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1.
Schizophr Res ; 70(2-3): 287-91, 2004 Oct 01.
Article in English | MEDLINE | ID: mdl-15329304

ABSTRACT

FMRI was used to study cortical activation patterns in nine healthy male subjects and nine high-functioning male schizophrenia patients during a letter verbal fluency task. Both groups showed similar patterns of activation, however, in controls the activation was primarily in the left broca area, while for schizophrenia patients, it was more bilateral. These data indicate that high-functioning schizophrenia patients show a reduced language lateralization of the frontal cortex compared to healthy controls.


Subject(s)
Frontal Lobe/metabolism , Frontal Lobe/physiopathology , Language Tests , Magnetic Resonance Imaging , Schizophrenia/metabolism , Schizophrenia/physiopathology , Verbal Behavior , Vocabulary , Adult , Functional Laterality/physiology , Humans , Male
2.
J Neuroimmunol ; 145(1-2): 139-47, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14644040

ABSTRACT

Nogo-A is a protein associated with central nervous system (CNS) myelin thought to impair regenerative responses and to suppress sprouting and plastic changes of synaptic terminals. In this study, we report that serum IgM autoantibodies to the recombinant large N-terminal inhibitory domain of Nogo-A are a frequent finding in multiple sclerosis (MS) and acute inflammatory (IND) and non-inflammatory neurological diseases (OND), but not in neurodegenerative diseases (ND), systemic inflammatory disease and healthy controls. Furthermore, we demonstrate intrathecal production of anti-Nogo-A antibodies measured by increased IgG indices. Intrathecal anti-Nogo antibodies were significantly more frequent in patients with relapsing-remitting as compared to chronic progressive (CP) MS. We also found a highly significant negative correlation of these antibody responses with age indicating that they are more frequent in younger patients. We finally demonstrate that human anti-Nogo-A antibodies recognize native Nogo-A in brain extracts, oligodendrocytes and cells expressing human Nogo-A.


Subject(s)
Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Autoantigens/immunology , Multiple Sclerosis/immunology , Myelin Proteins/immunology , Acute Disease , Adult , Aged , Animals , Autoantibodies/biosynthesis , Autoantibodies/metabolism , Brain/immunology , Brain/metabolism , CHO Cells , Cells, Cultured , Central Nervous System Diseases/blood , Central Nervous System Diseases/cerebrospinal fluid , Central Nervous System Diseases/immunology , Cricetinae , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/biosynthesis , Immunoglobulin M/blood , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Nogo Proteins , Oligodendroglia/immunology , Oligodendroglia/metabolism , Rats , Transfection
3.
Am J Psychiatry ; 160(10): 1802-8, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14514494

ABSTRACT

OBJECTIVE: Memory impairment has been well documented in schizophrenia. In a previous study, the authors investigated patterns of brain activity during episodic encoding and recognition of words in remitted, stable schizophrenia outpatients being treated with novel antipsychotics. The same procedure was used in this study to investigate unmedicated patients during an acute episode of schizophrenia. METHOD: Functional magnetic resonance imaging was used to study regional brain activation in 10 unmedicated patients experiencing an acute episode of schizophrenia and 10 healthy comparison subjects during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite intact recognition performance, patients with schizophrenia showed reduced activation of anterior prefrontal, posterior cingulate, and retrosplenial areas relative to comparison subjects during word encoding. During word recognition, reduced activation was found in the patients' dorsolateral prefrontal and limbic/paralimbic regions. On the other hand, higher metabolism in bilateral anterior prefrontal cortices was observed. CONCLUSIONS: The results suggest that different neural pathways are engaged during episodic encoding and recognition of words in patients experiencing an acute episode of schizophrenia relative to healthy comparison subjects. Furthermore, acute psychosis may prevent practice effects, reflected in a failure to engage brain regions associated with successful episodic memory retrieval in healthy subjects.


Subject(s)
Cerebral Cortex/physiopathology , Magnetic Resonance Imaging , Memory Disorders/physiopathology , Memory Disorders/psychology , Recognition, Psychology , Schizophrenia/physiopathology , Schizophrenic Psychology , Acute Disease , Adult , Antipsychotic Agents/administration & dosage , Cerebral Cortex/pathology , Female , Frontal Lobe/physiopathology , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Occipital Lobe/physiopathology , Parietal Lobe/physiopathology , Schizophrenia/pathology , Vocabulary
4.
Psychiatry Res ; 123(1): 1-15, 2003 May 01.
Article in English | MEDLINE | ID: mdl-12738340

ABSTRACT

Functional magnetic resonance imaging was used to compare cortical activation patterns in healthy volunteers with those in patients with schizophrenia during a modified verbal Stroop task. Healthy subjects (n=13) and patients with schizophrenia (n=13) on stable antipsychotic treatment, matched on demographic variables, were included. Patients were preselected on the basis of good performance on a selective attention test. Patients with schizophrenia showed a significantly increased pattern of activation in the left and right inferior frontal cortex and the anterior cingulate cortex. A significant negative correlation between activation of the left prefrontal cortex and accuracy in the modified Stroop test was observed for healthy controls but not schizophrenia patients. Although both groups recruited the prefrontal cortex during the modified Stroop task, for the schizophrenia patients this activation was bilateral, whereas for the controls this activation was primarily in the left hemisphere, suggesting that patients with schizophrenia recruited more prefrontal regions to perform the task with the same accuracy as healthy controls. Our findings of increased activity across multiple areas of the brain, including dorsolateral frontal cortex and anterior cingulate, in patients with schizophrenia who perform relatively well on a task of selective attention give further evidence that task performance may be a confounding factor in the interpretation of neuroimaging results.


Subject(s)
Attention/physiology , Brain/blood supply , Brain/physiopathology , Magnetic Resonance Imaging , Schizophrenia/physiopathology , Adult , Antipsychotic Agents/therapeutic use , Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Female , Functional Laterality/physiology , Hemodynamics , Humans , Male , Neuropsychological Tests , Schizophrenia/drug therapy , Severity of Illness Index
5.
Am J Psychiatry ; 160(5): 911-8, 2003 May.
Article in English | MEDLINE | ID: mdl-12727695

ABSTRACT

OBJECTIVE: Verbal memory deficits are among the most severe cognitive deficits observed in patients with schizophrenia. This study examined patterns of brain activity during episodic encoding and recognition of words in patients with schizophrenia. METHOD: Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 10 healthy male comparison subjects and 10 male outpatients with schizophrenia during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite having intact performance in word recognition, the patients with schizophrenia had less activation of the right dorsolateral and anterior prefrontal cortex, right anterior cingulate, and left lateral temporal cortex during word encoding, compared with the healthy comparison subjects. During word recognition, the patients had impairments in activation of the bilateral dorsolateral prefrontal and lateral temporal cortices. CONCLUSIONS: Schizophrenia was associated with attenuated frontotemporal activation during episodic encoding and recognition of words. These results from an fMRI study replicate earlier findings derived from a positron emission tomography study.


Subject(s)
Cerebral Cortex/physiology , Magnetic Resonance Imaging , Memory/physiology , Neuropsychological Tests , Schizophrenia/diagnosis , Schizophrenic Psychology , Verbal Behavior/physiology , Adult , Ambulatory Care , Cerebral Cortex/physiopathology , Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Frontal Lobe/physiology , Frontal Lobe/physiopathology , Functional Laterality/physiology , Humans , Male , Memory Disorders/diagnosis , Memory Disorders/physiopathology , Recognition, Psychology/physiology , Retention, Psychology/physiology , Temporal Lobe/physiology , Temporal Lobe/physiopathology
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