The effects of electrical microstimulation on cortical signal propagation

Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation–elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated

Pharmaco-Based fMRI and Neurophysiology in Non-human Primates

Brain activity is continuously changing, among others reflecting the effects of neuromodulation on multiple spatial and temporal scales. By altering the input–output relationship of neural circuits, neuromodulators can also affect their energy expenditure, with concomitant effects on the hemodynamic responses. Yet, it is still unclear how to study and interpret the effects of different neuromodulators, for instance, how to differentiate their effects from underlying behavior- or stimulus-driven activity. Gaining insights into neuromodulatory processes is largely hampered by the lack of approaches providing information concurrently at different spatio-temporal scales. Here, we provide an overview of the multimodal approach consisting of functional magnetic resonance imaging (fMRI), pharmacology and neurophysiology, which we developed to elucidate causal relationships between neuromodulation and neurovascular coupling in visual cortex of anesthetized macaques

The Electrophysiological Background of the fMRI Signal

The ability to non-invasively study the architecture and function of the human brain constitutes one of the most exciting cornerstones for modern medicine, psychology and neuroscience. Current in vivo imaging techniques not only provide clinically essential information and allow new forms of treatment, but also reveal insights into the mechanisms behind brain function and malfunction. This supremacy of modern imaging rests on its ability to study the structural properties of the nervous system simultaneously with the functional changes related to neuronal activity. As a result, imaging allows us to combine information about the spatial organization and connectivity of the nervous system with information about the underlying neuronal processes and provides the only means to link perception and cognition with the neural substrates in the human brain

Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology

Cerebral small vessel disease (SVD) is a major contributor to stroke, cognitive impairment and dementia with limited therapeutic interventions. There is a critical need to provide mechanistic insight and improve translation between pre-clinical research and the clinic. A 2-day workshop was held which brought together experts from several disciplines in cerebrovascular disease, dementia and cardiovascular biology, to highlight current advances in these fields, explore synergies and scope for development. These proceedings provide a summary of key talks at the workshop with a particular focus on animal models of cerebral vascular disease and dementia, mechanisms and approaches to improve translation. The outcomes of discussion groups on related themes to identify the gaps in knowledge and requirements to advance knowledge are summarized