Yoshinao Kajikawa

Extracellular electrophysiological recordings reflect both the organization of neural activity and the geometry through which that activity is sampled. Here, we used biophysical modeling and experimental recordings from the macaque auditory cortex to determine how cortical activity is transformed across neural sources, extracellular signals, and recording geometries. In a biophysically detailed thalamocortical model, four separately instantiated cortical-column conditions spanning graded thalamic recruitment exhibited a graded response hierarchy across local field potential, current-source density, and multiunit activity, despite signal-dependent differences in the contributions of cortical neuronal populations. We then arranged independently simulated cortical columns into controlled spatial configurations and sampled the same underlying sources using virtual linear laminar and Directional and Scalable (DiSc) electrode arrays. The linear geometry primarily represented variation along cortical depth, whereas DiSc additionally represented circumferential variation associated with lateral source organization, demonstrating that recording geometry determines which spatial dimensions of common underlying activity are represented in extracellular measurements. Experimental recordings obtained with the corresponding geometries were consistent with these model-derived predictions: broadband-noise responses exhibited spatial organization shared across tone-evoked responses in both multidimensional DiSc maps and laminar profiles, despite substantial variation in frequency-dependent response magnitude across penetrations. Together, these results show that extracellular measurements represent an interaction between biological source organization and recording geometry. Biophysical forward modeling therefore provides a framework for determining which features of underlying circuit organization remain identifiable after extracellular sampling and for relating neural-interface design to the dimensions of cortical activity accessible experimentally.

Amplitude-modulation (AM) is critical for the perception of complex sounds, and transformations in AM encoding may underlie primate-specific aspects of complex sound perception. The nonhuman primate model provides an opportunity to understand what circuit mechanisms generate hierarchical and interhemispheric transformations of AM encoding in different circuits across the cortical hierarchy. To address this, here we report the encoding of AM signals as a function of cortical layer and hemisphere in primary area A1 and the tertiary parabelt (PB) area of five NHPs. We presented AM noise and click trains to awake NHPs while recording from linear array multielectrodes spanning cortical layers. A1 typically encoded all AM frequencies (1.6-200 Hz) with high ( > 90%) classification accuracy, while the PB encoded lower (∼1.6-25 Hz) frequencies. The laminar gradient observed in A1 (Granular > Infragranular > Supragranular was inverted in PB (Supragranular > Infragranular > Granular), consistent with differences in thalamocortical input. Both areas displayed enhanced AM encoding in the left hemisphere, restricted to the supragranular layers. These results represent the first analysis of AM encoding in the PB, in which we identify circuits differing in their temporal sensitivity across the hierarchy, and suggest local supragranular neuronal populations contribute to hemispheric specialization.

High-frequency (>60 Hz) neuroelectric signals likely have functional roles distinct from low-frequency (60 Hz) does not simply equate to neuronal spiking, they are highly correlated, having similar information encoding. High-gamma activity is typically considered broadband and poorly phase-locked to sensory stimuli and thus is typically analyzed after transformations into absolute amplitude or spectral power. However, those analyses discard signal polarity, compromising the interpretation of neuroelectric events that are essentially dipolar. In the spectrotemporal profiles of field potentials in auditory cortex, we show high-frequency spectral peaks not phase-locked to sound onset, which follow the broadband peak of phase-locked onset responses. Isolating the signal components comprising the high-frequency peaks reveals narrow-band high-frequency oscillatory events, whose instantaneous frequency changes rapidly from >150 to 60 Hz, which may underlie broadband high-frequency spectral peaks in previous reports. The laminar amplitude distributions of the isolated activity had two peak positions, while the laminar phase patterns showed a counterphase relationship between those peaks, indicating the formation of dipoles. Our findings suggest that nonphase-locked HGA arises in part from oscillatory or recurring activity of supragranular-layer neuronal ensembles in auditory cortex.

We investigated the time courses of saccade rate following visual stimuli during three conditions of free viewing in macaque monkeys. Under all conditions, saccade rate decreased transiently after the onset of visual stimuli. These results suggest that saccadic inhibition occurs during free viewing.

Field potentials (FPs) reflect neuronal activities in the brain, and often exhibit traveling peaks across recording sites. While traveling FPs are interpreted as propagation of neuronal activity, not all studies directly reveal such propagating patterns of neuronal activation. Neuronal activity is associated with transmembrane currents that form dipoles and produce negative and positive fields. Thereby, FP components reverse polarity between those fields and have minimal amplitudes at the center of dipoles. Although their amplitudes could be smaller, FPs are never flat even around these reversals. What occurs around the reversal has not been addressed explicitly, although those are rationally in the middle of active neurons. We show that sensory FPs around the reversal appeared with peaks traveling across cortical laminae in macaque sensory cortices. Interestingly, analyses of current source density did not depict traveling patterns but lamina-delimited current sinks and sources. We simulated FPs produced by volume conduction of a simplified 2 dipoles9 model mimicking sensory cortical laminar current source density components. While FPs generated by single dipoles followed the temporal patterns of the dipole moments without traveling peaks, FPs generated by concurrently active dipole moments appeared with traveling components in the vicinity of dipoles by superimposition of individually non-traveling FPs generated by single dipoles. These results indicate that not all traveling FP are generated by traveling neuronal activity, and that recording positions need to be taken into account to describe FP peak components around active neuronal populations. SIGNIFICANCE STATEMENT Field potentials (FPs) generated by neuronal activity in the brain occur with fields of opposite polarity. Likewise, in the cerebral cortices, they have mirror-imaged waveforms in upper and lower layers. We show that FPs appear like traveling across the cortical layers. Interestingly, the traveling FPs occur without traveling components of current source density, which represents transmembrane currents associated with neuronal activity. These seemingly odd findings are explained using current source density models of multiple dipoles. Concurrently active, non-traveling dipoles produce FPs as mixtures of FPs produced by individual dipoles, and result in traveling FP waveforms as the mixing ratio depends on the distances from those dipoles. The results suggest that not all traveling FP components are associated with propagating neuronal activity.

Traveling waves appear in various signals that measure neuronal activity. Some signals measured in animals have singles-cell resolution and directly point to neuronal activity. In those cases, activation of distributed neurons forms a wave front, and the front propagates across the cortical surface. Other signals are variants of neuroelectric potentials, i.e. electroencephalography, electrocorticography and field potentials. Instead of having fine spatial resolution, these signals reflect the activity of neuronal populations via volume conduction (VC). Sources of traveling waves in neuroelectric potentials have not been well addressed so far. As animal studies show propagating activation of neurons that spread in measured areas, it is often considered that neuronal activations during scalp waves have similar trajectories of activation, spreading like scalp waves. However, traveling waves on the scalp differ from those found directly on the cortical surface in several dimensions: traveling velocity, traveling distance and areal size occupied by single polarity. We describe that the simplest sources can produce scalp waves with perceived spatial dimensions which are actually a magnification of neuronal activity emanating from local sources due to VC. This viewpoint is not a rigorous proof of our magnification concept. However, we suggest the possibility that the actual dimensions of neuronal activity producing traveling waves is not as large as the dimension of the traveling waves.

Face recognition is an essential activity of social living, common to many primate species. Underlying processes in the brain have been investigated using various techniques and compared between species. Functional imaging studies have shown face-selective cortical regions and their degree of correspondence across species. However, the temporal dynamics of face processing, particularly processing speed, are likely different between them. Across sensory modalities activation of primary sensory cortices in macaque monkeys occurs at about 3/5 the latency of corresponding activation in humans, though this human simian difference may diminish or disappear in higher cortical regions. We recorded scalp event-related potentials (ERPs) to presentation of faces in macaques and estimated the peak latency of ERP components. Comparisons of latencies between macaques (112 ms) and humans (192 ms) suggested that the 3:5 ratio could be preserved in higher cognitive regions of face processing between those species.

BHA (aka high gamma) correlates with neuronal firing, but is generated mainly by dendritic processes separable from firing.

Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses.SIGNIFICANCE STATEMENTField potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed “local” (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers.

In somatosensory cortex, tactile stimulation within the neuronal receptive field (RF) typically evokes a transient excitatory response with or without postexcitatory inhibition. Here, we describe neuronal responses in which stimulation on the hand is followed by suppression of the ongoing discharge. With the use of 16-channel microelectrode arrays implanted in the hand representation of primary somatosensory cortex of New World monkeys and prosimian galagos, we recorded neuronal responses from single units and neuron clusters. In 66% of our sample, neuron activity tended to display suppression of firing when regions of skin outside of the excitatory RF were stimulated. In a small proportion of neurons, single-site indentations suppressed firing without initial increases in response to any of the tested sites on the hand. Latencies of suppressive responses to skin indentation (usually 12–34 ms) were similar to excitatory response latencies. The duration of inhibition varied across neurons. Although most observations were from anesthetized animals, we also found similar neuron response properties in one awake galago. Notably, suppression of ongoing neuronal activity did not require conditioning stimuli or multi-site stimulation. The suppressive effects were generally seen following single-site skin indentations outside of the neuron's minimal RF and typically on different digits and palm pads, which have not often been studied in this context. Overall, the characteristics of widespread suppressive or inhibitory response properties with and without initial facilitative or excitatory responses add to the growing evidence that neurons in primary somatosensory cortex provide essential processing for integrating sensory stimulation from across the hand.