Cortical Hemisphere Research Articles

Running speed and REM sleep control two distinct modes of rapid interhemispheric communication.

SUMMARYRhythmic gamma-band communication within and across cortical hemispheres is critical for optimal perception, navigation, and memory. Here, using multisite recordings in both rats and mice, we show that even faster ~140 Hz rhythms are robustly anti-phase across cortical hemispheres, visually resembling splines, the interlocking teeth on mechanical gears. Splines are strongest in superficial granular retrosplenial cortex, a region important for spatial navigation and memory. Spline-frequency interhemispheric communication becomes more coherent and more precisely anti-phase at faster running speeds. Anti-phase splines also demarcate high-activity frames during REM sleep. While splines and associated neuronal spiking are anti-phase across retrosplenial hemispheres during navigation and REM sleep, gamma-rhythmic interhemispheric communication is precisely in-phase. Gamma and splines occur at distinct points of a theta cycle and thus highlight the ability of interhemispheric cortical communication to rapidly switch between in-phase (gamma) and anti-phase (spline) modes within individual theta cycles during both navigation and REM sleep.

Recruitment of frontal sensory circuits during visual discrimination.

SummaryA long-range circuit linking the medial frontal cortex to the primary visual cortex (V1) has been proposed to mediate visual selective attention in mice during visually guided behavior. Here, we use in vivo two-photon functional imaging to measure the endogenous activity of axons of A24b/M2 neurons from this region projecting to layer 1 of V1 (A24b/M2-V1axons) in mice either passively viewing stimuli or performing a go/no-go visually guided task. We observe that while A24b/M2-V1axons are recruited under these conditions, this is not linked to enhancement of neural or behavioral measures of sensory coding. Instead, A24b/M2-V1axon activity is associated with licking behavior, modulated by reward, and biased toward the sensory cortical hemisphere representing the stimulus currently being discriminated.

Children with amblyaudia show less flexibility in auditory cortical entrainment to periodic non-speech sounds

We investigated auditory temporal processing in children with amblyaudia (AMB), a subtype of auditory processing disorder, via cortical neural entrainment. Evoked responses were recorded to click-trains at slow versus fast (8.5 versus 14.9/sec) rates in n = 14 children with AMB and n = 11 age-matched controls. Source and time-frequency analyses decomposed EEGs into oscillations (reflecting neural entrainment) stemming from the bilateral auditory cortex. Phase-locking strength in AMB depended critically on the speed of auditory stimuli. In contrast to age-matched peers, AMB responses were largely insensitive to rate manipulations. This rate resistance was seen regardless of the ear of presentation and in both cortical hemispheres. Children with AMB show a stark inflexibility in auditory cortical entrainment to rapid sounds. In addition to reduced capacity to integrate information between the ears, we identify a new functional characterization of AMB in the form of more rigid tagging of external auditory stimuli. Our neurophysiological findings may account for certain temporal processing deficits commonly observed in AMB and related auditory processing disorders (APDs) behaviorally. More broadly, our findings may inform communication strategies and future rehabilitation programs; increasing the rate of stimuli above a normal (slow) speech rate is likely to make stimulus processing more challenging for individuals with AMB/APD.

Hearing Instability in Children with Congenital Cytomegalovirus: Evidence and Neural Consequences.

Sensorineural hearing loss (SNHL) is a common sequela of congenital cytomegalovirus (cCMV), potentially exacerbating neurocognitive delay. The objectives of this study were to assess: (1) age at which SNHL in children with cCMV; (2) stimulability of the auditory system in children with cCMV following cochlear implantation (CI); and (3) whether features of magnetic resonance imaging (MRI) potentially are predictive of hearing outcomes. In this retrospective study of a prospectively acquired cohort, 123 children with cCMV who were referred for hearing loss at a single tertiary referral hospital over 20 years were compared with an unmatched comparative group of 90 children with GJB2-related deafness. Outcome measures were results of newborn hearing screening (NHS), behavioral audiograms, and, in a subgroup of cochlear implant (CI) users, responses from the auditory nerve and brainstem evoked by CI at initial activation, as well as lesional volume of FLAIR-hyperintense signal alterations on MRI. All but 3 of 123 children with cCMV had confirmed and persistent SNHL. At birth, 113 children with cCMV underwent NHS, 31 (27%) passed in both ears and 23 (20%) passed in one ear (no NHS data in 10 children). At the first audiologic assessment, 32 of 123 (26%) had normal hearing bilaterally; 35 of 123 (28%) had unilateral SNHL; and 57 of 123 (46%) had bilateral SNHL. More than half (67 of 123, 54%) experienced hearing deterioration in at least one ear. Survival analyses suggested that 60% of children who developed SNHL did so by 2.5 years and 80% by 5 years. In the children who passed NHS in one or both ears, 50% developed hearing loss by 3.5 years in the ear, which passed unilaterally (n=23 ears), and 50% by 5 years in bilateral passes (n=62 ears). Hearing loss was significant enough in all but one child with isolated high-frequency loss for rehabilitation to be indicated. Hearing thresholds in individual ears were in the CI range in 83% (102 of 123), although duration of deafness was sufficient to preclude implantation at our center in 13 children with unilateral SNHL. Hearing aids were indicated in 16% (20 of 123). Responses from the auditory nerve and brainstem to initial CI stimulation were similar in children with cCMV-related SNHL compared with GJB2-related SNHL. Characteristic white matter changes on MRI were seen in all children with cCMV-related SNHL (n=91), but the lesion volume in each cortical hemisphere did not predict degree of SNHL. cCMV-related SNHL is often not detected by NHS but occurs with high prevalence in early childhood. Electrophysiological measures suggest equivalent stimulability of the auditory nerve and brainstem with CI in children with cCMV and GJB2-related SNHL. Hyperintense white matter lesions on FLAIR MRI are consistently present in children with cCMV-related SNHL but cannot be used to predict its time course or degree. Combined, the data show early and rapid deterioration of hearing in children with cCMV-related SNHL with potential for good CI outcomes if SNHL is identified and managed without delay. Findings support universal newborn screening for cCMV followed by careful audiological monitoring. 3 Laryngoscope, 132:S1-S24, 2022.

Description of intracerebral hemorrhage locations, in the United States, based on international classification of diseases, tenth revision

ObjectivesIntroduction of the International Classification of Diseases, Tenth Revision (ICD-10) in 2015 was aimed for a more detailed classification of mortality statistics of diseases, such as classifying the anatomical locations for intracerebral hemorrhage (ICH). We aimed to describe the demographics and in-hospital mortality of specified ICH locations based on ICD-10 classification. Materials and methodsPatients with a principal diagnosis of spontaneous ICH in the United States, extracted from the Nationwide Inpatient Sample (NIS) from 2015 to 2018. Subgroups of ICH locations were analyzed individually for age, gender, ethnicity, in-hospital mortality, hospital length of stay (LOS), hospital cost, and EVD placement. ResultsDuring the study period, there were 408,285 ICH patients with a mean age of 66.28 (17.11) years, 52.09% male, mainly Intraventricular (21.87%) and cortical hemispheres (19.83%). Total ICH in-hospital mortality was 21.07%, while brainstem was associated with the highest in-hospital mortality (40.68%) followed by intraventricular (33.08%) and multiple localized locations (30.16%). The mean hospital length of stay was 9.56(14.10) days, and the mean hospital cost was $32,453.38(56,851.59). Intraventricular Hemorrhage had the highest hospital LOS 12.39(17.44) and the highest hospital cost $47,385.25(76,187.5). ConclusionsOur results characterized the demographics of ICH in the US with in-hospital mortality of one out of five patients. Detail breakdown of ICH locations can improve the mortality statistics and provide more information about the ICH locations with higher hospital expenses.

Hemispheric Asymmetry and Atypical Lobar Progression of Alzheimer-Type Tauopathy.

The spread of neurofibrillary tau pathology in Alzheimer disease (AD) mostly follows a stereotypical pattern of topographical progression but atypical patterns associated with interhemispheric asymmetry have been described. Because histopathological studies that used bilateral sampling are limited, this study aimed to assess interhemispheric tau pathology differences and the presence of topographically atypical cortical spreading patterns. Immunohistochemical staining for detection of tau pathology was performed in 23 regions of interest in 57 autopsy cases comparing bilateral cortical regions and hemispheres. Frequent mild (82% of cases) and occasional moderate (32%) interhemispheric density discrepancies were observed, whereas marked discrepancies were uncommon (7%) and restricted to occipital regions. Left and right hemispheric tau pathology dominance was observed with similar frequencies, except in Braak Stage VI that favored a left dominance. Interhemispheric Braak stage differences were observed in 16% of cases and were more frequent in advanced (IV-VI) versus early (I-III) stages. One atypical lobar topographical pattern in which occipital tau pathology density exceeded frontal lobe scores was identified in 4 cases favoring a left dominant asymmetry. We speculate that asymmetry and atypical topographical progression patterns may be associated with atypical AD clinical presentations and progression characteristics, which should be tested by comprehensive clinicopathological correlations.

Uncovering clinical and radiological asymmetry in progressive supranuclear palsy—Richardson’s syndrome

BackgroundRichardson’s syndrome (RS) is considered the most symmetric phenotype of progressive supranuclear palsy (PSP) as opposed to PSP with predominant corticobasal syndrome (PSP-CBS) or parkinsonism (PSP-P).ObjectivesEvaluate asymmetrical motor and higher cortical features in probable PSP-RS and compare the degree of asymmetry of cortical lobes and hemispheres between PSP-RS, PSP-CBS, PSP-P, and age-matched healthy controls (HC).MethodsAsymmetry of motor and higher cortical features evaluated with an extensive videotaped neurologic examination was investigated in 28 PSP-RS, 8 PSP-CBS, and 14 PSP-P. Brain MRI to compute the laterality index (LI) was performed in 36 patients as well as in 56 HC.ResultsIn PSP-RS, parkinsonism was the most common asymmetric motor feature (53.6%), followed by dystonia and myoclonus (21.4% and 17.9%, respectively). Among higher cortical features, limb apraxia was found asymmetric in about one-third of patients. PSP-RS disclosed higher LI for hemispheres compared to HC, indicating a greater degree of asymmetry (p = 0.003). The degree of asymmetry of clinical features was not different between PSP-RS and those qualifying for PSP-CBS or PSP-P. As for imaging, LI was not different between PSP-RS, PSP-CBS, and PSP-P in any cortical region.ConclusionsMotor and higher cortical features are asymmetric in up to 50% of PSP-RS who also present a greater degree of asymmetry in hemispheres compared to age-matched HC. Lateralization of clinical features should be annotated in PSP.

Development of functional organization within the sensorimotor network across the perinatal period.

In the mature human brain, the neural processing related to different body parts is reflected in patterns of functional connectivity, which is strongest between functional homologs in opposite cortical hemispheres. To understand how this organization is first established, we investigated functional connectivity between limb regions in the sensorimotor cortex in 400 preterm and term infants aged across the equivalent period to the third trimester of gestation (32–45 weeks postmenstrual age). Masks were obtained from empirically derived functional responses in neonates from an independent data set. We demonstrate the early presence of a crude but spatially organized functional connectivity, that rapidly matures across the preterm period to achieve an adult‐like configuration by the normal time of birth. Specifically, connectivity was strongest between homolog regions, followed by connectivity between adjacent regions (different limbs but same hemisphere) already in the preterm brain, and increased with age. These changes were specific to the sensorimotor network. Crucially, these trajectories were strongly dependent on age more than age of birth. This demonstrates that during the perinatal period the sensorimotor cortex undergoes preprogrammed changes determining the functional movement organization that are not altered by preterm birth in absence of brain injury.

Intracerebral Transplantation and <em>In Vivo</em> Bioluminescence Tracking of Human Neural Progenitor Cells in the Mouse Brain

Cell therapy has long been an emerging treatment paradigm in experimental neurobiology. However, cell transplantation studies often rely on end-point measurements and can therefore only evaluate longitudinal changes of cell migration and survival to a limited extent. This paper provides a reliable, minimally invasive protocol to transplant and longitudinally track neural progenitor cells (NPCs) in the adult mouse brain. Before transplantation, cells are transduced with a lentiviral vector comprising a bioluminescent (firefly-luciferase) and fluorescent (green fluorescent protein [GFP]) reporter. The NPCs are transplanted into the right cortical hemisphere using stereotaxic injections in the sensorimotor cortex. Following transplantation, grafted cells were detected through the intact skull for up to five weeks (at days 0, 3, 14, 21, 35) with a resolution limit of 6,000 cells using in vivo bioluminescence imaging. Subsequently, the transplanted cells are identified in histological brain sections and further characterized with immunofluorescence. Thus, this protocol provides a valuable tool to transplant, track, quantify, and characterize cells in the mouse brain.

Intracerebral Transplantation and <em>In Vivo</em> Bioluminescence Tracking of Human Neural Progenitor Cells in the Mouse Brain

Cell therapy has long been an emerging treatment paradigm in experimental neurobiology. However, cell transplantation studies often rely on end-point measurements and can therefore only evaluate longitudinal changes of cell migration and survival to a limited extent. This paper provides a reliable, minimally invasive protocol to transplant and longitudinally track neural progenitor cells (NPCs) in the adult mouse brain. Before transplantation, cells are transduced with a lentiviral vector comprising a bioluminescent (firefly-luciferase) and fluorescent (green fluorescent protein [GFP]) reporter. The NPCs are transplanted into the right cortical hemisphere using stereotaxic injections in the sensorimotor cortex. Following transplantation, grafted cells were detected through the intact skull for up to five weeks (at days 0, 3, 14, 21, 35) with a resolution limit of 6,000 cells using in vivo bioluminescence imaging. Subsequently, the transplanted cells are identified in histological brain sections and further characterized with immunofluorescence. Thus, this protocol provides a valuable tool to transplant, track, quantify, and characterize cells in the mouse brain.

Increasing motor cortex activation during grasping via novel robotic mirror hand therapy: a pilot fNIRS study

BackgroundMirror therapy (MT) has been used for functional recovery of the affected hand by providing the mirrored image of the unaffected hand movement, which induces neural activation of the cortical hemisphere contralateral to the affected hand. Recently, many wearable robots assisting the movement of the hand have been developed, and several studies have proposed robotic mirror therapy (RMT) that uses a robot to provide mirrored movements of the unaffected hand to the affected hand with the robot controlled by measuring electromyography or posture of the unaffected hand. In some cases of RMT a mirror is placed to allow the person to observe only the unaffected hand but in others users simply observe the robotically assisted hand performing the mirrored movements, as was the case in this study. There have been limited evaluations of the cortical activity during RMT compared to MT and robotic therapy (RT) providing passive movements despite the difference in the modality of sensory feedback and the involvement of motor intention, respectively.MethodsThis paper analyzes bilateral motor cortex activation in nine healthy subjects and five chronic stroke survivors during a pinching task performed in MT, RT, and RMT conditions using functional near infrared spectroscopy (fNIRS). In the MT condition, the person moved the unaffected hand and observed it in a mirror while the affected hand remained still. In RT condition passive movements were provided to the affected hand with a cable-driven soft robotic glove, while, in RMT condition, the posture of the unaffected hand was measured by a sensing glove and the soft robotic glove mirrored its movement on the affected hand.ResultsFor both groups, the RMT condition showed the greatest mean cortical activation on the motor cortex contralateral to the affected (non-dominant for the healthy group) hand compared to other conditions. Individual results indicate that RMT induces similar or greater neural activation on the motor cortex compared to MT and RT conditions. The interhemispheric activations of both groups were balanced in RMT condition. In MT condition, significantly greater activation was shown on the hemisphere ipsilateral to the affected (dominant for the healthy group) hand for both subject groups, while the contralateral side showed significantly greater activation for the healthy group in RT condition.ConclusionThe experimental results indicate that combining visual feedback, somatosensory feedback, and motor intention are important for greater stimulation on the contralateral motor cortex of the affected hand. RMT that includes these factors is hypothesized to achieve a more effective functional rehabilitation due to greater and more balanced cortical activation.

CiftiTools: A package for reading, writing, visualizing, and manipulating CIFTI files in R

There is significant interest in adopting surface- and grayordinate-based analysis of MR data for a number of reasons, including improved whole-cortex visualization, the ability to perform surface smoothing to avoid issues associated with volumetric smoothing, improved inter-subject alignment, and reduced dimensionality. The CIFTI grayordinate file format introduced by the Human Connectome Project further advances grayordinate-based analysis by combining gray matter data from the left and right cortical hemispheres with gray matter data from the subcortex and cerebellum into a single file. Analyses performed in grayordinate space are well-suited to leverage information shared across the brain and across subjects through both traditional analysis techniques and more advanced statistical methods, including Bayesian methods. The R statistical environment facilitates use of advanced statistical techniques, yet little support for grayordinates analysis has been previously available in R. Indeed, few comprehensive programmatic tools for working with CIFTI files have been available in any language. Here, we present the ciftiTools R package, which provides a unified environment for reading, writing, visualizing, and manipulating CIFTI files and related data formats. We illustrate ciftiTools’ convenient and user-friendly suite of tools for working with grayordinates and surface geometry data in R, and we describe how ciftiTools is being utilized to advance the statistical analysis of grayordinate-based functional MRI data.

Transcription factors Bcl11a and Bcl11b are required for the production and differentiation of cortical projection neurons.

The generation and differentiation of cortical projection neurons are extensively regulated by interactive programs of transcriptional factors. Here, we report the cooperative functions of transcription factors Bcl11a and Bcl11b in regulating the development of cortical projection neurons. Among the cells derived from the cortical neural stem cells, Bcl11a is expressed in the progenitors and the projection neurons, while Bcl11b expression is restricted to the projection neurons. Using conditional knockout mice, we show that deficiency of Bcl11a leads to reduced proliferation and precocious differentiation of cortical progenitor cells, which is exacerbated when Bcl11b is simultaneously deleted. Besides defective neuronal production, the differentiation of cortical projection neurons is blocked in the absence of both Bcl11a and Bcl11b: Expression of both pan-cortical and subtype-specific genes is reduced or absent; axonal projections to the thalamus, hindbrain, spinal cord, and contralateral cortical hemisphere are reduced or absent. Furthermore, neurogenesis-to-gliogenesis switch is accelerated in the Bcl11a-CKO and Bcl11a/b-DCKO mice. Bcl11a likely regulates neurogenesis through repressing the Nr2f1 expression. These results demonstrate that Bcl11a and Bcl11b jointly play critical roles in the generation and differentiation of cortical projection neurons and in controlling the timing of neurogenesis-to-gliogenesis switch.

Independent dynamics of low, intermediate, and high frequency spectral intracranial EEG activities during human memory formation

A wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various frequency ranges are coordinated across the space of the human cortex and time of memory processing is inconclusive. They can either be coordinated together across the frequency spectrum at the same cortical site and time or induced independently in particular bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated low frequency theta, intermediate frequency alpha and beta, and high frequency gamma power in a mosaic pattern of discrete cortical sites. A majority of the cortical sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and high frequency activities propagated in independent sequences across the visual, temporal and prefrontal cortical areas throughout subsequent phases of memory encoding. Our results provide a holistic, simplified model of the spectral activities engaged in the formation of human memory, suggesting an anatomically and temporally distributed mosaic of coordinated brain rhythms.

Cortical hemodynamic mechanisms of reversal learning using high-resolution functional near-infrared spectroscopy: A pilot study

ObjectivesReversal learning is widely used to analyze cognitive flexibility and characterize behavioral abnormalities associated with impulsivity and disinhibition. Recent studies using fMRI have focused on regions involved in reversal learning with negative and positive reinforcers. Although the frontal cortex has been consistently implicated in reversal learning, few studies have focused on whether reward and punishment may have different effects on lateral frontal structures in these tasks. MethodsDuring this pilot study on eight healthy subjects, we used functional near infra-red spectroscopy (fNIRS) to characterize brain activity dynamics and differentiate the involvement of frontal structures in learning driven by reward and punishment. ResultsWe observed functional hemispheric asymmetries between punishment and reward processing by fNIRS following reversal of a learned rule. Moreover, the left dorsolateral prefrontal cortex (l-DLPFC) and inferior frontal gyrus (IFG) were activated under the reward condition only, whereas the orbito-frontal cortex (OFC) was significantly activated under the punishment condition, with a tendency towards activation for the right cortical hemisphere (r-DLPFC and r-IFG). Our results are compatible with the suggestion that the DLPFC is involved in the detection of contingency change. We propose a new representation for reward and punishment, with left lateralization for the reward process. ConclusionsThe results of this pilot study provide insights into the indirect neural mechanisms of reversal learning and behavioral flexibility and confirm the use of fNIRS imaging in reversal-learning tasks as a translational strategy, particularly in subjects who cannot undergo fMRI recordings.

Cortical hemisphere preference and brainstem ear asymmetry reflect experience-dependent functional modulation of pitch

Temporal attributes of pitch processing at cortical and subcortical levels are differentially weighted and well-coordinated. The question is whether language experience induces functional modulation of hemispheric preference complemented by brainstem ear symmetry for pitch processing. Brainstem frequency-following and cortical pitch responses were recorded concurrently from Mandarin and English participants. A Mandarin syllable with a rising pitch contour was presented to both ears with monaural stimulation. At the cortical level, left ear stimulation in the Chinese group revealed an experience-dependent response for pitch processing in the right hemisphere, consistent with a functionalaccount. The English group revealed a contralateral hemisphere preference consistent with a structuralaccount. At the brainstem level, Chinese participants showed a functional leftward ear asymmetry, whereas English were consistent with a structural account. Overall, language experience modulates both cortical hemispheric preference and brainstem ear asymmetry in a complementary manner to optimize processing of temporal attributes of pitch.

Transneuronal delivery of designer cytokines: perspectives for spinal cord injury.

Transneuronal delivery of designer cytokines: perspectives for spinal cord injury.

Interhemispheric Cortico-Cortical Pathway for Sequential Bimanual Movements in Mice.

Animals precisely coordinate their left and right limbs for various adaptive purposes. While the left and right limbs are clearly controlled by different cortical hemispheres, the neural mechanisms that determine the action sequence between them remains elusive. Here, we have established a novel head-fixed bimanual-press (biPress) sequence task in which mice sequentially press left and right pedals with their forelimbs in a predetermined order. Using this motor task, we found that the motor cortical neurons responsible for the first press (1P) also generate independent motor signals for the second press (2P) by the opposite forelimb during the movement transitions between forelimbs. Projection-specific calcium imaging and optogenetic manipulation revealed these motor signals are transferred from one motor cortical hemisphere to the other via corticocortical projections. Together, our results suggest the motor cortices coordinate sequential bimanual movements through corticocortical pathways.

Aberrant cortico-thalamic structural connectivity in premature-born adults

Premature birth is associated with alterations in brain structure, particularly in white matter. Among white matter, alterations in cortico-thalamic connections are present in premature-born infants, and they have been suggested both to last until adulthood and to contribute to impaired cognitive functions. To test these hypotheses, 70 very premature-born adults and 67 full-term controls underwent cognitive testing and diffusion-weighted imaging. Each cortical hemisphere was parcellated into six lobes, from which probabilistic tractography was performed to the thalamus. Connection probability was chosen as metric of structural connectivity. We found increased cortico-thalamic connection probability between left prefrontal cortices and left medio-dorsal thalamus and reduced connection probability between bilateral temporal cortices and bilateral anterior thalami in very premature-born adults. Aberrant prefronto- and temporo-thalamic connection probabilities were correlated with birth weight and days on ventilation, respectively, supporting the suggestion that these connectivity changes relate with the degree of prematurity. Moreover, an increase in left prefronto-thalamic connection probability also correlated with lower verbal comprehension index indicating its relevance for verbal cognition. Together, our results demonstrate that cortico-thalamic structural connectivity is aberrant in premature-born adults, with these changes being linked with impairments in verbal cognitive abilities. Due to corresponding findings in infants, data suggest aberrant development of cortico-thalamic connectivity after premature birth with lasting effects into adulthood.

Biomarkers Based on Comprehensive Hierarchical EEG Coherence Analysis: Example Application to Social Competence in Autism (Preliminary Results).

Electroencephalography (EEG) coherence analysis, based on measurement of synchronous oscillations of neuronal clusters, has been used extensively to evaluate functional connectivity in brain networks. EEG coherence studies have used a variety of analysis variables (e.g., time and frequency resolutions corresponding to the analysis time period and frequency bandwidth), regions of the brain (e.g., connectivity within and between various cortical lobes and hemispheres) and experimental paradigms (e.g., resting state with eyes open or closed; performance of cognitive tasks). This variability in study designs has resulted in difficulties in comparing the findings from different studies and assimilating a comprehensive understanding of the underlying brain activity and regions with abnormal functional connectivity in a particular disorder. In order to address the variability in methods across studies and to facilitate the comparison of research findings between studies, this paper presents the structure and utilization of a comprehensive hierarchical electroencephalography (EEG) coherence analysis that allows for formal inclusion of analysis duration, EEG frequency band, cortical region, and experimental test condition in the computation of the EEG coherences. It further describes the method by which this EEG coherence analysis can be utilized to derive biomarkers related to brain (dys)function and abnormalities. In order to document the utility of this approach, the paper describes the results of the application of this method to EEG and behavioral data from a social synchrony paradigm in a small cohort of adolescents with and without Autism Spectral Disorder.