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Jakobsen, A.

Publications and source records attributed to Jakobsen, A..

3 recordsLinked to original sources

The Rhythm of Normality: A Comprehensive Normative Database for TMS-EEG Metrics with Reliability Characterization

BackgroundTranscranial Magnetic Stimulation combined with electroencephalography (TMS-EEG) offers unique insights into cortical excitability and connectivity, yet current analyses are primarily limited to group-level inferences with little validation of individual reliability and feature redundancy. ObjectiveTo construct a comprehensive, open-access, and reliable normative dataset of TMS-EEG features that enables individual-level comparison MethodsWe aggregated TMS-EEG data recorded over the primary motor cortex (M1) from 164 healthy adults (30.8 {+/-} 9.8 years; 88 female) across nine studies using harmonized acquisition and preprocessing pipelines. Reliability analysis was conducted on a test-retest subset (N=57) for 968 extracted features, evaluating systematic bias, absolute error, and relative reliability (Intraclass Correlation Coefficient categorized by the lower bound of the 95% confidence interval). Additionally, feature clustering was performed to quantify redundancy and correlations across the high-dimensional feature space. We then established normative distributions and developed an online benchmarking platform. ResultsReliability analyses (N=57) of the high-dimensional feature set revealed that 525 out of 968 features (54.3%) met at least moderate reliability standards (ICC lower bound > 0.5). Cluster analysis indicated substantial redundancy among metrics, with three distinct clusters having a moderate-to-high internal correlation (|r| = 0.64, 0.48, 0.39, respectively). Finally, normative data from the database identified abnormal results in a test patient, supporting the feasibility of individual-level classification in an open-science framework. ConclusionsHarmonization of data acquisition and analysis pipelines led to the development of a reliable normative M1 TMS-EEG reference. This publicly available resource provides a validated tool for future individual-level classifications and an open platform for ongoing community contributions.

neuroscience↗

REDUCED ALPHA-BAND PHASE COHERENCE AND CORTICAL COMPLEXITY IN FIBROMYALGIA: A TMS-EEG EXPLORATORY STUDY

ObjectivesCortico-spinal excitability of the primary motor cortex (M1) is reduced in fibromyalgia, and repetitive transcranial magnetic stimulation (TMS) targeting M1 normalizes these changes and relieves symptoms. TMS combined with electroencephalography (TMS-EEG) allows the measurement of M1 excitability and its connectivity to other regions, which may help clarify neurophysiological effects in fibromyalgia. We assessed cortical excitability, oscillatory activity, and complexity in individuals with fibromyalgia compared to pain-free healthy controls. MethodsGlobal and local mean field power, peak-to-peak amplitude, event-related spectral perturbation, intertrial coherence (ITC), natural frequency, and perturbational complexity index (PCIst) of the EEG response after left-M1 TMS were compared between groups (n=18 fibromyalgia; n=15 controls). Pain intensity, interference, relief of current therapy, mood, and quality of life were assessed in individuals with fibromyalgia. ResultsCompared with controls, individuals with fibromyalgia showed a reduction in the alpha-band ITC in middle and right parieto-occipital areas (P<0.05). Middle-parieto-occipital ITC negatively correlated with reported pain relief (rho=-0.552, p=0.019). The PCIst was lower in fibromyalgia compared with controls (P<0.01) and correlated with higher pain interference in general activity (rho=-0.486, p=0.042). ConclusionIndividuals with fibromyalgia showed abnormal cortical connectivity compared with asymptomatic controls. SignificanceTMS-EEG measurements may provide insights on brain connectivity relevant for therapy.

neuroscience↗

Developing single molecule methods for measuring the pathway proteins ERK, AKT, cyclin d and p70s6k in localized colon cancer in relation to mutation status

BackgroundThe aim of this study was to quantify the intracellular pathway proteins ERK, AKT, cyclin d and p70s6k in localized colon cancer tissue to investigate the possible prognostic values and the ability to be used as screening markers for upstream mutations.\n\nMethodsColon cancer tissue and autologous reference tissue were collected from 176 patients who underwent surgery for colon cancer. Assays for quantifying ERK, AKT, cyclin d and p70s6k proteins were developed using single molecule array (Simoa). KRAS/BRAF/PIK3CA mutation status was determined using droplet digital PCR.\n\nResultsPatients with BRAF mutations had decreased concentrations of ERK (p=0.0002), AKT (p=0.00004) and cyclin d (p=0.001) while no significant differences were found between patients with KRAS mutations and Wild type (Wt) patients. None of the investigated protein concentrations were associated with disease free survival or overall survival, if including all patients. However, when stratifying according to mutation status, significant correlations to overall survival were seen for patients with BRAF mutations and AKT (p=0.003) or ERK (p=0.046) and for patients with KRAS mutations and p70s6k (p=0.04). Furthermore, the combination of genetic mutations, stage 2 disease, and all of the investigated pathway proteins showed significant correlations to overall survival.\n\nConclusionsThere is a strong correlation between pathway protein concentrations and mutational BRAF status. Overall survival in colon cancer patients depend both on gene mutation status and pathway protein concentrations. As significant correlations were found between BRAF mutations and ERK, AKT and cyclin d, concentration measurements of these pathway proteins might be useful as screening for upstream mutations.

biochemistry↗