The Impact of Neurodegeneration on Network Connectivity: A Study of Change Detection in Frontotemporal Dementia

The neural response to unpredictable auditory events is suggested to depend on frontotemporal interactions. We used magnetoencephalography in patients with behavioral variant frontotemporal dementia to study change detection and to examine the impact of disease on macroscopic network connectivity underlying this core cognitive function. In patients, the amplitudes of auditory cortical responses to predictable standard tones were normal but were reduced for unpredictable deviant tones. Network connectivity, in terms of coherence among frontal, temporal, and parietal sources, was also abnormal in patients. In the beta frequency range, left frontotemporal coherence was reduced. In the gamma frequency range, frontal interhemispheric coherence was reduced whereas parietal interhemispheric coherence was enhanced. These results suggest impaired change detection resulting from dysfunctional frontotemporal interactions. They also provide evidence of a rostro-caudal reorganization of brain networks in disease. The sensitivity of magnetoencephalography to cortical network changes in behavioral variant frontotemporal dementia enriches the understanding of neurocognitive systems as well as showing potential for studies of experimental therapies for neurodegenerative disease.

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Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia

10.1101/028027 ◽

2015 ◽

Cited By ~ 1

Author(s):

Jovana Belic ◽

Per Halje ◽

Ulrike Richter ◽

Per Petersson ◽

Jeanette Hellgren Kotaleski

Keyword(s):

Primary Motor Cortex ◽

Effective Connectivity ◽

Spectral Characteristics ◽

Low Frequency ◽

Frequency Range ◽

Gamma Frequency ◽

High Gamma ◽

Freely Behaving ◽

Beta Frequency ◽

Cross Frequency Coupling

We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the control state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz) across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

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Impact of Imaging and Cerebrospinal Fluid Biomarkers on Behavioral Variant Frontotemporal Dementia Diagnosis within a Late-Onset Frontal Lobe Syndrome Cohort

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000441023 ◽

2015 ◽

Vol 41 (1-2) ◽

pp. 16-26 ◽

Cited By ~ 7

Author(s):

Welmoed A. Krudop ◽

Annemiek Dols ◽

Cora J. Kerssens ◽

Niels D. Prins ◽

Christiane Möller ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Frontotemporal Dementia ◽

Frontal Lobe ◽

Fdg Pet ◽

Late Onset ◽

Behavioral Variant Frontotemporal Dementia ◽

Diagnostic Certainty ◽

18F Fdg ◽

Frontal Lobe Syndrome ◽

The Impact

Background: The criteria for behavioral variant frontotemporal dementia (bvFTD) incorporate MRI and [18F]-FDG-PET. Cerebrospinal fluid (CSF) analysis is merely advised for excluding Alzheimer's disease. Aims: We aimed to assess the impact of biomarkers on diagnostic certainty and contingent changes of bvFTD diagnosis within the clinically relevant neuropsychiatric differential diagnosis of subjects with a late-onset frontal lobe syndrome (LOF). Methods: We included 137 patients with LOF, aged 45-75 years, 72% males. Biomarker disclosure was considered contributing after any substantial difference in diagnostic certainty or a diagnostic change. Percentages of contributing biomarkers were compared between three major diagnostic groups (bvFTD, psychiatry, other neurological disorders). Certainty levels in stable diagnostic groups were compared to those with a diagnostic change. Results: Biomarkers contributed in 53, 60 and 41% of the LOF patients for MRI, [18F]-FDG-PET and CSF, respectively. Biomarkers changed the diagnosis in 14% of cases towards bvFTD and in 13% from bvFTD into an alternative. Those that changed had a lower level of a priori diagnostic certainty compared to stable diagnoses. Conclusion: Our study not only supports the widely accepted use of MRI and [18F]-FDG-PET in diagnosing or excluding bvFTD, but also shows that CSF biomarkers aid clinicians in the diagnostic process.

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