Correlation between Topographic N400 Anomalies and Reduced Cerebral Blood Flow in the Anterior Temporal Lobes of Patients with Dementia

Abstract

In Alzheimer's disease (AD) patients, episodic memory impairments are apparent, yet semantic memory difficulties are also observed. While the episodic pathology has been thoroughly studied, the neurophysiological mechanisms of the semantic impairments remain obscure. Semantic dementia (SD) is characterized by isolated semantic memory deficits. The present study aimed to find an early marker of mild AD and SD by employing a semantic priming paradigm during electroencephalogram recordings. Event-related potentials (ERP) of early (P1, N1) and late (N400) word processing stages were obtained to measure semantic memory functions. Separately, baseline cerebral blood flow (CBF) was acquired with arterial spin labeling. Thus, the analysis focused on linear regressions of CBF with ERP topographical similarity indices in order to find the brain structures that showed altered baseline functionality associated with deviant ERPs. All participant groups showed semantic priming in their reaction times. Furthermore, decreased CBF in the temporal lobes was associated with abnormal N400 topography. No significant CBF clusters were found for the early ERPs. Taken together, the neurophysiological results suggested that the automatic spread of activation during semantic word processing was preserved in mild dementia, while controlled access to the words was impaired. These findings suggested that N400-topography alterations might be a potential marker for the detection of early dementia. Such a marker could be beneficial for differential diagnosis due to its low cost and non-invasive application as well as its relationship with semantic memory dysfunctions that are closely associated to the cortical deterioration in regions crucial for semantic word processing.

Functional connectivity in BOLD and CBF data: Similarity and reliability of resting brain networks

“…This finding has implications for rs-fcMRI studies in clinical populations. Specifically, the capability for reliable CBF quantification becomes crucial in patient studies where pathophysiology (Alsop et al, 2010; Detre et al, 2012; Detre et al, 2009; Grieder et al, 2013) or medication (Chen et al, 2011; Wang et al, 2011) is likely to alter global or regional CBF. In support for this notion, the major RBNs exhibit consistent, systematic differences in baseline CBF levels, regardless whether correction for global CBF is performed or not.…”

Diverging Progression of Network Disruption and Atrophy in Alzheimer’s Disease and Semantic Dementia

“…In a recent study, part of this sample’s anatomical MRI data had been published [23]. As can be seen in Table 1, the SD group consisted of only 6 patients.…”

Discovering EEG resting state alterations of semantic dementia

“…Following this, an opportunity to complement an attempt to predict SD based on resting-state EEG microstates could be to additionally collect N400-ERPdata of semantic priming. Grieder et al (2013) showed recently that an altered N400-topography separated well between healthy controls and patients with SD or AD. Although this ERP-marker was not specific for SD alone, a deviant N400-topography together with the presence of resting-state EEG microstate class E (instead of microstate class C) might ameliorate the diagnosis of SD.…”

“…This assumption is based on the fact firstly that brain atrophy in SD differs from AD, which should lead to altered neuronal generator configurations. Secondly, patients with SD show a more severe semantic memory deficit as patients with AD, which has been found to alter the topography of ERP microstates in relation to a semantic task (Grieder et al, 2013). However, no specific hypotheses were made on which parameter was expected to be altered in SD compared with the control groups, as no data was available in the literature for this purpose.…”

“…correct vs. incorrect sentences, related vs. unrelated word pairs) were expressed as differences in microstate onset, offset, duration, number of presence, and topography (Brandeis et al, 1995, Wirth et al, 2007, Grieder et al, 2012. Moreover, microstate differences were found between patient and control groups in a study that investigated alterations of brain activity in patients with AD and SD (Grieder et al, 2013). These results thus demonstrate that EEG microstate analysis is a powerful tool for disentangling the brain dynamics that are related to external stimuli as well as cognitive disorders.…”