The human K-complex represents an isolated cortical down-state.

The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated "down-states," a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation.

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.

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.

Sources of somatosensory input to the caudal belt areas of auditory cortex.

The auditory cortex of nonhuman primates is comprised of a constellation of at least twelve interconnected areas distributed across three major regions on the superior temporal gyrus: core, belt, and parabelt. Individual areas are distinguished on the basis of unique profiles comprising architectonic features, thalamic and cortical connections, and neuron response properties. Recent demonstrations of convergent auditory-somatosensory interactions in the caudomedial (CM) and caudolateral (CL) belt areas prompted us to pursue anatomical studies to identify the source(s) of somatic input to auditory cortex. Corticocortical and thalamocortical connections were revealed by injecting neuroanatomical tracers into CM, CL, and adjoining fields of marmoset (Callithrix jacchus jacchus) and macaque (Macaca mulatta) monkeys. In addition to auditory cortex, the cortical connections of CM and CL included somatosensory (retroinsular, Ri; granular insula, Ig) and multisensory areas (temporal parietal occipital, temporal parietal temporal). Thalamic inputs included the medial geniculate complex and several multisensory nuclei (suprageniculate, posterior, limitans, medial pulvinar), but not the ventroposterior complex. Injections of the core (A1, R) and rostromedial areas of auditory cortex revealed sparse multisensory connections. The results suggest that areas Ri and Ig are the principle sources of somatosensory input to the caudal belt, while multisensory regions of cortex and thalamus may also contribute. The present data add to growing evidence of multisensory convergence in cortical areas previously considered to be 'unimodal', and also indicate that auditory cortical areas differ in this respect.

Timing of pure tone and noise-evoked responses in macaque auditory cortex.

We compared onset latencies for characteristic frequency pure tone and broadband noise responses in AI and posterior belt regions of the auditory cortex in awake macaques. We found that (1) in AI, responses to characteristic frequency tones and broadband noise have similar latencies, (2) in belt regions, characteristic frequency tone and broadband noise latencies differ significantly; broadband noise latencies are shorter, while characteristic frequency tone latencies are longer than corresponding values in AI, (3) for both pure tone and broadband noise responses in AI, latency decreases with increasing characteristic frequency and (4) despite a similar inverse relationship of tone latency and local characteristic frequency in belt areas, broadband noise latencies are uniformly short, and appear unrelated to local characteristic frequency. Dissociation of broadband noise and pure tone latencies may reflect the use of parallel anatomical routes into belt regions.

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.

Neurosurgical access to cortical areas in the lateral fissure of primates.

In this report, a method is presented for gaining direct access to cortical areas within the lateral fissure of primates for neuroanatomical tracer injections and electrode array implantation. Compared to areas on the surface of the brain, the anatomical and physiological properties of areas within the fissure are poorly understood. Typically, access to these areas is indirectly achieved by ablating or passing through intervening areas. To enable direct experimental access, a neurosurgical technique was developed in primates whereby the banks of the lateral fissure were retracted with sparing of the vascular network and intervening areas. In some animals, anatomical tracers were directly injected into target fields without contamination of other areas. In others, multichannel electrode arrays were implanted into target areas for chronic recording of neural activity. Since, these techniques could be adapted for exploration of areas within other sulci, the approach represents an important advance in efforts to elucidate the functional organization of the primate cerebral cortex.

Laminar analysis of human neocortical interictal spike generation and propagation: current source density and multiunit analysis in vivo.

Multicontact microelectrodes were chronically implanted in epilepsy patients undergoing subdural grid implantation for seizure localization. Current source density and multiple unit activity of interictal spikes (IISs) were sampled every approximately 150 microm in a line traversing all layers of a cortical column. Our data suggest that interictal epileptiform events in humans are initiated by large postsynaptic depolarizations, consistent with the hypothesis that human IISs correspond to animal paroxysmal depolarization shifts. Furthermore, the cortical layer where the initial depolarization occurs may differ according to whether the IIS is locally generated or propagated from a distant location, and among the propagated IISs, whether the IIS is in the direct path of propagation or on the periphery of that path.

In vivo laminar electrophysiology co-registered with histology in the hippocampus of patients with temporal lobe epilepsy.

Laminar multiple microelectrodes have been developed to sample cortical and hippocampal activity in animals. If these measurements are adequately co-registered with the anatomy of the region, they can yield important information about its function and structure. In vivo laminar electrophysiological recordings from the human epileptic hippocampus are rare. However, histological and immunohistochemical analyses are widely used to determine the structural changes associated with temporal lobe epilepsy (TLE). Here we present data obtained by a combined approach: intraoperative recording of laminar field potentials, single and multiple unit activity under anesthesia, accompanied by histology and immunohistochemistry from the same hippocampal region of epileptic patients undergoing temporal lobectomy for drug-resistant TLE. The stability of the electrophysiology and the accuracy of its co-registration with histology were tested successfully. We have found large field potential spikes associated with bursting single units in CA1. Intracortical and subdural strip recordings from the lateral temporal cortex showed similar field potential activation patterns. A prominent oscillatory activity was present in the dentate gyrus with highly localized field potential gradient and multiple unit activity. This pattern could be used as a landmark defining the position of the electrode in the hippocampus. Our findings indicate that some aspects of the local and network epileptiform activity in the hippocampal formation are likely preserved under anesthesia. Electrophysiological identification of the functional state of the hippocampus together with its local structural correlates could further enhance our understanding of this disease.

Effect of deviant probability and interstimulus/interdeviant interval on the auditory N1 and mismatch negativity in the cat auditory cortex.

In passive oddball paradigm the effects of changes in interstimulus/interdeviant interval (ISI; IDI) and deviant probability were investigated on mismatch negativity (MMN), auditory N1 wave and the exogenous P1 component of the auditory event-related potential in the cat. An epidural electrode matrix was chronically implanted over the auditory fields of the neocortex, and the amplitudes of the aforementioned components were measured in the location of their amplitude maxima. Dependence of the MMN both on the ISI and IDI as well as deviant probability was revealed, while the amplitude of the P1 and N1 showed dependence merely on the ISI. This method can be used for separation of the two negative, often overlapping components in the cat.