Low-frequency local field potentials and spikes in primary visual cortex convey independent visual information

Local field potentials (LFPs) reflect subthreshold integrative processes that complement spike train measures. However, little is yet known about the differences between how LFPs and spikes encode rich naturalistic sensory stimuli. We addressed this question by recording LFPs and spikes from the primary visual cortex of anesthetized macaques while presenting a color movie.Wethen determined how the power of LFPs and spikes at different frequencies represents the visual features in the movie.Wefound that the most informative LFP frequency ranges were 1– 8 and 60 –100 Hz. LFPs in the range of 12– 40 Hz carried little information about the stimulus, and may primarily reflect neuromodulatory inputs. Spike power was informative only at frequencies <12 Hz. We further quantified “signal correlations” (correlations in the trial-averaged power response to different stimuli) and “noise correlations” (trial-by-trial correlations in the fluctuations around the average) of LFPs and spikes recorded from the same electrode. We found positive signal correlation between high-gamma LFPs (60 –100 Hz) and spikes, as well as strong positive signal correlation within high-gamma LFPs, suggesting that high-gamma LFPs and spikes are generated within the same network. LFPs<24 Hz shared strong positive noise correlations, indicating that they are influenced by a common source, such as a diffuse neuromodulatory input. LFPs<40 Hz showed very little signal and noise correlations with LFPs>40Hzand with spikes, suggesting that low-frequency LFPs reflect neural processes that in natural conditions are fully decoupled from those giving rise to spikes and to high-gamma LFPs

Comparing the Feature Selectivity of the Gamma-Band of the Local Field Potential and the Underlying Spiking Activity in Primate Visual Cortex

The local field potential (LFP), comprised of low-frequency extra-cellular voltage fluctuations, has been used extensively to study the mechanisms of brain function. In particular, oscillations in the gamma-band (30–90 Hz) are ubiquitous in the cortex of many species during various cognitive processes. Surprisingly little is known about the underlying biophysical processes generating this signal. Here, we examine the relationship of the local field potential to the activity of localized populations of neurons by simultaneously recording spiking activity and LFP from the primary visual cortex (V1) of awake, behaving macaques. The spatial organization of orientation tuning and ocular dominance in this area provides an excellent opportunity to study this question, because orientation tuning is organized at a scale around one order of magnitude finer than the size of ocular dominance columns. While we find a surprisingly weak correlation between the preferred orientation of multi-unit activity and gamma-band LFP recorded on the same tetrode, there is a strong correlation between the ocular preferences of both signals. Given the spatial arrangement of orientation tuning and ocular dominance, this leads us to conclude that the gamma-band of the LFP seems to sample an area considerably larger than orientation columns. Rather, its spatial resolution lies at the scale of ocular dominance columns

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn2+ is a metabolic toxin and a competitive inhibitor for Ca2+, and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl2 administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl2, respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl2 dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca2+ competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl2. Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl2 may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn2+ administration protocol

Feature Selectivity of the Gamma-Band of the Local Field Potential in Primate Primary Visual Cortex

Extracellular voltage fluctuations (local field potentials, LFPs) reflecting neural mass action are ubiquitous across species and brain regions. Numerous studies have characterized the properties of LFP signals in the cortex to study sensory and motor computations as well as cognitive processes like attention, perception and memory. In addition, its extracranial counterpart – the electroencephalogram – is widely used in clinical applications. However, the link between LFP signals and the underlying activity of local populations of neurons remains largely elusive. Here, we review recent work elucidating the relationship between spiking activity of local neural populations and LFP signals. We focus on oscillations in the gamma-band (30–90 Hz) of the LFP in the primary visual cortex (V1) of the macaque that dominate during visual stimulation. Given that in area V1 much is known about the properties of single neurons and the cortical architecture, it provides an excellent opportunity to study the mechanisms underlying the generation of the LFP

In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing

One of the main problems in systems biology is to obtain information on signal processing between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge its applicability. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. In the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps. Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps. The somatosensory cortex of male SD rats was stereotaxically injected with different Mn2+-containing solutions. Total amount of injected Mn2+ ranged between 1 and 16 nmol and the injected volumes between 10 and 80 nL. Osmolarity and pH effects were investigated injecting pH buffered solutions of Mn2+ (pH 7.3 in Tris-HCl buffer vs. 5.5 in H2O) at different concentration (0.05, 0.1 and 0.8 M MnCl2). Same amounts of Mn2+ (8nmol) delivered to the tissue at different infusion rates were also compared. Following the injection, T1-weighted MR imaging (250 mm isotropic resolution) was performed in a 7T scanner at different time points. Fifteen days after the injection animals were sacrificed and brains processed for histology. Nissl staining as well as GFAP and NeuN immunohistochemistry (selective staining for astrocytes and neurons, respectively) were performed in the brain sections to examine cellular toxicity. All injections produced connectivity maps consistent with the known anterograde projections of SI cortex based on classical neuronal tract-tracing techniques. Our results show that pH buffered solution improve the effectiveness of MEMRI, increasing T1 contrast in the projection sites. In addition, injections of pH buffered and isotonic solutions of 50 and 100 mM MnCl2 yielded more extensive connectivity maps, in particular, ipsiand contra-lateral corticocortical connections were evident in all animal injected with those solutions but not with the more usual MEMRI protocol (0.8M MnCl2 in H2O). Hypertonic and non-buffered solutions containing 8nmol Mn2+ resulted in neuronal death and astrogliosis in extensive areas around the injection point. In sharp contrast, no neuronal toxicity was observed with injections containing up to 8nmol of Mn2+ in isotonic solutions of up to 100 mM MnCl2 and pH 7.3. Slow infusion rates demonstrated also to be advantageous and permitted application of larger amounts of Mn2+ without toxic effects, resulting in better T1 contrast in the low density projection fields. Any sign of toxicity was observed in any condition in the projection fields. We conclude that refined protocols for MEMRI improve the quality and extension of connectivity maps and preserves tissue viability, assuring the application of this technique in longitudinal experiments

Smart MRI Agents Sensing Extracellular Calcium Fluctuations

Functional Magnetic Resonance Imaging (fMRI) is currently the main tool used for the study of function and dysfunction of the human brain. The current mainstay of fMRI, the so-called Blood-Oxygen-Level-Dependent (BOLD) contrast, capitalizes on the detection of changes in cerebral blood flow, volume and oxygenation, but cannot directly report neural activity, as it suffers from poor spatiotemporal resolution and specificity compared to the actual neural events. An alternative methodology could be that relying on the responsive, ‘smart’ contrast agents whose relaxivity depends on the concentration of substances directly related to neuronal activity. Ca2+ is an excellent marker closely linked to brain activation and is preferred target for various imaging methods. We report two Gd3+ chelates linked to a modified EGTA moiety that have a relaxivity response to extracellular Ca2+ fluctuations in the brain. The proton relaxivity of both Gd3+ complexes is sensitive to the variation of Ca2+ concentration. They are selective to Ca2+ with respect to the main competitor cation Mg2+. Upon interaction with Ca2+, the complexes exhibit high and reversible relaxivity changes; the relaxivity response of one complex upon addition of Ca2+ exceeds 80. Moreover, the relaxivity changes remain remarkable (>50) even in the medium mimicking the brain extracellular fluid, exhibiting a ~10 relaxivity change in the physiologically relevant Ca2+ concentration range (changes induced during the neural activity). These agents have great potential to be applied as functional MR markers and be used for the visualization of the neural processes. They can substantially increase the specificity and spatial resolution of the MR-detected signals and open new perspectives in fMRI

Distinct ensembles in the noradrenergic locus coeruleus are associated with diverse cortical states

The noradrenergic locus coeruleus (LC) is a controller of brain and behavioral states. Activating LC neurons en masse by electrical or optogenetic stimulation promotes a stereotypical "activated" cortical state of high-frequency oscillations. However, it has been recently reported that spontaneous activity of LC cell pairs has sparse yet structured time-averaged cross-correlations, which is unlike the highly synchronous neuronal activity evoked by stimulation. Therefore, LC population activity could consist of distinct multicell ensembles each with unique temporal evolution of activity. We used nonnegative matrix factorization (NMF) to analyze large populations of simultaneously recorded LC single units in the rat LC. NMF identified ensembles of spontaneously coactive LC neurons and their activation time courses. Since LC neurons selectively project to specific forebrain regions, we hypothesized that distinct ensembles activate during different cortical states. To test this hypothesis, we calculated band-limited power and spectrograms of local field potentials in cortical area 24a aligned to spontaneous activations of distinct LC ensembles. A diversity of state modulations occurred around activation of different LC ensembles, including a typical activated state with increased highfrequency power as well as other states including decreased high-frequency power. Thus-in contrast to the stereotypical activated brain state evoked by en masse LC stimulation-spontaneous activation of distinct LC ensembles is associated with a multitude of cortical states.Peer reviewe

Ready ... Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival Time

What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the “go” signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a “countdown” condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in “no-go” conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals

Contextual Feedback to Superficial Layers of V1

Neuronal cortical circuitry comprises feedforward, lateral, and feedback projections, each of which terminates in distinct cortical layers [1-3]. In sensory systems, feedforward processing transmits signals from the external world into the cortex, whereas feedback pathways signal the brain's inference of the world [4-11]. However, the integration of feedforward, lateral, and feedback inputs within each cortical area impedes the investigation of feedback, and to date, no technique has isolated the feedback of visual scene information in distinct layers of healthy human cortex. We masked feedforward input to a region of V1 cortex and studied the remaining internal processing. Using high-resolution functional brain imaging (0.8 mm(3)) and multivoxel pattern information techniques, we demonstrate that during normal visual stimulation scene information peaks in mid-layers. Conversely, we found that contextual feedback information peaks in outer, superficial layers. Further, we found that shifting the position of the visual scene surrounding the mask parametrically modulates feedback in superficial layers of V1. Our results reveal the layered cortical organization of external versus internal visual processing streams during perception in healthy human subjects. We provide empirical support for theoretical feedback models such as predictive coding [10, 12] and coherent infomax [13] and reveal the potential of high-resolution fMRI to access internal processing in sub-millimeter human cortex