Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents.

Slow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report propagating population activity in the thalamus of ketamine/xylazine-anesthetized rats and mice visualized by high-density silicon probe recordings. In both rodent species, propagation of spontaneous thalamic activity during up-states was most frequently observed in dorsal thalamic nuclei such as the higher order posterior (Po), lateral posterior (LP) or laterodorsal (LD) nuclei. The preferred direction of thalamic activity spreading was along the dorsoventral axis, with over half of the up-states exhibiting a gradual propagation in the ventral-to-dorsal direction. Furthermore, simultaneous neocortical and thalamic recordings collected under anesthesia demonstrated that there is a weak but noticeable interrelation between propagation patterns observed during cortical up-states and those displayed by thalamic population activity. In addition, using chronically implanted silicon probes, we detected propagating activity patterns in the thalamus of naturally sleeping rats during slow-wave sleep. However, in comparison to propagating up-states observed under anesthesia, these propagating patterns were characterized by a reduced rate of occurrence and a faster propagation speed. Our findings suggest that the propagation of spontaneous population activity is an intrinsic property of the thalamocortical network during synchronized brain states such as deep sleep or anesthesia. Additionally, our data implies that the neocortex may have partial control over the formation of propagation patterns within the dorsal thalamus under anesthesia.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

Associative and plastic thalamic signaling to the lateral amygdala controls fear behavior.

Decades of research support the idea that associations between a conditioned stimulus (CS) and an unconditioned stimulus (US) are encoded in the lateral amygdala (LA) during fear learning. However, direct proof for the sources of CS and US information is lacking. Definitive evidence of the LA as the primary site for cue association is also missing. Here, we show that calretinin (Calr)-expressing neurons of the lateral thalamus (Calr+LT neurons) convey the association of fast CS (tone) and US (foot shock) signals upstream from the LA in mice. Calr+LT input shapes a short-latency sensory-evoked activation pattern of the amygdala via both feedforward excitation and inhibition. Optogenetic silencing of Calr+LT input to the LA prevents auditory fear conditioning. Notably, fear conditioning drives plasticity in Calr+LT neurons, which is required for appropriate cue and contextual fear memory retrieval. Collectively, our results demonstrate that Calr+LT neurons provide integrated CS-US representations to the LA that support the formation of aversive memories.

The generation and propagation of the human alpha rhythm.

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

A silicon-based neural probe with densely-packed low-impedance titanium nitride microelectrodes for ultrahigh-resolution in vivo recordings.

In this study, we developed and validated a single-shank silicon-based neural probe with 128 closely-packed microelectrodes suitable for high-resolution extracellular recordings. The 8-mm-long, 100-µm-wide and 50-µm-thick implantable shank of the probe fabricated using a 0.13-µm complementary metal-oxide-semiconductor (CMOS) metallization technology contains square-shaped (20 × 20 µm2), low-impedance (~ 50 kΩ at 1 kHz) recording sites made of rough and porous titanium nitride which are arranged in a 32 × 4 dense array with an inter-electrode pitch of 22.5 µm. The electrophysiological performance of the probe was tested in in vivo experiments by implanting it acutely into neocortical areas of anesthetized animals (rats, mice and cats). We recorded local field potentials, single- and multi-unit activity with superior quality from all layers of the neocortex of the three animal models, even after reusing the probe in multiple (> 10) experiments. The low-impedance electrodes monitored spiking activity with high signal-to-noise ratio; the peak-to-peak amplitude of extracellularly recorded action potentials of well-separable neurons ranged from 0.1 mV up to 1.1 mV. The high spatial sampling of neuronal activity made it possible to detect action potentials of the same neuron on multiple, adjacent recording sites, allowing a more reliable single unit isolation and the investigation of the spatiotemporal dynamics of extracellular action potential waveforms in greater detail. Moreover, the probe was developed with the specific goal to use it as a tool for the validation of electrophysiological data recorded with high-channel-count, high-density neural probes comprising integrated CMOS circuitry.

Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe.

Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study.

Ongoing network state controls the length of sleep spindles via inhibitory activity.

Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in the thalamus; however, what determines their duration is presently unclear. Here, we measured somatic activity of excitatory thalamocortical (TC) cells together with axonal activity of reciprocally coupled inhibitory reticular thalamic cells (nRTs) and quantified cycle-by-cycle alterations in their firing in vivo. We found that spindles with different durations were paralleled by distinct nRT activity, and nRT firing sharply dropped before the termination of all spindles. Both initial nRT and TC activity was correlated with spindle length, but nRT correlation was more robust. Analysis of spindles evoked by optogenetic activation of nRT showed that spindle probability, but not spindle length, was determined by the strength of the light stimulus. Our data indicate that during natural sleep a dynamically fluctuating thalamocortical network controls the duration of sleep spindles via the major inhibitory element of the circuits, the nRT.

Physiological sharp wave-ripples and interictal events in vitro: what's the difference?

Sharp wave-ripples and interictal events are physiological and pathological forms of transient high activity in the hippocampus with similar features. Sharp wave-ripples have been shown to be essential in memory consolidation, whereas epileptiform (interictal) events are thought to be damaging. It is essential to grasp the difference between physiological sharp wave-ripples and pathological interictal events to understand the failure of control mechanisms in the latter case. We investigated the dynamics of activity generated intrinsically in the Cornu Ammonis region 3 of the mouse hippocampus in vitro, using four different types of intervention to induce epileptiform activity. As a result, sharp wave-ripples spontaneously occurring in Cornu Ammonis region 3 disappeared, and following an asynchronous transitory phase, activity reorganized into a new form of pathological synchrony. During epileptiform events, all neurons increased their firing rate compared to sharp wave-ripples. Different cell types showed complementary firing: parvalbumin-positive basket cells and some axo-axonic cells stopped firing as a result of a depolarization block at the climax of the events in high potassium, 4-aminopyridine and zero magnesium models, but not in the gabazine model. In contrast, pyramidal cells began firing maximally at this stage. To understand the underlying mechanism we measured changes of intrinsic neuronal and transmission parameters in the high potassium model. We found that the cellular excitability increased and excitatory transmission was enhanced, whereas inhibitory transmission was compromised. We observed a strong short-term depression in parvalbumin-positive basket cell to pyramidal cell transmission. Thus, the collapse of pyramidal cell perisomatic inhibition appears to be a crucial factor in the emergence of epileptiform events.

Drivers of the primate thalamus.

The activity of thalamocortical neurons is primarily determined by giant excitatory terminals, called drivers. These afferents may arise from neocortex or from subcortical centers; however, their exact distribution, segregation, or putative absence in given thalamic nuclei are unknown. To unravel the nucleus-specific composition of drivers, we mapped the entire macaque thalamus using vesicular glutamate transporters 1 and 2 to label cortical and subcortical afferents, respectively. Large thalamic territories were innervated exclusively by either giant vGLUT2- or vGLUT1-positive boutons. Codistribution of drivers with different origin was not abundant. In several thalamic regions, no giant terminals of any type could be detected at light microscopic level. Electron microscopic observation of these territories revealed either the complete absence of large multisynaptic excitatory terminals (basal ganglia-recipient nuclei) or the presence of both vGLUT1- and vGLUT2-positive terminals, which were significantly smaller than their giant counterparts (intralaminar nuclei, medial pulvinar). In the basal ganglia-recipient thalamus, giant inhibitory terminals replaced the excitatory driver inputs. The pulvinar and the mediodorsal nucleus displayed subnuclear heterogeneity in their driver assemblies. These results show that distinct thalamic territories can be under pure subcortical or cortical control; however, there is significant variability in the composition of major excitatory inputs in several thalamic regions. Because thalamic information transfer depends on the origin and complexity of the excitatory inputs, this suggests that the computations performed by individual thalamic regions display considerable variability. Finally, the map of driver distribution may help to resolve the morphological basis of human diseases involving different parts of the thalamus.

Phase advancement and nucleus-specific timing of thalamocortical activity during slow cortical oscillation.

The exact timing of cortical afferent activity is instrumental for the correct coding and retrieval of internal and external stimuli. Thalamocortical inputs represent the most significant subcortical pathway to the cortex, but the precise timing and temporal variability of thalamocortical activity is not known. To examine this question, we studied the phase of thalamic action potentials relative to cortical oscillations and established correlations among phase, the nuclear location of the thalamocortical neurons, and the frequency of cortical activity. The phase of thalamic action potentials depended on the exact frequency of the slow cortical oscillation both on long (minutes) and short (single wave) time scales. Faster waves were accompanied by phase advancement in both cases. Thalamocortical neurons located in different nuclei fired at significantly different phases of the slow waves but were active at a similar phase of spindle oscillations. Different thalamic nuclei displayed distinct burst patterns. Bursts with a higher number of action potentials displayed progressive phase advancement in a nucleus-specific manner. Thalamic neurons located along nuclear borders were characterized by mixed burst and phase properties. Our data demonstrate that the temporal relationship between cortical and thalamic activity is not fixed but displays dynamic changes during oscillatory activity. The timing depends on the precise location and exact activity of thalamocortical cells and the ongoing cortical network pattern. This variability of thalamic output and its coupling to cortical activity can enable thalamocortical neurons to actively participate in the coding and retrieval of cortical signals.

Phase entrainment of human delta oscillations can mediate the effects of expectation on reaction speed.

The more we anticipate a response to a predictable stimulus, the faster we react. This empirical observation has been confirmed and quantified by many investigators suggesting that the processing of behaviorally relevant stimuli is facilitated by probability-based confidence of anticipation. However, the exact neural mechanisms underlying this phenomenon are largely unknown. Here we show that performance changes related to different levels of expectancy originate in dynamic modulation of delta oscillation phase. Our results obtained in rhythmic auditory target detection tasks indicated significant entrainment of the EEG delta rhythm to the onset of the target tones with increasing phase synchronization at higher levels of predictability. Reaction times correlated with the phase of the delta band oscillation at target onset. The fastest reactions occurred during the delta phase that most commonly coincided with the target event in the high expectancy conditions. These results suggest that low-frequency oscillations play a functional role in human anticipatory mechanisms, presumably by modulating synchronized rhythmic fluctuations in the excitability of large neuronal populations and by facilitating efficient task-related neuronal communication among brain areas responsible for sensory processing and response execution.

Estimation of thalamocortical and intracortical network models from joint thalamic single-electrode and cortical laminar-electrode recordings in the rat barrel system.

A new method is presented for extraction of population firing-rate models for both thalamocortical and intracortical signal transfer based on stimulus-evoked data from simultaneous thalamic single-electrode and cortical recordings using linear (laminar) multielectrodes in the rat barrel system. Time-dependent population firing rates for granular (layer 4), supragranular (layer 2/3), and infragranular (layer 5) populations in a barrel column and the thalamic population in the homologous barreloid are extracted from the high-frequency portion (multi-unit activity; MUA) of the recorded extracellular signals. These extracted firing rates are in turn used to identify population firing-rate models formulated as integral equations with exponentially decaying coupling kernels, allowing for straightforward transformation to the more common firing-rate formulation in terms of differential equations. Optimal model structures and model parameters are identified by minimizing the deviation between model firing rates and the experimentally extracted population firing rates. For the thalamocortical transfer, the experimental data favor a model with fast feedforward excitation from thalamus to the layer-4 laminar population combined with a slower inhibitory process due to feedforward and/or recurrent connections and mixed linear-parabolic activation functions. The extracted firing rates of the various cortical laminar populations are found to exhibit strong temporal correlations for the present experimental paradigm, and simple feedforward population firing-rate models combined with linear or mixed linear-parabolic activation function are found to provide excellent fits to the data. The identified thalamocortical and intracortical network models are thus found to be qualitatively very different. While the thalamocortical circuit is optimally stimulated by rapid changes in the thalamic firing rate, the intracortical circuits are low-pass and respond most strongly to slowly varying inputs from the cortical layer-4 population.

Entrainment of neuronal oscillations as a mechanism of attentional selection.

Whereas gamma-band neuronal oscillations clearly appear integral to visual attention, the role of lower-frequency oscillations is still being debated. Mounting evidence indicates that a key functional property of these oscillations is the rhythmic shifting of excitability in local neuronal ensembles. Here, we show that when attended stimuli are in a rhythmic stream, delta-band oscillations in the primary visual cortex entrain to the rhythm of the stream, resulting in increased response gain for task-relevant events and decreased reaction times. Because of hierarchical cross-frequency coupling, delta phase also determines momentary power in higher-frequency activity. These instrumental functions of low-frequency oscillations support a conceptual framework that integrates numerous earlier findings.

Structural correlates of efficient GABAergic transmission in the basal ganglia-thalamus pathway.

Giant inhibitory terminals with multiple synapses, the counterparts of excitatory "detonator" or "driver" terminals, have not been described in the forebrain. Using three-dimensional reconstructions of electron microscopic images, we quantitatively characterize a GABAergic pathway that establishes synaptic contacts exclusively via multiple synapses. Axon terminals of the nigrothalamic pathway formed, on average, 8.5 synapses on large-diameter dendrites and somata of relay cells in the ventromedial nucleus of the rat thalamus. All synapses of a given terminal converged on a single postsynaptic element. The vast majority of the synapses established by a single terminal were not separated by astrocytic processes. Nigrothalamic terminals in the macaque monkey showed the same ultrastructural features both in qualitative and quantitative terms (the median number of synapse per target was also 8.5). The individual synapses were closely spaced in both species. The nearest-neighbor synaptic distances were 169 nm in the rat and 178 nm in the monkey. The average number of synapses within 0.75 microm from any given synapse was 3.8 in the rat and 3.5 in the monkey. The arrangement of synapses described in this study creates favorable conditions for intersynaptic spillover of GABA among the multiple synapses of a single bouton, which can result in larger charge transfer. This could explain faithful and efficient GABAergic signal transmission in the nigrothalamic pathway in the healthy condition and during Parkinson's disease. In addition, our structural data suggest that the rodent nigrothalamic pathway can be a valid model of the primate condition, when the mechanism of GABAergic transmission is studied.

Multisensory convergence in auditory cortex, II. Thalamocortical connections of the caudal superior temporal plane.

Recent studies of macaque monkey auditory cortex have revealed convergent auditory and somatosensory activity in the caudomedial area (CM) of the belt region. In the present study and its companion (Smiley et al., J. Comp. Neurol. [this issue]), neuroanatomical tracers were injected into CM and adjacent areas of the superior temporal plane to identify sources of auditory and somatosensory input to this region. Other than CM, target areas included: A1, caudolateral belt (CL), retroinsular (Ri), and temporal parietotemporal (Tpt). Cells labeled by injections of these areas were distributed mainly among the ventral (MGv), posterodorsal (MGpd), anterodorsal (MGad), and magnocellular (MGm) divisions of the medial geniculate complex (MGC) and several nuclei with established multisensory features: posterior (Po), suprageniculate (Sg), limitans (Lim), and medial pulvinar (PM). The principal inputs of CM were MGad, MGv, and MGm, with secondary inputs from multisensory nuclei. The main inputs of CL were Po and MGpd, with secondary inputs from MGad, MGm, and multisensory nuclei. A1 was dominated by inputs from MGv and MGad, with light multisensory inputs. The input profile of Tpt closely resembled that of CL, but with reduced MGC inputs. Injections of Ri also involved CM but strongly favored MGm and multisensory nuclei, with secondary inputs from MGC and the inferior division (VPI) of the ventroposterior complex (VP). The results indicate that the thalamic inputs of areas in the caudal superior temporal plane arise mainly from the same nuclei, but in different proportions. Somatosensory inputs may reach CM and CL through MGm or the multisensory nuclei but not VP.

Multisensory convergence in auditory cortex, I. Cortical connections of the caudal superior temporal plane in macaque monkeys.

The caudal medial auditory area (CM) has anatomical and physiological features consistent with its role as a first-stage (or "belt") auditory association cortex. It is also a site of multisensory convergence, with robust somatosensory and auditory responses. In this study, we investigated the cerebral cortical sources of somatosensory and auditory inputs to CM by injecting retrograde tracers in macaque monkeys. A companion paper describes the thalamic connections of CM (Hackett et al., J. Comp. Neurol. [this issue]). The likely cortical sources of somatosensory input to CM were the adjacent retroinsular cortex (area Ri) and granular insula (Ig). In addition, CM had reliable connections with areas Tpt and TPO, which are sites of multisensory integration. CM also had topographic connections with other auditory areas. As expected, connections with adjacent caudal auditory areas were stronger than connections with rostral areas. Surprisingly, the connections with the core were concentrated along its medial side, suggesting that there may be a medial-lateral division of function within the core. Additional injections into caudal lateral auditory area (CL) and Tpt showed similar connections with Ri, Ig, and TPO. In contrast to CM injections, these lateral injections had inputs from parietal area 7a and had a preferential connection with the lateral (gyral) part of Tpt. Taken together, the findings indicate that CM may receive somatosensory input from nearby areas along the fundus of the lateral sulcus. The differential connections of CM compared with adjacent areas provide additional evidence for the functional specialization of the individual auditory belt areas.

An oscillatory hierarchy controlling neuronal excitability and stimulus processing in the auditory cortex.

EEG oscillations are hypothesized to reflect cyclical variations in the neuronal excitability, with particular frequency bands reflecting differing spatial scales of brain operation. However, despite decades of clinical and scientific investigation, there is no unifying theory of EEG organization, and the role of ongoing activity in sensory processing remains controversial. This study analyzed laminar profiles of synaptic activity [current source density CSD] and multiunit activity (MUA), both spontaneous and stimulus-driven, in primary auditory cortex of awake macaque monkeys. Our results reveal that the EEG is hierarchically organized; delta (1-4 Hz) phase modulates theta (4-10 Hz) amplitude, and theta phase modulates gamma (30-50 Hz) amplitude. This oscillatory hierarchy controls baseline excitability and thus stimulus-related responses in a neuronal ensemble. We propose that the hierarchical organization of ambient oscillatory activity allows auditory cortex to structure its temporal activity pattern so as to optimize the processing of rhythmic inputs.

Selective GABAergic control of higher-order thalamic relays.

GABAergic signaling is central to the function of the thalamus and has been traditionally attributed primarily to the nucleus reticularis thalami (nRT). Here we present a GABAergic pathway, distinct from the nRT, that exerts a powerful inhibitory effect selectively in higher-order thalamic relays of the rat. Axons originating in the anterior pretectal nucleus (APT) innervated the proximal dendrites of relay cells via large GABAergic terminals with multiple release sites. Stimulation of the APT in an in vitro slice preparation revealed a GABA(A) receptor-mediated, monosynaptic IPSC in relay cells. Activation of presumed single APT fibers induced rebound burst firing in relay cells. Different APT neurons recorded in vivo displayed fast bursting, tonic, or rhythmic firing. Our data suggest that selective extrareticular GABAergic control of relay cell activity will result in effective, state-dependent gating of thalamocortical information transfer in higher-order but not in first-order relays.

Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity.

Accurate interpretation of functional MRI (fMRI) signals requires knowledge of the relationship between the hemodynamic response and the neuronal activity that underlies it. Here we address the question of coupling between pre- and postsynaptic neuronal activity and the hemodynamic response in rodent somatosensory (Barrel) cortex in response to single-whisker deflection. Using full-field multiwavelength optical imaging of hemoglobin oxygenation and electrophysiological recordings of spiking activity and local field potentials, we demonstrate that a point hemodynamic measure is influenced by neuronal activity across multiple cortical columns. We demonstrate that the hemodynamic response is a spatiotemporal convolution of the neuronal activation. Therefore, positive hemodynamic response in one cortical column might be explained by neuronal activity not only in that column but also in the neighboring columns. Thus, attempts at characterizing the neurovascular relationship based on point measurements of electrophysiology and hemodynamics may yield inconsistent results, depending on the spatial extent of neuronal activation. The finding that the hemodynamic signal observed at a given location is a function of electrophysiological activity over a broad spatial region helps explain a previously observed increase of local vascular response beyond the saturation of local neuronal activity. We also demonstrate that the oxy- and total-hemoglobin hemodynamic responses can be well approximated by space-time separable functions with an antagonistic center-surround spatial pattern extending over several millimeters. The surround "negative" hemodynamic activity did not correspond to observable changes in neuronal activity. The complex spatial integration of the hemodynamic response should be considered when interpreting fMRI data.

Responses of human anterior cingulate cortex microdomains to error detection, conflict monitoring, stimulus-response mapping, familiarity, and orienting.

Human anterior cingulate cortex (ACC) activity modulation has been observed in numerous tasks, consistent with a wide variety of functions. However, previous recordings have not had sufficient spatial resolution to determine whether microdomains (approximately one to two columns) are involved in multiple tasks, how activity is distributed across cortical layers, or indeed whether modulation reflected neuronal excitation, inhibition, or both. In this study, linear arrays of 24 microelectrodes were used to estimate population synaptic currents and neuronal firing in different layers of ACC during simple/choice reaction time, delayed word recognition, rhyming, auditory oddball, and cued conditional letter-discrimination tasks. Responses to all tasks, with differential responses to errors, familiarity, difficulty, and orienting, were recorded in single microdomains. The strongest responses occurred approximately 300-800 ms after stimulus onset and were usually a current source with inhibited firing, strongly suggesting active inhibition in superficial layers during the behavioral response period. This was usually followed by a sink from approximately 800 to 1400 ms, consistent with postresponse rebound activation. Transient phase locking of task-related theta activity in superficial cingulate layers suggested extended interactions with medial and lateral frontal and temporal sites. These data suggest that each anterior cingulate microdomain participates in a multilobar cortical network after behavioral responses in a variety of tasks.