No abstract

Resting-state functional magnetic resonance imaging (fMRI) has highlighted the rich structure of brain activity in absence of a task or stimulus. A great effort has been dedicated in the last two decades to investigate functional connectivity (FC), i.e. the functional interplay between different regions of the brain, which was for a long time assumed to have stationary nature. Only recently was the dynamic behaviour of FC revealed, showing that on top of correlational patterns of spontaneous fMRI signal fluctuations, connectivity between different brain regions exhibits meaningful variations within a typical resting-state fMRI experiment. As a consequence, a considerable amount of work has been directed to assessing and characterising dynamic FC (dFC), and several different approaches were explored to identify relevant FC fluctuations. At the same time, several questions were raised about the nature of dFC, which would be of interest only if brought back to a neural origin. In support of this, correlations with electroencephalography (EEG) recordings, demographic and behavioural data were established, and various clinical applications were explored, where the potential of dFC could be preliminarily demonstrated. In this review, we aim to provide a comprehensive description of the dFC approaches proposed so far, and point at the directions that we see as most promising for the future developments of the field. Advantages and pitfalls of dFC analyses are addressed, helping the readers to orient themselves through the complex web of available methodologies and tools.

1. Whole‐cell membrane current recordings under voltage clamp were made at room temperature from dispersed single cells of longitudinal smooth muscle of rabbit jejunum and dispersed single smooth muscle cells of rabbit ear artery using patch pipettes containing up to 10 mM‐EGTA Ca buffer. 2. Spontaneous transient outward currents (s.t.o.c.s) up to 250 pA in size and about 100 ms in duration were observed in conditions which might lead to an elevated internal Ca concentration. The amplitude distribution in some cells and form of the currents suggested that they were evoked by a quantal stimulus. 3. S.t.o.c. amplitude was voltage dependent and reversed at the K equilibrium potential. S.t.o.c.s. were blocked by 1 mM‐tetraethylammonium or 10 mM‐Ba applied externally or by perfusing Cs inside the cell. 4. Removing external Ca abolished s.t.o.c. activity in the jejunal cells but not in arterial cells. Increasing EGTA buffering within the cells from 1 mM or less to 10 mM abolished activity in both cell types. 5. Caffeine (5 mM) applied to the bathing solution stimulated rapid discharge of transient outward currents and then a prolonged period of inhibition. The stimulated discharge was sensitive to external Ca in jejunal cells but much less so in arterial cells. ACh applied by ionophoresis to jejunal cells or noradrenaline bath‐applied onto arterial cells also stimulated discharge of transients followed by a prolonged inhibitory phase. 6. It was suggested that s.t.o.c.s represent the simultaneous opening of up to 75‐100 Ca‐activated K channels at ‐40 mV in response to sudden discharge of Ca from internal stores when these became overloaded, and that this process may occur cyclically.