Over the last century, there has been a lot of accumulated evidence indicating that oscillatory activity in the brain can be related to behavior, and that particular brain states can be associated with <br />different neural processing and different behavioral states. The advances over the last decade in multi-site neural recordings in awake behaving animals, in electrochemical recordings, in molecular manipulations in the brain, and in precise behavioral measurements, bring a refreshed view of the relation between neural oscillations and behavior. The objective of this Research Topic is to bring attention to these developments.

Champalimaud Foundation

Exploring advances in understanding the relationship between neural activity and behavior

. <p>Research into the effects of dopamine depletion, neuronal oscillations, neural synchrony, gamma-band activity, rTMS, cannabinoids, local field potential oscillations, ripples, stimulus-evoked oscillations, and sensory integration processes have revealed a variety of findings:</p> <ul> <li>Dopamine depletion leads to changes in firing rate and neuronal synchrony in the basal ganglia, with blockade of either D1 or D2 type receptors producing similarly severe akinesia.</li> <li>Neuronal oscillations have been observed in the ventral prefrontal cortex of monkeys performing a visual memory task, and these oscillations may be instrumental for the dynamical integration of local and global neuronal processes underlying short-term memory.</li> <li>Neural synchrony has been proposed as a general mechanism for the coordination of distributed neural activity patterns, and has been linked to conscious cognition and found to be abnormal in major brain disorders.</li> <li>Gamma-band activity increases from the input to output layers of the cortex in the primary visual cortex of the alert macaque monkey.</li> <li>Changes in cross-frequency phase synchrony between alpha- and gamma-band oscillations can predict changes in behavior.</li> <li>Cannabinoid receptor activation can reduce burst frequency and reverse synchronized firing patterns in the hippocampus.</li> <li>Distinct relationships between gamma-50 and gamma-80 oscillations in ventral striatum and behavior, task events, and spiking activity in rats running a spatial decision task.</li> <li>Ripples in the rodent hippocampus have been linked to memory related neural processing.</li> <li>Microstimulation in barrel cortex of alert rats evokes 15-18 Hz oscillations that are modulated by motor behavior.</li> <li>Effective interactions from auditory cortex to STS prevail below 20 Hz, while interactions from STS to auditory cortex prevail above 20 Hz, suggesting that beta frequencies might be important for inter-areal coupling in the temporal lobe.</li> </ul>

Frontiers in Integrative Neuroscience

Brain oscillations and behavior.

Previous studies showed that dopamine depletion leads to both changes in firing rate and in neuronal synchrony in the basal ganglia. Since dopamine D1 and D2 receptors are preferentially expressed in striatonigral and striatopallidal medium spiny neurons, respectively, we investigated the relative contribution of lack of D1 and/or D2-type receptor activation to the changes in striatal firing rate and synchrony observed after dopamine depletion. Similar to what was observed after dopamine depletion, co-administration of D1 and D2 antagonists to mice chronically implanted with multielectrode arrays in the striatum caused significant changes in firing rate, power of the local field potential (LFP) oscillations, and synchrony measured by the entrainment of neurons to striatal local field potentials. However, although blockade of either D1 or D2 type receptors produced similarly severe akinesia, the effects on neural activity differed. Blockade of D2 receptors affected the firing rate of medium spiny neurons and the power of the LFP oscillations substantially, but it did not affect synchrony to the same extent. In contrast, D1 blockade affected synchrony dramatically, but had less substantial effects on firing rate and LFP power. Furthermore, there was no consistent relation between neurons changing firing rate and changing LFP entrainment after dopamine blockade. Our results suggest that the changes in rate and entrainment to the LFP observed in medium spiny neurons after dopamine depletion are somewhat dissociable, and that lack of D1- or D2-type receptor activation can exert independent yet interactive pathological effects during the progression of Parkinson's disease.

Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

Short-term memory requires the coordination of sub-processes like encoding, retention, retrieval and comparison of stored material to subsequent input. Neuronal oscillations have an inherent time structure, can effectively coordinate synaptic integration of large neuron populations and could therefore organize and integrate distributed sub-processes in time and space. We observed field potential oscillations (14–95 Hz) in ventral prefrontal cortex of monkeys performing a visual memory task. Stimulus-selective and performance-dependent oscillations occurred simultaneously at 65–95 Hz and 14–50 Hz, the latter being phase-locked throughout memory maintenance. We propose that prefrontal oscillatory activity may be instrumental for the dynamical integration of local and global neuronal processes underlying short-term memory.

Performance- and stimulus-dependent oscillations in monkey prefrontal cortex during short-term memory

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies.

Neural synchrony in cortical networks: history, concept and current status

Periodic activity patterns or oscillations within the gamma frequency band (20–80 Hz) have been implicated in sensory processing and cognition in many areas of the cerebral cortex, including primary visual cortex (V1). Although periodic activity appears to be a hallmark of cortical neurons, little is known about the dynamics of these activity patterns as signals progress within local cortical circuits. This study compares the strength of periodic activity between neurons in the input and output stages of cortical processing – neurons in layers 4 and 6 – of V1 in the alert macaque monkey. Our results demonstrate that while both populations of neurons display significant gamma-band activity, this activity increases from the input to output layers of the cortex. These data suggest that local cortical circuits enhance periodic activity within a cortical area.

Modulation of gamma-band activity across local cortical circuits

A governing assumption about repetitive transcranial magnetic stimulation (rTMS) has been that it interferes with task-related neuronal activity – in effect, by “injecting noise” into the brain – and thereby disrupts behavior. Recent reports of rTMS-produced behavioral enhancement, however, call this assumption into question. We investigated the neurophysiological effects of rTMS delivered during the delay period of a visual working memory task by simultaneously recording brain activity with electroencephalography (EEG). Subjects performed visual working memory for locations or for shapes, and in half the trials a 10-Hz train of rTMS was delivered to the superior parietal lobule (SPL) or a control brain area. The wide range of individual differences in the effects of rTMS on task accuracy, from improvement to impairment, was predicted by individual differences in the effect of rTMS on power in the alpha-band of the EEG (∼10 Hz): a decrease in alpha-band power corresponded to improved performance, whereas an increase in alpha-band power corresponded to the opposite. The EEG effect was localized to cortical sources encompassing the frontal eye fields and the intraparietal sulcus, and was specific to task (location, but not object memory) and to rTMS target (SPL, not control area). Furthermore, for the same task condition, rTMS-induced changes in cross-frequency phase synchrony between alpha- and gamma-band (>40 Hz) oscillations predicted changes in behavior. These results suggest that alpha-band oscillations play an active role cognitive processes and do not simply reflect absence of processing. Furthermore, this study shows that the complex effects of rTMS on behavior can result from biasing endogenous patterns of network-level oscillations.

Repetitive transcranial magnetic stimulation affects behavior by biasing endogenous cortical oscillations

Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA)-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg kg−1, i.p.) entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate). Injection of the high-affinity cannabinoid agonist (-)-11-hydroxy-8-tetrahydrocannabinol-dimethyl-heptyl (HU210, 100 μg kg−1, i.p.) following KA markedly reduced the burst frequency (% decrease in burst frequency) and reversed synchronized firing patterns back to baseline levels. Pre-treatment with the central cannabinoid receptor (CB1) antagonist N-piperidino-5-(4-clorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant, SR141716A 3 mg kg−1, i.p.) completely prevented the actions of HU210. The present results indicate that cannabinoids exert their antiepileptic effects by impeding pathological synchronization of neuronal networks in the hippocampus.

Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus

Local field potential (LFP) oscillations in the brain reflect organization thought to be important for perception, attention, movement, and memory. In the basal ganglia, including dorsal striatum, dysfunctional LFP states are associated with Parkinson's disease, while in healthy subjects, dorsal striatal LFPs have been linked to decision-making processes. However, LFPs in ventral striatum have been less studied. We report that in rats running a spatial decision task, prominent gamma-50 (45–55 Hz) and gamma-80 (70–85 Hz) oscillations in ventral striatum had distinct relationships to behavior, task events, and spiking activity. Gamma-50 power increased sharply following reward delivery and before movement initiation, while in contrast, gamma-80 power ramped up gradually to reward locations. Gamma-50 power was low and contained little structure during early learning, but rapidly developed a stable pattern, while gamma-80 power was initially high before returning to a stable level within a similar timeframe. Putative fast-spiking interneurons (FSIs) showed phase, firing rate, and coherence relationships with gamma-50 and gamma-80, indicating that the observed LFP patterns are locally relevant. Furthermore, in a number of FSIs such relationships were specific to gamma-50 or gamma-80, suggesting that partially distinct FSI populations mediate the effects of gamma-50 and gamma-80.

Low and high gamma oscillations in rat ventral striatum have distinct relationships to behavior, reward, and spiking activity on a learned spatial decision task

Fast oscillations or “ripples” are found in the local field potential (LFP) of the rodent hippocampus during awake and sleep states. Ripples have been found to correlate with memory related neural processing, however, the functional role of the ripple has yet to be fully established. We applied a Kalman smoother based estimator of instantaneous frequency (iFreq) and frequency modulation (FM) to ripple oscillations recorded in-vivo from region CA1 of the rat and mouse hippocampus during slow wave sleep. We found that (1) ripples exhibit stereotypical frequency dynamics that are consistent in the rat and mouse, (2) instantaneous frequency information may be used as an additional dimension in the classification of ripple events, and (3) the instantaneous frequency structure of ripples may be used to improve the detection of ripple events by reducing Type I and Type II errors. Based on our results, we propose that high temporal and spectral resolution estimates of frequency dynamics may be used to help elucidate the mechanisms of ripple generation and memory related processing.

Characterizing the dynamic frequency structure of fast oscillations in the rodent hippocampus

Stimulus-evoked oscillations have been observed in the visual, auditory, olfactory and somatosensory systems. To further our understanding of these oscillations, it is essential to study their occurrence and behavioral modulation in alert, awake animals. Here we show that microstimulation in barrel cortex of alert rats evokes 15–18 Hz oscillations that are strongly modulated by motor behavior. In freely whisking rats, we found that the power of the microstimulation-evoked oscillation in the local field potential was inversely correlated to the strength of whisking. This relationship was also present in rats performing a stimulus detection task suggesting that the effect was not due to sleep or drowsiness. Further, we present a computational model of the thalamocortical loop which recreates the observed phenomenon and predicts some of its underlying causes. These findings demonstrate that stimulus-evoked oscillations are strongly influenced by motor modulation of afferent somatosensory circuits.

Behavioral modulation of stimulus-evoked oscillations in barrel cortex of alert rats

Recent studies using functional imaging and electrophysiology demonstrate that processes related to sensory integration are not restricted to higher association cortices but already occur in early sensory cortices, such as primary auditory cortex. While anatomical studies suggest the superior temporal sulcus (STS) as likely source of visual input to auditory cortex, little evidence exists to support this notion at the functional level. Here we tested this hypothesis by simultaneously recording from sites in auditory cortex and STS in alert animals stimulated with dynamic naturalistic audio–visual scenes. Using Granger causality and directed transfer functions we first quantified causal interactions at the level of field potentials, and subsequently determined those frequency bands that show effective interactions, i.e. interactions that are relevant for influencing neuronal firing at the target site. We found that effective interactions from auditory cortex to STS prevail below 20 Hz, while interactions from STS to auditory cortex prevail above 20 Hz. In addition, we found that directed interactions from STS to auditory cortex make a significant contribution to multisensory influences in auditory cortex: Sites in auditory cortex showing multisensory enhancement received stronger feed-back from STS during audio–visual than during auditory stimulation, while sites with multisensory suppression received weaker feed-back. These findings suggest that beta frequencies might be important for inter-areal coupling in the temporal lobe and demonstrate that superior temporal regions indeed provide one major source of visual influences to auditory cortex.