Albuquerque, NM 87131
Phone: 505-272-5028
Fax: 505-272-4056
E-mail: hilleary@mind.unm.edu
Number of Human Subjects projects reported: 38
| MIND-02-0108M06981 | "Ultra-high field fMRI and MEG for praxis" |
| MIND-02-MGH 1999-P-008666/19 | "Toward the prevention of schizophrenia: Neurobiological studies of families with schizophrenia" |
| MIND-02-MGH 2000-P-002110 | "The Spatio-Temporal Dynamics of Processing Language Form and Content in Schizophrenia" |
| MIND-02-MGH 2001-P-000257/6 | "Functional and structural neuroimaging studies of higher cognitive function in schizophrenia" |
| MIND-02-MGH2002-P-00580/1 | "Multimodality imaging of cognitive processes in normal subjects" |
| MIND-02-MGHMcCarley | "Temporal Lobe Neocortical Abnormalities in Schizophrenia: A Structural, Functional and Clinical Perspective " |
| MIND-02-Minn 0206M26761 | "Genomics and white matter abnormalities in schizophrenia." |
| MIND-02-Minn VAMC 2896 | "The neural network of auditory verbal hallucinations" |
| MIND-02-Minn0006M55421 | "MEG Studies of Shcizophrenia" |
| MIND-02-Minn0205M25581 | "The Disregulation of Optimized Cognition in Schizophrenia" |
| MIND-02-UNM HRRC 02-051 | "Longitudinal assessment brain neurochemistry early in schizophrenia with high-field proton spectroscopy as a predictor of functional deterioration." |
| MIND-02-UNM HRRC 03-108 | "A Magnetic Resonance Spectroscopy Study of Glutamate Metabolism and Neuronal Integrity in Children and Adolescents with Schizophrenia-Spectrum Disorders" |
| MIND-02-UNM-HRRC 02-267 | "Dynamic Systems Mediating Verbal and Spatial Working Memory Tasks as Characterized by MEG" |
| MIND-03-UNM HRRC 02-502 | "A fMRI Study of Temporal Cognition" |
| MIND-04-IA-01 | "MIND Clinical Imaging Consortium Protocol: A Joint Study of First Episode and Chronic Schizophrenia" |
| MIND-04-MA-01 | "Event-Related fMRI Study of Transitive Inference in Schizophrenia" |
| MIND-04-MA-02 | "Spatiotemporal Dynamics of Context Processing in Schizphrenia" |
| MIND-04-MA-03 | "Use of Linguistic and Non-Linguistic Context in Language Comprehension in Schizophrenia " |
| MIND-04-MA-04 | "Toward the prevention of schizophrenia: Neurobiological studies of families with schizophrenia " |
| MIND-04-MA-05 | "Auditory, Sensorimotor, and Language Area Mapping Using MEG With and Without fMRI Constraints " |
| MIND-04-MA-06 | "Cognitive Science Research: Various Memory and Language, Visual Object Recognition, and Novelty and Attention Studies " |
| MIND-04-MA-09 | "Schizophrenia Consortium" |
| MIND-04-MN-01 | "In-Vivo Measurement of Glutamatergic Neurotransmission " |
| MIND-04-MN-02 | "National Consortium Project" |
| MIND-04-MN-03 | "The Disregulation of Optimized Cognition in Schizophrenia" |
| MIND-04-MN-04 | "Investigating Brain Function, Connectivity and Neurochemistry in Health and Disease: High Field Magnetic Resonance Methodologies" |
| MIND-04-MN-05 | "MEG Studies of Schizophrenia" |
| MIND-04-MN-06 | "Clinical Research MEG Core" |
| MIND-04-NM-01 | "Magnetoencephalographic studies of information processing in normal subjects" |
| MIND-04-NM-02 | "Neural Mechanisms of Temporal Processing Disturbances in Schizophrenia " |
| MIND-04-UNM-02 | "MIND Clinical Imaging Consortium" |
| MIND-05-MA-01 | "The MEG Alzheimers Consortium" |
| MIND-05-MA-02 | "Visual Responses to Local Stimuli " |
| MIND-05-MA-03 | "Multimodal Imaging of Cognitive Processes: Contextual Predictions Facilitate Visual Cognition" |
| MIND-05-MN-01 | "Adolescent Psychosis Classification " |
| MIND-05-UNM-01 | "White Matter Correlates of Higher Cognitive Functioning in Normals" |
| MIND-05-UNM-04 | "Assessment of Lateralized Hippocampal Function in Schizophrenia" |
| MIND-05-UNM-05 | "Reliability of Proton-Magnetic Resonance Spectroscopy Brain Measures in Persons with Schizophrenia " |
"Ultra-high field fMRI and MEG for praxis"
Principal Investigator: Dr. Apostolos P. Georgopoulos, Minnesota Veterans Research Institute
Project started in: 2002
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: 08/24/04
IRB approval number: 0210M34182
Explanation of IRB approval:
Shared IRB with Dr. Kamil Urgubil (Study titled "Investigating Brain Function, Connectivity and Neurochemistry in Health and Disease: High Field Magnetic Resonance Methodologies)
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 8
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project was conducted to combine data from functional magnetic resonance imaging (fMRI) at ultra high field strength (7 Tesla) and magnetoencephalography (MEG) in an attempt to utilize the high spatial resolution of the fMRI and the high temporal resolution of the MEG for a better understanding of brain function. Since data cannot be acquired simultaneously using both technologies, the Minnesota Partner Site has adopted the strategy to use the same subjects, performing the identical experiment in the two methods, and then attempt to bridge the gap. In preliminary experiments, eight subjects were studied and valid data obtained from three of the group. However, since such data acquisition was being performed for the first time at 7 Tesla, it was discovered that the radio frequency (RF) coils utilized were suboptimal for visualizing the cortex on the superior parietal lobule. Consequently, efforts in 2005 focused on developing multichannel array technology (coils and receivers) for this application.
"Toward the prevention of schizophrenia: Neurobiological studies of families with schizophrenia"
Principal Investigator: Dr. Ming T. Tsuang, Massachusetts General Hospital
Project started in: 2002
This project ended in fiscal year 2005.
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: 05/29/03
IRB approval number: n/a
Explanation of IRB approval:
Project was apparently concluded in 2003 with $96,803 in spending and involving 10 human subjects.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/04 to 12/31/04
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Abstract:
Project concluded in 2003.
Objectives: The objective was to better identify the neural substrate of schizophrenia by identifying subsyndromal phenomenology that may be transmitted in persons at risk for this illness. This study focused on temporal-limbic brain regions and their pre-frontal connections that have been identified previously as critical in understanding the nature of schizophrenia. A second aim was to identify the specificity of these hypotheses for schizophrenia compared with persons with bipolar psychotic disorders.
Methodology: Twenty-four persons in each group were studied and 50 normal controls for a total of 146 subjects over three years. Subjects were given diagnostic interviews and cognitive testing to assess IQ, attention span, working and declarative memory, executive function, language domains, and motor function. Patients then participated in functional and structural imaging procedures.
Exposure to Ionizing Radiation, Radioactive Substances, and Chemical Substances: Not applicable.
Involvement of Human Subjects:
Procedures involving Human Subjects: Subjects were recruited from local hospital clinics and consumer groups (National Alliance for the Mentally Ill). Subjects were given written, informed consent. Subjects did undergo cognitive testing and magnetic resonance imaging (MRI) procedures.
Risks: Subjects may become bored or fatigued during testing. All subjects will be given numerous breaks. All subjects were free to withdraw at any time without consequence.
Privacy/Confidentiality/Consent: Study information will be kept confidential to the extent allowed by law. The Food and Drug Administration and the sponsor of the study may access study records. In publications resulting from the study no names will be used.
"The Spatio-Temporal Dynamics of Processing Language Form and Content in Schizophrenia"
Principal Investigator: Dr. Gina Kuperberg, Massachusetts General Hospital
Project started in: 2002
This project ended in fiscal year 2005.
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: 05/28/04
IRB approval number: 2000-P-002110 CR#4
Explanation of IRB approval:
Study ended.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND fiscal year
Type(s) of Human Subjects Involvement:
a. Objectives: The objective is to identify abnormalities in the temporal dynamics of processing language form and content in schizophrenia using event related potentials (ERPs).
b. Methodology: Patients/subjects did undergo magnetoencephalography (MEG) and funtional magnetic resonance imaging (fMRI) studies (at least five weeks apart). They were presented with different stimulus paradigms including neutral versus positive versus negative critical words in sentences and concrete versus abstract critical words in sentences. Both paradigms with half the speakers in each condition will contain a contextual anomoly, and participants will judge whether or not the sentences make sense. Sentences will be presented word by word in the same pseudorandom counterbalanced sequence.
c. Exposure to Ionizing Radiation, Radioactive Substances, and Chemical Substances: None.
d. Involvement of Human Subjects: Subjects will be consented and all study procedures explained. Subjects will be reminded throughout the study that they can withdraw at any time. Subjects will be tested using MEG and fMRI with the above-described cognitive tests. All information will be kept as confidential as possible according to the rules of the institution.
Risks: Subjects may become bored or fatigued during testing. All subjects will be given numerous breaks. All subjects are free to withdraw at any time without consequence.
Privacy/Confidentiality/Consent: Study information will be kept confidential to the extent allowed by law. The Food and Drug Administration and the sponsor of the study may access study records. In publications resulting from the study no names will be used.
"Functional and structural neuroimaging studies of higher cognitive function in schizophrenia"
Principal Investigator: Dr. Stephan Heckers, Massachusetts General Hospital
Project started in: 2002
This project ended in fiscal year 2005.
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: 02/17/04
IRB approval number: NA
Explanation of IRB approval:
Study not continued in 2005.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Objectives: These projects investigate the cognitive and neuropsychological basis of deficits in higher cognitive function in schizophrenia using structural and functional neuroimaging techniques. In other projects we have established that schizophrenic patients show specific and selective deficits in working memory, declarative memory, and language function. This study will use new methods for the acquisition and analysis of functional and structural data sets, using functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and cortical flat mapping techniques.
Methodology: This study consists of six functional neuroimaging experiments. Men and women aged 18 to 55, right-handed and with a normal verbal IQ, will be studied. Schizophrenic subjects will be recruited as outpatients and must meet inclusion criteria consisting of being on a stable dose of antipsychotic medication for at least six weeks or unmedicated, no substance abuse, and ability to give informed consent. Subjects will be given rating scales to assess symptoms using the Scale to Assess Negative Symptoms, Scale to Assess Positive Symptoms, Simpson-Angus Movement Rating Scale, Global Assessment Scale, Abnormal Involuntary Movement Scale, and Brief Psychiatric Rating Scale instruments.
Exposure to Ionizing Radiation, Radioactive Substances, and Chemical Substances: Not applicable.
Involvement of Human Subjects:
Procedures involving Human Subjects: Subjects will be recruited and given a series of neuroimaging procedures including fMRI and MEG.
Risks: The risks are minimal as both procedures are non-invasive. Subjects will be given many breaks and may withdraw at any time without consequence.
Privacy/Confidentiality/Consent: Subjects must provide written, informed consent. All information will be kept confidential. The Food and Drug Administration and the sponsor of this study may access study files. Publications resulting from this study will not mention any names.
"Multimodality imaging of cognitive processes in normal subjects"
Principal Investigator: Dr. Caroline West, Massachusetts General Hospital
Project started in: 2002
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: 05/26/05
IRB approval number: 2002-P-00580
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 16
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project conducted two experiments, one using functional magnetic resonance imaging (fMRI) and one using electroencephalography (EEG), applying an identical stimulus of real-world events for both cases. The fMRI experiment was used to identify precise locations in the brain of the neuronal activity mediating comprehension of the videos. The EEG experiment revealed the millisecond-by-millisecond timecourse of the evoked activity. In addition, this effort was coordinated with Dr. Gina Kuperberg (see Project MIND-04-MA-03) to examine the deficits in comprehension of real-world events in schizophrenia. EEG and fMRI data were collected on 16 healthy volunteers.
"Temporal Lobe Neocortical Abnormalities in Schizophrenia: A Structural, Functional and Clinical Perspective"
Principal Investigator: Dr. Robert W. McCarley, Massachusetts General Hospital
Project started in: 2002
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: M10543-108
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 06/23/05
IRB approval number: M10543-108
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 30
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project examined four separate hypotheses: (1) At first hospitalization of patients with schizophrenia, but not with manic psychosis, left-lateralized gray matter volume reduction would be found in the Middle Temporal Gyrus (MTG), as would bilateral reduction in Inferior Temporal Gyrus (ITG). These anatomical indicators point to the early presence of abnormalities found in chronic schizophrenia. (2) The second hypothesis anticipated that an enlarged longitudinal sample would show post-initial hospitalization progression of gray matter volume reduction in the left superior temporal gyrus (STG) in schizophrenia, compared with manic psychosis, with most of the change occurring in the first six months following initial hospitalization. In contrast, the abnormalities in the MTG and ITG would not show progression, thus pointing out a pivotal role for the STG in schizophrenia diagnosis. In 2005, ten new subjects or restudy subjects were scanned by magnetic resonance imaging (MRI) for longitudinal sampling against hypotheses one and two. (3) The third hypothesis supposed that in chronic schizophrenia, compared with healthy controls, STG measurements over longer time periods (2.5 years) would show a progressive gray matter volume reduction, although at a lesser rate than in acute schizophrenia. In 2005, substantial completion of this study (begun in 2003) was accomplished with data for 30 subjects. (4) Finally, the fourth hypothesis looked at the evoked potential in schizophrenia associated with face processing. This premise theorized that the N170 would show a reduction proportional to the fusiform gyrus gray matter volume reduction and that gamma elctroencephaolgraphy (EEG) processing abnormalities to steady state auditory gamma input would be associated with auditory hallucinations, indicating elementary circuit abnormalities in the schizophrenic auditory and para-auditory cortex. In 2005 substantial completion of N170 study was accomplished with data for approximately 30 subjects and substantial progress made on the Gamma EEG portion of the effort with approximately 20 subjects.
"Genomics and white matter abnormalities in schizophrenia."
Principal Investigator: Dr. Kelvin O. Lim, University of Minnesota
Project started in: 2002
This project ended in fiscal year 2005.
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: 11/14/04
Explanation of IRB approval:
Project completed in 2003 with estimated funding of $66,666 and one human subject involved.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Project was completed in 2003. This notice is submitted so that it can be removed from the roster.
Objectives: The recent availability of gene chip arrays has allowed the efficient examination of gene expression in complex disorders. Postmortem gene expression studies in schizophrenia have recently reported the reduced expression of sets of genes related to myelination. In vivo neuroimaging studies have revealed potential white matter metabolic and microstructural abnormalities in schizophrenia. The overall aim of this proposal is to perform a pilot antimortem study examining the relationship between white matter abnormalities, detected by recently developed in vivo magnetic resonance measures, and selected white matter related candidate genes, identified through completed and ongoing gene expression and other genomic studies. This pilot proposal would be the first to combine in vivo neuroimaging measures with genomics information. The information would be complementary to that obtained through postmortem studies and provide a logical extension of postmortem studies.
Methodology: The investigators planned to study 40 patients with schizophrenia and 48 healthy controls. All subjects will be between 18 and 50 years of age. All subjects will be scanned and blood samples collected.
Exposure to Ionizing Radiation, Radioactive Substances, and Chemical Substances: Not applicable.
Involvement of Human Subjects:
Procedures involving Human Subjects: See above.
Risks: The risks are minimal. Blood draws can result in bruising at the site where it was drawn. The scan is non-invasive and presents minimal risk. Subjects may become bored or fatigued during some of the tasks. Breaks will be given to help prevent this. All subjects will provide written, informed consent prior to study participation. Subjects are free to withdraw from the study at any time without consequence.
Privacy/Confidentiality/Consent: All information will be kept confidential. The Food and Drug Administration and study sponsor may access study records. In publications resulting from this study, no names will be used.
"The neural network of auditory verbal hallucinations"
Principal Investigator: Dr. Massoud Stephane, Minneapolis Veterans Administration Medical Center
Project started in: 2002
This project ended in fiscal year 2005.
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: 09/13/03
IRB approval number: 2896-A
Explanation of IRB approval:
Project was completed in 2003 and IRB aligned with that time period.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Project completed in 2003.
Objectives: Research focusing on individual psychotic symptoms avoids the diagnostic ambiguity of schizophrenia. Auditory verbal hallucinations (AVH) affect up to 70 percent of schizophrenic patients. AVH research could clarify important aspects of the pathophysiology of schizophrenia. However, this research faces a set of challenges that include:
1) Unpredictability of the occurrence of AVH: this makes direct study a rare opportunity. An abnormal experience is likely to be related to a dysfunction of brain mechanisms underlying normal functions. As AVH arise from a speech disorder, efforts should be made to study language processing in hallucinating patients. Language is linked to a set of distinct, non-overlapping, but interconnected processors. They subserve sublexical, lexical, syntactic, and discourse components and work in concert with other cognitive resources such as attention and working memory. Characterizing language processing in hallucinating patients would shed light on AVH neural mechanisms.
2) Phenomenological variations of AVH: all AVH meet the basic definition - perception of speech in the auditory modality without corresponding external stimuli. However, they vary among multiple phenomenological dimensions, such as repetitive or systematized content, and linguistic complexity (hearing words, sentences, or conversations). There is evidence that the phenomenological variations correspond to variability in the underlying pathophysiology. For example, AVH with repetitive content respond to treatment with antiobsessional agents. A number of positron emission tomography (PET) studies show the activating profile of verbal stimulations varies with the linguistic complexity of the stimuli. Therefore, it is necessary to subgroup AVH according to the phenomenological variables in order to clarify neural substrates.
3) AVH, like most brain dysfunctions and functions, are related to a serial and parallel distributed neural network. Therefore, temporospatial imaging such as magnetoencephalography (MEG) is a particularly suitable method for AVH research. As antipsychotics alter the magnetic signal, studying drug free and naive patients is advantageous.
We hypothesize that AVH result from the dysfunction of a serial and parallel distributed neural network which includes language neural mechanisms. The phonomenological variation of AVH and the associated patterns of cognitive and linguistic deficits are related to pathologies at different locations along this network. The aims are: characterization of cognitive and language processing deficits associated with each phenomenological variable, and characterization of the parallel and serial neural network associated with AVH by MEG.
Methodology: Thirty drug-free or naive patients with a history of AVH and 30 controls will undergo assessment of symptoms and neuropsychological testing. Subjects will then be imaged in resting states and during hallucinations (patients).
Exposure to Ionizing Radiation, Radioactive Substances, and Chemical Substances: Not applicable.
Involvement of Human Subjects:
Procedures involving Human Subjects: See above.
Risks: The risks are minimal as no procedures are invasive. Subjects may become bored or fatigued during some of the tasks. Breaks will be given to help prevent this. All subjects will provide written, informed consent prior to study participation. Subjects are free to withdraw from the study at any time without consequence.
"MEG Studies of Shcizophrenia"
Principal Investigator: Dr. Jose Pardo, University of Minnesota and Minnapolis Veterans Admin. Med. Ctr.
Project started in: 2002
This project ended in fiscal year 2005.
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: 06/13/03
Explanation of IRB approval:
Project completed in prior period with final IRB approval date of 06/13/2003.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/03 to 12/31/03
Explanation:
Final reporting period for project was 01/01/2003 to 12/31/2003 with 10 subjects involved.
Type(s) of Human Subjects Involvement:
Project completed in 2003.
Objectives: It has recently been discovered that when schizophrenia patients look at words (simple, common, and concrete nouns) or read them aloud, brain activation spreads abnormally to other language areas that healthy control subjects do not recruit based on the instructions for the task. This spread occurs despite the preserved ability to read aloud. The phenomenon call been termed "spreading neuronal activation" by the investigators. This study aims to answer three questions about this abnormality: (1) Does spreading neuronal activation reflect the degree of thought disorder in patients (and will medications alter this pattern)? (2) Is spreading neuronal activation caused by dysfunction in automatic or attentional processing? and (3) What cognitive operations do schizophrenic patients employ to result in such patterns of brain activity (and can healthy subjects also produce such patterns given the right task instructions)? To answer these questions, the investigators will apply functional magnetic resonance imaging (fMRI) to measure brain activation as patients and controls process single nouns under varying instructions (context).
The anticipated outcome of this research is greater understanding of spreading neuronal activation, a process likely to account for disturbances of language and thought so common in schizophrenia. In addition, data from ongoing studies using magnetoencephalography (MEG) to study word processing in schizophrenia have the potential to combine synergistically with fMRI data using multimodal techniques to visualize both spatial and temporal components of spreading neuronal activation in patients. Such information is pivotal toward understanding the disease mechanisms, which history has proven is essential to design rationally new and effective treatments.
Methodology: Fifteen patients and 15 controls will be recruited. All subjects will be right handed, and controls will be matched for age, gender, and IQ. Subjects will undergo fMRI scanning while completing the known task.
Exposure to Ionizing Radiation, Radioactive Substances, and Chemical Substances: Not applicable.
Involvement of Human Subjects:
Procedures involving Human Subjects: See above.
Risks: The risks are minimal as no procedures are invasive. Subjects may become bored or fatigued during some of the tasks. Breaks will be given to help prevent this. All subjects will provide written, informed consent prior to study participation. Subjects are free to withdraw from the study at any time without consequence.
Privacy/Confidentiality/Consent: All information will be confidential. The Food and Drug Administration and the study sponsor may access study records. Publications resulting from this study will not mention names.
"The Disregulation of Optimized Cognition in Schizophrenia"
Principal Investigator: Dr. Tonya White, University of Minnesota
Project started in: 2002
This project ended in fiscal year 2005.
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: 05/10/05
IRB approval number: 0205M25581
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 96
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project represents phase one of a planned two-year project to study the neural networks modulated by the prefrontal cortex. In 2005, this project began with specific Aim #1 to study 80 healthy volunteers (8 to 25 years of age) using measures of control of attention and action, including working memory, using behavioral and eye-tracking measures. In addition, 30 youths with schizophrenia and 30 matched healthy controls were also studied, using both the tasks mentioned in specific Aim #1 (ages 8 to 25 years), and with a functional magnetic resonance imaging (fMRI) study of the Sternberg Item Recognition Paradigm (ages 8 to 17 years). Since the Sternberg Item Recognition Paradigm was utilized in the first episode study, this will provide data on the neurodevelopmental trajectory of the Sternberg in both schizophrenia and healthy volunteers. It is anticipated that these subjects will be re-tested in two years.
"Longitudinal assessment brain neurochemistry early in schizophrenia with high-field proton spectroscopy as a predictor of functional deterioration."
Principal Investigator: Dr. Juan Bustillo, MIND Institute/ UNM
Project started in: 2002
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: HRRC 02-051
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 01/18/04
IRB approval number: 02-051
Explanation of IRB approval:
No human subjects for 2005.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Objectives: The purpose of the study is to evaluate whether various brain chemicals in persons with schizophrenia change after the person begins treatment with antipsychotic medications.
Despite effective symptom reduction with antipsychotic medications, the majority of schizophrenia patients fail to achieve premorbid status and functional outcomes are generally poor. N-acetylaspartate (NAA), a marker of neuronal viability, is related to cognitive function and may predict functional outcome. NAA is reduced in prefrontal, thalamic, and mesial temporal brain regions in chronically-treated schizophrenia but may be normal early in the disease. The clinical significance and mechanisms accounting for this NAA reduction are poorly understood. A second line of evidence suggests that glutamine (Gln) may be elevated early in the illness. Glutamine concentrations primarily reflect glutamate (Glu) cleared from the synapse, providing an in-vivo index of glutamatergic neurotransmission. It has been postulated that in schizophrenia there is a progressive excitotoxic process involving hyperglutamatergia, which disrupts neuronal function and accounts for the global cognitive defects and poor psychosocial outcomes of the illness, despite the beneficial symptom reducing effects of antipsychotic medication.
Methodology: A special brain study technology called magnetic resonance spectroscopy (MRS) will be used in this study. The antipsychotic medications that may be used in this study include quetiapine, risperidone, haloperidol, and clozapine, all of which have been repeatedly proven to treat the symptoms of schizophrenia. In addition to the MRS, subjects will also receive cognitive assessments.
The project uses high-field (4T) 1H-MRS to study NAA, Gln, and Glu in antipsychotic-naïve and minimally-treated schizophrenia. These neurometabolites will be measured in four regions where metabolic abnormalities have been previously reported: anterior cingulate, frontal white matter, medial thalamus, and hippocampus. 1H-MRS assessments will be repeated at 1, 6, and 12 months. Treatment with antipsychotic medications will be standardized and symptoms, side-effects, cognitive, and social function will be assessed prospectively. A group of healthy volunteers will also be followed longitudinally. This project will address three specific pressing issues: (1) the location and temporal evolution of brain NAA reductions during the first year of treatment in schizophrenia; (2) the relationship between NAA reductions and cognitive and social function outcomes; and (3) the relationship between abnormalities in glutamatergic metabolism and NAA reductions during the first year of treatment. Documentation that reductions of NAA are clinically relevant and are preceded and "driven" by hyperglutamatergia would, for example, support the early use of antiglutamatergic agents to prevent functional deterioration in schizophrenia.
"A Magnetic Resonance Spectroscopy Study of Glutamate Metabolism and Neuronal Integrity in Children and Adolescents with Schizophrenia-Spectrum Disorders"
Principal Investigator: Dr. Rhoshel Lenroot, MIND Institute/ UNM
Project started in: 2002
This project ended in fiscal year 2005.
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: 03/24/04
IRB approval number: 03-108
Explanation of IRB approval:
Study ended.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/04 to 12/31/04
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Schizophrenia is widely viewed as related to disturbances in neural development, and schizophrenia which manifests during childhood appears to be a more severe form of the disease. Glutamate (Glu) is a neurotransmitter which plays an important role in normal brain development. Studies in adults with schizophrenia have found evidence of abnormalities in glutamate function, possibly resulting in a neurotoxic effect. However, no studies have been done focusing on glutamate function in children and adolescents with schizophrenia. The overall goal of this study is to obtain preliminary cross-sectional data regarding glutamate metabolism and its relationship to brain structure and function in children and adolescents with schizophrenia. Comparisons will be made with a healthy control group. Measures of glutamate, glutamine (Gln), and N-acetylaspartate (NAA), a marker of neuronal integrity, will be obtained using high-field (4 Tesla) 1 H-MRS. Gln concentrations primarily reflect Glu cleared from the synapse, providing an in-vivo measure of glutamatergic neurotransmission. Nueromatabolites will be examined in three areas with previous evidence of metabolic abnormalities: the anterior cingulate, the medial thalamus, and the hippocampus. Each subject will also have a separate scan to obtain high-resolution structural data for correlation with metabolic measures. Measures of brain function will include a neurocognitive battery and neurological examination. Tanner stages will be obtained as a measure of maturity. This will be the first study of glutamate function in children and adolescents with schizophrenia. Our findings should provide insight into the mechanisms of the disease and help to guide the possible use of medications that affect glutamate function in children.
Methods: We plan to continue to use high-field (4T) single-voxel 1H-MRS to compare glutamate function in children and adolescents with schizophrenia-spectrum disorders and healthy controls. We will also seek to characterize the relationship of glutamate function with measures of NAA, brain structures, cognitive function, and physical maturation. Study procedures will consist of a diagnostic interview based on the scale for affective disorders and schizophrenia (K-SADS) and comprehensive assessment of symptoms and history (CASH), a physical examination including neurological exam and Tanner staging of sexual maturity, a neurocognitive test battery, and two magnetic resonance imaging studies. Measures of brain metabolites including glutamine, glutamate, and N-acetylaspartate will be obtained using a 4 Tesla Varian scanner. High resolution morphometric data will be collected in a separate session on a 1.5 Tesla scanner using a sequence developed by colleagues at the University of Iowa. We are requesting a second year of funding in order to study forty new subjects: twenty children and adolescents with schizophrenia-spectrum disorders and twenty healthy controls.
"Dynamic Systems Mediating Verbal and Spatial Working Memory Tasks as Characterized by MEG"
Principal Investigator: Dr. Cheryl J. Aine, MIND Institute/ UNM
Project started in: 2002
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: 02-267
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: The MIND Institute
Most recent approval: 05/31/05
IRB approval number: 02-267
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 5
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Objectives: One hypothesis concerning the etiology of schizophrenia is that subtle neuropathological changes, such as cell loss or reduced neuropil, occur during development and later manifest in adolescence as a functional disruption in connectivity and communication in neuronal circuits involved in the coordination of mental activity. Most neuroimaging studies examining the neurophysiological basis of schizophrenia have demonstrated that working memory tasks, particularly spatial working memory tasks, are quite effective for revealing deficits in schizophrenic patients. Working memory processes appear to involve a large distributed network of cortical/subcortical areas.
The spatial and verbal working memory (WM) protocols focus on elucidating the brain dynamics associated with working memory and delayed recognition memory in schizophrenic brains and normal controls. Magnetoencephalography (MEG) combined with anatomical magnetic resonance imaging (MRI) are particularly useful for the temporal and spatial separation of sensory activity, encoding, and delayed recognition memory, all within the same WM protocol. In addition, effective use of cross-correlation techniques (cross-correlations in source space) can help identify functional neural circuits involved in encoding and recognition memory processes and the degree to which disparate brain regions respond together as a unit in schizophrenic brains compared to their normative control counterparts.
Method: Ten medicated schizophrenic patients and 10 age-matched controls will participate in two WM tasks (spatial and verbal) using the same physical stimuli. Single digits will be located within each cell of a 4 x 4 grid (16 cells total). All but one of the digits will be displayed in green color while the digit to be attended for future recognition will be displayed in red. A variant of the Sternberg task will be used where either memory set sizes of 1 or 3 will be used in order to examine the effect of memory load. The memory set items are presented sequentially in time. In the spatial task, subjects are instructed to encode the location of the red digit, while in the verbal task, subjects are instructed to encode the digit number itself. Neuromagnetic measurements will be made using a Neuromag 122-channel system at the Veterans Administration Medical Center. Automated analysis of the data will be accomplished by conducting limited searches through the pre-defined head volumes. Source locations will be displayed on the MRIs and their calculated timecourses will be evaluated statistically. It is predicted that schizophrenic patients will reveal a deficit in sustaining activity in the different brain regions involved in the task, which prevent a prefrontal-parietal circuit from communicating effectively between the constituent regions, thus having a negative impact on behavioral performance measures.
"A fMRI Study of Temporal Cognition"
Principal Investigator: Dr. Deborah Harrington, MIND Institute/UNM
Project started in: 2003
This project ended in fiscal year 2005.
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: 08/10/04
IRB approval number: HRRC 02-502
Explanation of IRB approval:
Study ended in 2003.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/03 to 12/31/03
Explanation:
Last reporting period involving human subjects involvement.
Type(s) of Human Subjects Involvement:
Objectives: The mechanisms by which the brain times events and stores them in memory for later use is of great interest. The purpose of this research is to use magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to study the brain systems that control our ability to perceive and remember the amount of time that has passed. The working hypothesis is that the basal ganglia regulate the "timekeeper" mechanism.
Methodology: Methodology is centered on the use of MEG and fMRI to study brain systems.
Exposure to Ionizing Radiation, Radioactive Substances, and Chemical Substances: Not applicable.
Involvement of Human Subjects:
Procedures involving Human Subjects: Subjects will be asked to perform a variety of tasks to assess the ability to distinguish different intervals of time and different pitches of sound. These involve listening to sounds through earphones and then pressing a button on a keyboard or lifting a finger. These tasks will be performed while the subject is undergoing MEG and the fMRI.
Risks: Subjects will need to lie still in the MRI machine during testing. This test will take up to 90 minutes. Subjects will be given breaks at regular intervals. The MRI machine makes a loud banging noise. Efforts to make subjects comfortable will be made including providing earplugs or other support. Patients with pacemakers, metal in their body, aneurysm clips, ear implants or nerve stimulators will not be able to participate in this study. Pregnant women will also be excluded from participation in this study. All subjects may withdraw from the study at any time without consequence.
Privacy/Confidentiality/Consent: The study records may be made available to the Food and Drug Administration and the University of New Mexico Research and Review Committee. Otherwise, subject records will be kept strictly confidential.
"MIND Clinical Imaging Consortium Protocol: A Joint Study of First Episode and Chronic Schizophrenia"
Principal Investigator: Dr. Beng Ho, University of Iowa
Project started in: 2004
Funding for Human Subjects Research:
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: The MIND Institute
Most recent approval: 12/05/05
IRB approval number: 8103070
Explanation of IRB approval:
This is an extension from last year.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 51
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This is a collaborative project with a common investigational protocol for all the MIND Institute sites. In summary, for the University of Iowa site, a goal of 80 subjects was targeted at the rate of approximately two patients and/or control subjects per week. The controls for the first episode (FE) group were followed and rescanned annually, as were the FE patients.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 12/20/05
IRB approval number: 1998010017
Explanation of IRB approval:
This is an extension from last year.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 39
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This is a collaborative project with a common investigational protocol for all the MIND Institute sites. In summary, for the University of Iowa site, a goal of 80 subjects was targeted at the rate of approximately two patients and/or control subjects per week. The controls for the first episode (FE) group were followed and rescanned annually, as were the FE patients.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 10/11/05
IRB approval number: 199701024
Explanation of IRB approval:
This is a extension from last year.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 80
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This is a collaborative project with a common investigational protocol for all the MIND Institute sites. In summary, for the University of Iowa site, a goal of 80 subjects was targeted at the rate of approximately two patients and/or control subjects per week. The controls for the first episode (FE) group were followed and rescanned annually, as were the FE patients.
"Event-Related fMRI Study of Transitive Inference in Schizophrenia"
Principal Investigator: Dr. Stephan Heckers, Massachusetts General Hospital
Project started in: 2004
This project ended in fiscal year 2005.
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 1
Identifier or number: 2001P-00258
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 01/15/04
IRB approval number: 2001P-00258
Explanation of IRB approval:
PI left organization.
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: Massachusetts General Hosptial
Most recent approval: 01/15/04
IRB approval number: 2001P-000446
Explanation of additional approval:
PI left Institution
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Transitive inference (TI) is the ability to infer relationships about the sequential order of items that have not been studied together. Recent animal studies have provided compelling evidence that this relational memory ability depends on the integrity of the hippocampus (Dusek and Eichenbaum, 1997). In addition, we have recently provided the first evidence that TI judgments are also associated with significant hippocampal activation in humans (Heckers et al., 2003). Thus, TI allows us to study relational memory in humans with a paradigm that can be explored further in animals.
A recent behavioral study has demonstrated selective deficits in TI in subjects with schizophrenia (Titone et al, 2003). While schizophrenia subjects were able to infer relationships between items that did not require a flexible representation of an underlying sequence, they were less accurate when asked to order items that required TI judgments. Taken together, there is compelling evidence that TI is associated with significant hippocampal activation in humans and that this process is impaired in schizophrenia.
Methods:
We will use an event-related study design in a 3T Siemens scanner to study blood oxygen level dependent (BOLD) signal change in the medial temporal lobe in 20 healthy subjects and 20 patients with schizophrenia. Prior to scanning, subjects will be trained on pairs of arbitrary visual stimuli. Some of these pairs are taken from a larger list of sequentially ordered visual stimuli (#1 to #6), whereas others are non-overlapping individual pairs (i.e., A-B, C-D, etc.). During scanning, subjects will then be shown novel pairings from either the overlapping or the non-overlapping stimulus sets. Stimulus pairs will be presented in a randomized fashion. Functional images will be analyzed for whole brain activation patterns using the statistical parametric mapping version 2 (SPM2) data processing software package and for medial temporal lobe activation using six individually outlined regions of interest (amygdala, uncus, hippocampal body, entorhinal cortex, perirhinal cortex, and parahippocampal cortex).
"Spatiotemporal Dynamics of Context Processing in Schizphrenia"
Principal Investigator: Dr. Dara Manoach, Massachusetts General Hosptial
Project started in: 2004
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: 2002P-000444
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 03/01/05
IRB approval number: 2002P-000444
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 10
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project identified the neural basis of the perseverative effects of inhibition in schizophrenia using a saccadic task. The research plan was structured on the hypothesis that successful inhibition, as measured by antisaccade (AS) performance, is increased with activation of frontal eye fields (FEF) and, in schizophrenia, this activity is exaggerated and compensatory brain regions recruited. In addition, as a secondary hypothesis, it was anticipated that the effects of inhibition would "carry-over." Trials preceded by inhibition, were characterized by decreased FEF activity and delayed responses. This effect was again exaggerated in schizophrenia patients. In 2005, functional magnetic resonance imaging/magnetoencephalography (fMRI/MEG) studies of 20 first episode (FE) patients, 20 chronic medicated patients, and 20 healthy subjects were conducted under this protocol.
"Use of Linguistic and Non-Linguistic Context in Language Comprehension in Schizophrenia"
Principal Investigator: Dr. Gina Kuperberg, Anthinoula A. Martinos Center / Massachusetts General Hospital
Project started in: 2004
Funding for Human Subjects Research:
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: The MIND Institute
Most recent approval: 05/11/05
IRB approval number: 2000P-002107
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 25
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Under this project, two functional magnetic resonance imaging (fMRI) experiments were conducted in patients with schizophrenia and matched healthy controls to compare the use of linguistic and non-linguistic context. The differences between patients and controls were identified in the spatiotemporal dynamics of activation within a left-lateralized temporal-prefrontal network. Also, the relationship between the observed neurophysiological abnormalities and clinical symptoms of schizophrenia were examined.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 05/12/05
IRB approval number: 2000P-002100
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
Under this project, two functional magnetic resonance imaging (fMRI) experiments were conducted in patients with schizophrenia and matched healthy controls to compare the use of linguistic and non-linguistic context. The differences between patients and controls were identified in the spatiotemporal dynamics of activation within a left-lateralized temporal-prefrontal network. Also, the relationship between the observed neurophysiological abnormalities and clinical symptoms of schizophrenia were examined.
"Toward the prevention of schizophrenia: Neurobiological studies of families with schizophrenia"
Principal Investigator: Dr. Larry Seidman, Anthinoula A. Martinos Center / Massachusetts General Hospital
Project started in: 2004
Funding for Human Subjects Research:
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: The MIND Institute
Most recent approval: 04/28/05
IRB approval number: 1999P-008666/20
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 18
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project was conducted to explore two objectives: First, to better identify the neural substrate of schizophrenia by identifying subsyndromal phenomenology that is transmitted in persons at risk for the illness. This was accomplished through focusing on cortical and limbic brain regions that have been identified previously as critical in understanding the vulnerability to schizophrenia, including the hippocampus, amygdala, parahippocampal and cingulate gyri, and dorsolateral and orbital prefrontal cortices, using structural and functional neuroimaging, as well as assessments of related attention, verbal declarative memory, working memory, and executive functions. Functional magnetic resonance imaging (fMRI) tasks were the measures of working memory and verbal encoding. The second objective was to identify the specificity of brain activation in persons with schizophrenia and their first-degree relatives, compared with persons with bipolar psychotic disorders and in their relatives. In 2005, the relationship of cognitive measures and brain activation was examined for approximately 30 subjects, 10 controls, 10 persons at genetic risk for psychoses, and 10 first episode psychotic patients.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 01/27/05
IRB approval number: 2002P-001984
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project was conducted to explore two objectives: First, to better identify the neural substrate of schizophrenia by identifying subsyndromal phenomenology that is transmitted in persons at risk for the illness. This was accomplished through focusing on cortical and limbic brain regions that have been identified previously as critical in understanding the vulnerability to schizophrenia, including the hippocampus, amygdala, parahippocampal and cingulate gyri, and dorsolateral and orbital prefrontal cortices, using structural and functional neuroimaging, as well as assessments of related attention, verbal declarative memory, working memory, and executive functions. Functional magnetic resonance imaging (fMRI) tasks were the measures of working memory and verbal encoding. The second objective was to identify the specificity of brain activation in persons with schizophrenia and their first-degree relatives, compared with persons with bipolar psychotic disorders and in their relatives. In 2005, the relationship of cognitive measures and brain activation was examined for approximately 30 subjects, 10 controls, 10 persons at genetic risk for psychoses, and 10 first episode psychotic patients.
"Auditory, Sensorimotor, and Language Area Mapping Using MEG With and Without fMRI Constraints"
Principal Investigator: Dr. Steve Stufflebeam, Massachusetts General Hosptial
Project started in: 2004
Funding for Human Subjects Research:
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: The MIND Institute
Most recent approval: 05/25/05
IRB approval number: 2002P-001238
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project continues an effort funded in 2004 to localize auditory function in schizophrenia using magnetoencephalography (MEG) and magnetic resonance imaging (MRI). In 2005, this experimental paradigm was further verified and optimized to improve the accuracy of the mapping technique, which has application in clinical pre-surgical mapping. In addition, the technique was applied to epilepsy patients and expanded to examine language mapping and visual mapping as well. The various mapping examinations involved from nine to 30 subjects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 08/02/05
IRB approval number: 2002P-001235/4
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 9
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
This project continues an effort funded in 2004 to localize auditory function in schizophrenia using magnetoencephalography (MEG) and magnetic resonance imaging (MRI). In 2005, this experimental paradigm was further verified and optimized to improve the accuracy of the mapping technique, which has application in clinical pre-surgical mapping. In addition, the technique was applied to epilepsy patients and expanded to examine language mapping and visual mapping as well. The various mapping examinations involved from nine to 30 subjects.
"Cognitive Science Research: Various Memory and Language, Visual Object Recognition, and Novelty and Attention Studies"
Principal Investigator: Dr. Caroline West, Massachusetts General Hosptial
Project started in: 2004
This project ended in fiscal year 2005.
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 4
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: The MIND Institute
Most recent approval: 05/28/04
IRB approval number: 2002P-000580
Explanation of IRB approval:
Study ended.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/01/05 to 12/31/05
Explanation:
MIND Institute fiscal year
Type(s) of Human Subjects Involvement:
A. Combined MRI and MEG studies of cognitive functions
AIM A.1A. Multimodal imaging of human auditory cognition
Background
Recent studies have suggested the existence of segregated auditory-cortex pathways for processing of object/content and location features, termed the "what" and "where" processing streams. Our recent findings suggest that the anterior and posterior auditory N1 (N1a and N1p) responses may reflect processing within these subsystems.
Methods
We will use functional magnetoencephalography (fMEG) to empirically test how the human auditory cortex processes "what" and "where" information and how selective attention modulates this processing. To quantify the effects of post-stimulus inhibition on the N1a and N1p sources, we will parametrically vary (a) the phonetic features, (b) inter-trial interval between "standard" and subsequent "deviant" stimuli, and (c) the number of standard stimuli preceding each deviant stimulus.
AIM A.IB. Effects of alcohol, novelty, and semantics on spatiotemporal stages of verbal processing
Background
There is evidence that alcohol impairs behavioral measures of verbal categorization and memory. However, the effects of alcohol intoxication on the brain have not been adequately studied in tasks using complex semantic stimuli.
Methods
We are currently using a lexical decision task that manipulates semantics (words vs. pronounceable non-words) and novelty (rarely presented perceptually distinctive stimuli vs. frequent stimuli) when subjects are given a moderately low dose of alcohol or placebo.
AIM A.IC. Multimodal imaging of the semantic processing of concrete and abstract sentences
Background
Our previous research suggests that multiple systems are involved in the processing of word meanings. In particular, concrete words have access to semantic representations in an image-based system in addition to the verbal system, while abstract words primarily access the verbal system. Our preliminary functional magnetic resonance imaging (fMRI) findings revealed that abstract words access representations in bilateral orbito-frontal cortex (OFC) and the left inferior frontal gyrus (IFG) while concrete words access the lateral occipito-temporal (OT) region bilaterally and the left anterior inferior temporal gyrus (ITG).
Methods
In addition to completing the fMRI study, we will employ the identical task (sentence congruency decision) using the anatomical MEG (aMEG) technique. We hypothesize that the N400 sources localized with aMEG will be weighted more strongly in frontal regions (OFC and IFG) for abstract words and in temporal regions for concrete words (OT and ITG), in accordance with the fMRI effects.
AIM A.ID. Biological bases of inhibition in development and psychopathology
Background
The new modified n-back task developed by Dr. Kristina Ciesielski, who has been in residence at the Massachusetts General Hospital Nuclear Magnetic Resonance (MGH NMR) Center as a visiting scientist from the University of New Mexico, could be considered as a possible tool for early diagnostic work with children who are at risk for mental/cognitive disorders. Before such consideration, however, more validation clinical studies are necessary.
Methods
The fMRI and MEG studies are in progress with 16 obsessive compulsive disorder (OCD) children and their biological parents using the modified n-back task and delayed matching-to-sample task (DMST) and with patients with frontal-cerebellar abnormalities (children treated for cancer).
B. Motivation mapping and its application to delineating endophenotypes in depression and stimulant addiction
Background
Recent studies suggest a correspondence between gene function and brain circuitry activation during motivationally salient stimuli. This project focuses on the determination of heritability to circuitry-based endophenotypes in healthy controls. The upcoming ye