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

Article type: Research Article

Authors: Grieder, Matthiasa; * | Crinelli, Raffaella M.b | Jann, Kaya; c | Federspiel, Andreaa | Wirth, Mirankad | Koenig, Thomasa | Stein, Mariaa | Wahlund, Lars-Olofb | Dierks, Thomasa

Affiliations: [a] Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland | [b] Karolinska Institute, Department NVS, Division of Clinical Geriatrics, Stockholm, Sweden | [c] Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA | [d] Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA

Correspondence: [*] Correspondence to: Matthias Grieder, PhD, Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, Bolligenstrasse 111, CH-3000 Bern 60, Switzerland. Tel.: +41 319328351; Fax: +41 319309961; E-mail: grieder@puk.unibe.ch.

Keywords: Alzheimer's disease, cerebral blood flow, event-related potential, magnetic resonance imaging, N400, semantic dementia, semantic memory, volumetry

DOI: 10.3233/JAD-121690

Journal: Journal of Alzheimer's Disease, vol. 36, no. 4, pp. 711-731, 2013

Accepted 11 April 2013
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Published: 5 August 2013
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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.

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