The beauty of diversity in cognitive neuroscience: The case of sex‐related effects in language production networks

Over the past few decades, several studies have focused on potential sex‐related differences in the trajectories of language development and functioning. From a behavioral point of view, the available literature shows controversial results: differences between males and females in language production tasks may not always be detectable and, even when they are, are potentially biased by sociological and educational confounding factors. The problem regarding potential sex‐related differences in language production has also been investigated at the neural level, again with controversial results. The current minireview focuses on studies assessing sex‐related differences in the neural networks of language production. After providing a theoretical framework of language production, it is shown that the few available investigations have provided mixed results. The major reasons for discrepant findings are discussed with theoretical and methodological implications for future studies.

explanation of such discrepancies may be found in the study by Ardila and Rosselli (1996) who analyzed discourse production in a cohort of 180 Spanish-speaking healthy adults showing that women produced more words than men only among adults aged between 51 and 65 years. On the contrary, younger women and men (aged between 16 and 50 years) produced speech samples with similar amounts of words. Therefore, age is apparently a critical variable affecting sexrelated differences in talkativeness. How about the efficiency of lexical production? In a study by Halpern (1992) women were better than men on tasks of language production and verbal fluency.
More recently, Weiss, Kemmler, et al. (2003) assessed potential sex-related differences in cognitive functions (including language) in a cohort of 97 students (51 women). The participants were asked, among other things, to perform a semantic and a phonological fluency task. Women performed better in the semantic condition but were no different than men in the phonological one. Semantic fluency tasks represent an indirect way to assess the extension of a person's mental lexicon (i.e., the number of known words). Tombaugh et al. (1999) failed to find any significant differences between women and men on either semantic or phonological fluency tasks in a large cohort of 1300 individuals. However, their performance was significantly biased by factors such as age (older people may know more words but may also experience slowed and less efficient abilities of lexical selection) and, most of all, level of education (persons with high education typically know more words and perform better on such tasks). Unfortunately, in the study by Weiss, Kemmler, et al. (2003) the two groups were not balanced for age.
Furthermore, women had also higher verbal IQs. Altogether, these factors might have biased their results. It appears, then, that the available evidence on sex-related differences in language production may not always be detectable and, even when they are, may be potentially biased by sociological and educational confounding factors. Nonetheless, sex-related differences can be observed in the prevalence of congenital disorders also affecting language development and functioning as shown, for example, by the higher incidence of developmental disorders such as developmental dyslexia, primary language impairment, and autism spectrum disorders in boys (e.g., Baron-Cohen et al., 2005;Chilosi et al., 2021;McCarthy & Arnold, 2011).
The problem regarding potential sex-related differences in language production has also been investigated at the neural level.
Indeed, growing evidence suggests that male and female brains might process information with both shared and, at least partially, specific neural networks (e.g., Hill et al., 2014;Xu et al., 2020). For example, in a meta-analysis of studies focusing on sex differences in phonological and visuospatial working memory networks, Hill et al. (2014) showed not only larger activations in limbic and prefrontal areas (e.g., bilateral amygdalae and cingulate gyri) in females and wider activations in the inferior parietal lobe (IPL) and superior parietal lobe (SPL) and the precuneus in males but also shared activations in other regions of the brain (e.g., bilateral middle frontal gyri [MFGs], left cingulate gyrus, left IPL and SPL, and left middle temporal gyrus [MTG]). Nonetheless, the available literature on gender differences in the neural networks underpinning language processing is quite controversial (e.g., Kaiser et al., 2008;Sato, 2020).
Let us consider the long-lasting debate about potential sexrelated similarities/differences in lateralization. Under the assumption that linguistic (mostly lexical and grammatical) skills are usually left-lateralized, studies have focused on the possibility that male and female brains have different functional organizations. Already Chrichton-Browne (1879) had suggested that the symmetry between the two hemispheres may be stronger in women than men. In a seminal review on this topic, gathering data from clinical studies of patients with brain lesions, psycholinguistic investigations on healthy participants, as well as anatomical and electrophysiological investigations, McGlone (1980) concluded that male brains may be more asymmetrical than female brains in both linguistic and non-linguistic functions. This apparently suggests that language processing is more left lateralized in men than in women highlighting the possibility of a bilateral organization for female brains (Harris, 1980). More recently, in a voxel-based morphometric analysis of the brains of 465 healthy adults, Good et al. (2001) showed that male brains have increased leftward asymmetry in posterior temporal areas related to language processing.
However, results from several investigations are all but univocal as many did not provide evidence for a difference in lateralization of lexical functions between men and women (e.g., Allendorfer et al., 2012;Garn et al., 2009;Watkins et al., 2001). For example, Watkins et al. (2001) did not report lateralization differences among the sexes in a cohort of 124 participants. The inconsistency of such results has also been highlighted by recent reviews (e.g., Wallentin, 2009) and metanalyses (e.g., Sommer et al., 2008).
Analyzing the effect sizes of the neuroimaging studies included in their metanalysis, Sommer et al. (2008) showed that the resulting mean weighted effect size was so weak that the often-reported differences in lateralization may be found only in some linguistic tasks

Significance
Over the past few decades, few functional studies have focused on potential sex-related differences in the neural networks of language production. However, they have provided mixed results. This minireview focuses on the major reasons for discrepant findings: developmental issues, lack of control of critical variables that are known to affect language development and its neural organization (e.g., socioeconomical status, bilingualism), different sample sizes, methodological differences affecting task choice, and the lack of a clear theoretical background about the cognitive and neural underpinnings of language production. Finally, this review highlights theoretical and methodological implications for future studies.

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MARINI and may even be absent at the population level (see also Sommer et al., 2004). Another highly controversial issue concerns the potential volumetric and functional differences between male and female brains in the neural networks processing language. Despite long-dated claims regarding gender differences on language networks, an influential critical review highlighted that the available evidence is not clear enough to account for their inclusion as a large confounding factor in neuroimaging studies of language processing (Wallentin, 2009).
The current paper aims at commenting on the results from neuroimaging studies focusing on language production under the lens of the current knowledge about the cognitive and neural underpinnings of linguistic production. After describing an influential neurocognitive model for language production, the results from functional studies will be discussed to comment on the presence or absence of potential sex-related differences in the neural correlates of language production.
First, the speaker needs to generate a communicative intention and a structure or mental depiction of the contents of what (s)he wants to convey (mental model or story scenario generation) that will serve as a foundation for the development of the story structure (Gernsbacher, 1990). In this preliminary stage of message preparation language interacts with other cognitive abilities such as attention, executive functions, working memory, long-term semantic and episodic declarative memory (e.g., Ferretti et al., 2017;Mozeiko et al., 2011): the abilities to focus the attention to the goal at hand, plan what must be said next, monitor one's own production, and inhibit potentially distracting actions are crucial. Furthermore, the speaker needs to consider the interlocutors' expectations by generating a theory of their mind, and both linguistic (i.e., what has already been said) and extralinguistic (e.g., information about the place and time in which the conversation takes place) context. This preliminary stage of discourse generation requires the recruitment of vast areas in bilateral frontal lobes. Activations in the orbitofrontal cortex (BA 47 and BA 11), anterior cingulate gyrus (ACG, BA 24), and supplementary motor area (SMA, BA 6) as well as in the dorsolateral prefrontal cortices (DLPFCs) have been frequently reported (e.g., Hirschfeld et al., 2008). Of note, lesions to the ACG and SMA are often related to a reduced propension to speak (e.g., Devinsky et al., 1995) suggesting a role of these areas in the generation of the motivation to speak. On the other hand, the activations in bilateral DLPFCs have been implicated in executive functions (Yuan & Raz, 2014). For example, patients with lesions to left (Coelho et al., 2012) and right (Marini, 2012) DLPFC may experience deficits in planning and monitoring the contents of their narratives. In this preliminary stage of message preparation, a key role is also played by the ability to generate a communicative intention. According to Catani and Bambini (2014), this complex ability is likely implemented in epicenters in medial and dorsomedial prefrontal areas involved in mentalizing (Lombardo et al., 2010;Van Overwalle, 2009) and connected to Broca's area through the frontal aslant tract (Catani, Dell'acqua, Vergani, et al., 2012). Of note, this tract of fibers extends to more frontal areas involved in theory of mind generation which is another major component of the initial stages of discourse planning. A role in the integration of higher-order language has also been proposed for the forceps minor of the corpus callosum (e.g., Mamiya et al., 2018;Solso et al., 2016).
Once the story structure has been generated, the speaker needs to organize it in sequences to be converted in propositions and eventually verbalized through processes of conceptual preparation, lexical selection, lexical access, and production (e.g., Indefrey & Levelt, 2000). The stage of conceptual preparation allows for the activation of a target lexical concept (i.e., a concept "for which there is a lexical item in the mental lexicon" Levelt, 2001; page 13,464) that best fits with the communicative intention of the speaker. The activated lexical concept triggers a process of lexical selection where the semantic information contained in the lexical concept is spread to lemmas in the mental lexicon (Roelofs, 1992). A lemma is a complex information containing the grammatical category of the word and all its morphosyntactic valences that are necessary for grammatical encoding (i.e., the generation of the sentence). Neuroimaging studies using reading and lexical generation tasks showed that the activation of the lexical concept and the subsequent stage of lexical selection are related to activations in a network involving the left temporal lobe (i.e., the temporal pole, BA 38; anterior aspects of the inferior temporal gyrus (ITG) and the fusiform gyrus, BA 37), the left IFG (i.e., posterior aspect of Broca's area, BA 44; precentral sulcus, BA 6), and portions of the cerebellum (e.g., De Zubicaray et al., 2006;Indefrey, 2011). In this regard, consolidated neuropsychological evidence (e.g., Damasio et al., 1996) suggests that the left temporal lobe contributes to keep the lexical concept active in memory until the target word has been selected. The left IFG might also contribute to this network thanks to its role in phonological working memory and for its potential implication in the ability to select informative words, that is, words that are linguistically and pragmatically sound in the communicative context (Marini & Urgesi, 2012;Mazzon et al., 2019).
As for white matter (WM) tracts crucial for the phase of lexical selection, a critical role is apparently played by the anterior portions of the frontal aslant tract, the inferior fronto-occipital fasciculus, and the anterior thalamic radiations (Corrivetti et al., 2019).
Once the lemma has been activated, its morphosyntactic information likely interacts with a basic recursive combinatorial operation called Merge (Chomsky, 1995) that triggers sentence generation and placement of the selected lemma in the correct position in the sentence. A recent meta-analysis supports the role of a fronto-temporal network in this process (Zaccarella et al., 2017). Within this network, the posterior aspect of left pars opercularis (BA44) and the infero-posterior aspect of the superior temporal gyrus (STG) (BA22) are connected through the long segment of the arcuate fasciculus.
Namely the left pars opercularis has been proposed to act as the syntactic merger (e.g., Zaccarella & Friederici, 2015), whereas the pSTS/ STG complex maps the morphosyntactic information associated to words to the syntactic structures generated by left pars opercularis (e.g., den Ouden et al., 2012). A role in this phase of grammatical encoding is likely played also by the left caudate nucleus in the basal ganglia that has been found related to the detection of syntactic anomalies (Moro et al., 2001).
The selected lemma spreads its activation to the word's phonological code with a speed which is dependent on the word's frequency (stage of phonological encoding). Growing evidence supports a role for the posterior aspect of the left STG/MTG in phonological code retrieval and of the left IFG in phonological encoding (Indefrey, 2011). Furthermore, recent evidence supports the hypothesis that also the cingulum-cingulate gyrus, which connects the cingulate gyrus with other brain regions, plays a role in phonological processing (e.g., Walton et al., 2018). This phonological information must then be combined into syllables which receive a stress pattern resulting in a phonological word. A process of phonetic encoding will then convert the retrieved phonemes in abstract articulatory representations (i.e., the articulatory score) that will eventually be produced during the stage of articulation. These last two stages of message production are implemented in a wide network involving cortical and subcortical areas: phonetic encoding (SMA and left anterior insula; e.g., Dronkers, 1996;Carreiras et al., 2006); articulation (left precentral gyrus, left thalamus, basal ganglia, and dentate nucleus in the right cerebellar hemisphere; e.g., Peeva et al., 2010;Tettamanti et al., 2005). Of note, growing evidence suggests that these epicenters are interconnected by a wide array of WM pathways with the inclusion of posterior fronto-striatal and frontal aslant tracts, corpus callosum, and the cortico-spinal tract (e.g., Corrivetti et al., 2019).

| PUTATI V E S E X-R E L ATE D D IFFEREN CE S IN THE NEUR AL NE T WORK S FOR L ANG UAG E PRODUC TION
The available literature was searched using PubMed. The search included studies assessing sex differences in language production with neuroimaging techniques. The titles and abstracts of the selected papers were checked and only those papers reporting original research, reviews or metanalyses including healthy children, adolescent, and adults were selected. Studies focusing on patients with developmental disorders, acquired brain injuries, and/or neurodegenerative syndromes were excluded. The results showed that over the past 30 years few investigations have been carried out to directly explore potential sex-related differences in brain activations on linguistic production tasks. Namely, the research yielded 13 original studies (4 focusing on children), two metanalyses and one systematic review. Unfortunately, these studies have mainly assessed such relation focusing on lexical selection skills (i.e., lexical generation tasks) and not giving the possibility to relate potential sex-related differences to specific phases of discourse production. Buckner et al. (1995) performed two PET experiments on a cohort of university students and workers. In the former, 12 male and 20 female right-handed adult participants who were native English speakers aged between 18 and 35 years performed an overt verb generation task where they were asked to read nouns and say aloud the corresponding verbs. In the latter, 12 male and 17 female adult participants (same participants as the former experiment) were administered a stem completion task requiring them to read three-letter word stems and then say aloud English words that could complete the sequence. Both tasks required participants to produce words but with an important difference: in the stem completion task the beginning of the word had already been presented with a facilitation in the process of lexical retrieval. In the verb generation task the provided noun activated the corresponding lexical concept that triggered the process of lexical selection and access. Accordingly, both tasks elicited shared activations in the left inferior frontal gyrus (IFG) (BA 44 and 45) that is involved in stages of lexical selection, lemma activation, and phonological code retrieval. Of note, during the verb generation task participants showed further activations in more anterior aspects of the left IFG (BA 10 and 46). Interestingly, even if the activations were similar between males and females in both tasks, in the verb generation task such activations were larger in males. Obviously, the reason for such slight difference is not easily interpretable (also considering the lack of differences in reaction times between male and female participants in this investigation). Furthermore, the available structural evidence about potential sex-related differences in the left IFG are quite controversial (Blanton et al., 2004;Su et al., 2008;Wilke et al., 2007). were assessed before entering the scanner with tasks assessing, among other things, lexical comprehension, naming, phonological and semantic fluency. Interestingly, the two groups did not differ on any language measure. They were administered two verb generation tasks during the fMRI session. The former was a block-design covert verb generation task requiring participants to hear nouns and covertly generate the corresponding verbs. The latter was an event-related verb generation task requiring participants to listen to concrete nouns and then provide one of three possible answers | 637 MARINI depending on the instructions: (1) Mentally generate the verbs associated with the noun (covert generation); (2) Speak out the related verbs (overt generation); and (3) Repeat the heard noun (overt noun repetition). Behaviorally, males and females performed similarly on the overt verb generation task. Furthermore, both groups showed similar language lateralization and broadly similar activation patterns. Nonetheless, a few differences could be found after controlling for performance. Indeed, males showed greater activations in the right MFG and superior frontal gyrus (SFG), right caudate nucleus, and ACG. Furthermore, better performance on verb generation this time correlated with increased right caudate nucleus in basal ganglia and ACG activation in males and with increased right MFG/SFG activation in females, suggesting that males and females might use partially different strategies in language processing but with similar outcomes. Overall, then, this study supports the possibility that performance may be a significant variable to account for when considering potential sex-related differences in the neural correlates of lexical production. Interestingly, female participants had a more bilateral pattern of activations spanning to both right and left IFG (BA 44,45,47) and DLPFC (BA 9, 46) supporting the long-debated possibility of a more enhanced lateralization of linguistic networks in males. Of note, however, such differences were evident in the younger participants aged 4 to 6 years. This result apparently indicates that boys might have a left-lateralized fronto-temporal network already at the age of 4 years, whereas girls might lateralize such functions later in time. In this regard, however, it should be reminded that this study employed only 80 participants who were split in 5 age groups containing each a female and a male subgroup. As for children aged 4 to 6, the analyses had been performed on barely five males and five girls. This leaves open the possibility of a low generalizability of such analyses to the general population. Indeed, other studies did not find gender-related differences in children or adolescents involved in verb generation tasks employing MEG (e.g., Kadis et al., 2011) or fMRI (e.g., Plante et al., 2006;Wood et al., 2004).
Using a different task to elicit words, Weiss, Siedentopf, et al. (2003) assessed potential sex differences on a phonological fluency task in 20 right-handed healthy psychology students (10 males). The task consisted in producing as many words as possible beginning with specific phonemes. The two groups did not differ on this test. Indeed, they all had high performance on it as they had been selected among the most proficient in a greater cohort of 97 individuals (Weiss, Kemmler, et al., 2003). While performing the task, both groups showed similar activations in bilateral prefrontal cortex, cingulate gyrus, and in the right cerebellum.
Importantly, the between-group analysis showed a lack of differences between men and women. This apparently suggests that previous reports about sex differences on such tasks may be biased by task performance rather than by gender as also noted by Allendorfer et al. (2012).
More recently, Gauthier et al. (2009) recruited 44 Frenchspeaking university students divided in four groups made of 11 participants each according to their sex (males vs. females) and proficiency level on a verbal fluency task performed before the experiment (high-proficient vs. low-proficient). During the fMRI scanning they were administered a covert phonological fluency task. Again, all groups showed similar activations on the neural network typically associated with lexical selection and access (including, e.g., the IFG, the ACG, the cerebellum, and basal ganglia). However, the authors reported also some differences related to sex and performance level. Indeed, men with high proficiency showed more activations than men with lower proficiency in the right precuneus and left DLPFC, whereas men with lower proficiency showed higher activations in the right IFG. With respect to those with high proficiency, women with low proficiency had increased activation in the left ACG. Interestingly, the authors also reported a sex main effect that was independent of performance levels: men had greater activations in the left ITG, cerebellum, ACG and PCG, right SFG, right DLPFC, and lingual gyrus.
A third way to elicit words is overt picture naming. In a PET experiment, Grabowski et al. (2003) examined this ability in 62 healthy adults (31 men) balanced for age (mean age 33 years) and educational level (mean 15 years). During scanning, participants were asked to name aloud the stimuli portrayed in a series of color photographs depicting concrete entities (e.g., animals, fruits and vegetables, musical instruments, etc…). Males and females performed similarly on the naming task in terms of both accuracy and latency. However, men showed increased activation in left ITG and left frontal pole, whereas women had higher activations in the right IFG and the right precentral gyrus.
In Garn et al. (2009)  Overall, the studies employing lexical production tasks provided mixed results. Indeed, two metanalyses have supported the idea that in lexical production tasks it is very difficult to derive a coherent picture by the available evidence. In a metanalysis of studies assessing potential gender differences in handedness, asymmetry of the Planum Temporale, and functional lateralization of language, Sommer et al. (2008)  This was further confirmed by other eight studies on 510 subjects employing semantic decision tasks where, again, no difference in lateralization was found between male and female participants.
More recently, Sato (2020) performed a systematic review and metanalysis of studies aimed at assessing potential sex-related differences in language processing confirming that sex differences in the BOLD signal or cerebral blood flow was highly inconsistent across fMRI and PET studies.
To date only two studies have focused on potential sex-related differences in discourse production (Angelopoulou et al., 2020;Kaiser et al., 2007). Kaiser et al. (2007) explored potential genderrelated differences on a covert narrative production task with fMRI.
Namely, they asked a cohort of 44 bilingual healthy young adults

| CON CLUS IONS
This brief overview about the potential existence of gender-related differences in the neural networks of language production has shown that the available evidence on this topic is quite controversial (e.g., Kaiser et al., 2008;Sato, 2020). On production tasks male and female brains might process linguistic information with both shared and, at least partially, specific neural networks that may reflect the use of different strategies at the individual level rather than at the gender level. Indeed, in a recent metanalysis Sato (2020) showed that the sex-related differences found in neuroimaging studies focusing on language processing are quite heterogeneous failing to find a coherent direction in these results.
Indeed, one of the major problems faced by studies focusing on sexrelated differences in brain structure and function is the need to control for several potentially confounding variables that might bias their results (Chen et al., 2007). The available evidence on sex-related differences in language production may not always be detectable and, even when they are, may be potentially biased by developmental, environmental, sociological, and educational confounding factors.

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Studies involving children, adolescents or adults may report different findings because of developmental issues (see Etchell et al., 2018 for a systematic review on this topic). For example, let us consider the Basal Ganglia. These subcortical nuclei are an epicenter of languagerelated neural networks implicated in both grammatical and phonetic encoding (in stages of lemma activation and articulation). Even after correcting for global brain volume, studies focusing on these subcortical structures reveal a consistent gender-related difference with females having greater gray matter volumes (e.g., Lange et al., 1997;Sowell et al., 2002;Wilke et al., 2007). These differences are likely related to the expression of sex hormones during development: higher levels of testosterone are associated with decreases in the volume of caudate nucleus (Herting et al., 2014). Furthermore, together with education level, age might also determine sex-related differences in talkativeness (Ardila & Rosselli, 1996) and affect performance on fluency tasks (Tombaugh et al., 1999) that, in turn, might determine a different organization of the corresponding neural networks.
It is therefore crucial that studies focusing on sex-related differences in language production match their participants according to their age and education level. Another problem regards the lack of control of critical variables that are known to affect language development, functioning, and neural organization such as Socio-Economical Status (Romeo et al., 2018) and linguistic exposure (i.e., in bilinguals; Sulpizio et al., 2020). With the exception of Kaiser et al. (2007), the reviewed studies did not mention whether their participants were monolingual or bilingual and what was their personal history of language exposure. As to this regard, accumulating evidence suggests that bilingualism impacts cognitive functions and the neural organization of language (e.g., Tao et al., 2021). It remains unclear, however, if such impact is similar across the two genders. This is an issue worth exploring in future investigations.
The performance of the participants is another significant variable to account for when considering potential sex-related differences in the neural correlates of linguistic production (Allendorfer et al., 2012). An additional bias might depend on different experimental protocols and data processing. As to this regard, even in absence of sex-related differences in brain activations in areas related to semantic processing on a metalinguistic task (semantic judgment), in Xu et al. (2020) a dynamic causal modeling analysis revealed different effects on modulatory connections within the semantic networks (including three major epicenters in this study: left IFG, SPL, and STG) for men and women. In male participants, the analysis showed more inhibitory influence from left IFG to left STG, whereas female participants showed more inhibitory influence from left SPL to left STG. Furthermore, in the same study a network-based statistics analysis showed stronger connections linking distant prefrontal and parietal areas in females, whereas in males stronger connections were shorter and restricted to frontal areas.
Different sample sizes (Wallentin, 2009) and methodological differences affecting task choice (e.g., Harrington & Farias, 2008) represent other major issues. As for sample size, two meta-analyses showed that the available evidence on the potential lateralization of linguistic functions may be biased by the number of participants: smaller samples showed greater bilateral activations in women than in men; larger cohorts apparently did not confirm such effect (Sommer et al., 2004(Sommer et al., , 2008. Furthermore, studies have often employed different tasks assessing different linguistic functions but collapsing their conclusions in a broad idea of "language" organization in the brain in males and females. Kansaku and Kitazawa (2001) have clearly shown that different tasks may bias the identification of gender differences.
For example, discourse-, rather than lexical-, related tasks might lead to the identification of gender differences. Kansaku et al. (2000) assessed with fMRI brain activations using a story listening task. After correcting for a control condition where the same story was played in reverse mode, the authors found a stronger bilateral activation in the STG and MTG for women (whereas men had stronger left-lateralized activation in the same areas) but no effect of sex-related laterality on other areas such as the MTG. Interestingly, similar findings were observed also on a study with English speakers (Phillips et al., 2000) and likely reflected higher levels of linguistic and conceptual integration required for both narrative comprehension and production. This leads to a final consideration regarding the need for more studies focusing on aspects of language processing that have been neglected so far in the literature on this topic. Indeed, the available evidence on language production is mainly restricted to lexical production tasks (i.e., verb generation, semantic or phonological fluency, and picture naming). Even when discourse production was used to elicit language production, the focus of the analyses was restricted to lexical production skills. However, language is not only lexical skills. There is much more than this, including phases of communicative intention generation, discourse planning and monitoring. We simply do not know almost anything about potential sex-related differences in some stages of narrative discourse and message production such as discourse conceptualization. Future investigations are required to further our knowledge also on these critical aspects of language production.

AUTH O R CO NTR I B UTI O N S
A.M. conceptualized the paper, wrote the original draft, reviewed it according to reviewers' suggestions and edited the final draft.

ACK N OWLED G EM ENT
Open Access Funding provided by Universita degli Studi di Udine within the CRUI-CARE Agreement.

CO N FLI C T O F I NTE R E S T
The author has no conflict of interest to declare.

PE E R R E V I E W
The peer review history for this article is available at https://publo ns.com/publo n/10.1002/jnr.25096.