Six-dimensional dynamic tractography atlas of language connectivity in the developing brain.

During a verbal conversation, our brain moves through a series of complex linguistic processing stages: sound decoding, semantic comprehension, retrieval of semantically coherent words, and overt production of speech outputs. Each process is thought to be supported by a network consisting of local and long-range connections bridging between major cortical areas. Both temporal and extratemporal lobe regions have functional compartments responsible for distinct language domains, including the perception and production of phonological and semantic components. This study provides quantitative evidence of how directly connected inter-lobar neocortical networks support distinct stages of linguistic processing across brain development. Novel six-dimensional tractography was used to intuitively visualize the strength and temporal dynamics of direct inter-lobar effective connectivity between cortical areas activated during each linguistic processing stage. We analysed 3401 non-epileptic intracranial electrode sites from 37 children with focal epilepsy (aged 5-20 years) who underwent extra-operative electrocorticography recording. Principal component analysis of auditory naming-related high-gamma modulations determined the relative involvement of each cortical area during each linguistic processing stage. To quantify direct effective connectivity, we delivered single-pulse electrical stimulation to 488 temporal and 1581 extratemporal lobe sites and measured the early cortico-cortical spectral responses at distant electrodes. Mixed model analyses determined the effects of naming-related high-gamma co-augmentation between connecting regions, age, and cerebral hemisphere on the strength of effective connectivity independent of epilepsy-related factors. Direct effective connectivity was strongest between extratemporal and temporal lobe site pairs, which were simultaneously activated between sentence offset and verbal response onset (i.e. response preparation period); this connectivity was approximately twice more robust than that with temporal lobe sites activated during stimulus listening or overt response. Conversely, extratemporal lobe sites activated during overt response were equally connected with temporal lobe language sites. Older age was associated with increased strength of inter-lobar effective connectivity especially between those activated during response preparation. The arcuate fasciculus supported approximately two-thirds of the direct effective connectivity pathways from temporal to extratemporal auditory language-related areas but only up to half of those in the opposite direction. The uncinate fasciculus consisted of <2% of those in the temporal-to-extratemporal direction and up to 6% of those in the opposite direction. We, for the first time, provided an atlas which quantifies and animates the strength, dynamics, and direction specificity of inter-lobar neural communications between language areas via the white matter pathways. Language-related effective connectivity may be strengthened in an age-dependent manner even after the age of 5.

Spontaneous modulations of high-frequency cortical activity.

OBJECTIVE: We clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state. METHODS: We studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70-110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation. RESULTS: The dynamic atlas demonstrated transient high-gamma suppression in the striatal cortex before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%. CONCLUSIONS: We successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades. SIGNIFICANCE: Measuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic.

Four-dimensional tractography animates propagations of neural activation via distinct interhemispheric pathways.

OBJECTIVE: To visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES). METHODS: This methodological study included three patients with drug-resistant focal epilepsy who underwent measurement of cortico-cortical spectral responses (CCSRs) during bilateral stereo-electroencephalography recording. We delivered SPES to 83 electrode pairs and analyzed CCSRs recorded at 268 nonepileptic electrode sites. Diffusion-weighted imaging (DWI) tractography localized the interhemispheric white matter pathways as streamlines directly connecting two electrode sites. We localized and visualized the putative SPES-related fiber activation, at each 1-ms time window, based on the propagation velocity defined as the DWI-based streamline length divided by the early CCSR peak latency. RESULTS: The resulting movie, herein referred to as four-dimensional tractography, delineated the spatiotemporal dynamics of fiber activation via the corpus callosum and anterior commissure. Longer streamline length was associated with delayed peak latency and smaller amplitude of CCSRs. The cortical regions adjacent to each fiber activation site indeed exhibited CCSRs at the same time window. CONCLUSIONS: Our four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways. SIGNIFICANCE: Our novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function.

Dynamic tractography: Integrating cortico-cortical evoked potentials and diffusion imaging.

INTRODUCTION: Cortico-cortical evoked potentials (CCEPs) are utilized to identify effective networks in the human brain. Following single-pulse electrical stimulation of cortical electrodes, evoked responses are recorded from distant cortical areas. A negative deflection (N1) which occurs 10-50 â€‹ms post-stimulus is considered to be a marker for direct cortico-cortical connectivity. However, with CCEPs alone it is not possible to observe the white matter pathways that conduct the signal or accurately predict N1 amplitude and latency at downstream recoding sites. Here, we develop a new approach, termed "dynamic tractography," which integrates CCEP data with diffusion-weighted imaging (DWI) data collected from the same patients. This innovative method allows greater insights into cortico-cortical networks than provided by each method alone and may improve the understanding of large-scale networks that support cognitive functions. The dynamic tractography model produces several fundamental hypotheses which we investigate: 1) DWI-based pathlength predicts N1 latency; 2) DWI-based pathlength negatively predicts N1 voltage; and 3) fractional anisotropy (FA) along the white matter path predicts N1 propagation velocity. METHODS: Twenty-three neurosurgical patients with drug-resistant epilepsy underwent both extraoperative CCEP recordings and preoperative DWI scans. Subdural grids of 3 â€‹mm diameter electrodes were used for stimulation and recording, with 98-128 eligible electrodes per patient. CCEPs were elicited by trains of 1 â€‹Hz stimuli with an intensity of 5 â€‹mA and recorded at a sample rate of 1 â€‹kHz. N1 peak and latency were defined as the maximum of a negative deflection within 10-50 â€‹ms post-stimulus with a z-score > 5 relative to baseline. Electrodes and DWI were coregistered to construct electrode connectomes for white matter quantification. RESULTS: Clinical variables (age, sex, number of anti-epileptic drugs, handedness, and stimulated hemisphere) did not correlate with the key outcome measures (N1 peak amplitude, latency, velocity, or DWI pathlength). All subjects and electrodes were therefore pooled into a group-level analysis to determine overall patterns. As hypothesized, DWI path length positively predicted N1 latency (R2 â€‹= â€‹0.81, ߠ​= â€‹1.51, p â€‹= â€‹4.76e-16) and negatively predicted N1 voltage (R2 â€‹= â€‹0.79, ߠ​= â€‹-0.094, p â€‹= â€‹9.30e-15), while FA predicted N1 propagation velocity (R2 â€‹= â€‹0.35, ߠ​= â€‹48.0, p â€‹= â€‹0.001). CONCLUSION: We have demonstrated that the strength and timing of the CCEP N1 is dependent on the properties of the underlying white matter network. Integrated CCEP and DWI visualization allows robust localization of intact axonal pathways which effectively interconnect eloquent cortex.

Four-dimensional map of direct effective connectivity from posterior visual areas.

Lower- and higher-order visual cortices in the posterior brain, ranging from the medial- and lateral-occipital to fusiform regions, are suggested to support visual object recognition, whereas the frontal eye field (FEF) plays a role in saccadic eye movements which optimize visual processing. Previous studies using electrophysiology and functional MRI techniques have reported that tasks requiring visual object recognition elicited cortical activation sequentially in the aforementioned posterior visual regions and FEFs. The present study aims to provide unique evidence of direct effective connectivity outgoing from the posterior visual regions by measuring the early component (10-50 â€‹ms) of cortico-cortical spectral responses (CCSRs) elicited by weak single-pulse direct cortical electrical stimulation. We studied 22 patients who underwent extraoperative intracranial EEG recording for clinical localization of seizure foci and functionally-important brain regions. We used animations to visualize the spatiotemporal dynamics of gamma band CCSRs elicited by stimulation of three different posterior visual regions. We quantified the strength of CCSR-defined effective connectivity between the lower- and higher-order posterior visual regions as well as from the posterior visual regions to the FEFs. We found that effective connectivity within the posterior visual regions was larger in the feedforward (i.e., lower-to higher-order) direction compared to the opposite direction. Specifically, connectivity from the medial-occipital region was largest to the lateral-occipital region, whereas that from the lateral-occipital region was largest to the fusiform region. Among the posterior visual regions, connectivity to the FEF was largest from the lateral-occipital region and the mean peak latency of CCSR propagation from the lateral-occipital region to FEF was 26 â€‹ms. Our invasive study of the human brain using a stimulation-based intervention supports the model that the posterior visual regions have direct cortico-cortical connectivity pathways in which neural activity is transferred preferentially from the lower-to higher-order areas. The human brain has direct cortico-cortical connectivity allowing a rapid transfer of neural activity from the lateral-occipital region to the FEF.

Spatiotemporal dynamics of auditory and picture naming-related high-gamma modulations: A study of Japanese-speaking patients.

OBJECTIVE: To characterize the spatiotemporal dynamics of auditory and picture naming-related cortical activation in Japanese-speaking patients. METHODS: Ten patients were assigned auditory naming and picture naming tasks during extraoperative intracranial EEG recording in a tertiary epilepsy center. Time-frequency analysis determined at what electrode sites and at what time windows during each task the amplitude of high-gamma activity (65-95 Hz) was modulated. RESULTS: The superior-temporal gyrus on each hemisphere showed high-gamma augmentation during sentence listening, whereas the left middle-temporal and inferior-frontal gyri showed high-gamma augmentation peaking around stimulus offset. Auditory naming-specific high-gamma augmentation was noted in the bilateral superior-temporal gyri as well as left frontal-parietal-temporal perisylvian network regions, whereas picture naming-specific augmentation was noted in the occipital-fusiform regions, bilaterally. The inferior pre- and postcentral gyri on each hemisphere showed modality-common high-gamma augmentation time-locked to overt responses. CONCLUSIONS: The spatiotemporal dynamics of auditory and picture naming-related high-gamma augmentation in Japanese-speaking patients were qualitatively similar to those previously reported in studies of English-speaking patients. SIGNIFICANCE: The cortical dynamics for auditory sentence recognition are at least partly shared by cohorts speaking two distinct languages. Multicenter studies regarding the clinical utility of high-gamma language mapping across Eastern and Western hemispheres may be feasible.