Cognitive decline and dementia have become important public health issues in our time as medical science has increased lifespan and our society becomes progressively older. A great deal of the cognitive decline due to aging can be explained by decline in working memory (WM), a mental function central to cognition in which aging deficits appear almost universally. Attempts to use WM training to increase WM ability in older adults has had some success, but the transfer of performance enhancements caused by this training to other cognitive skills is controversial. Another intervention that shows much promise is noninvasive stimulation of cerebral cortex using transcranial magnetic stimulation (TMS), which has been shown to increase performance in many cognitive tasks. In previous work we developed a paradigm using fMRI-guided TMS in which we identified a cortical network sensitive to the effects of sleep deprivation and to WM and targeted it with TMS, almost completely remediating the deficits in WM performance caused by the sleep deprivation, and whose effects outlasted TMS stimulation by at least a day. We then applied this paradigm to healthy young and older adults, to assess the effects of aging on WM. Stimulation to the left lateral occipital complex, a region involved in the maintenance of visual information, enhanced WM performance in both young and older groups. Here we propose to use our fMRI-guided TMS enhancement paradigm to stimulate dorsolateral prefrontal cortex (DLPFC), a region involved not only in the maintenance of items in WM, but also in their manipulation, in order to create WM performance enhancements that will be long lasting and that will transfer to other cognitive tasks as well. This will be achieved through three studies. In the first we will stimulat both old and young healthy adults while they perform different WM tasks that will increasingly engage DLPFC in order to demonstrate enhancement of WM performance that is greater in the older adults. In the second and third studies, older adults will receive active or sham TMS over two weeks of daily sessions while they perform the WM tasks. In the second study, we hope to demonstrate that the cumulative effect of multiple TMS sessions, in tandem with the synergistic effects of simultaneous TMS + WM training, create WM performance enhancements greater than those found with WM training alone, whose effects are long-lasting, continuing a month following the course of TMS sessions. In the third, we will investigate whether the WM enhancements generated by the two- weeks of TMS sessions will generalize to other cognitive tasks. Success of these studies will provide proof in principle for long-lasting, transferable effects of TMS in remediating WM and more general cognitive deficits due to aging, and point to a possible non-invasive brain stimulation therapy for cognitive decline in healthy aging and in dementia.
Cognitive decline and dementia have become important public health issues in our time as medical science has increased lifespan and our society becomes progressively older. All individuals experience some measure of cognitive decline as they age, and many elderly individuals consider cognitive decline the most debilitating aspect of aging. This study will examine methods by which noninvasive brain stimulation could remediate cognitive deficits caused by aging in a long-lasting way that will also cause improvement in other cognitive abilities, opening up development of brain stimulation therapies for cognitive decline in aging.
| Smith, J Evan; Peterchev, Angel V (2018) Electric field measurement of two commercial active/sham coils for transcranial magnetic stimulation. J Neural Eng 15:054001 |
