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Christine Fennema-Notestine

Publications and source records attributed to Christine Fennema-Notestine.

10 recordsLinked to original sources
PubMed2026

Predicted brain-regional gene expression patterns in individuals living with Alzheimer's disease.

Studying brain gene expression in Alzheimer's Disease (AD) remains difficult as postmortem brain is difficult to access, cannot be used to guide donor treatment, may be confounded by environmental factors before and after death, and is difficult to link to early AD states or disease progression. To circumvent these limitations, several studies have tested blood transcriptome biomarkers for AD. However, gene-expression levels in the blood have limited correlation with those in the brain. To evaluate the potential of monitoring Alzheimer's progression with peripheral data, we used transcriptome-imputation to identify brain-region-specific AD-associated gene-expression differences in cohorts with blood-based transcriptome data. This approach provides a high-resolution image of AD-associated molecular differences in the brains of individuals actively living with disease. We analyzed eight AD studies (777 AD cases, 779 cognitively unimpaired controls), imputing transcriptomes in 10 brain regions via the Brain Gene Expression and Network Imputation Engine (BrainGENIE). Hundreds of differentially expressed genes (DEGs) associated with AD were identified in nine brain regions, with anterior cingulate cortex and amygdala showing the most differential expression. AD-associated genes were enriched in pathways such as proteostasis, mitochondrial dysfunction, and immune activation. We observed significant yet moderate concordance between imputed AD-associated changes and those directly measured in the dorsolateral prefrontal cortex and cerebellum. These transcriptomic changes can guide future in vitro studies focused on pathogenesis or be targets of novel therapeutic development. In conclusion, we demonstrated the scope and utility of brain expression imputation from the peripheral transcriptome, laying the groundwork for biomarker discovery and prospective AD studies.

Alzheimer Disease↗
PubMed2006

Quantitative evaluation of automated skull-stripping methods applied to contemporary and legacy images: effects of diagnosis, bias correction, and slice location.

Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143-155); 3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [2004] Neuroimage 22:1060-1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [1997] IEEE Trans Med Imag 16:41-54; Shattuck et al. [2001] Neuroimage 13:856-876) to manually stripped images. The methods were applied to uncorrected and bias-corrected datasets; Legacy and Contemporary T1-weighted image sets; and four diagnostic groups (depressed, Alzheimer's, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation-Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1-weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies.

Adult↗
PubMed2005

Does amygdalar perfusion correlate with antidepressant response to partial sleep deprivation in major depression?

This study used functional MRI (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: (1) baseline perfusion in right and left amygdalae will be greater in responders than in nonresponders; (2) following partial sleep deprivation (PSD), perfusion in responders' right and left amygdalae would decrease. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD. Baseline bilateral amygdalar perfusion was greater in responders than nonresponders. Clusters involving both amygdalae decreased from baseline to PSD specifically in responders. Right amygdalar perfusion diverged with PSD, increasing in nonresponders and decreasing in responders. These novel amygdalar findings are consistent with the overarousal hypothesis of SD as well as other functional imaging studies showing increased baseline amygdalar activity in depression and decreased amygdalar activity with remission or antidepressant medications.

Adolescent↗
PubMed2005

Effects of methamphetamine dependence and HIV infection on cerebral morphology.

OBJECTIVE: The authors examined the separate and combined effects of methamphetamine dependence and HIV infection on brain morphology. METHOD: Morphometric measures obtained from magnetic resonance imaging of methamphetamine-dependent and/or HIV-positive participants and their appropriate age- and education-matched comparison groups were analyzed. Main effects of age, HIV infection, methamphetamine dependence, and the interactions of these factors were examined in analyses of cerebral gray matter structure volumes. RESULTS: Independent of the effect of age, HIV infection was associated with reduced volumes of cortical, limbic, and striatal structures. There was also some evidence of an interaction between age and HIV infection such that older HIV-positive participants suffered disproportionate loss. Methamphetamine dependence was surprisingly associated with basal ganglia and parietal cortex volume increases, and in one of these structures-the nucleus accumbens-there appeared to be a larger effect in younger methamphetamine abusers. Neurocognitive impairment was associated with decreased cortical volumes in HIV-positive participants but with increased cortical volumes in methamphetamine-dependent participants. CONCLUSIONS: These results suggest significant brain structure alterations associated with both HIV infection and methamphetamine dependence. The regional patterns of the changes associated with these factors were distinct but overlapping, and the effects on brain volumes were opposing. Although the results of the present study provide little information about the specific mechanisms leading to the unexpected methamphetamine effects, they may be related to glial activation or neuritic growth, both of which have been associated with methamphetamine exposure in animal studies. These results have implications for the interpretation of brain morphological findings in methamphetamine-dependent, HIV-positive individuals, a group whose numbers are unfortunately increasing.

Adult↗
PubMed2005

Bilingualism affects picture naming but not picture classification.

Bilinguals named pictures in their dominant language more slowly (and with more errors) than did monolinguals. In contrast, bilinguals named the same pictures as quickly as did monolinguals on the fifth presentation (in Experiment 2) and classified them (as human made or natural) as quickly and accurately as did monolinguals (in Experiment 1). In addition, bilinguals retrieved English picture names more quickly if they knew the name in both Spanish and English (on the basis of a translation test that bilinguals completed after the timed tasks), and monolingual response times for the same materials suggested that this finding was not obtained simply because names that were easier to translate were easier in general. These findings suggest that bilinguals differ from monolinguals at a postconceptual processing level, that implicit activation of lexical representations in the nontarget language can facilitate retrieval in the target language, and that being bilingual is analogous to having a lexicon full of lower frequency words, relative to monolinguals.

Adolescent↗
PubMed2004

Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss.

BACKGROUND: In the absence of significant opportunistic infection, the most common alterations on neuroimaging in the brains of patients with AIDS include enlarged cerebrospinal fluid spaces, white-matter loss, volume loss in striatal structures, and white-matter signal abnormalities. Although previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them. OBJECTIVE: To examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV) encephalitis and neurodegeneration. DESIGN: Morphometric analysis of magnetic resonance imaging in seropositive cases with matched seronegative controls, and the correlation of these volumes to neuropathological measures in autopsied seropositive cases. SETTING: University of California, San Diego, HIV Neurobehavioral Research Center. SUBJECTS: Twenty-one seropositive subjects studied at autopsy and 19 seronegative cases. MAIN OUTCOME MEASURES: In vivo structural magnetic resonance imaging data analyzed by quantitative methods, with comparison of volumes from magnetic resonance imaging and neuropathological data from autopsies. RESULTS: The HIV-seropositive subjects demonstrated cerebrospinal fluid increases relative to seronegative controls. These increases were associated with a significant decrease in the volumes of cerebral and cerebellar white matter, caudate nucleus, hippocampus, and, to a lesser extent, cerebral cortex. The volume of cerebral white-matter tissue with elevated signal was also increased. This signal elevation in white matter predicted the autopsy diagnosis of HIV encephalitis, as well as the extent of dendritic loss as assessed by analysis of microtubule-associated protein 2 immunoreactivity. CONCLUSIONS: White-matter and cortical damage resulting from HIV disease are closely related. In vivo magnetic resonance imaging may be a valuable adjunct in the assessment of patients at risk for developing HIV encephalitis.

Adult↗
PubMed2003

More "mapping" in brain mapping: statistical comparison of effects.

The term "mapping" in the context of brain imaging conveys to most the concept of localization; that is, a brain map is meant to reveal a relationship between some condition or parameter and specific sites within the brain. However, in reality, conventional voxel-based maps of brain function, or for that matter of brain structure, are generally constructed using analyses that yield no basis for inferences regarding the spatial nonuniformity of the effects. In the normal analysis path for functional images, for example, there is nowhere a statistical comparison of the observed effect in any voxel relative to that in any other voxel. Under these circumstances, strictly speaking, the presence of significant activation serves as a legitimate basis only for inferences about the brain as a unit. In their discussion of results, investigators rarely are content to confirm the brain's role, and instead generally prefer to interpret the spatial patterns they have observed. Since "pattern" implies nonuniform effects over the map, this is equivalent to interpreting results without bothering to test their significance, a practice most of the experimentally-trained would eschew in other contexts. In this review, we appeal to investigators to adopt a new standard of data presentation that facilitates comparison of effects across the map. Evidence for sufficient effect size difference between the effects in structures of interest should be a prerequisite to the interpretation of spatial patterns of activation.

Brain Mapping↗
PubMed2003

Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: a structural MRI study.

The very high sensitivity and specificity of odor identification tasks in discriminating between Alzheimer's patients and normals suggests that they reflect the presence of underlying neuropathology. Significant neuropathological changes are seen in areas critical to processing olfactory information, even in the early stages of Alzheimer's disease (AD). The current study was designed to investigate whether performance on olfactory tasks (odor threshold and odor identification) was related to volumetric MRI measures of mesial temporal areas central to olfactory information processing and important in the neuropathology of AD. Participants were 8 male and 5 female patients with probable AD, and 10 male and 12 female normal age-matched controls, diagnosed at the UCSD Alzheimer's Disease Research Center. The study investigated correlations between volumetric measures of hippocampus, the parahippocampal gyrus and the amygdala, and the psychophysical measures of olfactory function. Robust relationships were observed between mesial temporal lobe volumes and olfactory functional measures. The finding of a strong relationship between left hippocampal volume and performance on the odor identification task (r = .85) is compatible with a left-hemisphere superiority for verbally mediated olfactory tasks. The findings suggest a neural substrate for the breakdown in functional performance on verbally mediated odor identification tasks in Alzheimer's disease and suggest the utility of quantitative MRI measures and psychophysical performance in the assessment of AD. These results support the potential clinical utility of inclusion of odor identification tests in diagnostic batteries for detecting AD.

Aged↗
PubMed2002

Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder.

BACKGROUND: To examine neuroanatomical morphometry in adult female victims of intimate partner violence with and without posttraumatic stress disorder. METHODS: Seventeen nonvictimized comparison subjects and 22 victims of intimate partner violence, 11 with and 11 without posttraumatic stress disorder, were studied. Using quantitative magnetic resonance imaging, three mesial temporal lobe areas were measured: hippocampus, amygdala, and parahippocampal gyrus. Additionally, whole brain morphometry provided fluid, gray, and white matter volumes of the cortex and cerebellum for exploratory analyses. Relationships of morphometric measures to symptoms, abuse history, and neuropsychological function were examined. RESULTS: Intimate partner violence subjects with posttraumatic stress disorder did not demonstrate significantly smaller hippocampal or other mesial temporal lobe volumes. Overall, intimate partner violence subjects had smaller supratentorial cranial vaults and smaller frontal and occipital gray matter volumes relative to nonvictimized comparison subjects. Supratentorial cranial vault volume was negatively correlated with severity of childhood physical abuse, but not with intimate partner violence or posttraumatic stress disorder severity. Trails B performance was negatively correlated with frontal gray matter volume. CONCLUSIONS: These findings are inconsistent with prior reports of smaller hippocampal volumes in patients with posttraumatic stress disorder. Rather, the findings point to cerebral abnormalities that may reflect the influence of early trauma on neurodevelopmental processes or denote brain morphometric characteristics of persons at increased risk for serious psychosocial adversity.

Adult↗