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Summary: Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols. : Noninvasive fMRI in macaques is an essential tool in translation research. Xu et al. establish the individual functional parcellation of the macaque cortex and demonstrate that brain organization is unique, reproducible, and valid, serving as a fingerprint for an individual macaque. Keywords: macaque, parcellation, cortical areas, gradient, functional connectivity

BHA (aka high gamma) correlates with neuronal firing, but is generated mainly by dendritic processes separable from firing., Broadband high-frequency activity (BHA; 70 to 150 Hz), also known as “high gamma,” a key analytic signal in human intracranial (electrocorticographic) recordings, is often assumed to reflect local neural firing [multiunit activity (MUA)]. As the precise physiological substrates of BHA are unknown, this assumption remains controversial. Our analysis of laminar multielectrode data from V1 and A1 in monkeys outlines two components of stimulus-evoked BHA distributed across the cortical layers: an “early-deep” and “late-superficial” response. Early-deep BHA has a clear spatial and temporal overlap with MUA. Late-superficial BHA was more prominent and accounted for more of the BHA signal measured near the cortical pial surface. However, its association with local MUA is weak and often undetectable, consistent with the view that it reflects dendritic processes separable from local neuronal firing.

Introduction Transcranial electric stimulation (TES) is an emerging technique to non-invasively modulate brain function. However, the spatiotemporal distribution of electric fields during TES remains poorly understood. Objectives In this study we perform direct intracranial measurements of the electric field generated by transcranial alternating current (tACS) in epilepsy patients and cebus monkeys and evaluate the capacity of finite element method (FEM) models to predict the spatial distribution of measured electric fields. Methods Two presurgical epilepsy patients, with ca. 100 intracranially implanted electrodes participated in a single TES session. Two sponge electrodes (25 cm2) were attached over the left and right temporal cortex and a current of 1 mA with a frequency of 1 Hz was applied for 2 min. In two cebus monkeys three electrodes, with a total of 32 contacts were permanently implanted with posterior-anterior orientation. In multiple sessions intracranial EEG was recorded during TES. We varied the frequency of stimulation from 1–150 Hz and computed amplitude and phase relationships of recorded voltages. We constructed FEM models with increasing anatomical complexity for one epilepsy patient and compared the measured and simulated electric fields. Results Voltage magnitude slightly decreased with stimulation frequency up to 10% and small phase differences between electrode contacts up to a few degrees were observed. Electric field strengths were strongest in superficial brain regions with maximum values of 0.5 mV/mm ( Download : Download high-res image (1MB) Download : Download full-size image Fig. 1). Comparison of measured and simulated potentials and electric fields showed very high correlation values for the potentials (r = 0.95) and correlations of r = 0.7 for the electric fields. Evaluating the predictive value of increasingly complex FEM models highlighted the importance of accurate skull modeling especially in the vicinity of skull defects ( Download : Download high-res image (746KB) Download : Download full-size image Fig. 2). Conclusion We conducted a comprehensive evaluation of intracranial electric field during TES in both human patients and monkeys. Our results indicate that TES currents spread in a linear ohmic manner and capacitive effects are small indicating that the quasi-static approximation is well justified in the low frequency range. The spatial variation of the electric fields can be captured using realistic FEM models.

Introduction Cellular targets of transcranial electric stimulation (TES) are not well understood. Due to a number of factors including size, packing, myelination and orientation of predominant cell types and related variations in conductivity across layers, some cortical layers may be more susceptible to stimulation than others. Current biophysical models of TES do not account for laminar specific differences in the electric field distribution. Objectives In this study we systematically mapped the electric field distribution during TES across cortical layers as a function of electrode montage, stimulation frequency and cortical depth. Methods Using laminar multielectrode recordings (100 μm spacing, 24 contacts, implanted in V1) in an anesthetized cebus monkey we recorded TES induced potentials for two montages: 1. Anterior-Posterior current direction, electrodes placed over V1 and forehead. 2. Left–Right current direction, electrodes placed over bilateral temples. Stimulation intensity was 100 μA applied through round (3.14 cm2) Ag/AgCl electrodes. Measurements were performed using alternating currents with frequencies from 1–150 Hz for different depths (from dura through GM and WM). Electric fields were computed as the first spatial derivative of recorded potentials. Results We found a marked influence of the laminar structure on the electric field distribution ( Download : Download high-res image (624KB) Download : Download full-size image Fig. 1A) with locally increased field strengths (Layer IV/V). This effect was dependent on current direction (Fig. 1B). The amplitude and phase of recorded potentials varied in a frequency and spatially dependent manner ( Download : Download high-res image (444KB) Download : Download full-size image Fig. 2). Conclusion Our results highlight differential effects of electric field propagation across cortical layers. Locally enhanced electric fields are likely due to currents passing across conductivity mismatches between layers. This effect is dependent on current orientation. Magnitude and phase of recorded potentials varied across the depth of cortex demonstrating changes in local electric properties of brain tissue. Larger phase shifts in deeper WM regions could be related to stronger capacitive influences from myelinated axons. In summary our results show previously unreported laminar specific effects of TES electric fields making a first step in the identification of cell specific targets for TES.

SUMMARY Inhibition plays an essential role in shaping and refining the brain’s representation of sensory stimulus attributes. In primary auditory cortex (A1), so-called ‘‘sideband’’ inhibition helps to sharpen the tuning of local neuronal responses. Several distinct types of anatomical circuitry could underlie sideband inhibition, including direct thalamocortical (TC) afferents, as well as indirect intracortical mechanisms. The goal of the present study was to characterize sideband inhibition in A1 and to determine its mechanism by analyzing laminar profiles of neuronal ensemble activity. Our results indicate that both lemniscal and nonlemniscal TC afferents play a role in inhibitory responses via feedforward inhibition and oscillatory phase reset, respectively. We propose that the dynamic modulation of excitability in A1 due to the phase reset of ongoing oscillations may alter the tuning of local neuronal ensembles and can be regarded as a flexible overlay on the more obligatory system of lemniscal feedforward type responses.