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. 2021 Jan 14;31(6):2845–2854. doi: 10.1093/cercor/bhaa392

Sulcal Morphology in Cingulate Cortex is Associated with Voluntary Oro-Facial Motor Control and Gestural Communication in Chimpanzees (Pan troglodytes)

William D Hopkins 1,✉, Emmanuel Procyk 2, Michael Petrides 3, Steven J Schapiro 4,5, Mary Catherine Mareno 6, Celine Amiez 7
PMCID: PMC8107786  PMID: 33447847

Abstract

Individual differences in sulcal variation within the anterior and mid-cingulate cortex of the human brain, particularly the presence or absence of a paracingulate sulcus (PCGS), are associated with various motor and cognitive processes. Recently, it has been reported that chimpanzees possess a PCGS, previously thought to be a unique feature of the human brain. Here, we examined whether individual variation in the presence or absence of a PCGS as well as the variability in the intralimbic sulcus (ILS) are associated with oro-facial motor control, handedness for manual gestures, and sex in a sample of MRI scans obtained in 225 chimpanzees. Additionally, we quantified the depth of the cingulate sulcus (CGS) along the anterior–posterior axis and tested for association with oro-facial motor control, handedness, and sex. Chimpanzees with better oro-facial motor control were more likely to have a PCGS, particularly in the left hemisphere compared to those with poorer control. Male chimpanzees with better oro-facial motor control showed increased leftward asymmetries in the depth of the anterior CGS, whereas female chimpanzees showed the opposite pattern. Significantly, more chimpanzees had an ILS in the left compared to the right hemisphere, but variability in this fold was not associated with sex, handedness, or oro-facial motor control. Finally, significant population-level leftward asymmetries were found in the anterior portion of the CGS, whereas significant rightward biases were evident in the posterior regions. The collective results suggest that the emergence of a PCGS and enhanced gyrification within the anterior and mid-cingulate gyrus may have directly or indirectly evolved in response to selection for increasing oro-facial motor control in primates.

Keywords: chimpanzees, cingulate cortex, medial frontal cortex, oro-facial motor control, paracingulate sulcus

The cingulate sulcus (CGS) is a prominent and evolutionarily conserved fold on the medial wall of each cerebral hemisphere. It is a primary sulcus and, as such, is one of the first to appear during gestational development (Armstrong et al. 1995; Tamraz and Comair 2000). The CGS extends in an anterior-to-posterior direction and is located anterior and superior to the corpus callosum. The midcingulate and anterior cingulate cortex, lying within and ventral to the CGS, comprises areas 25, 24, 32, 32′, and 24′ and clinical, neuroanatomical, and functional imaging studies have implicated these areas in a variety of cognitive, affective, and emotional processes (Devinsky et al. 1995; Bush et al. 2000; Allman et al. 2001; Paus 2001; Hadland et al. 2003; Procyk et al. 2016; Loh, Petrides, et al. 2017b).

At the level of the midcingulate and anterior cingulate cortex, in addition to the CGS, two other sulci belonging to this cortical region are consistently observed in the human brain: the paracingulate sulcus (PCGS) and the intralimbic sulcus (ILS). These sulci run parallel dorsally and ventrally with respect to the CGS. The PCGS and ILS are secondary folds that appear later than the primary sulci in gestational development (Armstrong et al. 1995; Tamraz and Comair 2000). Unlike the primary sulci that are present in 100% of hemispheres, the PCGS and the ILS are less frequently present in human brains (Paus et al. 1996; Amiez et al. 2018).

In humans, it is well documented that there is individual variation in sulcal morphology in the region of the cingulate cortex and this variability is associated with different clinical disorders as well as motor and cognitive functions (Fornito et al. 2008b). For instance, the presence of the PCGS has been reported to be more prevalent in (1) the left compared to the right hemisphere (2) males compared to females, and (3) schizophrenic males compared to non-schizophrenics (Paus et al. 1996; Yucel et al. 2001; Yucel et al. 2002; Huster et al. 2007; Fornito et al. 2008a; Leonard et al. 2009; Park et al. 2013; Wei et al. 2017).

There is also evidence that certain regions within the midcingulate cortex are implicated in motor control. For instance, three motor regions have been identified in the midcingulate cortex in monkeys, and stimulation in these regions elicits movements of the hand, mouth, arms, and legs (Dum and Strick 1991; Luppino et al. 1991). More recently, in functional magnetic resonance imaging (fMRI) work, comparable motor regions have been identified in the human brain in relation to movement of different body parts, including hand, eye, tongue, and foot movement (Amiez and Petrides 2014). Interestingly, there are differences in the distribution of motor foci between individuals with and those without a PCGS. For subjects with a PCGS, the tongue and saccade foci migrate anteriorly into the PCGS region, while the hand and foot foci remain located in the CGS. For individuals without a PCGS, all four regions are topographically located along CGS region.

In the context of the findings by Amiez and Petrides (2014), in the present study, we examined whether individual variation in the sulcal morphology of the cingulate cortex (including the CGS, PCGS, and ILS) might be associated with oro-facial motor control in chimpanzees. Our specific interest in examining the association between oro-facial motor control and variation in CGS/PCGS/ILS morphology in chimpanzees stems primarily from four bodies of research. First, in a comparative study of the sulcal morphology in the anterior cingulate region of human, chimpanzee and Old World monkey brains, Amiez et al. (2019) have recently demonstrated that the PCGS is observed in both human and chimpanzee brains, but not in Old World monkey brains, in contrast to the ILS which was observed in the four primate species examined. The presence of a PCGS in the chimpanzee brain has also been confirmed both cytoarchitectonically and in terms of functional connectivity (Amiez et al. 2020).

Second, Gavrilov et al. (2017) have found in monkeys that neurons within the midcingulate, ventral-lateral premotor, and pre-supplementary motor cortex respond prior to and during the production of species-specific vocalizations that have been brought under voluntary stimulus control. Third, previous studies in both wild and captive chimpanzees have demonstrated that the production and use of both species-specific and novel learned sounds are under voluntary control (Hopkins et al. 2007; Hopkins et al. 2011; Crockford et al. 2012; Wallez et al. 2012; Schel et al. 2013). For instance, Leavens et al. (2004) and others (Liebal et al. 2004; Hostetter et al. 2007) have demonstrated that captive chimpanzees produce several sounds to capture the attention of an otherwise inattentive individual (herein referred to as attention-getting sounds, AG). AG sounds have been described as “kisses,” “extended food grunts,” and “raspberries,” with this latter type being by far the most prevalent and the only one that has been described in wild chimpanzees (Watts 2016). Kisses involve the chimpanzee pursing their lips and sucking air inward through the narrow gap in the lips. By contrast, raspberries also involve pursing the lips but the apes expel air through them. Extended food grunts are a low-frequency, atonal sounds that involve the larynx (see Taglialatela et al. 2012 for description and sonographs).

Fourth, it has been hypothesized that the anterior and/or midcingulate cortex plays a fundamental role in the initiation of joint attention in developing children and in adults (Benga 2005; Hopkins and Taglialatela 2012; Mundy 2018). This hypothesis is particularly relevant because the functional role of AG sounds by chimpanzees is to capture the attention of otherwise inattentive individuals. Evidence supporting this claim comes from the fact that AG sounds are produced more often when the recipient of this communication signal is oriented away from the subjects compared to when they are face-to-face (Leavens et al. 2004); thus, the chimpanzees understand that 1) the recipient of their intended communicative interaction is not in the same line of sight (or knowledge state) and 2) it is necessary to gain first their visual attention before signaling for a desired object or food (typically with a manual gesture) (Lurz et al. 2018).

In summary, because AG sound production is under voluntary control and serves the function of initiating joint attention, it was hypothesized that differences in sulcal morphology of the cingulate cortex would differ between chimpanzees that reliably produced AG sounds (AG+) compared to those that do not (AG−). It was further hypothesized that any differences between AG+ and AG− apes would be specific to the anterior or mid-regions of the CGS, because these are the areas hypothesized to be part of the joint attention system and overlap with regions involved in motor functions in both monkeys and humans. To test these hypotheses, the sulcal morphology of the cingulate cortex was characterized in two ways. First, for each hemisphere and subject, the presence or absence of a paracingulate (PCGS+, PCGS−) and intralimbic (ILS+, ILS−) sulcus was assessed by an expert rater (see example in Fig. 1). The presence or absence of these two sulci was then compared between AG+ and AG− chimpanzees, as well as between sexes (males, females) and hand preference groups (left-, ambiguous-, right handed). Second, following previously used methods (Hopkins et al. 2017a), the CGS was extracted and the depth of the fold quantified along the anterior–posterior axis using the software program BrainVisa. The average depth of the CGS and its asymmetry along the anterior–posterior axis was then compared across AG+ and AG− apes, sex, and handedness groups.

Figure 1.

Figure 1

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Illustration of the PCGS, CGS, and intra-limbic (ILS) sulci on the medial wall of the left and right hemispheres of chimpanzee brains.

Methods

Subjects

In vivo magnetic resonance images (MRI) and behavioral data were obtained from 225 captive chimpanzees housed at the Yerkes National Primate Research Center (YNPRC) and the National Center for Chimpanzee Care (NCCC) of the University of Texas MD Anderson Cancer Center. There were 135 females and 90 males, ranging from 6 to 53 years of age. The methods for measuring hand preference for manual gestures and the production of AG sounds by the apes have been described in detail elsewhere (Hopkins et al. 2005; Taglialatela et al. 2012). For gesture handedness, there were 44 left-, 134 right-handed and 47 apes that failed to show a significant hand preference (i.e., ambiguously handed). In terms of AG sound production, 115 individuals were classified as never producing AG sounds (AG−), while the remaining 110 apes were observed to produce at least 1 AG sound within a 6-trial testing paradigm (AG+). Within the AG+ group, the number of sounds produced in 6 test trials ranged between 1 and 6 (Mean = 3.72, SE= 0.031).

MRI Image Collection

Scans were obtained at the time the chimpanzees were being surveyed for their annual physical examinations. Subjects were first immobilized by ketamine (10 mg/kg) or telazol (3–5 mg/kg) and subsequently anesthetized with propofol (40–60 mg/(kg/h)) following standard procedures at the YNPRC and NCCC facilities. The YNPRC subjects were then transported to the MRI facility, while the NCCC subjects were wheeled to the mobile imaging unit. The subjects remained anesthetized for the duration of the scans, as well as the time needed to transport them between their home cage and the imaging facility (between 5 and 10 min) or the mobile imaging unit (total time ~5 min). Subjects were placed in the scanner chamber in a supine position with their head fitted inside the human-head coil. Scan duration ranged between 40 and 60 min as a function of brain size.

Seventy-seven chimpanzees were scanned using a 3.0 Tesla scanner (Siemens Trio, Siemens Medical Solutions USA, Inc., Malvern, Pennsylvania, USA) at the YNPRC. T1-weighted images were collected using a three-dimensional gradient echo sequence (pulse repetition = 2300 ms, echo time = 4.4 ms, number of signals averaged = 3, matrix size = 320 × 320, voxel dimension 0.6 × 0.6 × 0.6 mm). Additionally, 139 NCCC and 9 YNPRC chimpanzees were scanned using a 1.5 Tesla Phillips scanner (the Netherlands). T1-weighted images were collected in the transverse plane using a gradient echo protocol (pulse repetition = 19.0 ms, echo time = 8.5 ms, number of signals averaged = 8, and a 256 × 256 matrix, voxel dimension 0.7 × 0.7 × 1.2 mm). After completing MRI procedures, the subjects were temporarily housed in a single enclosure for 6–12 h to allow the effects of the anesthesia to wear off, after which they were returned to their social group.

Extraction and Measurement of Sulci

The sequence of the post-image processing steps performed on the scans is shown in Fig. 2a–h. The sulci were extracted from the native space T1-weighted image based on a method that derives from a pipeline initially dedicated to the human brain and freely distributed as a BrainVISA toolbox (http://brainvisa.info) (Mangin et al. 2004). To account for the differences in chimpanzee anatomy compared to that of humans, a number of adjustments were performed before the scans were processed using the pipeline procedure within BrainVISA. Specifically, chimpanzee MRI volumes were skull-stripped, cropped, and reformatted at 0.625 mm isotropic resolution using ANALYZE 11.0 software and subsequently imported into BrainVISA.

Figure 2.

Figure 2

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(a–h) Pipeline procedures for extraction of cortical sulci using Brainvisa (see text for description).

The pipeline process of extracting the sulci from the cortex involved a number of steps (Mangin et al. 2004) (see Fig. 2a–h). To align the native space brain, the anterior and posterior commissures were manually specified on the MRI at the point where they intersect with the mid-sagittal slice. The first step was to correct for spatial inhomogeneities in the signal intensity, providing a spatially smooth bias field with a stable distribution of tissue intensities (Fig. 2b). Next, the processing of the signal histogram and mathematical morphology were performed using an automatic analysis of the voxel intensities for the entire brain to obtain a binary mask of the brain (Fig. 2c). Adjustments were sometimes necessary in the histogram process to determine gray and white matter means for chimpanzee brain scans. The mask was then split into the left and right hemispheres and the cerebellum (Fig. 2d). A negative mold of the white matter was computed from the split-brain mask. The outside boundary of this mold results from a 5-mm morphological closing of the masked hemisphere, filling up the folds. The gray/white interface is the inside boundary that preserves deformations and assures the spherical topology of the mold (Fig. 2e). Finally, the mold was skeletonized to detect cortical folding, while topological constraints guaranteed the resulting surfaces would have no holes (Mangin 2000; Mangin et al. 2004) (Fig. 2f and g). The folds making up the CGS in each hemisphere were selected manually (Fig. 2h) by the examiner using a 3D visualization interface and following standard anatomical landmarks described for the chimpanzee brain (Bailey et al. 1950; Hopkins et al. 2014) and the total surface area and average depth computed for the CGS in each hemisphere (Fig. 3).

Figure 3.

Figure 3

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(a–d) CGS extraction and parameterization for obtaining measures of depth along the anterior–posterior axis (see text for description).

Quantifying CGS Depth Along the Superior to Inferior Planes

The selected CGS was meshed using a triangular mesh, and the resulting surface was parameterized in order to create a longitudinal coordinate system (Coulon et al. 2006) (Fig. 3a–d). The parameterization process was constrained by the anterior and posterior sulcus extremities, automatically detected using the extrema of the first non-zero eigenfunction of the mesh Laplacian (e1 and e2, Fig. 3b). From these points, a smooth and quasi-isometric (i.e., with minimal metric distortions) coordinate field is extrapolated, that localizes all mesh surface points according to their relative position along the sulcus between the two extremities (Fig. 3c). The coordinate field extends along the length of the CGS from the anterior (y = 1) to the posterior (y = 100) ends of the sulcus. Depth was measured at 100 sulcal length positions in an anterior-to-posterior progression along the parameterized sulcal mesh surface. Position 1 was located at the most inferior point of CGS, anterior to the genu of the corpus callosum, while position 100 was located where the ascending limb of the CGS terminated on the medial wall in the parietal lobe (see Fig. 3c). At each position, y, along the length, the depth is computed by measuring a geodesic distance (in millimeters) from the brain envelope to the fundus of the sulcus (Fig. 3d).

Qualitative Judgment of PCGS

One rater (C.A.) who is an expert in the assessment of the presence of the PCGS and ILS rated all hemispheres and individuals as having the sulcus present or absent. C.A. was blind to the sex, handedness, and AG grouping of all subjects. Unlike in the human brains, no attempt was made to distinguish between a present versus a prominent PCGS within the chimpanzee sample. We used non-parametric statistics to test whether there were 1) interhemispheric differences in the presence of the PCGS and ILS (using the McNemar test) and 2) whether the presence of a PCGS or ILS was associated with sex, handedness and AG sound production within each hemisphere (using Chi-square tests of independence).

Data Analysis

For the parameterization analyses, rather than compare each of the 100 points along the sulcus within each hemisphere, we computed average depth values for every 5 positions. Thus, we obtained 20 depth measures for each hemisphere along the anterior–posterior plane (1 to 20). From these measures, we computed 1) mean depth between the hemispheres at each position [MeanDepth = (R + L)/2] and 2) asymmetry scores in depth at each position [AQ = (R—L)/((R + L) ×.5)]. For the AQ scores, positive values indicated rightward asymmetries and negative values indicated leftward biases. For all analyses using inferential statistics, alpha was set to P < 0.05 and post-hoc analyses, when necessary, were performed using Tukey’s honestly significant difference test.

Results

Qualitative Data Analysis

For this initial analysis, for each chimpanzee, whether a PCGS or ILS was present in both hemispheres (PCGS+/+; ILS+/+), one hemisphere (PCGS+/−; ILS+/−) or neither hemisphere (PCGS−/−; ILS−/−) was calculated. Their distributions were then compared in relation to sex, hand preference, and vocal group. A significant association was found between vocal group and the presence of a PCGS X2(2, N = 225) = 6.385, P = 0.041. The percentage of PCGS+/+, PCGS+/− and PCGS−/− chimpanzees in relation to vocal group is shown in Figure 4a. The highest percentage of AG+ apes were found in the PCGS+/+, followed by PCGS+/−, then PCGS−/− apes. In the next analysis, the presence (PCGS+) or absence (PCGS−) of a PCGS was tested for its association with sex, hand preference, and vocal group within each hemisphere. A significant association was found between vocal group and the presence of a PCGS in the left X2(1, N = 225) = 7.323, P = 0.007, but not the right hemisphere X2(1, N = 225) = 1.323, P = 0.250.

Figure 4.

Figure 4

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(a) Percent of chimpanzee AG+ and AG− chimpanzees that possessed a PCGS in both hemispheres (PCGS+/+), one hemisphere (PCGS+/−), or neither hemisphere (PCGS−/−). (b) Percent of AG+ and AG− chimpanzees that possessed a PCGS+ or not PCGS− in the left hemisphere. (c) Percent of AG+ and AG− chimpanzees that possessed a PCGS+ or not PCGS− in the right hemisphere.

The percentage of PCGS+ and PCGS− chimpanzees in relation to vocal group can be seen in Figure 4b and c. A significantly higher proportion of AG+ chimpanzees had a PCGS in the left hemisphere compared to AG− apes. No other significant associations were found between sex, hand preference and the presence of a PCGS. Note that no significant associations were found between sex, AG group or gesture handedness and the presence of an ILS bilaterally, unilaterally, or in neither hemisphere. When considering the presence or absence of an ILS within the left or right hemisphere, separately, we found a significant association with gesture handedness and ILS for the left X2(1, N = 225) = 8.640, P = 0.013 but not right hemisphere X2(1, N = 225) = 7.417, P = 0.299. A significantly higher proportion of right-handed chimpanzees (77%) had an ILS in the left hemisphere compared to individuals with ambiguous (23%) or left-handedness (0%). No other significant associations were found between sex, gesture handedness, or AG group with the presence of an ILS.

AG Sound Production and CS Depth and Asymmetry

Two repeated measures analyses of covariance were performed. In the first analysis, the mean depth between the two hemispheres was the dependent measure, while the AQ values were the dependent measure for the second analysis. For both analyses, CGS region (position 1 to 20) was the repeated measure, while sex (male, female), gesture handedness (left-, ambiguous- and right handed), and vocal grouping were the between group factors. Age and scanner magnet were covariates. For the average depth between the two hemispheres, there was a significant two-way interaction between sex and vocal group F(1, 211) = 4.456, P = 0.036. Post hoc analysis indicated that AG+ males (Mean = 11.368, SE = 0.205) had greater depths than AG+ females (Mean = 10.618, SE = 0.205), but did not differ from AG− males (Mean = 11.030, SE = 0.276) or AG− females (Mean = 11.118, SE = 0.166).

For the AQ data, a significant main effect for gesture handedness was found F(2, 211) = 5.241, P = 0.006, as well as a three-way interaction between sex, vocal grouping, and CGS region F(19, 4009) = 2.293, P = 0.001. For the main effect of gesture handedness, post-hoc analysis indicated that right-handed chimpanzees (Mean = −.003, SE = 0.001) had greater leftward AQ scores compared with left-handed (Mean = 0.005, SE = 0.002) and apes with ambiguous hand preferences (Mean = 0.002, SE = 0.002). No significant differences in AQ scores were found between ambiguously handed and left-handed apes. The mean AQ scores for each CGS region and vocal group within the male and female chimpanzees are shown in Figure 5a and b. For males, AG+ chimpanzees had greater leftward scores for CGS regions 1 to 4 compared to AG− apes. For females, AG− had greater leftward AQ scores in CGS regions 2 and 3 compared to AG+ individuals.

Figure 5.

Figure 5

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Mean asymmetry (AQ) scores (+/− SE) in female (a) and male (b) chimpanzees that were classified AG+ or AG− at each region along the CGS anterior–posterior axis.

Population-Level Asymmetry

Finally, the analysis of the AQ scores showed a significant main effect for region F(19, 4009) = 2.560, P = 0.001, suggesting that the overall patterns of asymmetry varied along the anterior–posterior axis. To what extent nonhuman primates exhibit population-level neuroanatomical asymmetries remains a topic of some debate (Crow 2009; Rogers et al. 2013); thus, as a means of further exploration of the general pattern of asymmetry within the CGS, we tested for population asymmetries using one sample t-tests on the AQ scores for the 20 CGS points along the anterior–posterior plane. The mean AQ scores at each position are shown in Figure 6. Though the asymmetries were relatively small, significant leftward asymmetries were found for CGS positions 1 to 8 and significant rightward biases were found for CGS positions 14 through 19.

Figure 6.

Figure 6

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Mean asymmetry (AQ) scores (+/− SE) for the CGS in the entire sample at each region along the anterior–posterior axis.

When considering the unilateral PCGS and ILS data, we performed a McNemar test (Odds Ratio, OR) to evaluate whether there were significant interhemispheric differences in the presence or absence of each sulcus. There was no significant difference in the prevalence of a PCGS between the left (n = 28) and right hemispheres (n = 33), OR = 1.178, P = 0.608; however, significantly more chimpanzees had an ILS in the left (n = 29) compared to right hemisphere (n = 9), OR = 3.222, P < 0.001.

Discussion

Four major findings emerged from this investigation. First, chimpanzees that reliably produce attention getting (AG) sounds were more likely to have a PCGS, particularly in the left hemisphere compared to those that did not. Second, when considering the depth of the CGS along the anterior–posterior axis, AG+ males showed a leftward asymmetry in the anterior cingulate region compared to AG− males. In contrast, AG+ females showed a rightward asymmetry compared to AG− females. Third, again when considering the depth of the CGS, there were population-level asymmetries along an anterior–posterior gradient, with leftward asymmetries present in the anterior portions and rightward biases in the posterior segments. Moreover, for the entire cingulate, right-handed chimpanzees showed greater leftward asymmetries compared to ambiguously- and left-handed individuals. Finally, there was a significantly higher number of right-handed chimpanzees that had an ILS in their anterior cingulate region in the left hemisphere compared to those with ambiguous or left-handedness. Further, independent of their handedness, when an ILS but not a PCGS was present, the ILS was observed more often in the left compared to the right hemisphere.

Regarding the qualitative assessment of the presence or absence of a PCGS, there are at least two important findings in the context of previous reports in human subjects. First, the presence of a PCGS was significantly higher in AG+ compared to AG− apes, particularly in the left hemisphere. We believe these findings are the first evidence of a functional correlate of PCGS variation in a nonhuman primate and follows the recent demonstration that some chimpanzees do possess a PCGS that was previously thought to be a unique feature of the human brain (Amiez et al. 2019). Thus, as in humans, variation in the presence of the PCGS is functionally relevant to at least one behavioral characteristic or trait in chimpanzees. Second, Amiez et al. (2020) have recently reported that functional connectivity and the cytoarchitectonic variation observed within the PCGS of chimpanzees are distinct. Specifically, as is the case in humans, there is displacement of area 32 from the dorsal bank of the CGS when the PCGS is present but lack of displacement in its absence. Based on these collective findings, it seems that the presence of a PCGS and the ability to learn new sounds and to use them in functionally meaningful ways are newly evolved traits and it is tempting to speculate that they evolved together and are perhaps limited to Hominids (Amiez et al. 2019). Indeed, Croxson et al. (2018) have recently examined within and between species variability in gray matter and cortical expansion between humans and rhesus monkeys. These authors reported that one area that was uniquely variable to humans and without any homolog in the macaque brain was the dorsal medial cortex, which would include regions that encompass the paracingulate cortex. Our results suggest that chimpanzees may exhibit an intermediate pattern of dorsal medial prefrontal evolution between rhesus monkeys and humans that supports increasingly sophisticated motor and cognitive processes observed between these species.

There were two notable differences between humans and chimpanzees with regard to the PCGS and ILS. In contrast to humans, there were no population-level asymmetries or sex differences in the occurrence of a PCGS in chimpanzees (Paus et al., 1996; Wei et al., 2017). Moreover, chimpanzees showed a leftward asymmetry for the presence of an ILS and previous studies have not reported a population-level bias in humans for this sulcus (Amiez et al. 2019). Thus, when viewed together, chimpanzees show a leftward asymmetry in ILS, but not PCGS, whereas humans show a leftward asymmetry in the PCGS, but not the ILS. Because the ILS is only observed in brains that lack a PCGS, it is possible that the lateralized presence of an ILS in the left hemisphere in chimpanzee brains may constitute an evolutionary transition in lateralized sulcal organization within the anterior and midcingulate cortex from chimpanzees to humans (Amiez et al. 2019).

In the human brain, the leftward asymmetry of the PCGS has been shown to correlate with the lateralization of Broca’s area in the left hemisphere in right-handed human subjects (Toga and Thompson 2003); however, we are not aware of any study assessing the impact of the presence of an ILS on lateralization for language tasks or more generally, on any motor or cognitive task performance. In the chimpanzee, we found an association between gesture handedness and the distribution of the ILS in the left, but not right hemisphere. These results are consistent with previous reports in chimpanzees that right-handed individuals have greater leftward asymmetries in the inferior frontal gyrus and the pli-de-passage fronto-parietal moyen where the hand primary motor area is located within the precentral gyrus (Taglialatela et al. 2006; Hopkins et al. 2017b).

Though no population-level bias was found for the presence of a PCGS in the chimpanzees, we did find significant leftward biases in the depth of the anterior region of the CGS and rightward biases in the posterior region. In humans, several studies have reported directional biases in the anterior cingulate, with the direction of the asymmetries depending on the level of analysis such as the overall volume, gray matter volume, local gyrification, or surface area (Paus et al. 1996; Yucel et al. 2001; Huster et al. 2007; Fornito et al. 2008a; Park et al. 2013; Pizzagalli et al. 2016).

We know of no studies in humans that have parameterized the CGS and quantified depth asymmetries along the anterior–posterior plane, making it difficult to interpret the data from chimpanzees in a larger comparative context. The only other study to report on asymmetries in the CGS in nonhuman primates was in a sample of 357 vervet monkeys by Fears et al. (2011). These investigators reported that the terminal point of the posterior CGS, where it intersects with the midsagittal sulcus, was more caudal in the left compared to the right hemisphere. Whether chimpanzees or any other nonhuman primate species exhibit this asymmetry is unknown.

AG sound production was associated with asymmetries in the anterior portion of the cingulate in a sex-dependent manner. AG+ males showed a significant leftward asymmetry compared to AG− males, whereas AG+ females showed an increased rightward bias compared to AG− females. It is unclear why males and females would differ with respect to directional asymmetries in the production of AG sounds, but a similar set of findings have been found for AG+ and AG− chimpanzees on the depth of the central sulcus. Hopkins et al. (2017a) found that AG+ males showed a larger leftward asymmetry in the depth of the intermediate and ventral portions of the central sulcus compared to AG− males, whereas females showed the opposite pattern. In short, in two separate studies, males and females have been reported to differ in their pattern of association between the use of AG sounds and asymmetries in the brain regions of interest. It should also be noted that in two separate captive chimpanzee populations and in one wild population, the percentage of chimpanzees that produce AG sounds is significantly higher in males than females (Taglialatela et al. 2012; Watts 2016). However, it remains unclear why sex differences in the use of AG sounds between males and females would be explicitly linked to lateralization in the brain. One possibility is a sex difference in oro-facial motor control of AG sounds by chimpanzees. Specifically, previous studies have reported rightward oro-facial asymmetries in the production of AG sounds (Losin et al. 2008; Wallez et al. 2012); however, it is important to acknowledge that no sex differences in oro-facial asymmetries were reported in these studies.

There are at least three limitations to this study. First, we cannot make any inferences about causal relationships between 1) AG sound production and both the presence of a PCGS or in the patterns of asymmetries in the anterior and midcingulate regions or 2) between ILS asymmetry and gesture handedness. That is, it is unclear whether the presence of a PCGS is a consequence of learning to produce AG sounds or the presence of a PCGS facilitates the acquisition and use of AG sounds. Likewise, it is unclear if the leftward ILS asymmetry is a consequence of being right-handed or vice versa. The core issue here is to what extent development of primary and secondary sulci is influenced by post-natal experiential factors. In human and nonhuman primates, primate cortical sulci are developing during the prenatal stages, suggesting that they emerge during embryonic development. Further, in human brains, it has recently been reported that post-natal factors have very limited effects on the development of sulcal pits, which reflect the earliest developmental milestones in cortical folding and include the cingulate cortex (Le Guen et al. 2018). Based on these findings and because the ILS and PCGS are secondary sulci and emerge during prenatal development, it seems unlikely that post-natal experiences influence their development. On the other hand, the mere presence of cortical sulci during prenatal development does not necessarily imply that they are invariant to post-natal influences and some of the assumptions regarding the early role of neuronal development in relation to cortical folding in primate brains have been challenged (Rash et al. 2019). At present, we are inclined to argue that the presence of either an ILS or PCGS may reflect expansion of anterior cingulate cortical areas 24 and 32 that may influence the subsequent development of AG sounds and/or gesture handedness, but we cannot rule out other explanations.

Second, when a PCGS was present in the chimpanzees, we did not make a distinction between its mere presence or prominence as is often used in the characterization of human brains, which some might view as a limitation. There was certainly some degree of variability in the prominence of the PCGS between chimpanzees, including its anterior-position in the medial wall, but given the novelty of the study, we adopted a more conservative approach to the characterization of the PCGS. Third, oro-facial motor control was broadly defined in this study and, therefore, no distinction was made between chimpanzees that produced different types of AG sounds, which may involve varying degrees of voluntary control of facial musculature. As noted above, AG sounds have been described as “kisses”, “extended food grunts” and “raspberries”, with this latter type being by far the most prevalent (Taglialatela et al. 2012; Leavens et al. 2014) and the only one that has been described in wild chimpanzees (Watts 2016).

In summary, the collective findings from the present study suggest that sulcal variation in the anterior/midcingulate cortex is associated with oro-facial motor control in chimpanzees. The findings further showed that the presence of a PCGS, particularly in the left hemisphere, was associated with the production and use of attention-getting sounds by chimpanzees. Though previous studies in humans have reported a number of functional and clinical associations with PCGS variation, these data are the first evidence of their association with behavioral phenotypes in nonhuman primates. Thus, the functional significance of variation in the PCGS predates the split from the last common ancestor of chimpanzees and humans, and appears to be linked to increasingly sophisticated oro-facial motor and non-verbal socio-communicative processes. It should be noted that, though macaque monkeys lack a PCGS, stimulation of Broca’s area homologs induce orofacial movements (Petrides et al. 2005) and tracer studies has been shown that there are cortico-cortical connections between these regions and the cortex of the CGS (Frey et al. 2014). Similarly, in humans, functional connectivity studies have shown that the rostral cingulate motor area in particular is linked to Broca’s region (Loh et al. 2017a). These anatomical findings further add to the suggestion made here that expansion of a circuit that includes Broca’s region in the inferior frontal region in the left hemisphere and its targets in the midcingulate motor region in the left hemisphere are reflections of adjustments that begun in hominid brains and are related to the expanded socio-communicative processes of the hominid brain. These abilities have reached their highest level of development in the human brain, leading to language. Future studies in primates, particularly in chimpanzees, focusing on both anatomical and functional connectivity between regions within the anterior and midcingulate regions, including the PCGS, and Broca’s area will provide important data on the evolution of the medial frontal cortex in relation to socio-communicative and motor control processes in primates (Loh et al. 2017a).

Funding

The National Institutes of Health (grants NS-42867, NS-73134, HD-60563); Human Frontiers Science Program (grant RGP0044). The NCCC chimpanzees are supported by Cooperative Agreement (U42-OD011197). The Yerkes Center and NCCC are fully accredited by the AAALAC International. American Psychological Association guidelines for the ethical treatment of animals were adhered to during all aspects of this study. E.P. and C.A. are employed by the Centre National de la Recherche Scientifique and supported by the labex CORTEX ANR-11-LABX-0042 of Université de Lyon.

Contributor Information

William D Hopkins, Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA.

Emmanuel Procyk, Univ Lyon, Université Claude Bernard Lyon I, Institut National de la Santé Et de la Recherche Médicale, Stem Cell and Brain Research Institute U1208, Bron, France.

Michael Petrides, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.

Steven J Schapiro, Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA; Department of Experimental Medicine, University of Copenhagen, Copenhagen, Denmark.

Mary Catherine Mareno, Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA.

Celine Amiez, Univ Lyon, Université Claude Bernard Lyon I, Institut National de la Santé Et de la Recherche Médicale, Stem Cell and Brain Research Institute U1208, Bron, France.

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