Behavioural Neurology Adynamic spoken language in corpus callosum dysgenesis

sensory-motor


Q7
The corpus callosum is the largest white matter fibre tract in the mammalian brain.It transverses the midline to connect the left and right cerebral hemispheres and plays an integral role in facilitating and coordinating interhemispheric information transfer (Goldstein et al., 2024).Corpus callosum dysgenesis (CCD) is a congenital brain malformation that occurs in utero due to a wide variety of genetic malformations (Edwards et al., 2014;Paul et al., 2007).The aetiology of CCD is variable and the exact genetic cause remains unknown in some cases, but an increasing number of cases can be linked to specific genetic abnormalities (e.g., DCC mutation e Marsh et al., 2017), or less commonly, environmental factors (e.g., foetal alcohol exposure e Riley et al., 1995).CCD can be categorised as partial, where part of the callosal tract remains intact, or complete, where the corpus callosum is entirely absent (Paul et al., 2007).Having complete versus partial CCD is not reliably associated with differential outcomes (Paul et al., 2007).CCD may occur as an isolated malformation, or, more commonly, in conjunction with other brain abnormalities (e.g., abnormal sulcation, and altered circuitry such as Probst bundles, sigmoid bundles, and aberrant midbrain and ventralfrontal tracts) or as a part of an identifiable syndrome (e.g., Vici Syndrome, Aicardi Syndrome, Andermann Syndrome) (Edwards et al., 2014;Paul et al., 2007;Tovar-Moll et al., 2007).The prevalence of CCD is estimated to be approximately 1 in 4000 (Glass et al., 2008), although recent studies suggest that it may be as frequent as 1 in 1000 live births (Bayram et al., 2020).

Cognition and language in CCD
There is significant variability in cognitive outcomes associated with CCD (Brown & Paul, 2019;Siffredi et al., 2013).Since CCD often occurs alongside multiple additional neurological abnormalities, it is difficult to isolate the effects of callosal dysgenesis (Brown & Paul, 2019).Even when studies are restricted to individuals with primary (i.e., non-syndromic) CCD, cognitive outcomes are still highly heterogeneous.For example, measures of intelligence quotient (IQ) range from impaired to highly superior, although they can fall within the average range (Paul et al., 2007).Despite this heterogeneity, a core neuropsychological syndrome appears to be associated with CCD (Brown & Paul, 2019).The three components of this profile include slowed processing speed, poor interhemispheric transfer of sensory-motor information, and difficulties with complex problem solving; these deficits are linked to the reduced transfer of information between hemispheres (Brown & Paul, 2019).Core language skills, such as comprehension and reading, are generally intact in individuals with CCD (Bartha-Doering et al., 2021;Paul et al., 2003).However, there are multiple reports in the literature of language problems that pertain to complex linguistic, "higher-order", or "paralinguistic" language functions (Bartha-Doering et al., 2021).For example, individuals with CCD may have difficulties understanding proverbs, nonliteral language, and humour (Brown et al., 2005;Paul et al., 2003;Rehmel et al., 2016).There are also differences documented in the narrative language, or spontaneous speech, of individuals with CCD.For example, one study found that participants with CCD produced narratives that lacked logic and social insight, and included unusual content, compared to controls (Paul et al., 2004).Another study found that social, emotional, and cognitive inferences were missing from the narratives of individuals with CCD (Turk et al., 2010).Further, in a social decision-making task, individuals with CCD provided inadequate elaboration on consequences of decisions where there were multiple alternatives, compared to more limited options (Young et al., 2019).The narratives produced by individuals with ACC may be similar to those with autism spectrum disorders (ASD), in that both groups exhibit greater difficulty with imaginative elaboration in their spontaneous speech (Renteria-Vazquez et al., 2022).These studies speak to differences in the quality of spontaneous speech in individuals with CCD; however, the quantity of spontaneous speech has not been a major focus of prior research in CCD (Barker et al., 2021).

Verbal adynamia
Reduced quantity of spontaneous speech output in the context of intact core language skills is known as verbal adynamia.In its most severe form, adynamia is known as dynamic aphasia, which is an almost complete paucity of spontaneous speech (also known as propositional language) with normal reading, naming, comprehension, and repetition abilities.Dynamic aphasia has been conceptualised as an "aphasia without aphasia" (Luria & Tsvetkova, 1968); in other words, an individual presents with aphasia (i.e., does not produce spoken language spontaneously), but upon testing it becomes clear that this lack of spoken language is not due to a disruption of language per se, because they are capable of naming objects, and reading, repeating, and comprehending words and sentences.Rather, the individual is unable to use spoken language in a novel and spontaneous way for the purpose of communication.Dynamic aphasia has been linked to dysfunction of the frontal lobes of the brain (Robinson et al., 1998(Robinson et al., , 2005(Robinson et al., , 2006(Robinson et al., , 2015)).Clinically, reduced spontaneous speech is typically observed on complex scene description tasks where individuals are asked to describe what is happening in a pictorial scene.
To date, two studies have reported the presence of adynamia, the less severe or "sub-clinical" form of dynamic aphasia, in CCD.First, a longitudinal study of an individual with complete CCD found that the number of utterances he produced was reduced, and his conversational language was filled with pauses and lacked fluency, yet he had sufficient comprehension, written language, single word, and phonological abilities (Stickles et al., 2002).More recently, we reported a case of an adult male with partial CCD, whose language profile was described as adynamic, presenting as a subclinical form of dynamic aphasia (Barker et al., 2021).Like the Stickles et al. (2002) case, this individual's spontaneous speech was reduced and characterised by lengthy pauses.He was also found to have difficulty generating and selecting ideas for verbal expression, which contributed to his lack of spontaneous speech (Barker et al., 2021).Although the interpretations of both the Stickles et al. (2002) and Barker et al. (2021) Barker et al. case had partial rhombencephalosynapsis and temporal malformations), both cases had CCD and a similar pattern of reduced and pause-filled spontaneous speech in the context of persevered core linguistic functions.What remains unknown is whether this "verbal adynamia" is a feature of CCD more generally, beyond these single cases.A third study documented a case of "developmental dynamic dysphasia" in an adolescent male who did not have CCD but had congenital cortical abnormalities that encompassed bilateral inferior frontal regions, as well as abnormal white matter tracts, including aberrant callosal fibres, and a lack of corticospinal tract crossing at the pyramidal decussation and congenital mirror movements (Berthier et al., 2020).This participant's verbal communication was severely impaired, but his reading, spelling, naming, repetition, and auditory comprehension were largely within normal limits.It is unclear how the aberrant callosal fibres or disrupted corticospinal tract contributed to his impaired spontaneous speech output.

Mechanisms of spontaneous speech production
The production of spontaneous speech is supported by multiple complex cognitive processes, including higher-order executive and attentional, as well as linguistic, functions (Barker et al., 2020).In the context of reduced propositional language, as in adynamia or dynamic aphasia, disruptions to three mechanisms have been investigated: 1) the generation of ideas ("idea generation"); 2) the selection of ideas from an array of competing alternatives ("idea selection"); and 3) the sequencing of ideas (Robinson et al., 1998(Robinson et al., , 2005(Robinson et al., , 2006(Robinson et al., , 2015;;Robinson, 2013).As an example, if someone is describing their favourite holiday, they have to generate concepts or ideas to discuss (e.g., location, food, accommodation, activities), select which of these ideas to talk about, and then sequence the ideas in an order that makes sense to the listener, without repeating the same idea.Problems with any of these mechanisms, in isolation (e.g., Robinson et al., 1998Robinson et al., , 2005Robinson et al., , 2015) ) or in combination (e.g., Robinson, 2013;Robinson et al., 2006), are purported to underpin dynamic aphasia.Genuine impairments in idea generation tend to extend beyond the verbal domain, into nonverbal domains, and are measured using verbal and nonverbal fluency tasks.Deficits in idea generation may be linked to an inability to continue generating ideas over an extended period of time (i.e., poor "energization") (Barker et al., 2018;Robinson et al., 2006Robinson et al., , 2015)), or can be associated with apathy (Horne et al., 2023).

Current study
The present study aims to investigate spontaneous speech in a group of adults with CCD.Specifically, we aim to identify whether adynamic spontaneous speech is present at the group level in a cohort of adults with CCD.We hypothesise, in line with the case reported by Barker et al. (2021), that individuals with CCD will produce fewer narrative words per minute compared to controls and will have difficulty generating and selecting ideas for propositional language.We will also determine the relative contributions of idea generation and selection problems to spontaneous speech in CCD.
Finally, exploratory analyses will investigate whether deficient energization, apathy, and slowed processing speed are potential underlying factors.

Method
No part of the study procedure or analysis plan was preregistered in a time-stamped, institutional registry prior to the research being conducted.Below we report how we determined our sample size, all data exclusions, all inclusion/ exclusion criteria, whether inclusion/exclusion criteria were established prior to data analysis, all manipulations, and all measures in the study.

Participants
All participants, including individuals with CCD and controls, were recruited and tested between 2015 and 2023.Inclusion criteria were determined prior to data analysis.The current study included 25 adults (mean age ¼ 39.8 years) with CCD (9 males, 16 females; 12 complete CCD, 13 partial CCD 1 ) (see Table 1).All CCD participants had their diagnosis confirmed by the research team when they underwent MRI scanning using either the Siemens 7T Magnetom or the Siemens 3T Magnetom Prisma spectrometers located at the Centre for Advanced Imaging at the University of Queensland.We used high resolution (.75 mm/1 mm isotropic voxel size respectively for the two spectrometers) T1-weighted anatomical scan for the diagnoses.The control group comprised 39 adults (mean age ¼ 37.7 years; 22 males, 17 females) with no known neurological or psychiatric history.Individuals with CCD were recruited through the Australian Disorders of the Corpus Callosum (AusDoCC) support group, and controls were recruited via the University of Queensland volunteer networks and word-of-mouth.The CCD and control group sample sizes were the maximum possible sample sizes given finite project resources (e.g., participant availability, funding), and are comparable to other recent studies in the field (e.g., Renteria-Vazquez et al., 2022;Young et al., 2019).This study

Cognitive and language baseline
A battery of standardised cognitive and language tests was administered to the CCD and control groups.IQ was estimated via reading errors on the National Adult Reading Test e 2nd Edition (NART) (Nelson & Willison, 1991).Fluid intelligence was measured using the Advanced Progressive Matrices (APM) (Raven, 1976).The Trail Making A test gave an estimation of psychomotor processing speed (Reitan, 1956), and the word reading condition from the Stroop test measured verbal processing speed (Trenerry et al., 1989).Praxic function was tested via the imitation of meaningless hand gestures and the production of symbolic hand gestures (e.g., salute).Spelling and arithmetic were assessed using the Oral Graded Difficulty Spelling Test (OGDST) (Baxter & Warrington, 1994) and Arithmetic Test (OGDAT) (Jackson & Warrington, 1986) tests.The Sydney Language Battery (SYD-BAT) tested naming, single word repetition, and semantic association skills (Savage et al., 2013).Nonword Reading from the Psycholinguistic Assessments of Language Processing in Aphasia (PALPA) (Kay et al., 1996) and Sentence Repetition (3e6 words in length) (McCarthy & Warrington, 1984) tests were also administered.The Synonym Test (Warrington et al., 1998) provided a measure of abstract and concrete single word comprehension.Self-reported depression and anxiety symptoms were assessed via the Hospital Anxiety and Depression Scale (HADS) (Snaith & Zigmond, 1994), and levels of self-reported apathy were measured using the Apathy Evaluation Scale (AES) (Marin et al., 1991).

Spontaneous speech
To measure spontaneous speech rate, the Cookie Theft Scene from the Boston Diagnostic Aphasia Exam (Goodglass & Kaplan, 1972) was administered. 2The Cookie Theft Scene is a black-and-white line drawing of a complex (i.e., multiple actions taking place) scene, and participants are asked to "describe everything you see happening in this picture".The examiner timed 60 sec on a stopwatch, and if the participant indicated that they had finished describing the picture before 60 sec had passed, the examiner was permitted to give a simple prompt such as "anything else?".Otherwise, the examiner remained silent for the duration of the task.Participants' descriptions were voice recorded and subsequently transcribed, and transcriptions included all words and sounds produced by the participant across the 60sec task duration.Contractions were transcribed as their component words (doesn't ¼ does not).To calculate narrative words per minute (WPM), nonwords (e.g., "umm"), repairs (e.g., the sil e sink), stutters (e.g., ch ch children), direct repetitions (the the child; unless the word is being used for emphasis e.g., very very small), comments unrelated to the task ("how much longer do I have"), habitual starters (e.g., "okay so"), and stereotyped phrases that begin a paragraph (e.g., "once upon a time") were subtracted from the total WPM.

Fluency: generation and sequencing
A range of verbal and nonverbal fluency tasks were administered to investigate idea generation and sequencing.Participants completed verbal (word) fluency under two conditions: phonemic (letter) and semantic (category) word fluency (Benton, 1968;Strauss et al., 2006).These tasks required participants to generate as many words as possible with a 60-sec time limit.For the phonemic fluency task, participants were asked to generate words beginning with the letters "F", "A" and "S", and not to provide numbers (e.g., sixty), proper nouns (e.g., Spain, September), or the same word with different endings (e.g., speak, speaker, speaking).
For the semantic fluency task, participants were asked to generate animal names (e.g., horse, cow).Participants also completed two nonverbal fluency tasks: design fluency and gesture fluency.The design fluency task required participants to draw as many abstract designs as possible within a specified time period, with either no constraints on the designs (free design fluency, 5 min), or with the instruction that each design comprise only four lines (fixed design fluency, 4 min) (Jones-Gotman & Milner, 1977;Robinson et al., 2012).The gesture fluency task required participants to generate as many hand gestures as possible across 2 min, that either conveyed meaning (meaningful condition, e.g., waving) or did not convey meaning (meaningless condition) (Jason, 1985;Robinson et al., 2021).The number of items produced on fluency tasks provides an estimate of an individual's ability to efficiently generate ideas over a specific time period, and genuine impairments in idea generation may extend across verbal and nonverbal domains (Robinson et al., 2006(Robinson et al., , 2015)).Therefore, the total number of correct responses generated was taken as a measure of idea generation (Robinson et al., 2006(Robinson et al., , 2015)).Problems with sequencing are also apparent on fluency tasks, characterised by a high number of perseveration (repetition) errors (Robinson, 2013).Therefore, the number of perseveration errors on verbal fluency tasks provided a measure of sequencing.

Idea selection
Two experimental tasks measuring idea selection were administered: "sentence completion" and "sentence from a single word" (Barker et al., 2022;Barker & Robinson, 2019;Robinson et al., 2005Robinson et al., , 2010)).These tasks have previously been used to demonstrate idea section impairments in clinical populations (e.g., focal lesions) (Robinson et al., 2010) and healthy ageing (Barker et al., 2022).An impairment of idea selection is defined as markedly more impaired performance when a stimulus elicits multiple response options ("low constraint") compared to a single response option ("high constraint"); that is, the person has difficulty selecting an idea when a greater number of options are available.The sentence 2 Four participants (n ¼ 3 CCD participants, n ¼ 1 control) completed the Beach Scene from the Queen Square Screening Test for Cognitive Deficits (Warrington, 1989), which is also a complex scene description task.Results did not change when these participants were excluded from analyses.completion task requires the participant to respond to a sentence stem with a single word to complete the sentence (e.g., Water and sunshine help plants … "grow").The task included a high constraint condition and a low constraint condition; high constraint sentences had a single dominant response (as per the previous example), while low constraint sentences elicited multiple, equally likely response options (e.g., There was something wrong with the … "computer", "man", "procedure").The sentence from a single word task required participants to generate a sentence from a single word cue (e.g., "table" e There is a table in the dining room).In the high constraint condition the word stimuli were proper nouns, which elicit a dominant idea (e.g., London), whereas in the low constraint condition the stimuli were high frequency words, which elicit multiple ideas (e.g., chair e dining chair, office chair, to chair a meeting).Response times, defined as the time between the end of the stimulus cue and the beginning of the participant response, were timed with a stopwatch.Responses were marked as an error if they were not meaningful or grammatically correct, or if they omitted the target stimulus.The "selection ratio" was calculated as the degree to which an individual was slower in the low constraint condition (selection ratio ¼ low constraint/high constraint) (Barker et al., 2021(Barker et al., , 2022)).

Measure availability
The idea selection task stimuli ("sentence completion" task and "sentence from a single word" task) are publicly archived and available at https://osf.io/2by95/.Legal copyright restrictions prevent public archiving of all other measures, including cognitive and language baseline tests (NART, APM, Trail Making A, Stroop test, OGDST, OGDAT, SYDBAT, PALPA, sentence repetition, Synonym Test, HADS, AES) and propositional language tasks (Cookie theft scene, Beach scene, phonemic fluency, semantic fluency, gesture fluency, design fluency).These tests can be obtained from the copyright holders in the cited references.

Demographics and baseline variables
To compare demographics between the CCD group and controls, we conducted two independent groups t-tests (continuous dependent variables: age, education) and two chisquared tests (categorical variables: sex, handedness).All cognitive and language baseline task variables, as well as all propositional language task variables, were checked for normality, via visual inspection of histograms and QeQ plots, and the calculation of skewness and kurtosis values (cut-offs per Byrne, 2016;Hair et al., 2010).The following task variables were deemed to be non-normally distributed, warranting nonparametric analyses: praxic function, SYDBAT repetition, sentence repetition, nonword reading, and the perseveration error variables from the verbal fluency tasks.To compare the CCD and control groups on the cognitive and language baseline tasks, we ran a series of independent-groups t-tests (nonparametric ManneWhitney U when the assumption of normality was violated), with a ¼ .05 as the threshold for statistical significance.

Propositional language variables
To determine whether there was a group difference between CCD and control participants in spontaneous speech quantity (narrative WPM), we ran a 2-group ANCOVA with age and NART-estimated IQ 3 as covariates.To investigate group differences on the experimental propositional language tasks (fluency task variables, idea selection task variables), we ran a series of 2-group MANCOVAs (CCD group vs control group), again with age and NART-estimated IQ as covariates. 3Given the different underlying processes, we separated the verbal and nonverbal fluency (idea generation) and idea selection variables into separate 2-group MANCOVA analyses (verbal ¼ 2 dependent variables: phonemic/letter fluency and semantic/category fluency; nonverbal ¼ 4 dependent variables: meaningless gesture fluency, meaningful gesture fluency, free design fluency, fixed design fluency; selection ¼ 2 dependent variables: sentence completion and sentence from a single word selection ratios).
Finally, to investigate the relative contributions of idea selection and idea generation mechanisms to spontaneous speech in CCD, we ran Pearson's bivariate correlations between spontaneous speech WPM, a fluency task composite score, and an idea selection task composite score within the CCD group only.p-values were Bonferroni corrected.

Data availability
All deidentified individual-level data and analysis code used in the current study are available at https://osf.io/2by95/.Raw files cannot be publicly archived due to ethical restrictions; because this is a rare disorder, individuals are identifiable based on demographics and raw test responses.Raw data may be requested from the corresponding author (gail.robinson@uq.edu.au).All requests are subject to approval from relevant ethics committees and will require a formal data sharing agreement to be established.

Demographics
Demographic characteristics of the CCD and control groups are summarised in  In terms of core language skills, the CCD and control groups were not significantly different on tests of naming (p ¼ .116),abstract/concrete word comprehension (p ¼ .239and .834,respectively), sentence repetition (p ¼ .101),nor nonword reading (p ¼ .109).However, the CCD group did perform significantly below controls on single word repetition, and semantic association (all p < .05),though it is worth noting that both the CCD and control groups scored very close to the ceiling on these tasks (see Table 2 for means and maximum scores).Inspection of the raw data revealed that two CCD participants made at least one error on both the single word repetition and sentence repetition tasks, and one of these two participants was also the only participant to score below the cut-off score for clinical impairment on the SYDBAT semantic association task (<24/30) (Savage et al., 2013).Both of these participants had a history of language problems and one had an intellectual disability.Overall, the cognitive and language baseline tests demonstrate a high degree of heterogeneity within the CCD group, including some mild problems with specific core language skills in the context of largely intact language abilities, and some difficulties with motor execution.
Regarding self-reported anxiety symptoms, both the CCD and control group means fell slightly above the clinical cut-off for mild anxiety (>7), and the groups were not statistically significantly different from one another (p ¼ .138).Approximately 67% of the CCD group and 54% of the control group had anxiety symptoms above normal limits; two individuals with CCD and one control participant scored within the severe range (>14).Levels of self-reported depression were lower in both groups, with both group means being well below the clinical cut-off (<7) and not significantly different (p ¼ .309).Three individuals with CCD and two controls scored in the range of mild depressive symptoms, all other participants were within normal limits.However, levels of self-reported apathy were significantly higher in the CCD group (p < .001),with 30% of the CCD group reporting symptoms in the clinical range (>38).To ensure that the individuals with core language difficulties (n ¼ 2, identified in the previous section) were not driving this result, we re-ran this analysis with these two individuals excluded.The group difference remained significant (p ¼ .008).

Idea generation and sequencing
For the verbal fluency tasks, there was a significant multivariate main effect of group (F(2,58) ¼ 5. Regarding perseveration errors on the verbal fluency tasks, the CCD and control group means fell below 1 on both the phonemic and semantic fluency tasks.In addition, the majority of participants in both groups produced 1 perseveration error on phonemic fluency (96% of the CCD group; 77% of the control group) and semantic fluency (96% of the CCD group; 84% of the control group).Nonparametric ManneWhitney U analyses revealed that there was no statistically significant difference between the CCD and control groups on semantic fluency perseveration errors (p ¼ .926);however, on phonemic fluency, controls unexpectedly produced significantly more perseverations than CCD participants (p ¼ .034).Overall, this suggests that individuals with CCD are not perseverative in their ideas, and therefore problems with sequencing are unlikely on the whole.

Idea selection
To determine whether participants with CCD have reduced idea selection, we compared the "selection ratio" with the control group (the proportional slowing of responses in the low constraint condition of the idea selection tasks).There was no statistically significant multivariate main effect of group (F(2,48) ¼ 1.75, p ¼ .186,h p 2 ¼ .068).

Relative contributions of idea generation versus selection
Composite idea generation and idea selection scores were calculated (Fluency composite ¼ phonemic fluency total þ semantic fluency total þ free design fluency total þ fixed design fluency total þ meaningful gesture fluency total þ meaningless gesture fluency total.Selection composite ¼ sentence completion selection ratio þ sentence from a single word selection ratio).Pearson's bivariate correlations within the CCD group revealed that the fluency composite was significantly correlated with spontaneous speech output WPM (r ¼ .630,p Bonferroni ¼ .004),while the selection composite was not (r ¼ À.326, p Bonferroni ¼ .320).

Exploratory analyses: complete versus partial CCD
We ran a series of independent-groups t-tests to explore whether individuals with complete versus partial CCD performed differently on the propositional language tasks.There were no statistically significant group differences on any of the propositional language tasks: narrative WPM, phonemic/ letter fluency, semantic/category fluency, design fluency, gesture fluency, or selection ratios (all p > .05).

Exploratory analyses: energization, apathy, and processing speed
Reduced spontaneous speech due to difficulties with idea generation may be underpinned by problems with energization, defined as a waning ability to generate responses over time, apathy, which is an impairment of motivation, or slowed processing speed.To investigate these possibilities, we ran several exploratory analyses.First, we calculated an "energization ratio" for the word fluency tasks, by dividing the number of correct responses generated in the first 15 sec by the total number generated across 60 sec (see Barker et al., 2018).This allowed us to determine what proportion of the total words were generated in the first 15 sec.Ratios closer to one suggest problems with energization, or an inability to continue to respond over time.In a 2-group MANCOVA, controlling for NART-IQ and age, there was no significant multivariate main effect of group (F(2,58 suggesting that the CCD group did not have an impaired ability to continue responding over time.Symptoms of apathy were self-reported via the AES (see baseline tests).When apathy (AES score) was added as a covariate the difference between the CCD and control groups on the picture description task was no longer statistically significant (p Processing speed was measured via the Trail Making A test (psychomotor processing speed) and the word reading condition of the Stroop test (verbal processing speed) (see baseline tests).We opted to explore two measures of processing speed, one nonverbal and one verbal, because no single test purely assesses processing speed (Marco et al., 2012).When psychomotor processing speed (Trails A time in seconds) was added as a covariate into the ANCOVA model, the difference between the CCD and control groups on the picture description task was no longer statistically significant (p ¼ .075,h p 2 ¼ .062).
Similarly, when covarying for processing speed in the verbal fluency MANCOVA model, there was no longer a significant multivariate main effect of group (F(2,51 Overall, although the results are somewhat mixed, they suggest that apathy and processing speed are likely contributing to reduced idea generation, particularly in the verbal domain, as well as lower rates of spontaneous speech (see Table 3   Q3 ).

Discussion
Although core language skills are generally reported to be intact in individuals with CCD, previous studies have demonstrated problems with higher-order or complex language skills (Bartha-Doering et al., 2021).However, spontaneous speech e the fluent generation of language that includes novel ideas e is underexamined in CCD.Analysis of spoken language across various tasks indicates those with CCD demonstrate a reduction in social, emotional, and cognitive inference, and inadequate elaboration compared to controls (Paul et al., 2004;Turk et al., 2010;Young et al., 2019), and similar to those with ASD (Renteria-Vazquez et al., 2022).A handful of case studies have documented reduced spontaneous speech output in individuals with CCD, in the context of relatively preserved core language skills.This is the hallmark of verbal adynamia, or, in severe cases, dynamic aphasia.Thus, we aimed to examine spontaneous speech output in a As predicted, the CCD group was reduced in their spontaneous speech output; that is, individuals with CCD produced significantly fewer narrative words per minute compared to controls.Apart from a few scattered impairments, the core language skills of the CCD group were satisfactory overall, suggesting an adynamic profile.A paucity of spontaneous speech, alongside other higher-order language problems such as a poor understanding of nonliteral language and affective prosody (e.g., Brown et al., 2005;Paul et al., 2003;Rehmel et al., 2016), can have implications for social communication, making it difficult to maintain social and familial relationships, symptoms reported by individuals with CCD (Maxfield et al., 2023).Future research should consider designing interventions and therapeutic strategies aimed at improving social communication for individuals with CCD, and families informed that reduced spontaneous speech may be a potential feature of CCD.
The results from the propositional language task investigation revealed that participants with CCD had significant difficulties with idea generation.Impairments in idea generation tend to extend beyond the verbal domain, into nonverbal domains (e.g., design fluency), with reductions across verbal and nonverbal fluency tests (Robinson et al., 2006(Robinson et al., , 2015)).In the current study, the CCD group performed significantly below controls on five of the six fluency tasks, including verbal and nonverbal fluency.The results of previous research align well with our current finding of reduced idea generation in CCD.For example, the lack of emotional and cognitive content in the narratives of individuals with CCD (Turk et al., 2010;Young et al., 2019), or even the inclusion of atypical content (Paul et al., 2004), hints at the types of ideas that might not be generated in spontaneous speech.Likewise, the reduced abilities of individuals with CCD to interpret nonliteral language (Brown et al., 2005;Paul et al., 2003;Rehmel et al., 2016) or to imagine hypothetical future consequences (Young et al., 2019) are relevant to idea generation, because it is likely that these nonliteral or imaginative propositions would not be present in their spontaneous speech.Lending further weight to this, a recent, important study by Renteria-Vazquez et al. (2022) found that, in their descriptions of animated triangles, participants with CCD showed a diminished capacity for social imagination and narrative elaboration; in other words, individuals with CCD struggled to generate ideas beyond the immediate stimulus (Renteria-Vazquez et al., 2022).While the current study did not include any content or semantic analysis, we believe the adynamic profile reported here dovetails nicely with this previous work.
Our exploratory analyses suggested that the problems with idea generation in the CCD group did not reflect impaired energization, which is defined as an inability to sustain responding over time (Stuss & Alexander, 2007).In individuals with energization impairments, we observe a "drop-off" pattern where responding wanes over time, and the majority of responses are produced at the beginning of the task.This has been documented in individuals with damage to the superior medial frontal lobes (Stuss & Alexander, 2007), and the neurodegenerative disease progressive supranuclear palsy (Barker et al., 2018;Robinson et al., 2015).However, this did not appear to be the case in the current cohort of individuals with CCD.Instead, it appears as though apathy and slowed processing speed may be contributing factors.When selfreported apathy was added to our analysis, the group differences on two fluency tasks, as well as the spontaneous speech task, became nonsignificant.Similarly, when processing speed was included as a covariate, the group differences on three fluency tasks and the spontaneous speech task were nonsignificant.While the presence of apathy and slowed processing speed do not entirely explain the results e for example, group differences on the gesture fluency tasks remained significant even when apathy and processing speed were included in the model e our findings hint that these factors may be somewhat linked to reductions in spontaneous speech and idea generation in CCD, alongside an intrinsic response generation impairment.The fact that gesture fluency group differences remained significant even after controlling for apathy and processing speed may hint that these factors are more related to verbal than nonverbal idea generation.Alternatively, it is also possible that differences in task length may have contributed to the findings here.The verbal fluency tasks are only 1 min in duration, while gesture fluency allows 2 min.The effects of apathy (i.e., slow initiation) and slowed processing speed may be more apparent when time is limited.
Apathy is not a well-documented feature of CCD.Although there are reports of apathy in several case studies (e.g., Calabr o et al., 2015;Palermo et al., 2019), to our knowledge apathy has not been the focus of a group-level study in CCD.In our sample, 30% of the CCD group had clinically significant levels of apathy, and an additional 25% had elevated levels that fell just below the cut-off.This could be a potential target for intervention, which may have flow-on effects in increasing spontaneous speech; this is a novel approach that is already being explored in other neurological disorders (e.g., Parkinson's disease e Mosley & Robinson, 2023).By contrast, slowed processing speed has been identified as a core neuropsychological deficit in CCD (Brown & Paul, 2019), even underlying some executive dysfunction (Marco et al., 2012).It would be interesting for future research to investigate the relationship between apathy and slow processing speed; for example, is slow processing speed an effect of apathy?How often do they co-occur?In our current CCD cohort, apathy and processing speed were moderately correlated (r ¼ À.47, p ¼ .023),and this finding should be explored further.
Our current findings have key consistencies, as well as important inconsistencies, with prior literature.Firstly, we have demonstrated reductions in spontaneous speech at the group level in CCD.This is consistent with prior case studies (Barker et al., 2021;Stickles et al., 2002), and suggests that difficulties with propositional language may be a key feature of CCD.Regarding the underlying mechanisms, impaired idea selection was an important contributing factor to the Barker et al. (2021) participant's lack of spontaneous speech, and may have contributed to narrative elaboration difficulties of individuals with CCD on a social problem-solving task where multiple possible responses were available (Young et al., 2019).In the current study, we did not find clear evidence of difficulties with idea selection at the group level.However, we acknowledge the variability within our CCD cohort; it is likely that a subgroup of participants had deficient idea selection, which may have been masked in the group-level analysis.For example, close inspection of the raw data revealed three participants with CCD who had selection ratios of close to 4 (similar to the Barker et al., 2021 participant, whose selection ratio was 3.8), meaning that they were four times slower to respond in the low constraint condition.Future research could investigate whether there are any unique spontaneous speech features, or neuroanatomical differences, in the subgroup of CCD participants who demonstrate selection problems.
The Barker et al. (2021) case also demonstrated mild problems with idea generation, but these deficits were not as pronounced as the selection impairments.The authors suggested that mildly impaired idea generation may have played a small role (Barker et al., 2021).The findings of the current study suggest that impaired idea generation is a key underlying mechanism contributing to reduced spontaneous speech in CCD.This was supported by the exploratory correlation analyses, which showed that performance on the fluency tasks was significantly correlated with spontaneous speech output, while performance on the idea selection tasks was not.Problems with sequencing did not appear to be an issue for the Barker et al. (2021) case, nor in our current CCD cohort.
Neuroanatomically, it is logical that individuals with CCD would have difficulties with spontaneous speech, as the production of propositional language relies on a distributed network of brain regions that includes both the left and right cerebral hemispheres (Hodgson et al., 2021;Troiani et al., 2008).The process of idea generation specifically has been purported to draw on bilateral frontal regions (Robinson et al., 2015), and stronger functional connectivity between left and right temporal areas is associated with better language abilities (language comprehension, naming, and verbal fluency) in individuals with CCD (Bartha-Doering et al., 2021).Disruptions in inter-hemispheric connectivity may limit the transfer of information required to successfully produce fluent, novel, spontaneous speech.However, a detailed MRI analysis of the cortical mantle, white matter, deep grey nuclei was not conducted in the current study, and therefore any comments on neural mechanisms is speculation.It is also possible that the spontaneous speech problems may have arisen from cortical involvement and aberrant association fibres in both hemispheres, which could affect frontal-subcortical circuits.Linking adynamic language in CCD to specific neuroanatomical abnormalities is an important next step for research in the field.
This study is both strengthened and limited by the heterogeneity of the CCD cohort.On one hand, it is a large and relatively representative cohort of individuals with CCD, making the results more widely applicable to the CCD population than if we had selected a subgroup based on a particular characteristic.On the other hand, including such a heterogeneous sample means that impairments that may be problematic but less common would not have been revealed in the group level analyses (e.g., selection difficulties).Nevertheless, adynamia in CCD does have important implications, and should, at the very least, be screened for at the time of presentation (whether they are presenting due to developmental problems or incidentally), and the information made available to the individual's support team if appropriate.Future research should consider investigating the association between propositional language problems and neuroanatomical findings in CCD; for example, whether aberrant frontal lobe connectivity has any effect on spontaneous speech (for a case of an individual with impaired spontaneous speech in the context of CCD and a sigmoid bundle, see Knight et al., 2023).Interestingly, in the current cohort, there were no statistical differences between participants with complete versus partial CCD on the propositional language tasks, but additional neuroanatomical correlates should be examined.It is also important to note the limitations of our apathy data and mood questionnaire data, as both are based on selfreport, and individuals with CCD may less reliable reporters than their close family members (e.g., Mangum et al., 2021), and therefore future research should consider including obtaining this information from multiple sources.
Overall, this is the first group-level study to demonstrate that spontaneous speech is significantly reduced in individuals with CCD in the context of sound core language abilities, suggesting an adynamic language profile.In addition, we found that difficulties with idea generation likely underpinned the lack of spontaneous speech in CCD participants.Exploratory analyses revealed that apathy and slowed processing speed may have been key contributors to poor idea generation and thus reduced spontaneous speech, although these factors did not entirely explain our results.

Q4
Some raw and processed data supporting this research are publicly available, while some are subject to TOPcompliant restrictions.See TOP Guidelines Assessment in Available online at www.sciencedirect.comScienceDirectJournalhomepage: www.elsevier.com/locate/cortex cases are somewhat complicated by comorbid i.e., the Stickles et al. case had a malformed region of the medial left hemisphere posteriorly, and the Please cite this article as: Barker, M. S., et al., Adynamic spoken language in corpus callosum dysgenesis, Cortex, https://doi.org/10.1016/j.cortex.2024.07.021 neuroanatomical malformations (

Table 1 e
Demographic characteristics for CCD participants and controls.
1The partial dysgenesis group includes n ¼ 3 individuals with hypoplasia of the corpus callosum.

Table 1 .
The groups were not significantly different in age (p ¼ .603),with both means in the late 30s.The control group had a significantly higher level of education than the CCD group (p ¼ .016);this is not unexpected as some individuals with CCD have developmental disorders that may make formal education difficult to access.There were more females than males in the CCD group, and the opposite was true for the control group, though this difference was not statistically significant (p ¼ .111).Right-handers formed the majority of both groups, but there were more left-handers and ambidextrous individuals in the CCD group (p ¼ .002).
3 NART-IQ was included as a covariate in lieu of education, because education data were missing for n ¼ 6 (24%) of the CCD group.Please cite this article as: Barker, M. S., et al., Adynamic spoken language in corpus callosum dysgenesis, Cortex, https://doi.org/10.1016/j.cortex.2024.07.0213.3.Cognitive and language baseline Table2summarises the cognitive, language, and mood baseline measures.Overall, there was much greater variability in the CCD group, as indicated by larger standard deviations and wider ranges.On average, both the CCD and control groups were within normal limits in terms of estimated IQ based on the NART and were not statistically different from each other (p ¼ .114).CCD participants scored significantly below controls on matrix reasoning, indicating lower fluid intelligence (p < .001),and had slower psychomotor and verbal processing speed than controls (both p < .001).While spelling abilities did not significantly differ between the two groups (p ¼ .475),arithmetic was significantly poorer in the CCD group (p < .001).On the tests of praxis, the CCD group performed significantly below the control group in the imitation of meaningless hand gestures (p ¼ .019)and the execution of symbolic gestures (p ¼ .006).Although both groups performed, on average, close to the task ceiling, inspection of the raw data revealed six participants with CCD who had significant problems performing hand movements (>2 errors on meaningless gesture imitation, !2 errors on symbolic gesture execution).

Table 2 e
Cognitive, language, and mood baseline measures.Statistical significance at the .05level is indicated by bold italicised text.NART ¼ National Adult Reading Test.APM ¼ Advanced Progressive Matrices.OGDST ¼ Oral Graded Difficulty Spelling Test.OGDAT ¼ Oral Graded Difficulty Arithmetic Test.SYDBAT ¼ Sydney Language Battery.HADS ¼ Hospital Anxiety and Depression Scale.AES ¼ Apathy Evaluation Scale.
Note.Test names and maximum scores are provided in parentheses following the cognitive domain.Means are provided with standard deviations in parentheses; range is in square brackets.NART errors were converted to standardised scores using the Bright Q2 et al. (2018) norms.Unless otherwise stated, p-values determined via independent-groups t-test.a ManneWhitney U test.Please cite this article as: Barker, M. S., et al., Adynamic spoken language in corpus callosum dysgenesis, Cortex, https://doi.org/10.1016/j.cortex.2024.07.021 15, p ¼ .009,h p 2 ¼ .151).
meaningful (p < .001,h p 2 ¼ .351)and meaningless (p ¼ .003,h p 2 ¼ .176)gestures than controls.The CCD group also produced fewer designs than controls under the fixed condition of the design fluency task (p ¼ .022,h p 2 ¼ .106),but the group difference on the free design fluency task was not statistically significant (p ¼ .089,h p 2 ¼ .060).To ensure that motor difficulties were not driving the significant group differences, we re-ran all nonverbal fluency analyses with the participants who scored below the ceiling on the praxis baseline tasks excluded (n ¼ 6, identified in the previous section).The results were unchanged (meaningful gesture fluency p < .001,h p 2 ¼ .308,meaningless gesture fluency p ¼ .015,h p 2 ¼ .136,fixed design fluency p ¼ .044h p 2 ¼ .095,free design fluency p ¼ .222,h p 2 ¼ .036).Taken together, these fluency task results suggest that individuals with CCD may have difficulties with idea generation, potentially spanning both verbal and nonverbal domains.

Table 3 e
Performance of the CCD group and controls on the propositional language tasks.Note.WPM ¼ words per minute.Means are provided with standard deviations in parentheses.Unless otherwise stated, p-values determined via MANCOVA with age and NART-estimated IQ as covariates.Please cite this article as: Barker, M. S., et al., Adynamic spoken language in corpus callosum dysgenesis, Cortex, https://doi.org/10.1016/j.cortex.2024.07.021 larger cohort of individuals with CCD and investigate the mechanisms that underpin propositional language production: idea generation, idea selection, and sequencing.
a ManneWhitney U test performed.Statistical significance at the .05level is indicated by bold italicised text.b This statistically significant result was in the direction opposite to what would be expected, i.e., controls performing more poorly than CCD group.