Quantitative proton magnetic resonance spectroscopy detects abnormalities in dorsolateral prefrontal cortex and motor cortex of patients with frontotemporal lobar degeneration

Abstract

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease of the frontal and temporal neocortex. The single most common pathology underlying FTLD is neuronal degeneration with ubiquitin-positive but tau-negative inclusions consisting of Tar DNA binding proteins (TDP-43). Inclusions containing TDP-43 in neurons are also the most common pathology underlying motor neuron disease (MND). The present study tested the hypothesis that abnormal metabolite patterns within the dorsolateral prefrontal cortex (DLPFC) as well as the motor cortex (MC) may be observed in FTLD patients without motor disorders, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six FTLD patients with cognitive damage and ten controls underwent multivoxel (1)H MRS. Absolute concentrations of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) were measured from the DLPFC, the MC and the parietal cortex (PC, an internal control). Statistical analyses were performed for group differences between FTLD patients and controls. Comparisons were also made across brain regions (PC and DLPFC; PC and MC) within FTLD patients. Significant reductions in NAA and Cr along with increased Cho and mI were observed in the DLPFC of FTLD patients compared to controls. Significantly lower NAA and higher Cho were also observed in the MCs of patients as compared to controls. Within the FTLD patients, both the MC and the DLPFC exhibited significantly decreased NAA and elevated Cho compared to the PC. However, only the DLPFC had significantly lower Cr and higher mI. Abnormal metabolite pattern from the MC supports the hypothesis that FTLD and MND may be closely linked.

Fig. 1

¹H MRSI grid overlaid over axial T2 weighted image demonstrating the location of voxels from DLPFC, MC and PC regions of the brain

Fig. 2

Representative spectra from different cortical regions of an FTLD patient demonstrating various metabolites. Numbers in parenthesis indicate the metabolite concentrations in mM

Fig. 3

Bar diagrams demonstrating comparison of mean metabolite concentration (mM units) between normal controls (Cont) and FTLD patients (FTLD) from DLPFC, MC and PC regions. Error bars indicate ± 1SD. *indicates statistical significance (p < 0.05)

Fig. 4

Bar diagrams showing variations in mean concentration (mM units) of metabolites from different cortical regions within FTLD patients. Error bars indicate ± 1SD. * indicates that results from ANOVA test are significant (p <0.05)