EEG/ECoG/EMG publications

Study objectives: The activity of the noradrenergic system of the locus coeruleus (LC) is high in wake and low in sleep. LC promotes arousal and EEG activation, as well as attention, working memory, and cognitive flexibility. These functions rely on prefrontal cortex and are impaired by sleep deprivation, but the extent to which LC activity changes during wake remains unclear. Moreover, it is unknown whether noradrenergic neurons can sustain elevated firing during extended wake. Recent studies show that relative to LC neurons targeting primary motor cortex (M1), those projecting to medial prefrontal cortex (mPFC) have higher spontaneous firing rates and are more excitable. These results suggest that noradrenaline (NA) levels should be higher in mPFC than M1, and that during prolonged wake LC cells targeting mPFC may fatigue more, but direct evidence is lacking. Methods: We performed in vivo microdialysis experiments in adult (9-10 weeks old) C57BL/6 mice implanted for chronic electroencephalographic recordings. Cortical NA levels were measured during spontaneous sleep and wake (n = 8 mice), and in the course of sleep deprivation (n = 6). Results: We found that absolute NA levels are higher in mPFC than in M1. Moreover, in both areas they decline during sleep and increase during wake, but these changes are faster in M1 than mPFC. Finally, by the end of sleep deprivation NA levels decline only in mPFC. Conclusions: Locus coeruleus (LC) neurons targeting prefrontal cortex may fatigue more markedly, or earlier, than other LC cells, suggesting one of the mechanisms underlying the cognitive impairment and the increased sleep presure associated with sleep deprivation. Commentary: A commentary on this article appears in this issue on page 11.

Although resting-state functional connectivity is a commonly used neuroimaging paradigm, the underlying mechanisms remain unknown. Thalamo-cortical and cortico-cortical circuits generate oscillations at different frequencies during spontaneous activity. However, it remains unclear how the various rhythms interact and whether their interactions are lamina-specific. Here we investigated intra- and inter-laminar spontaneous phase-amplitude coupling (PAC). We recorded local-field potentials using laminar probes inserted in the forelimb representation of rat area S1. We then computed time-series of frequency-band- and lamina-specific current source density (CSD), and PACs of CSD for all possible pairs of the classical frequency bands in the range of 1-150 Hz. We observed both intra- and inter-laminar spontaneous PAC. Of 18 possible combinations, 12 showed PAC, with the highest measures of interaction obtained for the pairs of the theta/gamma and delta/gamma bands. Intra- and inter-laminar PACs involving layers 2/3-5a were higher than those involving layer 6. Current sinks (sources) in the delta band were associated with increased (decreased) amplitudes of high-frequency signals in the beta to fast gamma bands throughout layers 2/3-6. Spontaneous sinks (sources) of the theta and alpha bands in layers 2/3-4 were on average linked to dipoles completed by sources (sinks) in layer 6, associated with high (low) amplitudes of the beta to fast-gamma bands in the entire cortical column. Our findings show that during spontaneous activity, delta, theta, and alpha oscillations are associated with periodic excitability, which for the theta and alpha bands is lamina-dependent. They further emphasize the differences between the function of layer 6 and that of the superficial layers, and the role of layer 6 in controlling activity in those layers. Our study links theories on the involvement of PAC in resting-state functional connectivity with previous work that revealed lamina-specific anatomical thalamo-cortico-cortical connections.

Behavioral studies support the concept of an auditory spatial attention gradient by demonstrating that attentional benefits progressively diminish as distance increases from an attended location. Damage to the right inferior parietal cortex can induce a rightward attention bias, which implicates this region in the construction of attention gradients. This study used event-related potentials (ERPs) to define attention-related gradients before and after repetitive transcranial magnetic stimulation (rTMS) to the right inferior parietal cortex. Subjects (n = 16) listened to noise bursts at five azimuth locations (left to right: -90°, -45°, 0° midline, +45°, +90°) and responded to stimuli at one target location (-90°, +90°, separate blocks). ERPs as a function of non-target location were examined before (baseline) and after 0.9 Hz rTMS. Results showed that ERP attention gradients were observed in three time windows (frontal 230-340, parietal 400-460, frontal 550-750 ms). Significant transient rTMS effects were seen in the first and third windows. The first window had a voltage decrease at the farthest location when attending to either the left or right side. The third window had on overall increase in positivity, but only when attending to the left side. These findings suggest that rTMS induced a small contraction in spatial attention gradients within the first time window. The asymmetric effect of attended location on gradients in the third time window may relate to neglect of the left hemispace after right parietal injury. Together, these results highlight the role of the right inferior parietal cortex in modulating frontal lobe attention network activity.

Background: To dissect the intricate workings of neural circuits, it is essential to gain precise control over subsets of neurons while retaining the ability to monitor larger-scale circuit dynamics. This requires the ability to both evoke and record neural activity simultaneously with high spatial and temporal resolution. New method: In this paper we present approaches that address this need by combining micro-electrocorticography (μECoG) with optogenetics in ways that avoid photovoltaic artifacts. Results: We demonstrate that variations of this approach are broadly applicable across three commonly studied mammalian species - mouse, rat, and macaque monkey - and that the recorded μECoG signal shows complex spectral and spatio-temporal patterns in response to optical stimulation. Comparison with existing methods: While optogenetics provides the ability to excite or inhibit neural subpopulations in a targeted fashion, large-scale recording of resulting neural activity remains challenging. Recent advances in optical physiology, such as genetically encoded Ca(2+) indicators, are promising but currently do not allow simultaneous recordings from extended cortical areas due to limitations in optical imaging hardware. Conclusions: We demonstrate techniques for the large-scale simultaneous interrogation of cortical circuits in three commonly used mammalian species.

There has been continued interest in clinical objective measures of binaural processing. One commonly proposed measure is the binaural interaction component (BIC), which is obtained typically by recording auditory brainstem responses (ABRs)—the BIC reflects the difference between the binaural ABR and the sum of the monaural ABRs (i.e., binaural − (left + right)). We have recently developed an alternative, direct measure of sensitivity to interaural time differences, namely, a following response to modulations in interaural phase difference (the interaural phase modulation following response; IPM-FR). To obtain this measure, an ongoing diotically amplitude-modulated signal is presented, and the interaural phase difference of the carrier is switched periodically at minima in the modulation cycle. Such periodic modulations to interaural phase difference can evoke a steady state following response. BIC and IPM-FR measurements were compared from 10 normal-hearing subjects using a 16-channel electroencephalographic system. Both ABRs and IPM-FRs were observed most clearly from similar electrode locations—differential recordings taken from electrodes near the ear (e.g., mastoid) in reference to a vertex electrode (Cz). Although all subjects displayed clear ABRs, the BIC was not reliably observed. In contrast, the IPM-FR typically elicited a robust and significant response. In addition, the IPM-FR measure required a considerably shorter recording session. As the IPM-FR magnitude varied with interaural phase difference modulation depth, it could potentially serve as a correlate of perceptual salience. Overall, the IPM-FR appears a more suitable clinical measure than the BIC.

A change-related component of the auditory evoked response long thought to be preattentive and preconscious may actually require consciousness.

The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9–T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.

In everyday conversation, viewing a talker's face can provide information about the timing and content of an upcoming speech signal, resulting in improved intelligibility. Using electrocorticography, we tested whether human auditory cortex in Heschl's gyrus (HG) and on superior temporal gyrus (STG) and motor cortex on precentral gyrus (PreC) were responsive to visual/gestural information prior to the onset of sound and whether early stages of auditory processing were sensitive to the visual content (speech syllable versus non-speech motion). Event-related band power (ERBP) in the high gamma band was content-specific prior to acoustic onset on STG and PreC, and ERBP in the beta band differed in all three areas. Following sound onset, we found with no evidence for content-specificity in HG, evidence for visual specificity in PreC, and specificity for both modalities in STG. These results support models of audio-visual processing in which sensory information is integrated in non-primary cortical areas.

The neural basis of human speech is unclear. Intracranial electrophysiological recordings have revealed that high-gamma band oscillations (70-150Hz) are observed in the frontal lobe during speech production and in the temporal lobe during speech perception. Here, we tested the hypothesis that the frontal and temporal brain regions had high-gamma coherence during speech. We recorded electrocorticography (ECoG) from the frontal and temporal cortices of five humans who underwent surgery for medically intractable epilepsy, and studied coherence between the frontal and temporal cortex during vocalization and playback of vocalization. We report two novel results. First, we observed high-gamma band as well as theta (4-8Hz) coherence between frontal and temporal lobes. Second, both high-gamma and theta coherence were stronger when subjects were actively vocalizing as compared to playback of the same vocalizations. These findings provide evidence that coupling between sensory-motor networks measured by high-gamma coherence plays a key role in feedback-based monitoring and control of vocal output for human vocalization.

In Parkinson's disease patients in the OFF medication state, basal ganglia local field potentials exhibit changes in beta and gamma oscillations that correlate with reduced voluntary movement, manifested as rigidity and akinesia. However, magnetoencephalography and low-resolution electrocorticography (ECoG) studies in Parkinson's patients suggest that changes in sensorimotor cortical oscillations differ from those of the basal ganglia. To more clearly define the role of sensorimotor cortex oscillatory activity in Parkinson's, we performed intraoperative, high-resolution (4 mm spacing) ECoG recordings in 10 Parkinson's patients (2 females, ages 47-72) undergoing deep brain stimulation (DBS) lead placement in the awake, OFF medication state. We analyzed ECoG potentials during a computer-controlled reaching task designed to separate movement preparation from movement execution and compared findings to similar invasive recordings in eight patients with essential tremor (3 females, ages 59-78), a condition not associated with rigidity or akinesia. We show that (1) cortical beta spectral power at rest does not differ between Parkinson's and essential tremor patients (p = 0.85), (2) early motor preparation in Parkinson's patients in the OFF medication state is associated with a larger beta desynchronization compared to patients with essential tremor (p = 0.0061), and (3) cortical broadband gamma power is elevated in Parkinson's patients compared to essential tremor patients during both rest and task recordings (p = 0.004). Our findings suggest an oscillatory profile in sensorimotor cortex of Parkinson's patients that, in contrast to the basal ganglia, may act to promote movement to oppose the anti-kinetic bias of the dopamine-depleted state.

Spectro-Temporal Receptive Fields (STRFs) were estimated from both multi-unit sorted clusters and high-gamma power responses in human auditory cortex. Intracranial electrophysiological recordings were used to measure responses to a random chord sequence of Gammatone stimuli. Traditional methods for estimating STRFs from single-unit recordings, such as spike-triggered-averages, tend to be noisy and are less robust to other response signals such as local field potentials. We present an extension to recently advanced methods for estimating STRFs from generalized linear models (GLM). A new variant of regression using regularization that penalizes non-zero coefficients is described, which results in a sparse solution. The frequency-time structure of the STRF tends toward grouping in different areas of frequency-time and we demonstrate that group sparsity-inducing penalties applied to GLM estimates of STRFs reduces the background noise while preserving the complex internal structure. The contribution of local spiking activity to the high-gamma power signal was factored out of the STRF using the GLM method, and this contribution was significant in 85 percent of the cases. Although the GLM methods have been used to estimate STRFs in animals, this study examines the detailed structure directly from auditory cortex in the awake human brain. We used this approach to identify an abrupt change in the best frequency of estimated STRFs along posteromedial-to-anterolateral recording locations along the long axis of Heschl's gyrus. This change correlates well with a proposed transition from core to non-core auditory fields previously identified using the temporal response properties of Heschl's gyrus recordings elicited by click-train stimuli.

The cerebellum is a critical sensorimotor structure that exhibits protracted postnatal development in mammals. Many aspects of cerebellar circuit development are activity dependent, but little is known about the nature and sources of the activity. Based on previous findings in 6-day-old rats, we proposed that myoclonic twitches, the spontaneous movements that occur exclusively during active sleep (AS), provide generalized as well as topographically precise activity to the developing cerebellum. Taking advantage of known stages of cerebellar cortical development, we examined the relationship between Purkinje cell activity (including complex and simple spikes), nuchal and hindlimb EMG activity, and behavioral state in unanesthetized 4-, 8-, and 12-day-old rats. AS-dependent increases in complex and simple spike activity peaked at 8 days of age, with 60% of units exhibiting significantly more activity during AS than wakefulness. Also, at all three ages, approximately one-third of complex and simple spikes significantly increased their activity within 100 ms of twitches in one of the two muscles from which we recorded. Finally, we observed rhythmicity of complex and simple spikes that was especially prominent at 8 days of age and was greatly diminished by 12 days of age, likely due to developmental changes in climbing fiber and mossy fiber innervation patterns. All together, these results indicate that the neurophysiological activity of the developing cerebellum can be used to make inferences about changes in its microcircuitry. They also support the hypothesis that sleep-related twitches are a prominent source of discrete climbing and mossy fiber activity that could contribute to the activity-dependent development of this critical sensorimotor structure.

High gamma power has become the principal means of assessing auditory cortical activation in human intracranial studies, albeit at the expense of low frequency local field potentials (LFPs). It is unclear whether limiting analyses to high gamma impedes ability of clarifying auditory cortical organization. We compared the two measures obtained from posterolateral superior temporal gyrus (PLST) and evaluated their relative utility in sound categorization. Subjects were neurosurgical patients undergoing invasive monitoring for medically refractory epilepsy. Stimuli (consonant-vowel syllables varying in voicing and place of articulation and control tones) elicited robust evoked potentials and high gamma activity on PLST. LFPs had greater across-subject variability, yet yielded higher classification accuracy, relative to high gamma power. Classification was enhanced by including temporal detail of LFPs and combining LFP and high gamma. We conclude that future studies should consider utilizing both LFP and high gamma when investigating the functional organization of human auditory cortex.

Significance Over the past decade, human posterior parietal cortex (PPC) has been unexpectedly implicated in remembering and memory-related decision making. Functional neuroimaging indicates that memory-related responses differ across PPC, and patients with PPC lesions show subtle to significant changes in memory behavior. These surprising observations have motivated novel theorizing, yet current understanding of PPC contributions to memory is limited by the absence of temporal information about activity in PPC subregions as retrieval decisions unfold. In this study, recordings from the human brain show for the first time that distinct temporal and functional profiles of activity are present in PPC subregions as participants make recognition memory decisions. These new findings inform theories of parietal functional contributions to memory, decision making, and attention.

Humans have a capacity for hierarchical cognitive control-the ability to simultaneously control immediate actions while holding more abstract goals in mind. Neuropsychological and neuroimaging evidence suggests that hierarchical cognitive control emerges from a frontal architecture whereby prefrontal cortex coordinates neural activity in the motor cortices when abstract rules are needed to govern motor outcomes. We utilized the improved temporal resolution of human intracranial electrocorticography to investigate the mechanisms by which frontal cortical oscillatory networks communicate in support of hierarchical cognitive control. Responding according to progressively more abstract rules resulted in greater frontal network theta phase encoding (4-8 Hz) and increased prefrontal local neuronal population activity (high gamma amplitude, 80-150 Hz), which predicts trial-by-trial response times. Theta phase encoding coupled with high gamma amplitude during inter-regional information encoding, suggesting that inter-regional phase encoding is a mechanism for the dynamic instantiation of complex cognitive functions by frontal cortical subnetworks.

Behavioral and EEG studies suggest spatial attention is allocated as a gradient in which processing benefits decrease away from an attended location. Yet the spatiotemporal dynamics of cortical processes that contribute to attentional gradients are unclear. We measured EEG while participants (n = 35) performed an auditory spatial attention task that required a button press to sounds at one target location on either the left or right. Distractor sounds were randomly presented at four non-target locations evenly spaced up to 180° from the target location. Attentional gradients were quantified by regressing ERP amplitudes elicited by distractors against their spatial location relative to the target. Independent component analysis was applied to each subject's scalp channel data, allowing isolation of distinct cortical sources. Results from scalp ERPs showed a tri-phasic response with gradient slope peaks at ~300 ms (frontal, positive), ~430 ms (posterior, negative), and a plateau starting at ~550 ms (frontal, positive). Corresponding to the first slope peak, a positive gradient was found within a central component when attending to both target locations and for two lateral frontal components when contralateral to the target location. Similarly, a central posterior component had a negative gradient that corresponded to the second slope peak regardless of target location. A right posterior component had both an ipsilateral followed by a contralateral gradient. Lateral posterior clusters also had decreases in α and β oscillatory power with a negative slope and contralateral tuning. Only the left posterior component (120-200 ms) corresponded to absolute sound location. The findings indicate a rapid, temporally-organized sequence of gradients thought to reflect interplay between frontal and parietal regions. We conclude these gradients support a target-based saliency map exhibiting aspects of both right-hemisphere dominance and opponent process models.

In rats, forelimb movements can be evoked from two distinct cortical regions, the rostral (RFA) and the caudal (CFA) forelimb areas. RFA and CFA have numerous reciprocal connections, and their projections reach several common targets, which allows them to interact at multiple levels of the motor axis. Lesions affecting these areas result in profound and persistent deficits, supporting their essential role for the production of arm and hand movements. Whereas rats are widely used to study motor control and recovery following lesions, little is known as to how cortical motor areas in this model interact to generate movements. To study interactions between RFA and CFA, we used paired-pulse protocols with intracortical microstimulation techniques (ICMS). A conditioning stimulus (C) in RFA was applied simultaneously, or before a test stimulus (T) in CFA. The impact of RFA conditioning on CFA outputs was quantified by recording electromyographic signals (EMG) signals from the contralateral arm muscles. We found that stimulation of RFA substantially modulates the intensity of CFA outputs while only mildly affecting the latency. In general, the effect of RFA conditioning changed from predominantly facilitatory to inhibitory with increasing delays between the C and the T stimulus. However, inspection of individual cortical sites revealed that RFA has a wide range of influence on CFA outputs with each interstimulation delay we used. Our results show that RFA has powerful and complex modulatory effects on CFA outputs that can allow it to play a major role in the cortical control of forelimb movements.

Humans can accurately localize sounds even in unfavourable signal‐to‐noise conditions. To investigate the neural mechanisms underlying this, we studied the effect of background wide‐band noise on neural sensitivity to variations in interaural level difference ( ILD ), the predominant cue for sound localization in azimuth for high‐frequency sounds, at the characteristic frequency of cells in rat inferior colliculus ( IC ). Binaural noise at high levels generally resulted in suppression of responses (55.8%), but at lower levels resulted in enhancement (34.8%) as well as suppression (30.3%). When recording conditions permitted, we then examined if any binaural noise effects were related to selective noise effects at each of the two ears, which we interpreted in light of well‐known differences in input type (excitation and inhibition) from each ear shaping particular forms of ILD sensitivity in the IC . At high signal‐to‐noise ratios ( SNR ), in most ILD functions (41%), the effect of background noise appeared to be due to effects on inputs from both ears, while for a large percentage (35.8%) appeared to be accounted for by effects on excitatory input. However, as SNR decreased, change in excitation became the dominant contributor to the change due to binaural background noise (63.6%). These novel findings shed light on the IC neural mechanisms for sound localization in the presence of continuous background noise. They also suggest that some effects of background noise on encoding of sound location reported to be emergent in upstream auditory areas can also be observed at the level of the midbrain.

Understanding the dynamics of brain activity manifested in the EEG, local field potentials (LFP), and neuronal spiking is essential for explaining their underlying mechanisms and physiological significance. Much has been learned about sleep regulation using conventional EEG power spectrum, coherence, and period-amplitude analyses, which focus primarily on frequency and amplitude characteristics of the signals and on their spatio-temporal synchronicity. However, little is known about the effects of ongoing brain state or preceding sleep-wake history on the nonlinear dynamics of brain activity. Recent advances in developing novel mathematical approaches for investigating temporal structure of brain activity based on such measures, as Lempel-Ziv complexity (LZC) can provide insights that go beyond those obtained with conventional techniques of signal analysis. Here, we used extensive data sets obtained in spontaneously awake and sleeping adult male laboratory rats, as well as during and after sleep deprivation, to perform a detailed analysis of cortical LFP and neuronal activity with LZC approach. We found that activated brain states—waking and rapid eye movement (REM) sleep are characterized by higher LZC compared with non-rapid eye movement (NREM) sleep. Notably, LZC values derived from the LFP were especially low during early NREM sleep after sleep deprivation and toward the middle of individual NREM sleep episodes. We conclude that LZC is an important and yet largely unexplored measure with a high potential for investigating neurophysiological mechanisms of brain activity in health and disease.

Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.