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Altered Neuronal Activity Topography Markers in the Elderly with Increased Atherosclerosis.

ABSTRACT: Background: Previously, we reported on vascular cognitive impairment (VCI) templates, consisting of patients with VCI associated with carotid stenosis (>60%) using a quantitative electroencephalographic (EEG) technique called neuronal activity topography (NAT). Here using the VCI templates, we investigated the hypothesis that internal carotid artery-intima-media thickness (ICA-IMT) is associated with EEG spectrum intensity (sNAT) and spectrum steepness (vNAT). Methods: A total of 221 community-dwelling elderly subjects were recruited. Four groups were classified according to quartiles of ICA-IMT as assessed by ultrasonography: control group A, normal (?0.9 mm); group B, mild atherosclerosis (1-1.1 mm); group C, moderate atherosclerosis (1.2-1.8 mm); and group D, severe atherosclerosis (?1.9 mm). EEG markers of power ratio index (PRI), and the binary likelihood of being in the VCI group vs. the that of being in control group A (sL _x:VCI-A , vL _x:VCI-A ) were assessed, respectively. Differences in mean total scores for PRI, sL _x:VCI-A , vL _x:VCI-A , between control group A and the other groups were compared using Dunnett's test, respectively. Results: The mean total scores of the PRI were 3.25, 3.00, 2.77, and 2.26 for groups A, B, C, and D, respectively. There was a significant decrease in the PRI in group D compared with group A (P = 0.0066). The mean total scores of the sL _x:VCI-A were -0.14, -0.11, -0.1, and -0.03 for groups A, B, C, and D, respectively. The sL _x:VCI-A in group D was significantly higher compared to that in group A (P < 0.0001). The mean total scores of the vL _x:VCI-A were -0.04,-0.01, 0.01, and 0.06 for group A, B, C, and D, respectively. The vL _x:VCI-A in group D and group C was significantly higher compared to that in group A, respectively (P < 0.0001, P = 0.02). Conclusion: Community-dwelling elderly subjects in the increased carotid atherosclerosis of ICA-IMT (?1.9 mm) were at greatest risk of an EEG change as assessed by NAT.

SUBMITTER: Shibata T

PROVIDER: S-EPMC5498522 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Altered Neuronal Activity Topography Markers in the Elderly with Increased Atherosclerosis.

Shibata Takashi T Musha Toshimitu T Kosugi Yukio Y Kubo Michiya M Horie Yukio Y Kuwayama Naoya N Kuroda Satoshi S Hayashi Karin K Kobayashi Yohei Y Tanaka Mieko M Matsuzaki Haruyasu H Nemoto Kiyotaka K Asada Takashi T

Frontiers in aging neuroscience 20170706

<b>Background:</b> Previously, we reported on vascular cognitive impairment (VCI) templates, consisting of patients with VCI associated with carotid stenosis (>60%) using a quantitative electroencephalographic (EEG) technique called neuronal activity topography (NAT). Here using the VCI templates, we investigated the hypothesis that internal carotid artery-intima-media thickness (ICA-IMT) is associated with EEG spectrum intensity (sNAT) and spectrum steepness (vNAT). <b>Methods:</b> A total of 2 ...[more]

PMID: 28729833

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Project description:ImportanceIn schizophrenia, working memory deficits appear to reflect abnormalities in the generation of gamma oscillations in the dorsolateral prefrontal cortex. The generation of gamma oscillations requires the phasic excitation of inhibitory parvalbumin-containing interneurons. Thus, gamma oscillations depend, in part, on the number of synaptic glutamate receptors on parvalbumin interneurons. However, little is known about the molecular factors that regulate glutamate receptor-mediated excitation of parvalbumin interneurons in schizophrenia.ObjectiveTo quantify in individuals with schizophrenia the expression of immediate early genes (NARP, ARC, and SGK1) regulating glutamate synaptic neurotransmission.Design, setting, and participantsPostmortem brain specimens (n = 206) were obtained from individuals with schizophrenia, bipolar disorder, or major depressive disorder and from well-matched healthy persons (controls). For a study of brain tissue, quantitative polymerase chain reaction, in situ hybridization, or microarray analyses were used to measure transcript levels in the dorsolateral prefrontal cortex at gray matter, laminar, and cellular levels of resolutions. This study was conducted between January 1, 2013, and November 30, 2014.Main outcomes and measuresExpression levels for NARP, ARC, and SGK1 messenger RNA (mRNA) were compared between specimens from individuals with schizophrenia and controls. Diagnostic specificity was assessed by quantifying NARP mRNA levels in specimens from individuals with mood disorders.ResultsBy quantitative polymerase chain reaction, levels of NARP mRNA were significantly lower by 25.6% in specimens from individuals with schizophrenia compared with the controls (mean [SD], 0.036 [0.018] vs 0.049 [0.015]; F1,114 = 21.0; P < .001). Levels of ARC (F1,112 = 0.93; P = .34) and SGK1 (F1,110 = 2.52; P = .12) were not significant. These findings were supported by in situ hybridization (NARP; individuals with schizophrenia vs controls: 40.1% lower [P = .003]) and microarray analyses (NARP; individuals with schizophrenia vs controls: 12.2% lower in layer 3 [P = .11] and 14.6% lower in layer 5 pyramidal cells [P = .001]). In schizophrenia specimens, NARP mRNA levels were positively correlated with GAD67 mRNA (r = 0.55; P < .001); the expression of GAD67 mRNA in parvalbumin interneurons is activity dependent. The NARP mRNA levels were also lower than healthy controls in bipolar disorder (-18.2%; F1,60 = 11.39; P = .001) and major depressive disorder (-21.7%; F1,30 = 5.36; P = .03) specimens, especially those from individuals with psychosis. In all 3 diagnostic groups, NARP mRNA levels were positively correlated (all r ≥ 0.53; all P ≤ .02) with somatostatin mRNA, the expression of which is activity dependent.Conclusions and relevanceGiven the role of NARP in the formation of excitatory inputs to parvalbumin (and perhaps somatostatin) interneurons, our findings suggest that lower NARP mRNA expression contributes to lower excitatory drive onto parvalbumin interneurons in schizophrenia. This reduced excitatory drive may lead to lower synthesis of γ-aminobutyric acid in these interneurons, contributing to a reduced capacity to generate the gamma oscillations required for working memory.

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Altered Neuronal Activity Topography Markers in the Elderly with Increased Atherosclerosis.

Publications

Altered Neuronal Activity Topography Markers in the Elderly with Increased Atherosclerosis.

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