Publications

Several procedures have been developed to enhance the rehabilitation of stroke patients. However, most techniques struggle to promote sustained recovery in the months following the treatment. Therefore, it is essential to understand the mechanisms that can be harnessed during treatment to potentiate retention of benefits and sustained recovery. While stroke patients often suffer from thalamocortical dysrhythmia (TCD), a perturbation in alpha (8-13 Hz) rhythms caused by decreased excitation in the cortico-thalamic projections, the functional relevance of TCD in stroke patients is not yet clear. We propose that TCD can be counteracted by combining focal stimulation of the motor cortex with virtual-reality (VR) based rehabilitation, which engages distributed networks associated with goal-oriented behavior. Critically, we investigate whether this can be the key to promoting sustained recovery in stroke patients. We compare thalamocortical rhythms and behavioral recovery in patients receiving Sham and bilateral tDCS stimulation of the motor cortex during therapy with the Rehabilitation Gaming System (RGS). Our results reveal that patients in the tDCS group show a sustained recovery in all clinical scales up to three months post-treatment, as opposed to the Sham group. Furthermore, we demonstrate that the slowing down of alpha rhythms can be counteracted by transcranial direct-current stimulation (tDCS), with a particular role for enhancing the excitability of parietal areas. That said, we found no correlation between changes in alpha rhythms and motor recovery. On one hand, our findings suggest that sustained recovery can be potentiated by tDCS-enhanced VR-based rehabilitation. On the other hand, enhancing the excitability of parietal areas while recruiting brain networks associated with goal-oriented behavior can successfully counteract TCD, even though this is likely not the main driver of sustained motor recovery.

JTD Keywords: Activation, Alpha rhythms, Deep brain-stimulation, Direct-current stimulation, Excitatory-inhibitory balance, Guidelines, Human thalamus, Involvement, Motor recovery, Quality-of-life, Rehabilitation, Sensitivity, Stroke, Transcranial direct-current stimulation

Alzheimer’s disease (AD) and other tauopathies are common neurodegenerative diseases in older adults; in contrast, abnormal tau deposition in neurons and glial cells occurs only exceptionally in children. Sarkosyl-insoluble fractions from sporadic AD (sAD) containing paired helical filaments (PHFs) were inoculated unilaterally into the thalamus in newborn and three-month-old wild-type C57BL/6 mice, which were killed at different intervals from 24 h to six months after inoculation. Tau-positive cells were scanty and practically disappeared at three months in mice inoculated at the age of a newborn. In contrast, large numbers of tau-positive cells, including neurons and oligodendrocytes, were found in the thalamus of mice inoculated at three months and killed at the ages of six months and nine months. Mice inoculated at the age of newborn and re-inoculated at the age of three months showed similar numbers and distribution of positive cells in the thalamus at six months and nine months. This study shows that (a) differences in tau seeding between newborn and young adults may be related to the ratios between 3Rtau and 4Rtau, and the shift to 4Rtau predominance in adults, together with the immaturity of connections in newborn mice, and (b) intracerebral inoculation of sAD PHFs in newborn mice does not protect from tau seeding following intracerebral inoculation of sAD PHFs in young/adult mice.

JTD Keywords: alzheimer's disease, alzheimer-disease, alzheimer’s disease, expression, mouse tau, neurofibrillary tangles, newborn, pathological tau, propagation, protein-tau, spread, tau seeding and spreading, thalamus, transgenic mice, Alzheimer disease, Alzheimer’s disease, Animals, Brain, Mice, Mice, inbred c57bl, Mice, transgenic, Neurofibrillary tangles, Newborn, Paired helical filaments, Tau proteins, Tau seeding and spreading, Tauopathies, Thalamus