Catecholamines Alter the Intrinsic Variability of Cortical Population Activity and Perception (original) (raw)
Related papers
bioRxiv (Cold Spring Harbor Laboratory), 2017
The ascending modulatory systems of the brain stem are powerful regulators of global brain state. Disturbances of these systems are implicated in several major neuropsychiatric disorders. Yet, how these systems interact with specific neural computations in the cerebral cortex to shape perception, cognition, and behavior remains poorly understood. Here, we probed into the effect of two such systems, the catecholaminergic (dopaminergic and noradrenergic) and cholinergic systems, on an important aspect of cortical computation: its intrinsic variability. To this end, we combined placebo-controlled pharmacological intervention in humans, recordings of cortical population activity using magnetoencephalography (MEG), and psychophysical measurements of the perception of ambiguous visual input. A low-dose catecholaminergic, but not cholinergic, manipulation altered the rate of spontaneous perceptual fluctuations as well as the temporal structure of "scale-free" population activity of large swaths of the visual and parietal cortices. Computational analyses indicate that both effects were consistent with an increase in excitatory relative to inhibitory activity in the cortical areas underlying visual perceptual inference. We propose that catecholamines regulate the variability of perception and cognition through dynamically changing the cortical excitation-inhibition ratio. The combined readout of fluctuations in perception and cortical activity we established here may prove useful as an efficient and easily accessible marker of altered cortical computation in neuropsychiatric disorders.
Catecholamine-Mediated Increases in Gain Enhance the Precision of Cortical Representations
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016
Neurophysiological evidence suggests that neuromodulators, such as norepinephrine and dopamine, increase neural gain in target brain areas. Computational models and prominent theoretical frameworks indicate that this should enhance the precision of neural representations, but direct empirical evidence for this hypothesis is lacking. In two functional MRI studies, we examine the effect of baseline catecholamine levels (as indexed by pupil diameter and manipulated pharmacologically) on the precision of object representations in the human ventral temporal cortex using angular dispersion, a powerful, multivariate metric of representational similarity (precision). We first report the results of computational model simulations indicating that increasing catecholaminergic gain should reduce the angular dispersion, and thus increase the precision, of object representations from the same category, as well as reduce the angular dispersion of object representations from distinct categories whe...
Catecholamine-mediated increases in neural gain improve the precision of cortical representations
2016
Neurophysiological evidence suggests that neuromodulators, such as norepinephrine and dopamine, increase neural gain in target brain areas. Computational models and prominent theoretical frameworks indicate that this should enhance the precision of neural representations, but direct empirical evidence for this hypothesis is lacking. In two functional MRI studies, we examine the effect of baseline catecholamine levels (as indexed by pupil diameter and manipulated pharmacologically) on the precision of object representations in the human ventral temporal cortex using angular dispersion, a powerful, multivariate metric of representational similarity (precision). We first report the results of computational model simulations indicating that increasing catecholaminergic gain should reduce the angular dispersion, and thus increase the precision, of object representations from the same category, as well as reduce the angular dispersion of object representations from distinct categories whe...
Cortical activity is more stable when sensory stimuli are consciously perceived
According to recent evidence, stimulus-tuned neurons in the cerebral cortex exhibit reduced variability in firing rate across trials, after the onset of a stimulus. However, in order for a reduction in variability to be directly relevant to perception and behavior, it must be realized within trial—the pattern of activity must be relatively stable. Stability is characteristic of decision states in recurrent attractor networks, and its possible relevance to conscious perception has been suggested by theorists. However, it is difficult to measure on the within-trial time scales and broadly distributed spatial scales relevant to perception. We recorded simultaneous magneto- and electroencephalography (MEG and EEG) data while subjects observed threshold-level visual stimuli. Pattern-similarity analyses applied to the data from MEG gradiometers uncovered a pronounced decrease in variability across trials after stimulus onset, consistent with previous single-unit data. This was followed by a significant divergence in variability depending upon subjective report (seen/ unseen), with seen trials exhibiting less variability. Applying the same analysis across time, within trial, we found that the latter effect coincided in time with a difference in the stability of the pattern of activity. Stability alone could be used to classify data from individual trials as “seen” or “unseen.” The same metric applied to EEG data from patients with disorders of consciousness exposed to auditory stimuli diverged parametrically according to clinically diagnosed level of consciousness. Differences in signal strength could not account for these results. Conscious perception may involve the transient stabilization of distributed cortical networks, corresponding to a global brain-scale decision.
Dopamine-InDissociation of BOLD and Neural Activity in Macaque Visual Cortex
Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory [1]. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear [2, 3 and 4], limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA’s involvement in diseases such as Parkinson’s and schizophrenia, it also plays a role in visual perception [5, 6, 7 and 8]. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects.
The International Journal of Neuropsychopharmacology, 2005
Magnetoencephalography (MEG) is a non-invasive method for studying magnetic fields generated by simultaneously firing neurons outside the skull. The skull, scalp and brain tissue do not distort magnetic fields, so the cortical activity can be easily measured. MEG is starting to be used to explore the effects of various psychopharmacological agents on resting brain, sensory and cognitive processing. Scopolamine and agents enhancing GABA functions have shown differential effects on cortical neural oscillations. Further, with GABA, serotonin, dopamine and acetylcholine transmissions have differential effects on early cortical and pre-attentional processing in the auditory and frontal cortices. Monoamines also differently regulate the activity of the somatosensory cortex. Taken together, MEG with a resolution of milliseconds allows exploration of focal cortical effects of psychopharmacological agents giving information different from other brain-imaging modalities.
Cholinergic shaping of neural correlations
A primary function of the brain is to form representations of the sensory world. Its capacity to do so depends on the relationship between signal correlations, associated with neuronal receptive fields, and noise correlations, associated with neuronal response variability. It was recently shown that the behavioral relevance of sensory stimuli can modify the relationship between signal and noise correlations, presumably increasing the encoding capacity of the brain. In this work, we use data from the visual cortex of the awake mouse watching naturalistic stimuli and show that a similar modification is observed under heightened cholinergic modulation. Increasing cholinergic levels in the cortex through optoge-netic stimulation of basal forebrain cholinergic neurons decreases the dependency that is commonly observed between signal and noise correlations. Simulations of correlated neural networks with realistic firing statistics indicate that this change in the correlation structure increases the encoding capacity of the network. acetylcholine | neural coding | neural correlations | neuromodulation | sensory processing C ortical network responses are shaped by neuromodulators to efficiently code the sensory world. For example, numerous studies have shown that cortical levels of the neurotransmitter acetylcholine impact behavioral and neural responses to sensory stimuli, improving discrimination performance (1–3) and generally increasing the amplitude of the neural responses (3–10). Although the response amplitude can contribute to the amount of information encoded by individual neurons, the encoding capacity of whole networks can be profoundly shaped by the neural correlations (11). Activity dependencies across neuronal pairs can be analyzed in terms of the correlation of their total activity (total correlations), in terms of the similarity of their receptive fields (signal correlations), or in terms of the similarity in the neurons' trial-to-trial variability (noise correlations) (12, 13). Whereas previous work analyzed the influence of acetylcholine on total correlations (4) or noise correlations (14), it is not clear how these variables alone might influence neural coding (15). Theoretical research indicates that encoding capacity depends on the details of the correlation structure, analyzed in terms of the relationship between signal and noise correlations (12, 15–18). Consistent with the latter observation, two studies have shown that attention (19) and learning (17) alter the relationship between signal and noise correlations in a manner that is thought to increase encoding capacity. Despite the established importance of the relationship between signal and noise correlations for neural coding, previous work has not analyzed how this relationship is affected by cholinergic modulation. For the purpose of evaluating the effect of increases in cortical acetylcholine on the correlation structure of the visual cortical network, our current study uses optogenetic stimulation of corti-cally projecting cholinergic neurons located in the basal forebrain. Specifically, we analyze the effect of cholinergic stimulation on the amplitudes of both signal and noise and on the relationship between signal and noise correlations. We find that increasing cho-linergic input to the cortex decreases the slope between signal and noise correlations, in a manner consistent with changes observed following behavioral manipulations (17, 19). To understand the impact of this change in the correlation structure on the capacity of the network to encode information, we use simulations of correlated neural networks with Poisson statistics. We find that the decrease in the correlations' slope increases the encoding capacity of the network. Results In this paper, we present a unique analysis of data from a previously reported experiment (3). The experiment measured the activity of mouse visual cortex neurons to repeated presentations of naturalistic movie sequences with or without concomitant optogenetic stimulation of basal forebrain cholinergic neurons (Fig. 1A). The goal of our work is to analyze the specific effect of cholinergic activity on both signal and noise correlations, as well as on the relationship between the two. Here, the neural signal is defined as the average number of spikes in response to a movie segment, and the neural noise is defined as the residual around the signal (12). This broad definition of signal implies that we are focusing on the analysis of the encoding of whole naturalistic images rather than certain individual features of the image. We estimated the neural signal corresponding to a given neuron as the number of spikes in a time bin, averaged over repeated presentations of a movie (Fig. 1B; see Methods for precise mathematical definitions). We estimated the noise, in each presentation, as the residual activity around the signal (12, 16). Given that the estimation of the signal and the noise are dependent on the duration of an individual time bin, all of the data reported here are calculated for several bin sizes, corresponding to divisors of the total movie length. Once we estimated the signal and the noise, we calculated the signal-to-noise ratios, the signal correlations, and the noise correlations (Methods). We calculated these values from the activity of 113 visual cortex neurons, and 793 neural pairs, from nine animals (Methods) and compared the values across two conditions (with or without optogenetic cholinergic stimulation). Significance The capacity of a network of neurons to represent the sensory world depends not only on the way individual neurons respond to sensory stimuli but also on the similarity of activity across neurons comprising the network. This similarity can be quantified as the correlation of activity across neuronal pairs, or neural correlations. This work presents a unique finding, demonstrating that a neuromodulator, in this case acetylcho-line, can produce specific changes in the correlation structure of the cortical network that ultimately increase the encoding capacity of the network.
PloS one, 2017
Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has t...
Deterministic functions of cortical acetylcholine
European Journal of Neuroscience, 2014
Traditional descriptions of the basal forebrain cholinergic projection system to the cortex have focused on neuromodulatory influences, that is, mechanisms that modulate cortical information processing but are not necessary for mediating discrete behavioral responses and cognitive operations. This review summarises and conceptualises the evidence in support of more deterministic contributions of cholinergic projections to cortical information processing. Through presynaptic receptors expressed on cholinergic terminals, thalamocortical and corticocortical projections can evoke brief cholinergic release events. These acetylcholine (ACh) release events occur on a fast, sub-second to seconds-long time scale ('transients'). In rats performing a task requiring the detection of cues as well as the report of non-cue events cholinergic transients mediate the detection of cues specifically in trials that involve a shift from a state of monitoring for cues to cue-directed responding. Accordingly, ill-timed cholinergic transients, generated using optogenetic methods, force false detections in trials without cues. We propose that the evidence is consistent with the hypothesis that cholinergic transients reduce detection uncertainty in such trials. Furthermore, the evidence on the functions of the neuromodulatory component of cholinergic neurotransmission suggests that higher levels of neuromodulation favor stayingon-task over alternative action. In other terms, higher cholinergic neuromodulation reduces opportunity costs. Evidence indicating a similar integration of other ascending projection systems, including noradrenergic and serotonergic systems, into cortical circuitry remains sparse, largely because of the limited information about local presynaptic regulation and the limitations of current techniques in measuring fast and transient neurotransmitter release events in these systems.