Interhemispheric Integration after Callosotomy: A Meta-Analysis of Poffenberger and Redundant-Target Paradigms

Abstract

The central role of the corpus callosum in integrating perception and cognition across the cerebral hemispheres makes it highly desirable for clinical and basic research to have a repertoire of experimental paradigms assessing callosal functioning. Here, the objective was to assess the validity of two such paradigms (Poffenberger, redundant-target paradigms) by conducting single-step meta-analyses on individual case data of callosotomy patients. Studies were identified by systematic literature search (source: Pubmed and WebOfKnowledge, date: 07.03.2022) and all studies were included that reported callosotomy case data for either paradigm. Twenty-two studies (38 unique cases) provided 116 observations of the crossed-uncrossed difference (CUD) for the Poffenberger paradigm, while ten studies (22 cases, 103 observations) provided bilateral redundancy gain (bRG) measures. Using linear-mixed models with "individual" and "experiment" as random-effects variable, the mean CUD was estimated at 60.6 ms (CI_95%: 45.3; 75.9) for commissurotomy, 43.5 ms (26.7; 60.2) for complete callosotomy, and 8.8 ms (1.1; 16.6) for partial anterior-medial callosotomy patients. The estimates of commissurotomy/callosotomy patients differed significantly from patients with partial callosotomy and healthy controls. The mean bRG_min (minimum unilateral reference) was estimated at 42.8 ms (27.1;58.4) for patients with complete and 30.8 ms (16.8; 44.7) for patients with partial callosotomy, both differing significantly from controls. One limitation was that different formulas for bRG were used, making it necessary to split the sample and reducing test power of some analyses. Nevertheless, the present findings suggest that both paradigms assess interhemispheric callosal integration, confirming their construct validity, but likely test distinct callosal functions.

Keywords: Brain asymmetry; Callosotomy; Commissurotomy; Corpus callosum; Split-brain.

Fig. 1

Illustration of the Poffenberger paradigm, exemplified for stimulation of the left visual field (LVF). The LVF stimulation leads to an initial contralateral representation of the stimulus in the right hemisphere (RH). According to the callosal-relay model, responding with the left hand to LVF stimulation, relies solely on intrahemispheric transfer of information as the left hand is also controlled by the RH. However, in the “crossed condition” (i.e., LVF stimulation and right-hand response) an additional interhemispheric transfer via the corpus callosum is required. The additional callosal transfer step is thought to result in response-time difference between crossed and uncrossed conditions (CUD). Callosotomy prevents the callosal transfer in the crossed condition, further increasing the CUD, as alternative (subcortical) routes for the interhemispheric information transfer have to be utilized

Fig. 2

Flow-chart summarizing the inclusion of studies into the present meta-analysis. Separately for Poffenberger (top half) and redundant-target paradigm (bottom half) the numbers of considered studies after initial identification (database search) as well as following the screening of abstracts and study text is reported. The number of studies included in the meta-analysis is also provided

Fig. 3

Overview of the categories used to classify the callosotomy patients found in the literature based on the spatial extent of the surgery. Light boxes indicate that the respective subregion was sectioned, while dark boxes indicate the region to be intact. The definition of anatomical subregions follows the division of the corpus callosum into thirds relative to the anterior–posterior extent of the structure as illustrated on the right. AC and HC refer to anterior and hippocampal commissure, respectively

Fig. 4

Comparison of the estimated mean and 95% confidence interval of CUD and bRG_min in patients with commissurotomy (Comm), with complete (pure) callosotomy (Call), with partial (anterior-medial) callosotomy (pCall), and controls. Estimates marked with an “a” represent (weighted) mean estimates while all other are determined using linear-mixed modelling (for details see text)

Fig. 5

Association of CUD and bRG measures as function of the used unilateral-reference method when calculating bRG. The prediction of bRG from CUD reached statistically significance only for the bRGavg estimate as indicated by the “*”. The different markers indicate patients with commissurotomy (□), complete callosotomy (○), and (any) partial callosotomy (△). The effect size (ez) of the prediction is given as explained variance