Critical Language Areas Show Increased Functional Connectivity in Human Cortex

Abstract

Electrocortical stimulation (ECS) mapping is routinely used to identify critical language sites before resective neurosurgery. The precise locations of these sites are highly variable across patients, occurring in the frontal, temporal, and parietal lobes-it is this variability that necessitates individual patient mapping. But why these particular anatomical sites are so privileged in each patient is unknown. We hypothesized that critical language sites have greater functional connectivity with nearby cortex than sites without critical functions, since they serve as central nodes within the language network. Functional connectivity across language, motor, and cleared sites was measured in 15 patients undergoing electrocortiographic (ECoG) mapping for epilepsy surgery. Critical language sites had significantly higher connectivity than sites without critical functions (P = 0.001), and this also held for motor sites (P = 0.022). These data support the hypothesis that critical language sites are highly connected within the local cortical network, perhaps explaining why their disruption with ECS leads to transient disturbances in language function. It is our hope that improved understanding of the mechanisms of ECS will permit improved surgical planning and perhaps contribute to the understanding of normal language physiology.

Figures

Figure 1.

Example of imaginary coherence. (A1) Example of volume conduction or common-mode noise. Two 10 Hz sine waves of different amplitudes (red and black traces) with additive random noise are shown. The 2 curves have a 0° phase difference, as might be seen with volume conduction or common-mode noise. (A2) The coherence of these 2 sine waves at 10 Hz is 1, while it is near zero at all other frequencies. This is robust to differences in relative signal amplitudes, one of the advantages of coherence analysis. (A3) The absolute value of the imaginary coherence, unlike regular coherence, has no peak at 10 Hz, since the 2 signals are in phase (i.e., there is no imaginary or phase component to the coherence). (B1) Example of phase-locked signals: two 10 Hz sine waves with additive random noise (red and black) with a fixed 90° phase relationship and different amplitudes. (B2) The coherence at 10 Hz is identical to that of A2, despite changes in amplitude and phase. (B3) However, the absolute value of the imaginary coherence at 10 Hz for these signals is 1, since they have a fixed, non-zero phase difference, likely reflective of a neural signal. (C) Imaginary coherence as a function of the phase difference between 2 arbitrary signals is shown. The imaginary coherence is zero when the 2 signals are exactly in phase or 180° out of phase, as might be seen with volume conduction or a shared reference. Imaginary coherence thereby reduces the probability of picking up spurious, non-physiological correlations. Coherence (and imaginary coherence) are robust to differences in signal amplitude, as shown by the sample signals in A1 and B1.

Figure 2.

Example of connectivity for language and cleared sites. Top panel: electrode locations for a 256-channel high-density ECoG grid. Middle panel: connectivity between a language site as confirmed by ECS (shown in blue) and all other sites (only top 25% of connections with the language site are shown for clarity). Bottom panel: connectivity between a site confirmed as cleared by ECS (shown in blue) and other sites (top 25% connections with the cleared site are shown for clarity). Note the increased local connectivity between the language site, as compared to the cleared site.

Figure 3.

Anatomical locations of electrodes. Electrode locations were co-registered and projected to a common brain. The proportion of language and cleared electrodes was similar across anatomical regions. Warping electrode locations to a standard brain introduces some errors (e.g., motor electrodes over the superior temporal gyrus, which were actually in the pre-, post-, or subcentral gyrus).

Figure 4.

Connectivity of language sites is higher than cleared or right-sided, non-dominant sites. (A) The median alpha band imaginary coherence of language sites (from left-sided, dominant hemispheres) was significantly higher than cleared sites in the same patients, and also higher than electrodes from non-dominant right-sided ECoG grids (non-dominant hemispheres are presumed to not have language sites). This was true when coherence was calculated during quiet rest (“Resting”, 2 leftmost bars), during language tasks (“Task”; middle 2 bars), or when the analysis was restricted to electrodes with significant local field potential modulations in response to language tasks (“Language Network”, right-sided bars). (B) Receiver operating characteristic (ROC) curve showing the rate of true positives and false positives as a function of a dynamic threshold of imaginary coherence.

Figure 5.

Connectivity as a function of frequency band. Median imaginary coherence is shown for each tested frequency band. Significant differences were found between language and cleared electrodes at all frequencies and between motor and cleared electrodes for theta and alpha frequency bands.