Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation

Li B, Virtanen JP, Oeltermann A, et al. Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation. eLife. 2017;6

Coupling of hippocampal theta and ripples with pontogeniculooccipital waves

The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis

Mapping cortical activity elicited with electrical microstimulation using fmri in the macaque

Over the last two centuries, electrical microstimulation has been used to demonstrate causal links between neural activity and specific behaviors and cognitive functions. However, to establish these links it is imperative to characterize the cortical activity patterns that are elicited by stimulation locally around the electrode and in other functionally connected areas. We have developed a technique to record brain activity using the blood oxygen level dependent (BOLD) signal while applying electrical microstimulation to the primate brain. We find that the spread of activity around the electrode tip in macaque area V1 was larger than expected from calculations based on passive spread of current and therefore may reflect functional spread by way of horizontal connections. Consistent with this functional transynaptic spread we also obtained activation in expected projection sites in extrastriate visual areas, demonstrating the utility of our technique in uncovering in vivo functional connectivity maps

Relationship between neural and hemodynamic signals during spontaneous activity studied with temporal kernel CCA

Functional magnetic resonance imaging (fMRI) based on the so-called blood oxygen level-dependent (BOLD) contrast is a powerful tool for studying brain function not only locally but also on the large scale. Most studies assume a simple relationship between neural and BOLD activity, in spite of the fact that it is important to elucidate how the “when” and “what” components of neural activity are correlated to the “where” of fMRI data. Here we conducted simultaneous recordings of neural and BOLD signal fluctuations in primary visual (V1) cortex of anesthetized monkeys. We explored the neurovascular relationship during periods of spontaneous activity by using temporal kernel canonical correlation analysis (tkCCA). tkCCA is a multivariate method that can take into account any features in the signals that univariate analysis cannot. The method detects filters in voxel space (for fMRI data) and in frequency–time space (for neural data) that maximize the neurovascular correlation without any assumption of a hemodynamic response function (HRF). Our results showed a positive neurovascular coupling with a lag of 4–5 s and a larger contribution from local field potentials (LFPs) in the γ range than from low-frequency LFPs or spiking activity. The method also detected a higher correlation around the recording site in the concurrent spatial map, even though the pattern covered most of the occipital part of V1. These results are consistent with those of previous studies and represent the first multivariate analysis of intracranial electrophysiology and high-resolution fMRI

Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area

decreases in neuronal activity in monkey visual area V

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