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. Author manuscript; available in PMC: 2023 Feb 22.
Published in final edited form as: Brain Cogn. 2021 Dec 16;156:105831. doi: 10.1016/j.bandc.2021.105831

An action-concept processing advantage in a patient with double motor cortex

Magdalena Miranda 1,2,, Cecilia Gonzalez Campo 1,3,, Agustina Birba 1,3,4, Alejandra Neely 4, Felipe Diego Toro Hernandez 4, Evelyng Faure 5,6, Gonzalo Rojas Costa 5,6,7, Agustín Ibáñez 1,3,4,8, Adolfo García 1,3,8,9,*
PMCID: PMC9944406  NIHMSID: NIHMS1864572  PMID: 34922210

Abstract

Patients with motor-area atrophy exhibit selective deficits in processing action-related meanings, suggesting a link between movement conceptualization and the amount of regional tissue. Here we examine such a relation in a unique opposite model: a rare patient with a double cortex (due to subcortical band heterotopia) in primary/supplementary motor regions, and no double cortex in multimodal semantic regions. We measured behavioral performance in action- and object-concept processing as well and resting-state functional connectivity. Both dimensions involved comparisons with healthy controls. Results revealed preserved accuracy in action and object categories for the patient. However, unlike controls, the patient exhibited faster performance for action than object concepts, a difference that was uninfluenced by general cognitive abilities. Moreover, this pattern was accompanied by heightened functional connectivity between the bilateral primary motor cortices. This suggests that a functionally active double motor cortex may entail action-processing advantages. Our findings offer new constraints for models of action semantics and motor-region function at large.

Keywords: motor cortex, subcortical band heterotopia, action semantics, functional connectivity, embodied cognition

1. Introduction

A prolific hotspot in cognitive neuroscience concerns the relationship between action semantics and motor circuits. Motor brain networks are recruited during action-concept processing in healthy subjects (García et al., 2019; Pulvermüller, 2013), and their atrophy entails distinct deficits in that domain (Birba et al., 2017). Then, would action-concept processing be boosted or disturbed in individuals with a double motor cortex? This unexplored question can offer unprecedented constraints for models of action semantics and motor-network function. To address the issue, we assessed action-semantic skills and functional connectivity (FC) patterns in a unique patient with subcortical band heterotopia (SBH) in primary and supplementary motor regions.

Action semantics refers to verbal and non-verbal stimuli denoting bodily movements (Cervetto et al., 2021; García & Ibáñez, 2016; García et al., 2019; Pulvermüller, 2013, 2018). This domain is grounded in motor circuits, including the primary and supplementary motor cortices, with contributions from multimodal semantic areas that integrate various sensory streams (Birba et al., 2021; Cappelletti, Fregni, Shapiro, Pascual-Leone, & Caramazza, 2008; Federmeier, Segal, Lombrozo, & Kutas, 2000; García et al., 2019; Hauk, Johnsrude, & Pulvermüller, 2004; Horoufchin, Bzdok, Buccino, Borghi, & Binkofski, 2018; Moguilner et al., 2021a, 2021b; Pulvermüller, Lutzenberger, & Preissl, 1999; Tomasino, Werner, Weiss, & Fink, 2007). Compatibly, patients with atrophy in motor regions are distinctively impaired in processing action words or pictures, even when several other conceptual categories (e.g., nouns and objects) are spared (Bak, 2013; Birba et al., 2017, 2021; Bocanegra et al., 2017; Bocanegra et al., 2015; Boulenger et al., 2008; García, Bocanegra, Herrera, Pino, et al., 2018; Luzzatti, Aggujaro, & Crepaldi, 2006; Shapiro & Caramazza, 2003). This link seems quite specific, as action-concept processing is uncompromised in patients whose brain damage does not mainly affect motor regions (Bak, 2003; Birba et al., 2021; Moguilner et al., 2021a, 2021b; Steeb et al., 2018). While this speaks of a direct link between motor-region integrity and behavioral outcomes, no study has tested the impact of an additional cortical band in such areas. Patients with SBH offer a rare and strategic opportunity to access this crucial testing ground for the field.

SBH (also known as double cortex syndrome) is a rare form of grey matter heterotopia, namely, a group of regional malformations caused by premature arrest of neuronal migration from the germinal matrix to the developing cortex (Barth, 1987; Guerrini, Dobyns, & Barkovich, 2008). The syndrome is characterized by a band of grey matter located deep within, and roughly paralleling, bilateral cortical structures mainly in anterior (including motor) regions (Dobyns et al., 1996; Gleeson, 2000; Matsumoto et al., 2001). Synaptic connections between both layers of gray matter have been observed in SBH patients (De Volder et al., 1994; Sprugnoli et al., 2018) and rodent models (Ackman et al., 2009; Chevassus-au-Louis & Represa, 1999). Bidirectional connections between heterotopic neurons and cortical/subcortical structures resemble those of normotopic neurons. This would allow for parallel processing of sensorimotor information in both cortices (Schottler, Couture, Rao, Kahn, & Lee, 1998), although coexisting aberrant connections could differentially shape FC in heterotopic cortices (Ackman et al., 2009; Chevassus-Au-Louis, Congar, Represa, Ben-Ari, & Gaiarsa, 1998). In SBH patients, both cortical regions and subcortical bands are recruited during motoric (Draganski, Winkler, Flugel, & May, 2004; Pinard et al., 2000) and linguistic (Briellmann et al., 2006) tasks –but see Keene et al. (2004). Accordingly, SBH offers a unique model to assess how action-semantic processing is affected by a functional double motor cortex.

Here we assessed a patient with SBH across bilateral motor brain regions (primary motor cortex, supplementary motor cortex) and no such pattern in multimodal semantic areas (fusiform gyrus, superior temporal gyrus). We administered a picture-word association (PWA) task involving congruent and incongruent action-verb and object-noun pairings, and obtained FC measures via functional magnetic resonance imaging (fMRI). Behavioral and neuroimaging outcomes were compared to those of matched healthy controls (HCs). We predicted that if action semantics benefits from the presence of two parallel pathways, as observed in SBH, the patient might exhibit an advantage for processing action-verb relative to object-noun items. Briefly, with this novel approach, we aim to inform current anatomo-functional models of action understanding.

2. Case description

The patient is a right-handed, Spanish-speaking, 18-year-old woman with 12 years of education. She was diagnosed with refractory epilepsy secondary to SBH at age 3, with one to three episodes per week including absences, tonic, and secondary generalized seizures. EEG analysis revealed independent multifocal interictal epileptiform activity with bilateral occipital ictal onset. Until age 9, the patient was treated with valproic acid and oxcarbacepin. At age 10, the patient incorporated levetiracetam and clobazam to her pharmacological treatment, and this was complemented with Atkins diet. At age 13, the patient was hospitalized due to regular seizures and lamotrigine was added to her treatment. A neuropsychological assessment conducted at the age of 18 revealed mild cognitive impairment and executive dysfunction, alongside preserved inhibitory control –for test descriptions and results, see Supplementary material, section 1. Neurological evaluation was normal at that age. At present, the patient works as a craftswoman.

A brain MRI showed a pattern of bilateral diffuse SBH (Figure 1A). Among other areas, grey matter heterotopia was evident bilaterally across key regions subserving action-concept processing, including the primary, premotor, supplementary, and presupplementary motor cortices (García et al., 2019; Pulvermüller, 2013, 2018; Vigliocco, Vinson, Druks, Barber, & Cappa, 2011). Conversely, multiple regions involved in multimodal semantic processing, crucially including the anterior fusiform and the superior temporal gyri, presented no heterotopia or any other alterations (Binder, Desai, Graves, & Conant, 2009; Pulvermüller, 2018; Vigliocco et al., 2011). No additional structural abnormality was seen on MRI. MRI acquisition and preprocessing steps are detailed in Supplementary material, section 2.

Figure 1.

Figure 1.

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Patient’s key heterotopic areas, functional connectivity (FC) patterns, and action-concept processing outcomes. A. Representative axial, sagittal, and coronal T1- weighted MRI images of patient’s grey matter heterotopia. Left inset images depict key heterotopic motor regions, implicated in action-concept processing (crosshairs, highlighted in red in the upper box). Right inset images depict the key non-heterotopic non-motor regions involved in multimodal semantic processing. B. Picture-word association task. B1. Schematic illustration of the task design. Each trial consisted of a black-and-white image and an accompanying action-verb word or object-noun word that could correspond with the picture (congruent trials, Con) or not (incongruent trials, Inc). B2. Behavioral performance on the Picture-Word Association task. The left inset shows non-significant accuracy differences between the patient and HCs. The middle inset shows reduced RT for the patient compared to HCs in both conditions. The right inset shows results of the between-condition subtraction analyses. Whereas latencies for the action and object conditions were quite similar (differing in ~70 ms), they were markedly greater for the patient, who responded to action concepts ~300 ms faster than to object concepts. Such subtraction difference between the patients and HCs was significant (p < .001) and it remained so after covarying for MoCA and IFS scores (p = .023). Boxplot whiskers show min and max values with the box extending over 25–75th percentiles. The line represents the median. C. Patient’s FC patterns. The left inset shows connectivity patterns over two brain views. The right inset shows the scatter plot of FC (y-axes) between each pair of ROIs (x-axes) for HCs (grey dots) and the patient (black triangles). ROI analysis including bilateral PMC and SMC hubs (orange nodes) as well as STG and FG hubs (blue nodes) showed increased connectivity between the RPMC and the LPMC (red line) in the patient compared to controls (left panel, axial and coronal views, p =.003, t = 3.41, pFDR = .04). No connectivity differences between the patient and controls were found among non-motor related ROIs (blue nodes, grey lines). On the right inset, line and error represent mean ± SEM of the control sample. The asterisk (*) denotes significant differences at p < .05 (FDR-corrected). HCs: healthy controls; FC: functional connectivity; RT: reaction time; LPMC: left primary motor cortex; RPMC: right primary motor cortex; LSMC: left supplementary motor cortex; RSMC: right supplementary motor cortex; LSTG: left superior temporal gyrus; RSTG: right superior temporal gyrus; LFG: left fusiform gyrus; RFG: right fusiform gyrus.

3. Methods

We report how we determined our sample size, all data exclusions (if any), all inclusion/exclusion criteria, whether inclusion/exclusion criteria were established prior to data analysis, all manipulations, and all measures in the study.

3.1. Control samples

As in previous single case works, two independent groups were used as control samples for behavioral and MRI analyses (Steeb et al., 2018; Torres-Prioris et al., 2020). In both cases, comparison between the patient and HCs were made via Crawford’s modified t-tests (Crawford & Garthwaite, 2002, 2012; Crawford & Howell, 1998), which is robust for non-normal distributions, presents low type-I error rates, and has yielded replicable results in previous single-case studies –even when single subjects are compared with small samples (Cervetto et al., 2018; García et al., 2017; Steeb et al., 2018; Torres-Prioris et al., 2020). The MRI control sample comprised 11 right-handed healthy women from the Yale Low-Resolution Controls (Yale Lowres) Database (Hampson et al., 2012; Lee et al., 2014; Roth, Johnson, Tokoglu, Murphy, & Constable, 2014; Scheinost et al., 2015; Scheinost et al., 2016; Shen, Papademetris, & Constable, 2010; Shen, Tokoglu, Papademetris, & Constable, 2013; X. Zhang et al., 2011). The sample had a mean age of 20.18 (SD = 1.78, range = 18–23), which did not statistically differ from the patient’s age (Crawford’s t-test: t = −1.17, p = .1339, z = −4.18). Note that similar sample sizes have yielded robust results in previous single-case studies (Cervetto et al., 2018; García et al., 2017; Gorno-Tempini, Murray, Rankin, Weiner, & Miller, 2004; Migliaccio et al., 2012).

For behavioral analysis, the patient’s performance on the experimental tasks was compared with that of 11 healthy women with no history of neurological or psychiatric disease, or alcohol/drug abuse. This group had a mean age of 18.72 (SD = 1.40) and an average of 11.91 (SD = 1.49) years of education. As shown through Crawford’s two-tailed t-tests, the control group matched the patient in terms of age (t = 0.06, p = .95, z = 0.06) and education level (t = −0.54, p = .60, z = −0.56).

All participants gave written informed consent in accordance with the Declaration of Helsinki, and written informed consent was obtained from the patient for the publication of this case report. The study was approved by the institutional ethics’ committee. No part of the study procedures or analyses was pre-registered prior to the research being conducted.

3.2. Picture-word association task

All participants completed a PWA task, built on previously validated stimuli. The task comprised 80 trials, each composed of a black-and-white image and an accompanying word (Bocanegra et al., 2017). Half the items belonged to the action-verb condition, and the remaining half corresponded to the object-noun condition. Each condition was composed of 20 congruent trials (e.g., the picture of a couple dancing with the Spanish verb meaning dance) and 20 incongruent trials (e.g., the picture of someone kneeling together with the Spanish word meaning swim). Incongruent trials were exclusively included to force genuine semantic decisions on the congruent trials (namely, the ones targeted by the task). For details about the stimuli, see Supplementary material, section 3.

Each trial began with a fixation cross (shown for a random period of 100–300 ms), followed by a two-element display composed of a picture and a word placed immediately below it. The picture-word dyad remained visible until the participant responded. Stimuli were presented in black color in the center of the screen against a white background. Sitting comfortably at a desk with a computer, participants were instructed to view each trial and press the right arrow to indicate ‘match’ or the left arrow to indicate ‘no match’ (Figure 1B.1). They were asked to perform the task as fast and accurately as possible. Each keystroke served to record the trial’s accuracy and response time (RT), while also triggering the following trial. The action-verb and object-noun conditions were counterbalanced across participants and across sessions for each single participant. Prior to the task, four practice trials (different from the 80 ones appearing in the task) were presented for familiarization purposes. Altogether, the task lasted approximately 10 min. Stimulus presentation and response collection were conducted using Matlab (MathWorks) with Psychtoolbox (Kleiner, 2007).

3.3. Behavioral data analysis

Comparisons between HCs and the patient for accuracy and reaction time (RT) data from congruent trials in the PWA task, as well as the difference between conditions in it, were analyzed via Crawford’s t-tests (Crawford & Garthwaite, 2002). This test provides a robust for non-normal distributions, presents low values of type I error, and has yielded replicable results in previous single-case studies –even when individual scores are compared with data from small samples (Baez et al., 2013; Couto et al., 2013; García et al., 2017). RT analyses were performed considering only correct trials and upon removal of all trials exceeding 2.5 SDs from the mean across participants, for HCs, and across trials, for the patient (Beauprez, Laroche, Perret, & Bidet-Ildei, 2019; Beauprez, Toussaint, & Bidet-Ildei, 2018). After rejection of incorrect trials and outliers, the number of remaining items (over 91% across participants and conditions) showed no significant difference between the object-noun and the action-verb conditions in either the patient (X2 = 0, p = 1) or HCs (X2 = 1.329, p = .249). Remaining items were also similar between the patient and HCs in both the action-verb (X2 = 0.010, p = .919) and the object-noun (X2 = 0, p = 1) conditions. Comparisons between conditions (considering means across participants, in the case of HCs, and across trials, in the case of the patient) were done using permutation tests of symmetry. Finally, to determine whether hypothesized differences between the patient and HCs were influenced by the former’s cognitive status and executive skills, all analyses were repeated with global MoCA and IFS scores as independent covariates. These analyses were based on a Bayesian Test for a Deficit allowing for Covariates (BTD-Cov) (Crawford, Garthwaite, & Ryan, 2011), as previously reported in single-case studies on action-concept processing (Cervetto et al., 2018).

3.4. Functional image acquisition, preprocessing, and analysis

For FC analyses, resting-state GRE-EPI volumes, slices parallel to the anterior-posterior commissures, covering the whole brain, were interleaved acquired with comparable parameters for the patient (TR = 2660 ms; TE = 30 ms; flip angle = 90º; 25 slices; voxel size = 3 × 3 × 3 mm; sequence duration = 10 minutes; number of volumes = 240) and the HCs (TR = 1555 ms; TE = 30 ms; flip angle = 80º; 46 slices,; voxel size = 3.44× 3.44 × 3.44 mm; sequence duration = 6 minutes; number of volumes = 240). Participants were asked to keep their eyes closed and to avoid moving or falling asleep (Barttfeld et al., 2012; Sedeño et al., 2014).

Resting-state fMRI scans were preprocessed using the Data Processing Assistant for Resting-State fMRI (DPARSF V2.3)(Chao-Gan & Yu-Feng, 2010), an open-access toolbox that generates automatic analysis pipelines for imaging data. For each preprocessing step, DPARFS called the Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST V.1.7) to process the data. Before preprocessing, the first five volumes of each subject’s resting-state session were discarded to ensure that magnetization achieved a steady state. Then, images were slice-time corrected (using as reference the middle slice of each volume) and aligned to the first scan of the session to correct head movement (SPM functions). To reduce the effect of motion and physiological artifacts (as cardiac and respiration effects), six motion parameters, cerebrospinal fluid (CSF), and white matter (WM) signals were removed as nuisance variables (REST default functions). CFS and WM masks for this procedure were derived from the tissue segmentation of each subject’s T1 scan in native space with SPM12 software (after the co-registration of each subject’s structural image with the fMRI one). Next, functional images were normalized to MNI space using the echo-planar imaging (EPI) template from SPM (Ashburner & Friston, 1999) and then they were smoothed using an 8-mm full-width-at-half-maximum isotropic Gaussian kernel (SPM functions). Finally, given the relevance of slow frequency in the analysis of resting-state networks,(Fox et al., 2005; Raichle, 2009) data were bandpass filtered between 0.01–0.08 Hz (REST functions). Participants had no movements greater than 3 mm and/or rotations higher than 3º. No differences between the patient and HCs were found in the mean (m) rotational (HCs: m = 0.033, SD = 0.023; SBH: m = 0.032. Crawford t-test: t = 0.02, p = .98, z = −0.026) and mean translational (HCs: m = 0.045, SD = 0.017; SBH: m = 0.029. Crawford t-test: t = −0.87, p = .40, z = −0.916) parameters.

FC was estimated based on two pairs of bilateral regions of interest (ROIs) established via the Automated Anatomical Labeling (AAL) atlas (Tzourio-Mazoyer et al., 2002). The first pair corresponded to motor areas implicated in action-concept processing, namely, the primary and supplementary motor cortices (Debaere, Wenderoth, Sunaert, Van Hecke, & Swinnen, 2003; García et al., 2019; Hetu et al., 2013; Tian et al., 2020; Vigliocco et al., 2011). The second pair was comprised of non-motor areas linked to multimodal semantic processing, namely, the superior temporal and fusiform gyri (Binder et al., 2009; Vigliocco et al., 2011). To calculate FC between the ROIs in each pair, we extracted the mean time-courses of each ROI by averaging the blood-oxygen-level-dependent signal of all their voxels. The connectivity strength between these ROIs was defined with Pearson’s correlation coefficient, as in previous reports (Gonzalez Campo et al., 2019; Sprugnoli et al., 2018); this yielded 12 values representing the pairwise connections for all motor ROIs (including heterotopic and non-heterotopic regions) and between all non-motor non-heterotopic ROIs. To compare these measures between groups, we applied Crawford’s t-tests (alpha = .05) corrected with the false discovery rate (FDR) method (García et al., 2017; Gonzalez Campo et al., 2019).

3.5. Data and code availability

All experimental data, as well as the scripts used for their collection and analysis, are fully available online (https://osf.io/skdc9/).

4. Results

4.1. Behavioral results

Accuracy for action-verb and object-noun trials did not differ significantly in the patient (X2 = 0, p = .50), in HCs (t = 0.54, p = .30), or between the patient and HCs (Figure 1B.2, left inset; Supplementary material 4). As expected, overall performance was slower for the patient (Figure 1B.2, middle inset; Supplementary material 4). Crucially, however, relative to object-noun trials, action-verb trials yielded higher RTs in HCs (t = 3.69, p < .001) and lower RTs in the patient (t = 2.07, p = .03) –Figure 1B.2, middle inset. This was confirmed by a subtraction analysis showing that the difference between conditions was greater in the patient than in HCs, even after covarying by both general cognitive skills and executive functions (Figure 1B.2, right inset; Supplementary material 4). Specifically, action-verb stimuli were processed ~300 ms faster than object-noun stimuli in the patient, while they were processed slightly slower (~70 ms) than object-noun stimuli in HCs.

4.2. Functional connectivity results

Relative to HCs, the patient exhibited enhanced FC between the left and right PMC (heterotopic motor-related regions) (t = 3.41, pFDR = .04; Figure 1C). No FC differences were observed between the patient and HCs across non-heterotopic non-motor regions (Figure 1C; Supplementary material 5).

5. Discussion

We studied action semantic processing in a patient with SBH in motor regions. Unlike HCs, the patient exhibited faster performance for action-verb than object-noun items. This pattern was uninfluenced by general cognitive dysfunction and was accompanied by heightened FC between the bilateral primary motor cortices. These findings can constrain models of action semantics and motor-region function at large.

As reported in other semantic association tasks (Cervetto et al., 2018), HCs responded more slowly to action than object trials. Conversely, despite preserved accuracy and overall slower processing in both conditions, the patient presented the exact opposite pattern. Previous research has shown that action-semantic processing is compromised by motor-region atrophy (Birba et al., 2017; García & Ibáñez, 2018). Indeed, disruption of particular motor hubs abolishes the delay for action association observed in HCs (Cervetto et al., 2018). Conversely, our results suggest that action semantic processing may be facilitated in the context of a functional double motor cortex. This pattern is noteworthy given that nouns are, by default, easier to process than verbs (Crepaldi et al., 2006; Matzig, Druks, Masterson, & Vigliocco, 2009; Shebani et al., 2017; Tyler, Bright, Fletcher, & Stamatakis, 2004; Zingeser & Berndt, 1990).

Moreover, this action-concept advantage survived covariation with IFS and MoCA outcomes, indicating their independence from executive and general cognitive functions. In line with previous results (Bocanegra et al., 2015, 2017; García et al., 2017; Ibáñez et al., 2013; Sambin et al., 2012), this indicates that distinct action-semantic skills are not a secondary manifestation of coarser-grained cognitive effects. Accordingly, motor-region SBH might play a direct role in the patient’s action-semantic advantage.

Indeed, the patient’s areas with SBH (primary and supplementary motor cortices) have been systematically implicated in action-semantic processing (Boulenger et al., 2008; Cappelletti et al., 2008; Federmeier et al., 2000; Kemmerer, Castillo, Talavage, Patterson, & Wiley, 2008; Moguilner et al., 2021a, 2021b; Pulvermüller, 2018; Steeb et al., 2018; Tomasino, Fink, Sparing, Dafotakis, & Weiss, 2008; Visser, Jefferies, Embleton, & Lambon Ralph, 2012). Previous SBH research shows that subcortical heterotopic bands in the primary motor cortex are functional during a motor task (Jirsch et al., 2006; Pinard et al., 2000) and that both middle prefrontal regions and subcortical bands can be active during language processing (Briellmann et al., 2006). Our study suggests that this particular neural pattern may underlie the patient’s action-concept processing advantage. Importantly, other areas involved in general semantic processing, such as the superior temporal and fusiform gyri (Binder et al., 2009; Binney, Embleton, Jefferies, Parker, & Ralph, 2010; García et al., 2019; Shimotake et al., 2015; Vigliocco et al., 2011), presented no signs of heterotopia, reinforces the potential specificity of the brain-behavior links mentioned above.

Compatibly, the patient’s selective hyperconnectivity pattern across motor regions points to a possible correlate of her behavioral profile. Indeed, enhanced FC between motor mechanisms is a key signature of action-concept processing (Birba, Beltran, et al., 2020), and, in patients typified by impaired motor function and action semantic processing, these domains are associated with lower motor region connectivity (Abrevaya et al., 2017; Hensel et al., 2019; Koenig et al., 2014). Moreover, the patient’s increased FC emerged exclusively in regions subserving action semantics (García et al., 2019), further pointing to a potential substrate of her skills in such a domain. This pattern raises the intriguing hypothesis of a potential brain coupling mechanism facilitating action semantic processing, a possibility that is reinforced by its diametrically opposite manifestation in HCs (who exhibited action-semantic interference during the PWA task). Future studies could further evaluate the role of motor-network hyperconnectivity in the motor-language coupling dynamics elicited during our PWA task.

Such findings can inform recent models in the embodied cognition framework (Birba et al., 2017; Pulvermüller, 2013, 2018). Previous work has shown that action-concept processing can be enhanced upon boosting motor-system activity, either through bodily training (Trevisan, Sedeño, Birba, Ibáñez, & García, 2017) or non-invasive brain stimulation (Pulvermüller, Hauk, Nikulin, & Ilmoniemi, 2005; Suárez-García et al., 2021; Tomasino et al., 2008; Willems, Labruna, D’Esposito, Ivry, & Casasanto, 2011). Yet, those effects respond to transient interventions with no bearing on the structural organization of motor networks. Conversely, our data suggest that modality-specific advantages on this domain can be observed in patients with a long-standing and functionally active double motor cortex. Thus, beyond the selective deficits observed in motor-region atrophy models (Birba et al., 2017), action-concept processing may be variously affected depending on the type of anatomical reconfiguration present in such circuits.

Yet, alternative interpretations may be entertained for the present findings. In particular, our study involved comparisons between action-verb and object-noun conditions, and frontal/motor brain regions are differentially engaged by verbs at large (Vigliocco et al., 2011). Therefore, the patient’s advantage for action concepts may not be specific to such a category. Were that the case, the observed effect might not reflect embodied mechanisms proper, but rather more general semantic/pragmatic and distributional cues distinguishing verbs from nouns (Vigliocco et al., 2011). Still, as revealed through multiple neuroscientific methods, motor brain mechanisms are more critically engaged by action verbs than other verb categories, crucially including abstract verbs (Birba, Beltran, et al., 2020; Birba, Vitale, et al., 2020; Cervetto, 2021; Fernandino et al., 2013a, 2013b; García et al., 2019; Moguilner et al., 2021b). Accordingly, present results may, indeed, reflect modality-specific effects. Future SBH studies could settle this debate by extending our design with action and non-action verb categories.

Interestingly, our results may also be partly interpreted as ‘paradoxical functional facilitation’, a notion that captures non-detrimental manifestations of brain anomalies (Kapur, 1996). Such phenomena may involve increased domain-specific processing to compensate for executive control deficits, the recruitment of alternative neuronal pathways, and the enhancement of local connectivity (Corrigan, Richards, Treffert, & Dager, 2012; Hughes, 2012; Kapur, 1996; Takahata & Kato, 2008; Valero-Cabre, Toba, Hilgetag, & Rushmore, 2020). In agreement with this notion, changes in brain networks due to aberrant functional connectivity in the SBH patient’s brain were described in this work but also reported in previous studies (Ackman et al., 2009; Chevassus-Au-Louis et al., 1998). The present case study could be partly explained in such terms, given the patient’s dysexecutive profile alongside her atypical organization of, and increased connectivity between, critical motor circuits. Still, note that this patient did not outperform HCs in any condition, suggesting that paradoxical facilitation may also operate by attenuating deficits in a relevant domain. New studies in the SBH population should explore further manifestations of processing advantages or attenuated impairment in motor-related cognitive functions. Our findings also invite new studies on the effects and multimodal imaging correlates of (paradoxical) functional facilitation in SBH and other conditions, including hyperlexic reading patterns in developmental language disorders (Turkeltaub et al., 2004).

Finally, our results also have implications for the characterization of SBH. Subcortical bands in motor regions have been implicated in action execution (Draganski et al., 2004; Jirsch et al., 2006; Keene et al., 2004; Pinard et al., 2000; Spreer et al., 2001), but no study has assessed how such patterns might impact modality-specific semantic functions. While previous studies have exclusively reported cognitive deficits in these patients (Briellmann et al., 2006; Janzen, Sherman, Langfitt, Berg, & Connolly, 2004; Keene et al., 2004), our results suggest that fine-grained motor-related domains may be less severely impaired under this particular neural configuration. Indeed, the subtraction analysis revealed a specific action-concept facilitation in the patient relative to HCs. While previous research has shown functional connectivity changes in SBH patients (Ackman et al., 2009; Chevassus-Au-Louis et al., 1998), our seems to be the first linking a fine-grained semantic advantage to heightened connectivity in putative circuits. Moreover, new studies in the SBH population should explore further potential processing advantages for motor-related cognitive domains.

6. Limitations and avenues for further research

Our study has some limitations. First, the control group had a modest size. Although the statistical tests we used are particularly robust in small groups (Crawford & Howell, 1998) and yield replicable results in single-case studies with similar or even smaller control samples (Cervetto et al., 2018; García et al., 2017), replications with higher Ns and trials would be desirable. Second, our design involved a maximum of 20 valid trials per condition. Although previous studies on action concepts and other semantic domains have reported replicable findings with similar and even lower numbers of trials (Ambrosini, Arbula, Rossato, Pacella, & Vallesi, 2019; Baadte & Meinhardt-Injac, 2019; Duta, Styles, & Plunkett, 2012; Frith, Cahill, Ridley, & Baker, 1992; García et al., 2017; García, Bocanegra, Herrera, Moreno, et al., 2018; Iodice, Meilan, Ramos, & Small, 2018; Moguilner et al., 2021b; Slachevsky et al., 2018; H. Zhang, Carlson, & Diaz, 2020; Zimmerman et al., 2015), future work should replicate our study with larger stimulus sets. Third, we were unable to obtain online fMRI recordings during the task. Even though offline brain measures can illuminate behavioral patterns in patient studies (Lin et al., 2018; Mohanty, Sethares, Nair, & Prabhakaran, 2020; Woodward & Cascio, 2015), it would be critical for future SBH studies to capture task-related markers of action-concept processing. Fourth, the observed differences may have been influenced by domain-general cognitive factors. Importantly, all significant results survived covariation for MoCA and IFS scores, suggesting that they were not primarily driven by general cognitive skills or executive abilities. However, further action-concept research should introduce additional tests or manipulations to explore the impact of other cognitive domains and strategies in SBH patients. Finally, longitudinal designs would be crucial to map progressive changes in the reported patterns.

7. Conclusion

This is the first study reporting better action-concept (relative to object-concept) processing in relation with motor-region SBH and increased motor-network connectivity. Our results reveal unprecedented links between the organization of action-related circuits and outcomes in a relevant semantic domain. Further research on rare models of motor-region reorganization can foster new theoretical and clinical developments at the crossing of cognitive neuroscience and behavioral neurology.

Supplementary Material

supplementary material

Funding

This work was supported by CONICET and FONCYT-PICT [grant numbers 2017–1818, 2017–1820]. Agustín Ibáñez is supported by grants of the Alzheimer’s Association GBHI ALZ UK-20-639295; Takeda CW2680521; ANID/FONDECYT Regular (1210195); ANID/FONDAP 15150012, Sistema General de Regalías (BPIN2018000100059), Universidad del Valle (CI 5316), and the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by the National Institutes of Aging (NIA) of the National Institutes of Health (NIH) under award number R01AG057234, an Alzheimer’s Association grant (SG-20-725707-ReDLat), the Rainwater Foundation, and the Global Brain Health Institute. Adolfo García is an Atlantic Fellow at the Global Brain Health Institute (GBHI) and is supported with funding from GBHI, Alzheimer’s Association, and Alzheimer’s Society (Alzheimer’s Association GBHI ALZ UK-22-865742); ANID, FONDECYT Regular (1210176); and Programa Interdisciplinario de Investigación Experimental en Comunicación y Cognición (PIIECC), Facultad de Humanidades, USACH. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health, Alzheimer’s Association, Rainwater Charitable Foundation, or Global Brain Health Institute.

Footnotes

Conflict of interest

The authors declare no conflicts of interest.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

supplementary material
NIHMS1864572-supplement-supplementary_material.docx (64.4KB, docx)

Data Availability Statement

All experimental data, as well as the scripts used for their collection and analysis, are fully available online (https://osf.io/skdc9/).

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