Introduction: Using dual-site transcranial magnetic stimulation (dsTMS), the effective functional connectivity between the primary motor cortex (M1) and adjacent brain areas can be investigated, such as the intrahemispheric dorsal premotor cortex (PMd) – M1 interaction. However, stimulating two brain regions in close proximity (e.g., ±2.3 cm for intrahemispheric PMd–M1) is subject to considerable spatial and technical restrictions.Objective/Hypothesis: Combining two overlapping standard figure-of-eight coils in a novel dsTMS setup potentially offers a solution for probing intrahemispheric interactions of adjacent brain regions.Methods: After a technical evaluation of its magnetic fields, this novel dsTMS setup was tested in vivo (n = 23) by applying a short-interval intracortical inhibition protocol (SICI). In addition, the dsTMS setup was used to investigate the intrahemispheric left PMd–M1 interaction (inter-stimulus interval: 6 ms, distance: 2.12 cm), and the induced E-fields were modeled using SimNIBS.Results: The technical evaluation yielded no major alterations of the magnetic fields due to coil overlap. In vivo, the setup could reliably elicit SICI. In addition, investigating intrahemispheric PMd–M1 interactions was feasible, with conditioning PMd at an intensity of 75% resting motor threshold 6 ms prior to the test stimulus to M1 resulting in modulation of M1 output.Conclusion: The presented dsTMS setup provides a novel way to stimulate two adjacent brain regions with fewer technical and spatial limitations than previous attempts. This enables more accurate and repeatable targeting of brain regions in close proximity and can facilitate innovation in the field of effective functional connectivity.
Interlimb coordination deteriorates due to aging. Due to its ubiquity in daily life, a greater understanding of the underlying neurophysiological changes is required. Here, we combined electroencephalography time-frequency spectral power and functional connectivity analyses to provide a comprehensive overview of the neural dynamics underlying the age-related deterioration of interlimb coordination involving all four limbs. Theta, alpha and beta oscillations in the frontal, central and parietal regions were analyzed in twenty younger (18–30 years) and nineteen older adults (65–78 years) during a complex interlimb reaction time task. Reaction time was significantly higher in older adults across all conditions, and the discrepancy between both age groups was largest in the most complex condition. Older adults demonstrated enhanced beta event-related desynchronization (i.e., the attenuation of beta power), which further increased along with task complexity and was positively linked to behavioral performance. Theta functional connectivity between frontal, central and parietal regions generally increased with movement complexity, irrespective of age group. Mainly frontoparietal alpha band functional connectivity was reduced in older adults compared to younger adults. Overall, spectral results suggest that enhanced beta desynchronization in older adults reflects a successful compensatory mechanism to cope with increased difficulty during complex interlimb coordination. Functional connectivity results indicate that theta and alpha band connectivity are prone to age and task-related modulations in a frequency specific manner. Future work could target these spectral and functional connectivity dynamics through non-invasive brain stimulation to potentially improve interlimb coordination in older adults.Funding Information: This study was supported by the Special Research Fund (BOF) of Hasselt University (BOF20KP18). Declaration of Interests: None.Ethics Approval Statement: All participants provided written informed consent. The study (B1152020000017) was approved by the local Ethical Committee of the University of Hasselt (Belgium) and was in accordance with the Declaration of Helsinki and its amendments (World Medical Association, 1964, 2008).
Background: Type 2 diabetes (T2DM) affects brain structure and function, and is associated with an increased risk of dementia and mild cognitive impairment. It is known that exercise training has a beneficial effect on cognition and the brain, at least in healthy people, but the impact of exercise training on cognition and the brain remains to be fully elucidated in patients with T2DM. Methods: This paper systematically reviews studies that evaluate the effect of exercise training on cognition in T2DM, and aims to indicate the most beneficial exercise modality for improving or preserving cognition in this patient group. In addition, the possible physiological mediators and targets involved in these improvements are narratively described in the second part of this review. Papers published up until October 2023 were searched by means of the electronic database PubMed. Studies directly investigating the effect of any kind of exercise training on the brain or cognition in patients with T2DM, or animal models thereof, were included, with the exception of human studies assessing cognition only at one time point, and studies combining exercise training with other interventions (e.g. dietary changes, cognitive training, etc.). Results: For the systematic part of the review, 24 papers were found to be eligible. 20 out of 24 papers (83.3%) showed a significant positive effect of exercise training on cognition in T2DM, of which four studies only showed a moderate significant effect. Four papers (16.7%) did not show a significant effect of exercise on cognition in T2DM, but two of them did show a positive trend. Similar effects were found for resistance and endurance exercise, with both possibly requiring a minimal intensity to reach cognitive improvement. In addition, BDNF, lactate, leptin, adiponectin, GSK3β, GLP-1, the AMPK/SIRT1 pathway, and the PI3K/Akt pathway were identified as plausible mediators directly from studies investigating the effect of exercise training on the brain in T2DM. Conclusion: Overall, exercise training beneficially affects cognition and the brain in T2DM, with resistance and endurance exercise having similar effects. However, additional studies comparing the effect of different exercise intensities are needed to determine the optimal exercise intensity for cognitive improvement. Furthermore, we were able to define several mediators involved in the effect of exercise training on cognition in T2DM, but further research is necessary to unravel the entire process.
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