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1.
Nat Neurosci ; 15(9): 1313-9, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22885850

ABSTRACT

Ongoing sensory input is critical for shaping internal representations of the external world. Conversely, a lack of sensory input can profoundly perturb the formation of these representations. The olfactory system is particularly vulnerable to sensory deprivation, owing to the widespread prevalence of allergic, viral and chronic rhinosinusitis, but how the brain encodes and maintains odor information under such circumstances remains poorly understood. Here we combined functional magnetic resonance imaging (fMRI) with multivariate (pattern-based) analyses and psychophysical approaches to show that a 7-d period of olfactory deprivation induces reversible changes in odor-evoked fMRI activity in piriform cortex and orbitofrontal cortex (OFC). Notably, multivoxel ensemble codes of odor quality in OFC became decorrelated after deprivation, and the magnitude of these changes predicted subsequent olfactory perceptual plasticity. Our findings suggest that transient changes in these key olfactory brain regions are instrumental in sustaining odor perception integrity in the wake of disrupted sensory input.


Subject(s)
Odorants , Prefrontal Cortex/physiology , Smell/physiology , Data Interpretation, Statistical , Humans , Image Processing, Computer-Assisted , Inflammation/etiology , Magnetic Resonance Imaging , Nasal Cavity/anatomy & histology , Nasal Cavity/innervation , Nasal Obstruction/etiology , Olfactory Pathways/anatomy & histology , Olfactory Pathways/physiology , Prefrontal Cortex/anatomy & histology , Psychomotor Performance/physiology , Rhinometry, Acoustic , Sensory Deprivation/physiology , Taste/physiology
2.
Schizophr Res ; 133(1-3): 82-90, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21872444

ABSTRACT

OBJECTIVE: Although magnetic resonance spectroscopy has identified metabolic abnormalities in adult and childhood schizophrenia, no prior studies have investigated the relationship between neurometabolites and thought disorder. This study examined this association in language-related brain regions using proton magnetic resonance spectroscopic imaging ((1)H MRSI). METHOD: MRSI was acquired bilaterally from 28 youth with childhood-onset schizophrenia and 34 healthy control subjects in inferior frontal, middle frontal, and superior temporal gyri at 1.5T and short echo time (TR/TE = 1500/30 ms). CSF-corrected "total NAA" (tNAA; N-acetyl-aspartate + N-acetyl-aspartyl-glutamate), glutamate + glutamine (Glx), creatine + phosphocreatine (Cr + PCr), choline compounds (Cho), and myo-inositol (mI) were assayed in manually drawn regions-of-interest partitioned into gray matter, white matter, and CSF and then coregistered with MRSI. Speech samples of all subjects were coded for thought disorder. RESULTS: In the schizophrenia group, the severity of formal thought disorder correlated significantly with tNAA in the left inferior frontal and superior temporal gyri and with Cr + PCr in left superior temporal gyrus. CONCLUSIONS: Neurometabolite concentrations in language-related brain regions are associated with thought disorder in childhood-onset schizophrenia.


Subject(s)
Brain/metabolism , Cognition Disorders/etiology , Magnetic Resonance Spectroscopy , Protons , Schizophrenia, Childhood/complications , Schizophrenia, Childhood/pathology , Adolescent , Analysis of Variance , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Brain/pathology , Child , Choline/metabolism , Creatine/metabolism , Dipeptides/metabolism , Female , Humans , Male , Neuropsychological Tests , Phosphocreatine/metabolism , Psychiatric Status Rating Scales , Statistics, Nonparametric
3.
J Am Acad Child Adolesc Psychiatry ; 50(7): 669-80, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21703494

ABSTRACT

OBJECTIVE: Given the fundamental role of thought disorder in schizophrenia, subtle communication disturbance may be a valuable predictor of subsequent development of psychosis. Here we examined the contribution of thought and communication disturbance to the prediction of outcome in adolescents identified as putatively prodromal for psychosis. METHOD: Transcribed speech samples were elicited from 105 adolescents (54 identified as being at clinical high risk for a first episode of psychosis [CHR], and 51 demographically comparable comparison subjects) and coded for formal thought disorder (FTD) and linguistic cohesion. We then examined the association of baseline FTD/cohesion with conversion to psychosis and social and role outcome at follow-up, approximately 1 year later. RESULTS: At baseline, CHR patients who subsequently converted to psychosis (CHR+) showed an elevated rate of illogical thinking and poverty of content (POC) in their speech, relative to both typically developing controls and CHR patients who did not convert to psychosis (CHR-). CHR+ youth also used significantly less referential cohesion at baseline, indicating that they provide fewer references to persons, objects, or events mentioned in preceding utterances. Multiple regression models indicated that, among measures of FTD/cohesion, illogical thinking was uniquely predictive of subsequent conversion to psychosis, whereas POC and referential cohesion were significant predictors of social and role functioning, respectively. CONCLUSIONS: Despite the absence of fully psychotic symptoms, putatively prodromal individuals evidence signs of communication disturbance that are qualitatively similar to those seen in schizophrenia and are predictive of both conversion to psychosis and psychosocial outcome. These findings suggest that FTD measures have prognostic significance for at-risk youth.


Subject(s)
Cognition Disorders/etiology , Psychotic Disorders/diagnosis , Schizophrenia/diagnosis , Schizophrenic Language , Adolescent , Case-Control Studies , Disease Progression , Early Diagnosis , Female , Humans , Longitudinal Studies , Los Angeles , Male , Multivariate Analysis , Psychotic Disorders/complications , Schizophrenia/complications
4.
Epilepsia ; 52(9): 1705-14, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21635240

ABSTRACT

PURPOSE: To investigate relationships between regional brain metabolites, social communication deficits, and seizure frequency in children and adolescents with cryptogenic epilepsy with complex partial seizures (CPS). METHODS: In 12 children and adolescents with CPS and 23 age- and gender-matched healthy controls, we acquired proton magnetic resonance spectroscopic imaging (MRSI) at 1.5 T and 30 ms echo-time from bilateral inferior frontal and superior temporal gyri, regions associated with social communication deficits. Videotaped speech samples of all the subjects were coded for social communication deficits and parents provided information on seizure frequency. KEY FINDINGS: Four MRSI findings emerged in right inferior frontal gyrus. N-acetyl-aspartate (NAA) plus N-acetyl-aspartyl-glutamate (NAAG)--together called "tNAA"--was 11.4% lower in patients with CPS than in controls. Choline-compounds (Cho) were 15.4% lower in CPS than in controls. Within CPS, higher tNAA was associated with more frequent seizures and abnormal social communication. SIGNIFICANCE: Localization of findings to right inferior frontal cortex supports the involvement of this area in social communication deficits and may be related to atypical lateralization of expressive language in pediatric epilepsy. Lower levels of tNAA and Cho may indicate local neuronal or glial damage or underpopulation due to excitotoxicity or other causes. The sensitivity of tNAA to seizure frequency suggests effects of ongoing CPS on neuronal and glial function in this brain region.


Subject(s)
Cerebral Cortex/metabolism , Communication Disorders/diagnosis , Communication Disorders/etiology , Epilepsy, Complex Partial/complications , Social Behavior Disorders/complications , Social Behavior Disorders/diagnosis , Adolescent , Aspartic Acid/analogs & derivatives , Case-Control Studies , Cerebral Cortex/pathology , Child , Choline , Creatine , Female , Functional Laterality , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy/methods , Male , Protons
5.
Epilepsy Behav ; 17(3): 402-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20149755

ABSTRACT

In this study the relationship between language skill and frontotemporal volumes was compared in 69 medically treated subjects with epilepsy and 34 healthy children, aged 6.1-16.6 years. Also, whether patients with linguistic deficits had abnormal volumes and atypical associations between volumes and language skills in these brain regions was determined. The children underwent language testing and MRI scans at 1.5 T. Brain tissue was segmented and frontotemporal volumes were computed. Higher mean language scores were significantly associated with larger inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus gray matter volumes in the epilepsy group and in the children with epilepsy with average language scores. Increased total brain and dorsolateral prefrontal gray and white matter volumes, however, were associated with higher language scores in the healthy controls. Within the epilepsy group, linguistic deficits were related to smaller anterior superior temporal gyrus gray matter volumes and there was a negative association between language scores and dorsolateral prefrontal gray matter volumes. These findings demonstrate abnormal development of language-related brain regions, and imply differential reorganization of brain regions subserving language in children with epilepsy with normal linguistic skills and in those with impaired language.


Subject(s)
Brain/pathology , Developmental Disabilities/etiology , Epilepsy/complications , Epilepsy/pathology , Language Development Disorders/etiology , Language Disorders/etiology , Adolescent , Child , Developmental Disabilities/pathology , Female , Humans , Imaging, Three-Dimensional , Language , Language Development Disorders/pathology , Language Disorders/pathology , Language Tests , Magnetic Resonance Imaging/methods , Male
6.
Ann N Y Acad Sci ; 1170: 324-32, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19686155

ABSTRACT

A key function of the sense of smell is to guide organisms towards rewards and away from dangers. However, because relatively few volatile chemicals in the environment carry intrinsic biological value, the meaning of an odor often needs to be acquired through learning and experience. The tremendous perceptual and neural plasticity of the olfactory system provides a design that is ideal for the establishment of links between odor cues and behaviorally relevant events, promoting appropriate adaptive responses to foods, friends, foes, and mates. This article describes recent human neuroimaging data showing the dynamic effects of olfactory perceptual learning and aversive conditioning on the behavioral discrimination of odor objects, with parallel plasticity and reorganization in the posterior piriform and orbitofrontal cortices. The findings presented here highlight the important role of experience in shaping odor object perception and in ensuring the human sense of smell achieves its full perceptual potential.


Subject(s)
Neuronal Plasticity , Odorants , Olfactory Perception , Avoidance Learning , Humans , Learning , Sensory Deprivation
7.
Epilepsia ; 50(11): 2466-72, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19624714

ABSTRACT

PURPOSE: This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age- and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables. METHODS: Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child. RESULTS: The CAE group had significantly smaller gray matter volumes of the left orbital frontal gyrus as well as both left and right temporal lobes compared to the age- and gender-matched children without epilepsy. In the CAE group these volumes were related to age, gender, ethnicity, and pregnancy complications but not to seizure, IQ, and psychopathology variables. In the group of children without epilepsy, however, the volumes were related to IQ. CONCLUSION: These findings suggest that CAE impacts brain development in regions implicated in behavior, cognition, and language. In addition to supporting the cortical focus theory of CAE, these findings also imply that CAE is not a benign disorder.


Subject(s)
Epilepsy, Absence/pathology , Frontal Lobe/pathology , Temporal Lobe/pathology , Age Factors , Atrophy/pathology , Brain/growth & development , Brain/pathology , Brain Mapping , Child , Child Behavior Disorders/diagnosis , Child Behavior Disorders/epidemiology , Cognition Disorders/diagnosis , Cognition Disorders/pathology , Electroencephalography , Epilepsy, Absence/diagnosis , Female , Functional Laterality/physiology , Humans , Intelligence Tests , Magnetic Resonance Imaging/statistics & numerical data , Neuropsychological Tests , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/epidemiology , Psychiatric Status Rating Scales , Sex Factors
8.
Epilepsy Behav ; 13(4): 593-9, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18652915

ABSTRACT

The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5-16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl's gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl's gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.


Subject(s)
Cognition Disorders/etiology , Epilepsy/complications , Epilepsy/pathology , Frontal Lobe/pathology , Temporal Lobe/pathology , Adolescent , Analysis of Variance , Brain Mapping , Case-Control Studies , Child , Child, Preschool , Cognition Disorders/pathology , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Psychiatric Status Rating Scales , Reproducibility of Results
9.
Epilepsy Behav ; 13(1): 131-8, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18440277

ABSTRACT

In this study, focus groups were used to examine parents' attitudes toward mental health services, use of mental health and other services, as well as service-related and other challenges encountered by parents of children with epilepsy. Both quantitative and qualitative analytic approaches were used to analyze the transcripts of 36 parents grouped into six focus groups by socioeconomic status (SES) (high, low) and ethnicity (African-American, Caucasian, Hispanic). The quantitative analyses demonstrated that, irrespective of SES and ethnicity, the parents were highly aware of their children's behavioral, emotional, and cognitive difficulties and the lack of knowledge about epilepsy among medical, educational, and mental health professionals. The higher-SES parents were significantly more concerned about inadequate educational services and the need for medical services, but less concerned about mental health and medical service use than the lower-SES parents. Insufficient knowledge about epilepsy and about services, parent emotional difficulties, and use of educational services differed significantly by ethnicity. The qualitative analyses highlighted the parents' concerns regarding misconceptions about epilepsy and the stigma toward mental health care among the African-American and Hispanic parents. These findings suggest the need for accessible and better-quality mental health, educational, and medical services for children with epilepsy irrespective of SES and ethnicity. They also underscore the importance of educating parents, service providers, and the general public about epilepsy.


Subject(s)
Attitude to Health , Epilepsy/psychology , Parent-Child Relations , Parents/psychology , Attitude to Health/ethnology , Ethnicity/psychology , Family Characteristics , Female , Health Services , Health Services Accessibility , Humans , Knowledge , Male , Social Class
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