O Itani

E Haddad

V Pitron

F Pichon

E Caumes

Focus on patients receiving long-term antimicrobial treatments for lyme borreliosis: No lyme but mostly mental disorders

1

Focus on patients receiving long-term antimicrobial treatments for Lyme borreliosis:

no Lyme but mostly psychiatric disorders

INTRODUCTION

Overdiagnosis and overtreatment of Lyme borreliosis is frequent [START_REF] Sigal | The Lyme disease controversy. Social and financial costs of misdiagnosis and mismanagement[END_REF]. Recent studies have found that only 10 to 15% of patients consulting with a presumed diagnosis of Lyme borreliosis were actually found with Lyme borreliosis [START_REF] Haddad | Holistic approach in patients with presumed Lyme Borreliosis leads to less than 10% of confirmation and more than 80% of antibiotic failures[END_REF][START_REF] Boullier | Consultation for presumed Lyme borreliosis: The need for a multidisciplinary management[END_REF][START_REF] Jacquet | Multidisciplinary management of patients presenting with Lyme disease suspicion[END_REF][START_REF] Kobayashi | Misdiagnosis of Lyme disease with unnecessary, antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic[END_REF]. Psychiatric disorders, including somatic symptom and related disorders as well as depressive disorders, were found in 25% of 301 patients in Paris, France [START_REF] Haddad | Holistic approach in patients with presumed Lyme Borreliosis leads to less than 10% of confirmation and more than 80% of antibiotic failures[END_REF], and 42.5 % of 209 patients in Connecticut, USA [START_REF] Reid | The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study[END_REF].

Overdiagnosing Lyme borreliosis leads to overtreatment. In two recently published studies, the rates of overtreatment were respectively 60% of 301 patients in Paris [START_REF] Haddad | Holistic approach in patients with presumed Lyme Borreliosis leads to less than 10% of confirmation and more than 80% of antibiotic failures[END_REF], and 84% of 911 patients in Baltimore, USA [START_REF] Kobayashi | Misdiagnosis of Lyme disease with unnecessary, antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic[END_REF]. Moreover, the maximum duration of treatment was 395 days in the Paris study [START_REF] Haddad | Holistic approach in patients with presumed Lyme Borreliosis leads to less than 10% of confirmation and more than 80% of antibiotic failures[END_REF] and reached 2555 days in the Baltimore study [START_REF] Kobayashi | Misdiagnosis of Lyme disease with unnecessary, antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic[END_REF].

By overtreating Lyme borreliosis, the underlying true disease remains undiagnosed and may progress. We evaluated patients referred with a presumptive diagnosis of Lyme borreliosis and receiving anti-microbial treatment for at least 180 days.

PATIENTS AND METHODS

We performed a retrospective observational monocentric study in the Infectious Diseases Department at the Pitié Salpêtrière University Hospital in Paris, France. We included all patients referred between January 1st, 2014 and June 30th, 2019 with a presumptive O. Itani, E. Haddad, V. Pitron, F. Pichon, E. Caumes diagnosis of Lyme borreliosis for which they received antimicrobial treatment for at least 180 days. The study being observational and retrospective, no consent form was collected.

Patients' charts were screened for a presumptive Lyme borreliosis diagnosis through the database of outpatients of a single physician crossed with his diagnostic list. Clinical and serological criteria for diagnosing Lyme borreliosis were based on The European Classification [START_REF] Stanek | Lyme borreliosis: clinical case definitions for diagnosis and management in Europe[END_REF]. Patients receiving antimicrobial treatment for less than 180 days were excluded.

Data on patient demographic (age, sex), Lyme borreliosis-related history (tick exposure, tick bites, erythema migrans), symptoms (duration, type and number of symptomatic organs), results of Lyme borreliosis serology assays (Enzyme-linked immunosorbent assay and Immunoblot), antimicrobial treatment (type, number, duration), and analgesics (type, number) were evaluated. Duration of antimicrobial treatment was defined as the time from the initial start of treatment. Because these patients were commonly prescribed successive antimicrobial courses, we deleted treatment-free days and evaluated cumulative days of treatment.

Finally, adverse drug events and final diagnoses were evaluated. Adverse drug reactions were evaluated according to the French rules [START_REF] Miremont-Salamé | Causality assessment in pharmacovigilance: The French method and its successive updates[END_REF]. The Diagnostic and Statistical Manual of Mental Disorders, V, was used to identify psychiatric disorders [START_REF]Diagnostic and Statistical Manual of Mental Disorders[END_REF]. Data were expressed as counts and percentages for categorical variables and as means for continuous variables. Analyses were done using Microsoft Excel 2011.

RESULTS

Of the 425 screened patients, 15 (3.5%) had received over 180 days of antimicrobial treatment: 11 (73%) were women, the median age was 44 (15-89) years, 7 (47%) were exposed to tick bites, and 4 (27%) were bitten by a tick. Median number of symptomatic organs was 4 (1-8) and median symptoms duration was 63 (6-240) months. Median duration of treatment was 476 (180-942) days. (Table )   Serologic testing by ELISA was performed in 14 patients: 10 had negative results and 4 had positive results that were not confirmed with Western Blot. One patient without serologic testing by ELISA had negative results with Western Blot only. (Table )   For one patient, the list of the antimicrobial treatments was not available. Among the remaining 14 patients, the most common antimicrobial treatments were macrolides (93%), anti-parasitic drugs (73%), tetracyclines (67%), and beta-lactam antibiotics (60%). Median number of antimicrobial treatment was 6.8 (1-18) per patient. Nine patients (60%) were also treated with analgesics with a median number of 1.4 (0-7) drugs per patient. (Table )   Adverse effects occurred in 4 patients (27%) with a median number of 0.6 (0-4) adverse effects per patient. They included antibiotic-associated colitis (Clostridium difficile) (1 case), fungal infections (oral thrush and genital candidiasis, 3 cases), and various adverse drug reactions [START_REF] Boullier | Consultation for presumed Lyme borreliosis: The need for a multidisciplinary management[END_REF]

cases). (Table)

There were no cases of confirmed Lyme borreliosis, and all our patients had other definable illnesses as cause of their complaints. The final diagnosis was a psychiatric disorder in 9 patients (60%): somatic symptom and related disorders (5 cases), depressive disorder, bipolar disorder, post-traumatic stress disorder, and factitious disorder imposed on another; a neurological disorder in 3 patients (20%): migraine with aura, Parkinson's disease, and cervical myelopathy; and various diseases for the three remaining patients: polypathologies, tuberculosis, and sleep apnoea syndrome. (Table)

DISCUSSION

Among these 15 patients, none had confirmed Lyme borreliosis, and 60% were diagnosed with a psychiatric disease. The mean antimicrobial treatment duration was 476 days, resulting in adverse effects among 27% of them.

In our population of 425 patients referred for presumptive Lyme disease, only 15 (3.5%) had received an antimicrobial treatment for more than 180 days. Previous studies reported greater numbers, with 14.5% of 165 patients treated more than 150 days in Connecticut [START_REF] Reid | The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study[END_REF], and 11% of 1061 patients treated more than 183 days in Baltimore [START_REF] Kobayashi | Misdiagnosis of Lyme disease with unnecessary, antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic[END_REF]. Our finding is possibly under-estimated because patients were referred to a single physician whose stances against the chronic form of Lyme borreliosis are known. Patients were predominantly women, which is consistent with results of previous studies.

In Connecticut, 65% of patients without Lyme borreliosis were women [START_REF] Reid | The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study[END_REF], whereas the same figure of 65% was found in Paris [START_REF] Haddad | Holistic approach in patients with presumed Lyme Borreliosis leads to less than 10% of confirmation and more than 80% of antibiotic failures[END_REF] and in Baltimore [START_REF] Kobayashi | Misdiagnosis of Lyme disease with unnecessary, antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic[END_REF]. Over-representation of women in these cohorts of patients without Lyme borreliosis is probably related to the differential diagnoses that include a large part of psychiatric disorders. Indeed, it has been shown that somatic symptom and related disorders, which are the leading cause of consultations in this setting, are more commonly found in women [START_REF] Van Wijk | Sex differences in physical symptoms: the contribution of symptom perception theory[END_REF].

Unsurprisingly none of our patients had Lyme borreliosis which underlines the growing phenomenon of Lyme borreliosis overdiagnosis. This phenomenon is fostered by patients' associations, important media coverage and the Internet, which spread inaccurate information and contribute to creating public confusion and anxiety [START_REF] Auwaerter | Antiscience and ethical concerns associated with advocacy of Lyme disease[END_REF]. Moreover very few of our patients had Lyme borreliosis-related history as only 47% had been potentially exposed to ticks, 27% reported tick bites and none reported erythema migrans or had positive serological testing.

Overdiagnosing Lyme borreliosis leads to undiagnosed underlying diseases. Nine (60%) of our patients were diagnosed with psychiatric diseases including 5 cases of somatic symptom and related disorders. This finding reflects its increasing prevalence in the general population and in all medical settings, including non-psychiatric ones [START_REF] Murray | Barriers to the diagnosis of somatoform disorders in primary care: protocol for systematic review of the current status[END_REF]. Indeed recently reported prevalence rates for somatic symptom and related disorders vary between 16.1% and 57.5% in primary care patients with a 12-month prevalence of 11% in the general population [START_REF] Murray | Barriers to the diagnosis of somatoform disorders in primary care: protocol for systematic review of the current status[END_REF]. Diagnosis of somatoform disorders is complex and therefore often delayed. Physicians may fear missing an organic disease and thus refrain from recognising such disorders. Patients remain with long-term unexplained complaints leading them to repeatedly use health services, which can be a wearisome and frustrating experience for both physicians and patients [START_REF] Murray | Barriers to the diagnosis of somatoform disorders in primary care: protocol for systematic review of the current status[END_REF]. Failure to diagnose psychiatric disorders may lead to worsening their substantial distress, or even increase suicidal behaviours. On the contrary, correctly labelling the disorder can help legitimize their complaints and start targeted treatment.

Our other final diagnoses included neurological disorders, tuberculosis, sleep apnoea syndrome, and poly-pathologies. Previous studies reported similar findings. In Connecticut 8% of 165 patients were assigned with a neurological disorder [START_REF] Reid | The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study[END_REF]. In Paris, among 301 patients, 12% had a neurological disorder, 5% had sleep apnoea syndrome and 5% polypathologies, although some of these patients were included in both studies [START_REF] Haddad | Holistic approach in patients with presumed Lyme Borreliosis leads to less than 10% of confirmation and more than 80% of antibiotic failures[END_REF]. Failure to diagnose the underlying disease leads to progression of severe and potentially contagious diseases, such as tuberculosis in one of our cases. With this in mind, it seems crucial to pursue etiological searches so as to provide appropriate care.

Antimicrobial treatments included drugs not known to be efficient against Lyme borreliosis, such as fluoroquinolones, trimethoprim/sulfamethoxazole, anti-parasitic drugs, antifungals and antivirals [START_REF] Stanek | Lyme borreliosis: clinical case definitions for diagnosis and management in Europe[END_REF]. As highlighted by other authors, we believe that physicians, who claim to treat chronic forms of Lyme borreliosis, propose widespread treatments to cover all potential diagnoses [START_REF] Kobayashi | Misdiagnosis of Lyme disease with unnecessary, antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic[END_REF]. Indeed their prescriptions include antimicrobial treatments intended to treat other tick-borne diseases. However, presumptive treatments also target potential side effects of antibiotics, which explains the prescription of metronidazole (for antibiotic-induced colitis) and fluconazole (for muco-cutaneous candidiasis). Moreover 60% of our patients were treated with different analgesics, sometimes up to opioids, which show that antimicrobials were not efficient in this subset of patients.

Adverse effects occurred in 4 patients (27%), which is much less than the rates of 55% of minor and 6% of major adverse effects found in one study [START_REF] Reid | The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study[END_REF]. Our finding is probably under-estimated because data was collected retrospectively and adverse effects were not specifically investigated. Some of the adverse effects noted were severe (colitis, prolongation of QT interval, sight impairment). This supports the general attitude of avoiding long-term antimicrobial treatment.

Our study has some limitations. As a retrospective observational study, it was subject to missing data resulting in under-estimating certain variables (treatment detail, analgesics, adverse effects). The aforementioned referral bias was another limitation. Our population was possibly different from other settings because based on the experience of a single physician in a single-centre at an academic hospital. Finally, data was evaluated on a limited number of patients.

CONCLUSION

Patients receiving treatment for presumed Lyme borreliosis for more than six months need a comprehensive approach including psychiatric expertise.


Charlotte Jacquemot

Anne-Catherine Bachoud-Lévi

A case-study of language-specific executive disorder

Keywords: Language processing, Executive functions, Domain-specific process, Domain-general process, Performance dissociation, Aphasia Language processing, Executive functions, Domain-specific process, Domaingeneral process, Performance dissociation, Aphasia

A case-study of language-specific executive disorder

Charlotte Jacquemot, Anne-Catherine Bachoud-

INTRODUCTION

Executive control includes a wide range of mechanisms such as sustained attention, inhibition, planning, flexibility, monitoring and initiation that provide resources for other cognitive functions [START_REF] Diamond | Executive Functions[END_REF]. Executive control is essential for regulating processes and resolving conflicts in order to orchestrate behavior according to our internal goals: It allows for monitoring and updating working memory information, for inhibiting irrelevant stimulusdriven responses and suppressing task-irrelevant information, and for shifting between processes or stimuli [START_REF] Miller | The prefontral cortex and cognitive control[END_REF].

More specifically, in the language domain, executive control improves the efficiency and fluidity of language, enabling on-line processing of language components (phonology, lexicon, syntax, semantic…) (Baddeley, 2003;Hoffman et al., 2009;[START_REF] Nozari | The ventrolateral prefrontal cortex facilitates processing of sentential context to locate referents[END_REF]. The impact of executive control in language is limited when comprehending canonical sentences such as active sentences when naming familiar pictures, when producing automatized sequences such as the days of the week or even when producing lexically expected words in sentences; the latter being the basis of the Hayling sentence completion test [START_REF] Burgess | The Hayling and Brixton Tests[END_REF] which provides an excellent illustration of the potential contribution of the executive control in language. In this task, the participant listens to a sentence in which the last word is missing. In section A, the patient has to simply complete the sentence such as "Before going to bed, we switch off the [light]". Whereas in section B, the patient is required to complete the sentence with a nonsense ending word, thus imposing inhibition of the spontaneous meaningful word.

Executive control is higher in section B, where in addition to word production and initiation, inhibition processes are required to perform the task. This supports the view that the executive control of language is modulated by task complexity and that language may involve monitoring, inhibition, switching or re-analysing of complex structures. Indeed, in speech comprehension, whereas canonical sentences elicit an automatic response, non-canonical sentences conflict with the automatic response and, hence, require a high-order executive control response [START_REF] Kotz | Syntactic language processing: ERP lesion data on the role of the basal ganglia[END_REF]Mestres-Misse et al., 2012). Executive control also plays a substantial role in disambiguation and reanalysis of semantic content or syntactic structure, when the communicative context requires selecting an appropriate interpretation among multiple alternatives (topic, speaker, etc) [START_REF] Jacquemot | What is the relationship between phonological shortterm memory and speech processing?[END_REF][START_REF] Kotz | Syntactic language processing: ERP lesion data on the role of the basal ganglia[END_REF][START_REF] Novick | Cognitive control and parsing: Reexamining the role of Broca's area in sentence comprehension[END_REF][START_REF] Ye | Executive control in language processing[END_REF]. In speech production, executive control allows for selecting the correct lexical items from semantic memory according to both the communicative intention and the context, as well as to plan and monitor the speech output (Indefrey & Levelt, 2004;[START_REF] Jefferies | The neural basis of semantic cognition: Converging evidence from neuropsychology, neuroimaging and TMS[END_REF][START_REF] Shao | Sources of individual differences in the speed of naming objects and actions: The contribution of executive control[END_REF].

An important issue is determining how language and executive control interact. Prior research has argued for a distinction between two separable systems: language and executive control, where domain-general executive resources apply in the language system similarly to other cognitive domains such as arithmetic, music, etc. According to this common view, even if domain-general executive resources are engaged during language processing and impact language performance, they are independent from language: language and executive resources can be selectively impaired and involved distinct networks. Indeed, there is much evidence from neuropsychological, brain imaging and behavioral studies indicating that even if executive control and language system interact, the two domains dissociate [START_REF] Ye | Executive control in language processing[END_REF]. In patients with brain lesion, double dissociations between language and executive control demonstrate that two systems may be independently impaired [START_REF] Fedorenko | Language and thought are not the same thing: Evidence from neuroimaging and neurological patients[END_REF]. Some severe aphasic patients perform flawlessly in executive tasks; conversely, patients without aphasia are impaired in executive tasks [START_REF] Reverberi | Cortical bases of elementary deductive reasoning: Inference, memory, and metadeduction[END_REF][START_REF] Varley | Evidence for cognition without grammar from causal reasoning and 'theory of mind'in an agrammatic aphasic patient[END_REF]. Brain imaging studies also show that executive control and language involve spatially and functionally different brain networks [START_REF] Fedorenko | The role of domain-general cognitive control in language comprehension[END_REF]. Whereas left-lateralized brain areas in frontal, temporal and parietal regions selectively and robustly respond to language processing, a bilateral fronto-parietal network responds to executively-demanding tasks regardless of the cognitive domain (language, memory, arithmetic, etc.) [START_REF] Duncan | Common regions of the human frontal lobe recruited by diverse cognitive demands[END_REF], suggesting that domain-general executive control is modulated by task complexity regardless of the domain. In addition, domain-general executive control ability predicts performance in complex language tasks, suggesting that domain-general control processes support language tasks. Nonverbal executive control abilities such as was assessed with the go/no go task or the Wisconsin Card-Sorting Test correlate with performance in complex language tasks such as producing words under conditions of high lexical competition or speeded action-naming tasks [START_REF] Shao | Sources of individual differences in the speed of naming objects and actions: The contribution of executive control[END_REF][START_REF] Taler | Lexical neighborhood density effects on spoken word recognition and production in healthy aging[END_REF]. Evidence also comes from multilingualism in which multilingual individuals have to intensively control their speech input and output to select the target language (among the languages they master), while inhibiting the one(s) they are not using [START_REF] Abutalebi | Language proficiency modulates the engagement of cognitive control areas in multilinguals[END_REF][START_REF] Hervais-Adelman | Executive control of language in the bilingual brain: Integrating the evidence from neuroimaging to neuropsychology[END_REF]. Bilingualism improves linguistic capacity -for example, multilingual individuals outperformed monolinguals in comprehending noncanonical sentences in the presence of linguistic interference [START_REF] Bialystok | Language proficiency and executive control in proactive interference: Evidence from monolingual and bilingual children and adults[END_REF][START_REF] Filippi | A bilingual advantage in controlling language interference during sentence comprehension[END_REF][START_REF] Filippi | Bilingual children show an advantage in controlling verbal interference during spoken language comprehension[END_REF]. Interestingly, monolingual and multilingual individuals perform at the same level with canonical sentences, suggesting that multilingual individuals show greater advantage in complex linguistic tasks when the executive demand is high. In parallel, being multilingual is associated with higher capacity in non-verbal executive control tasks which require rapid switching between rules, suppression of irrelevant information, monitoring and updating changes [START_REF] Bialystok | The bilingual adaptation: How minds accommodate experience[END_REF][START_REF] Bialystok | Bilingualism: Consequences for mind and brain[END_REF][START_REF] Pelham | Cognitive advantages and disadvantages in early and late bilinguals[END_REF]. Although these findings suggest that the enhanced executive control capacity observed in multilinguism is not specific to language but spreads to other cognitive domains, this multilinguism advantage has been recently questioned in a growing number of studies [START_REF] Filippi | Developmental trajectories of control of verbal and non-verbal interference in speech comprehension in monolingual and multilingual children[END_REF][START_REF] Lehtonen | Is bilingualism associated with enhanced executive functioning in adults? A meta-analytic review[END_REF][START_REF] Paap | Are bilingual advantages dependent upon specific tasks or specific bilingual experiences[END_REF][START_REF] Paap | There is no coherent evidence for a bilingual advantage in executive processing[END_REF]. Finally, impaired performance in children with specific language impairment (SLI), a developmental disorder affecting language F o r P e e r R e v i e w O n l y 6 acquisition when processing complex sentences, (Im-Bolter et al., 2006;[START_REF] Van Der Lely | Domain-specific cognitive systems: Insight from Grammatical-SLI[END_REF] correlates with their deficit in inhibition and working memory; this therefore suggests a link between general executive control ability and complex language tasks. Altogether, this suggests that executive control in language is supported by domain-general resources and modulated by the complexity of the linguistic task [START_REF] January | Co-localization of Stroop and Syntactic Ambiguity Resolution in Broca's Area: Implications for the Neural Basis of Sentence Processing[END_REF][START_REF] Novick | Cognitive control and parsing: Reexamining the role of Broca's area in sentence comprehension[END_REF]. However, this hypothesis does not preclude that executive processes specifically dedicated to language may complement general executive functions (Hsu et al., 2017;[START_REF] Hamilton | Dissociations among tasks involving inhibition: A single-case study[END_REF].

Here, by reporting the case of a patient with a dissociation between verbal and non-verbal executive tasks, we argue that there is a part of executive control specifically dedicated to language. This language-specific component of the executive network could be impaired independently of its non-verbal component. In tasks with high executive demand, the patient showed impaired performance in the verbal domain but spared performance in non-verbal domain. This language-specific executive disorder undermines the notion of domain-generality of executive control and suggests that some executive resources instead of being domaingeneral might be language-specific.

MATERIAL AND METHODS

Case report

Patient LG, right-handed and 50-years old, was working as a computer programmer (14 years of education) at the time of his stroke. He was admitted to the hospital for acute language difficulties. A CT scan showed a stroke encompassing the left anterior cingulate cortex (ACC) and the left caudate nucleus. LG was fluent but his spontaneous speech was sprinkled with semantic paraphasias and circumlocutions. The patient was tested from 3 to 9 months after the stroke. Healthy participants were included in this study to provide controls for the novel tasks.

The study was carried out in accordance with the recommendations of the code of ethics in French law for observational studies and of the Declaration of Helsinki. All participants consented to this research.

General neuropsychological assessment

Neuropsychological examination included verbal and non-verbal tests to assess global intellectual function, language, executive functions, working memory, visual processing, and attention. Whereas the assessment of LG's intellectual functioning with the non-verbal test of the Wechsler Adult Intelligence Scale (WAIS III) [START_REF] Wechsler | WAIS-III -Échelle d'intelligence de Wechsler pour adultes[END_REF] showed normal performance, LG's intellectual functioning assessed through verbal tests (WAIS III and Binois-Pichot Vocabulary Test) [START_REF] Binois | Test de vocabulaire: Manuel d'application[END_REF] showed only low average performance (see Table 1). Intellectual assessment revealed a discrepancy between non-verbal and verbal performance. Because intellectual functioning assessment is highly dependent on executive functions and language, we further explored executive ability in non-verbal and verbal domains.

In order to evaluate LG's non-verbal executive ability, we assessed non-verbal tasks from previous studies and contrasted tasks requiring low and high executive demand [START_REF] Calabria | Losing control of your languages: A case study[END_REF]Hoffman et al., 2009Hoffman et al., , 2011Hoffman et al., , 2012;;Hoffman, Jefferies, et al., 2013;[START_REF] Jefferies | Deficits of knowledge versus executive control in semantic cognition: Insights from cued naming[END_REF][START_REF] Jefferies | Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison[END_REF][START_REF] Thompson | Semantic control and modality: An input processing deficit in aphasia leading to deregulated semantic cognition in a single modality[END_REF]. The digit cancellation task [START_REF] Della Sala | A cancellation test. Its Reliability in Assessing Attentional Deficits in Alzheimer[END_REF]) is a three-step task which consists of cancelling a target digit, then two targets, and finally three target digits in a panel of numbers. It allows for assessing attention allocation. The Trail Making Test (TMT) consists of two parts (A and B) in which the participant is instructed to connect a set of dots as accurately and quickly as possible [START_REF] Tombaugh | Trail making test A and B: normative data stratified by age and education[END_REF]. Part A (TMT A) consists of digits and assesses both attention and motor speed while part B (TMT B), consisting of alternating digits and letters, assesses attention, motor speed and flexibility, thus requiring executive resources. The Raven progressive matrices task measures abstract reasoning [START_REF] Raven | Manual for Raven's progressive matrices and vocabulary scales[END_REF]. The participant is asked to identify the missing pattern within a series of geometrical patterns. In the Wisconsin Card-Sorting Test, which measures abstract reasoning, task switching and attention, the participant is asked to match cards with figures differing with respect to color, quantity, and shape [START_REF] Heaton | Wisconsin card sorting test manual; revised and expanded[END_REF]. The Rey figure is a complex figure that the participant is asked to copy (Fastenau et al., 1999). In the Ratcliff test, the participant is asked to decide in which hand human figures from the front, from the back or oriented upside down are holding a ball in order to assess spatial orientation [START_REF] Ratcliff | Spatial thought, mental rotation and the right cerebral hemisphere[END_REF]. The Protocole d'Evaluation des capacités Gnosiques Visuelles (PEGV) assesses visuospatial abilities, attention, working memory, planning, and monitoring to detect eventual visual agnosia. It comprises of several tasks (embedded pictures to recognize, intruder detection, functional matching, and categorical matching) [START_REF] Agniel | Protocole Montreal-Toulouse. Evaluation des gnosies visuelles et auditives[END_REF]. Patient LG performed within the normal range of all these non-verbal tests regardless of the executive demand of the task.

In contrast, LG displayed a dissociation in performance among verbal tasks, showing low performance when the executive demand was high but spared when the executive demand was low. More precisely, LG's speech quality was normal in a free narrative and open-ended conversation. He performed normally at picture-naming in both the DO80 (Oral Naming 80) [START_REF] Deloche | Test de denomination orale de 80 images[END_REF] and the naming part of the French version of the Boston Diagnostic Aphasia Examination (BDAE) [START_REF] Goodglass | HDAE, échelle d'évaluation de l'aphasie adaptation française du Boston diagnostic aphasia examination de H[END_REF]. Conversely, LG's performance was below the normal range in the Commands part of the BDAE, in which he was requested to carry out commands such as "place the watch on the other side of the pen and turn the card over", which imply subsequent embedded actions. He was also impaired in both [START_REF] Cardebat | Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level[END_REF], tests where subjects are required to orally elicit as many animal names (categorical) or words beginning with a specific letter (letter) in two minutes. In contrast to picture naming, fluency tasks require higher executive resources for monitoring and inhibiting the numerous competitors. Likewise, LG was impaired in the similarities subtest of the WAIS, a verbal task in which the participant has to describe how two auditory words or concepts are similar. This task assesses language conceptualization, verbal abstraction, and analogical verbal reasoning. It examines the ability to think abstractly and to find similarities among words or ideas that may not appear to be similar on the surface. LG was also impaired in section B of the Hayling sentence completion test [START_REF] Burgess | The Hayling and Brixton Tests[END_REF] but not in section A. Consistently, LG was performed flawlessly in the forward digit span, which is mostly an attentional and immediate memory task, but was impaired in the backward span [START_REF] Jacquemot | Improving language evaluation in neurological disorders: The French Core Assessment of Language Processing (CALAP)[END_REF][START_REF] Wechsler | WAIS-III -Échelle d'intelligence de Wechsler pour adultes[END_REF] which involves the executive control component of the verbal working memory (Baddeley, 2003b).

In summary, the general assessment demonstrated impaired performance in verbal tasks with high executive demand, but spared performance in verbal tasks with low executive demand and in all non-verbal tasks regardless of their executive demand. In order to directly assess the role of executive control in the patient's verbal deficit, we assessed language tasks in which the executive demand was modulated within-task.

Language assessment

Statistical methods

We performed case-control comparisons using the Crawford modified t-test [START_REF] Crawford | Point and interval estimates of effect sizes for the case-controls design in neuropsychology: Rationale, methods, implementations, and proposed reporting standards[END_REF] which calculates the probability that a single case comes from the distribution of a control sample. In addition, to demonstrate the existence of a dissociation between performance across two conditions, we compared the difference between LG's scores with the analogous difference [START_REF] Crawford | Point and interval estimates of effect sizes for the case-controls design in neuropsychology: Rationale, methods, implementations, and proposed reporting standards[END_REF]. Two-tailed p values are reported. For each task, the percent of correct response and standard deviation are reported. The correlation coefficient (r) among conditions in the control sample is also reported.

Language comprehension

Word comprehension was evaluated with an auditory word-picture matching task (Jacquemot et al., 2007). A total of 64 pictures of common concrete nouns were selected and were visually presented with an auditory word. The word was either the correct name of the picture (e.g., "bureau" /byro/ desk for a picture of a desk), an unrelated distractor (e.g., "pomme" /pom/ apple), a semantic distractor (e.g., "armoire" /armwar/ wardrobe), or a phonological distractor.

There were two types of phonological distractors: words and pseudowords, which were phonologically equidistant from the target word (e.g., the word /bylo/ whelk and the pseudoword /byfo/). Every picture was presented once with each auditory item (the identity and the four types of distractor) with a total of 320 trials.

LG was asked to decide whether the auditory word matched the picture. His performance was compared to that of matched controls (N=5; mean age: 52.2 2.16, p > 0.1; mean age of education: 14 3.9, p > 0.1).

Sentence comprehension was evaluated with a sentence-picture matching task. The patient was asked to decide whether an auditory sentence matched a picture [START_REF] Teichmann | The Role of the striatum in rule application: The model of Huntington's disease at early stage[END_REF]. We contrasted two syntactic conditions: sentences followed either the French canonical syntactic order (active and subject relative sentences, e.g. "The girl waters the flower that is white", N=16) or a non-canonical syntactic order (passive and object-relative sentences, e.g. "The flower that is white is watered by the girl", N=16) (Supplementary material, Table 1). The two conditions were matched for sentence length and word frequency. LG's performance was

Language production

Speech production was assessed through a word production task, using an oral definition [START_REF] Bachoud-Lévi | An influence of syntactic and semantic variables on word form retrieval[END_REF]. We contrasted two conditions: "concrete" and "abstract" in which the expected responses were respectively, concrete and abstract words as rated by control participants from 1 to 5. Since the definition of abstract and concrete is debated, the scale was rated arbitrarily between two examples tomato (1) and freedom (5) [START_REF] Bachoud-Lévi | An influence of syntactic and semantic variables on word form retrieval[END_REF]. The two conditions were matched for syllable length and word frequency. For each word, concrete (N=20) or abstract (N=20), a definition was constructed and presented orally to

LG who was asked to produce the word corresponding to the definition (Supplementary material, Table 2). LG's performance was compared to that of matched controls (N=17; mean age: 56.8 3.6, p > 0.1; mean education age: 14.2 2.6, p > 0.1).

We designed the CATEX® (CATegory / EXemplar) (Jacquemot & Bachoud-Lévi, 2019), a picture-naming task in which the executive demand is modulated independently of linguistic factors. We contrasted two conditions: "exemplar" and "category", in which the expected responses were respectively, exemplar and category words. In this task, LG and matched controls (N=37; mean age: 50.8 20.6, p > 0.1; mean education age: 11.4 4.95, p > 0.1) were asked to produce a single word describing two pictures either of the same item ("exemplar" condition, e.g. a banana and a peeled banana, with "banana" as the expected response) or of two different items from the same category ("category" condition, e.g. a banana and an apple, with "fruit" as the expected response). The production of category words is more demanding 12 of executive resources than the production of exemplar words, but conditions were equalised for linguistic demand. We selected exemplar (N=31) and category (N=31) items with a mean accuracy above 90% (data from a naming agreement pilot study with 40 participants), matched for syllable length (mean syllable number of Exemplar: 1.87 0.72; Category: 1.87 0.56; p = 1), phonemes number (mean phoneme number of Exemplar: 4.6 1.12; Category: 4.44 1.32; p = 0.6) and word frequency (mean word frequency 1 of Exemplar: 65.2 112.1; Category: 52.2 54.2; p = 0.6) (Supplementary material, Table 3).

Semantic cognition

Lambon [START_REF] Ralph | The neural and computational bases of semantic cognition[END_REF] refers to semantic cognition as the ability to use, manipulate and generalize knowledge acquired over a lifespan to support verbal and non-verbal behaviours. It combines semantic memory, referring to acquired knowledge and its executive control component regulating and organising both retrieval and access to semantic memory. To assess semantic cognition, we constructed non-verbal picture tasks such as anomalous picture detection, picture completion, categorical intruder detection and functional matching (N=140). In addition, we assessed LG's capacity to retrieve semantic information related to pictures of artefacts, animals, vegetables and tools (N=66).

LG had to answer yes/no questions with respect to pictures (e.g. "Is it edible?", "Does it fit in a shoe box?", "Is it from inside or outside the house?", N=308) (Jacquemot et al., 2012). Finally, we assessed whether LG understood the concept of "category" by asking him to produce a word from the same category of a given auditory word (N=28).

1 Lemma frequency from movies, www.lexique.org. For instance, on hearing the word "fork", the patient was expected to reply "knife", "spoon", etc.

RESULTS

Language comprehension

Word comprehension

In word comprehension, LG performed as well as controls (percent of correct responses, LG: 99.4%; controls: 99.80.3%; Z-score: -1.43; t = -1.4, df = 4, p = 0.16).

Sentence comprehension

In sentence comprehension, LG comprehended canonical sentences as well as controls, but his comprehension of non-canonical sentences was poorer than controls (percent of correct responses for canonical sentences, LG: 93,7%; controls: 999.6%; Z-score: -0.5; t = -0.52, df = 19, p > 0. 1; percent of correct responses for non-canonical sentences, LG: 81.3%; controls: 90.32.2%; Z-score: -3.8; t = -3.7, df = 19, p < 0.001; r = 0.59). The difference between LG's performance on canonical and non-canonical sentences differs significantly from the distribution of differences in controls (RSDT t = 3.3, p = 0.004, ES = 3.5) (Table 2).

Language production

Concrete and abstract word production

LG's production was flawless for concrete words, but impaired for abstract words compared to controls (correct responses for concrete words, LG: 95%; controls: 944%; Z-score: 0.22; t = 0.2, df = 16, p = 0.8; correct responses for abstract words, LG: 65%; controls: 90.65%; Z- 14 score: -5.17; t = -5.0, df = 16, p < 0.001; r = 0.21). The difference between LG's performance in concrete and abstract words differs significantly from the distribution of differences in controls2 (RSDT t = 3.9, p = 0.001, ES = 4.3), (Table 2). The distribution of LG's errors is reported Table 3.

Exemplar and category word production (CATEX)

In the CATEX, LG performed similarly to controls for the exemplar condition (correct responses, LG: 90.3%; controls: 945%; Z-score: -0.76; t = -0.75, df = 36, p = 0.45) but lower than controls for the category condition (correct responses, LG: 51.6%; controls: 89.18%; Zscore: -4.93; t = -4.9, df = 36, p < 0.001; r = 0.5). The difference between LG's performance in exemplar and category conditions differs significantly from the distribution of differences in controls (RSDT t = 4.1, p < 0.001, ES = -4.2), (Table 2).

Semantic cognition

LG's semantic cognition was intact. LG was unimpaired in non-verbal picture tasks: anomalous picture detection, picture completion, categorical intruder detection and functional matching (97.1% of correct responses). LG's capacity to retrieve semantic information related to pictures of artefacts, animals, vegetables and tools was flawless (100% of correct responses). LG performance in yes/no questions about semantic information related to depicted items on picture was spared too (98.8% of correct responses). He performed flawlessly in naming exemplars from the same category of pictures of items (96.4% of correct responses), indicating a spared understanding of the concept of category.

DISCUSSION

LG displayed a language disorder with normal intellectual abilities following a left ACC and left caudate nucleus lesion. He showed normal performance in executively-undemanding verbal tasks (i.e. section A of the Hayling test, automatic speech, forward digit span, picture naming, repetition, word comprehension) but impaired performance in executively-demanding verbal tasks requiring executive control (i.e. section B of the Hayling test, verbal fluency, backward digit span, similarities subtest of the WAIS, comprehension of commands and complex sentences). In contrast, his performance was unaffected in non-verbal tasks regardless of the executive demand: LG succeeded in both executively-undemanding tasks such as the TMT A and the digit cancellation test, as well as in executively-demanding tasks such as the Raven progressive matrices, the Wisconsin card-sorting test, the TMT B and tasks assessing visual, spatial and mental rotation skills, i.e. the Ratcliff test, the Rey figure copying test and the PEGV (Table 1). The results of the language assessment in which conditions of high and low executive demand were contrasted within each verbal task confirmed that LG was specifically impaired in conditions requiring high executive demand.

Unlike previous cases displaying a domain-general executive deficit affecting verbal and nonverbal tasks indiscriminately [START_REF] Calabria | Losing control of your languages: A case study[END_REF]Hoffman et al., 2012;[START_REF] Thompson | Semantic control and modality: An input processing deficit in aphasia leading to deregulated semantic cognition in a single modality[END_REF][START_REF] Vuong | The role of LIFG-based executive control in sentence comprehension[END_REF], LG displayed an impairment specific to verbal tasks requiring executive control to be performed while sparing capacities in non-verbal tasks.

Acknowledging that comparison between tasks might mask uncontrolled biases, we further assessed language through speech comprehension and production tasks in which we contrasted two conditions within tasks: low executive control demand versus high executive control demand while keeping constant linguistic parameters. Sentence length, syllable length and word frequency were matched between conditions in the sentence picture matching task, in the concrete/abstract word production task and in the CATEX® task, suggesting that LG's lower One could argue that LG suffers from a disorder of semantic cognition in which semantic control processes interact with semantic memory to ensure that the information accessed at any given moment is appropriate for the current task and context [START_REF] Jefferies | Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison[END_REF].

Indeed, two kinds of deficits affect semantic cognition: semantic dementia and semantic aphasia. Semantic dementia is characterized by an impairment of semantic memory affecting all tasks regardless of the modality (spoken and written words, pictures, environmental sounds, object use…) and lower performance for specific concept and unique features [START_REF] Patterson | Where do you know what you know? The representation of semantic knowledge in the human brain[END_REF]. For instance, patients with semantic dementia will forget the zebra stripes before forgetting a common feature in animals like its tail. Semantic dementia occurs after bilateral anterior temporal lobe damage. In contrast, semantic aphasia is due to an executive control deficit of semantic memory and associated with prefrontal or temporo-parietal infarcts.

Patients' performance with semantic aphasia is consistent across the different modalities but inconsistent across tasks since it depends of the executive control requirement of the tasks [START_REF] Jefferies | Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison[END_REF][START_REF] Noonan | Elucidating the nature of deregulated semantic cognition in semantic aphasia: Evidence for the roles of prefrontal and temporo-parietal cortices[END_REF]. Patients show deficits in executively demanding semantic tasks in both verbal and non-verbal domains [START_REF] Corbett | The use of cueing to alleviate recurrent verbal perseverations: Evidence from transcortical sensory aphasia[END_REF][START_REF] Corbett | Exploring multimodal semantic control impairments in semantic aphasia: Evidence from naturalistic object use[END_REF][START_REF] Jefferies | Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison[END_REF][START_REF] Thompson | Semantic control and modality: An input processing deficit in aphasia leading to deregulated semantic cognition in a single modality[END_REF]. In addition, their performance in language tasks is highly influenced by the degree of competition between concepts and the extent to which the task constrains semantic processing [START_REF] Krieger-Redwood | Conceptual control across modalities: Graded specialisation for pictures and words in inferior frontal and posterior temporal cortex[END_REF]. We can easily rule out semantic dementia in LG because the behavioural and anatomical data are not consistent with the etiology of this neurodegenerative disease: LG's performance in semantic cognition tasks is not impaired and the anterior parts of his temporal lobe are not damaged. It is also unlikely that LG had semantic aphasia for several reasons. First, when assessing semantic cognition, LG showed no impairment even in tasks requiring the control of semantic memory such as categorical intruder detection or functional matching. Second, contrary to patients with semantic aphasia who perform poorly on a variety of executive measures such as the WCST, the Raven matrices, the TMT B [START_REF] Jefferies | Deficits of knowledge versus executive control in semantic cognition: Insights from cued naming[END_REF][START_REF] Thompson | Semantic control and modality: An input processing deficit in aphasia leading to deregulated semantic cognition in a single modality[END_REF], LG was not impaired in non-verbal executive tasks. Third, in semantic aphasia, we would expect some difficulties in the auditory word-picture matching task, especially with semantic distractors and in the exemplar naming task, which was not the case with LG [START_REF] Jefferies | Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison[END_REF].

LG was impaired in speech production tasks in conditions that involve executive control (abstract and category words) in comparison to exemplar and concrete words production. This dissociation between performance in abstract and category words compared to concrete and exemplar words deserves special interest. What factors make abstract and category words special compared to concrete and exemplar words? Concrete words are associated to richer perceptual experiences and a higher number of active semantic features, than abstract words [START_REF] Gao | Distinguishing abstract from concrete concepts in supramodal brain regions[END_REF][START_REF] Jones | Deep dyslexia, imageability, and ease of predication[END_REF][START_REF] Paivio | Mental representations: A dual coding approach[END_REF]. As the meaning of abstract words does not refer to an object that may be perceived directly in the world (e.g. peace) and relates to intangible experiences or properties [START_REF] Paivio | Mental representations: A dual coding approach[END_REF], their context is highly variable (Hoffman, 2016). For example, "peace" combines different contextual frameworks. It may refer to a state of mind or to the status of two countries after a war. Similarly, a category refers to the relationships between several exemplars that may differ considerably (e.g., cats and lions are very different, but both are from the same category of felines). The meaning of abstract and category words is heavily dependent on the context -the so-called semantic diversity-in which they are being used (Hoffman et al., 2010(Hoffman et al., , 2015;;Hoffman, Jones, et al., 2013;[START_REF] Jefferies | The neural basis of semantic cognition: Converging evidence from neuropsychology, neuroimaging and TMS[END_REF][START_REF] Jefferies | Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison[END_REF]. In contrast to exemplar and concrete words, abstract and category words can occur in many different contexts: they refer to many meanings, less tangible items with lower 18 sensory-perceptual content and lower number of active semantic features. Hence, processing them requires greater demands on executive control of semantic knowledge to provide access to competing aspects of semantic cognition not dependent on any particular perceptual experience for retrieving the correct meaning in speech comprehension and selecting the correct word in production. This suggests that LG's verbal performance depends on the executive demand of the task (Table 2). Consistently, LG was also impaired in the sentence comprehension task, but only for non-canonical sentences, the condition that involves executive control in comparison to canonical sentences. LG's verbal performance is modulated by executive demand whereas non-verbal performance is unaffected by executive demand (Table 1). This dissociation between verbal and non-verbal domains suggests that executively-demanding language tasks rely at least partly on mechanisms different from those used in the non-verbal domain. This effect might be the result of an impaired interaction between language processing and a general executive system, where language modality would be specifically affected, or the result of an impaired language-specific executive component (Jacquemot & Bachoud-Lévi, in revision). It has been recently proposed that executive control involved in language tasks, instead of being considered as a domain general "central controller" may be an emergent property of distributed systems [START_REF] Eisenreich | Control without Controllers: Toward a Distributed Neuroscience of Executive Control[END_REF]. A similar proposal has been made in the domain of short-term memory, where short-term memory capacity is an emergent property of the language system relying on the links between the speech comprehension and speech production modalities rather than a separate system [START_REF] Jacquemot | What is the relationship between phonological shortterm memory and speech processing?[END_REF][START_REF] Majerus | Language repetition and short-term memory: An integrative framework[END_REF].

Another view is that rather than being domain-general, some mechanisms can become duplicated over evolution, with independent copies in different domains wrongly suggesting there are domain-general mechanisms [START_REF] Endress | Duplications and Domain-Generality[END_REF]. Whereas our study does not specifically address these hypotheses, LG's dissociation between executive verbal and non-verbal tasks The location of LG lesions in the left ACC and caudate nucleus enhance their role in the neuronal architecture underpinning executive functions dedicated to language. Previous literature showed that executive control is associated with a fronto-parietal network including the prefrontal cortex, the ACC, the temporo-parietal junction and basal ganglia [START_REF] Duncan | Common regions of the human frontal lobe recruited by diverse cognitive demands[END_REF][START_REF] Friederici | What's in control of language?[END_REF][START_REF] Monchi | Functional role of the basal ganglia in the planning and execution of actions[END_REF][START_REF] Noonan | Going beyond inferior prefrontal involvement in semantic control: Evidence for the additional contribution of dorsal angular gyrus and posterior middle temporal cortex[END_REF][START_REF] Pini | Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review[END_REF][START_REF] Ye | Executive control in language processing[END_REF]. Within this network, a key role is attributed to the ACC when effortful control is required [START_REF] Bush | Cognitive and emotional influences in anterior cingulate cortex[END_REF]. Functional and structural imaging studies on language showed that the caudate nucleus and putamen (dorsal striatum) played a critical role in language control and flexibility, notably in tasks involving selection among linguistic alternatives switching between languages [START_REF] Abutalebi | Language proficiency modulates the engagement of cognitive control areas in multilinguals[END_REF][START_REF] Crinion | Language control in the bilingual brain[END_REF][START_REF] Giavazzi | The role of the striatum in linguistic selection: Evidence from Huntington's disease and computational modeling[END_REF][START_REF] Hervais-Adelman | FMRI of Simultaneous Interpretation Reveals the Neural Basis of Extreme Language Control[END_REF]. Because they focused on the modulation of executive control in verbal tasks, these studies did not indicate whether some parts of the network would be specific to executive control in language or rather be involved in domain-general executive control. In contrast, LG's case allowed us to dissociate language-specific executive processes from non-verbal executive processes. A potential candidate for the language-specific executive network may involve the ACC and the caudate nucleus.

This patient case study shows that contrary to the traditional view, some executive processes are language-specific and can be selectively impaired without affecting non-verbal executive performance. We refer to executive control as a whole without distinguishing between different executive processes (flexibility, monitoring, inhibition, etc.). A further step would be to determine how domain-general and language-specific executive resources interact by focusing on each type of executive process and assessing them separately. Finally, investigating their

  the Revised Standardized Difference Test (RSDT,

  of matched controls (N=20; mean age: 46.1 6.6, p > 0.1; mean education age: 13.2 4.3, p > 0.1).

  executive conditions was not due to linguistic parameters. In addition, we ensured that LG had no semantic cognition impairment as demonstrated by LG's excellent performance in semantic cognition and category concept assessments.

  that verbal executively-demanding tasks rely on processes different from those involved in non-verbal executively-demanding tasks which may specifically be impaired.

  Picture naming task (CATEX). Items of the Exemplar and Category conditions.

Table 1

 1

	F
	o r
	P
	e e r
	R
	e v i e w
	O n l
	y

Table 3

 3

		Picture Naming	CATEX	Word finding from
						definition
		DO80	BDAE	Category	Exemplar	Concrete	Abstract
	Superordinate			5	1
	Semantic paraphasia	5	15	3	2		6
	Phonological paraphasia					1	1
	Circumlocution		5	5
	Single exemplar			2

Table 3 :

 3 Type of errors by LG in speech production tasks. The number of errors in each task is reported according to the error type. Superordinate error means that LG produced

	F
	o r
	P
	e e r
	R
	e v i e w
	O n l
	y

a word of a superordinate category instead of the correct word (i.e., animal instead of feline). Circumlocution error means that LG produced a phrase that circles around the target item (i.e., an item that can be found in a room instead of furniture). Single exemplar is an error that can only be produced in the Category condition of the CATEX task and where LG produced a word that corresponds to only one of the two exemplars he was presented with.

Table 1 :

 1 Sentence comprehension task. Items of the Canonical and Non-canonical conditions.

	Canonical sentences

Table 2 :

 2 Word finding from definitions. Items of the Abstract and Concrete conditions

Note that in controls, the absence of performance difference between concrete and abstract words, and exemplar and category words is not due to a ceiling effect, since their performance with abstract and category words are not at ceiling.

ACKNOWLEDGMENTS AND FUNDINGS

This work was supported by the Fondation Maladies Rares [Programme Sciences Humaines et Sociales & Maladies Rares to CJ], the Institut National de la Santé et de la Recherche Médicale [contrat Interface to ACBL] and the Agence Nationale de la Recherche [ANR-17-EURE-0017].

, 4727-4739. https://doi.org/10.1093/cercor/bhu158 Hoffman, P. (2016). The meaning of "life" and other abstract words: Insights from neuropsychology. J Neuropsychol, 10(2), 317-343. https://doi.org/10.1111/jnp.12065 Hoffman, P., Binney, R. J., & Lambon Ralph, M. A. (2015). Differing contributions of inferior prefrontal and anterior temporal cortex to concrete and abstract conceptual knowledge. Cortex, 63, 250-266. https://doi.org/10.1016/j.cortex.2014.09.001 Hoffman, P., Jefferies, E., Ehsan, S., Hopper, S., & Lambon-Ralph, M. A. (2009). Selective short-term memory deficits arise from impaired domain-general semantic control mechanisms. J Exp Psychol Learn Mem Cogn, 35(1), 137-156. https://doi.org/10.1037/a0013985 Hoffman, P., Jefferies, E., Ehsan, S., Jones, R. W., & Lambon-Ralph, M. A. (2012). How does linguistic knowledge contribute to short-term memory? Contrasting effects of impaired semantic knowledge and executive control. Aphasiology, 26(3-4), 383-403. Hoffman, P., Jefferies, E., Haffey, A., Littlejohns, T., & Lambon-Ralph, M. A. (2013). Domain-specific control of semantic cognition: A dissociation within patients with semantic working memory deficits. Aphasiology, 27(6), 740-764. https://doi.org/10.1080/02687038.2012.751578 Hoffman, P., Jefferies, E., & Lambon Ralph, M. A. (2010). Ventrolateral prefrontal cortex plays an executive regulation role in comprehension of abstract words: Convergent neuropsychological and repetitive TMS evidence. J Neurosci, 30(46), 15450-15456. https://doi.org/10.1523/JNEUROSCI.3783-10.2010 Hoffman, P., Jefferies, E., & Lambon-Ralph, M. A. (2011). Explaining semantic short-term memory deficits: Evidence for the critical role of semantic control. Neuropsychologia, 49(3), 368-381. https://doi.org/10.1016/j.neuropsychologia.2010.12.034 Hoffman, P., Jones, R. W., & Lambon-Ralph, M. A. ( 2013). Be concrete to be comprehended: Consistent imageability effects in semantic dementia for nouns, verbs, synonyms and associates. Cortex, 49(5), 1206-1218. https://doi.org/10.1016/j.cortex.2012.05.007 Hsu, N. S., Jaeggi, S. M., & Novick, J. M. (2017). A common neural hub resolves syntactic and non-syntactic conflict through cooperation with task-specific networks. BRAIN AND LANGUAGE, 166, 63-77. https://doi.org/10.1016/j.bandl.2016.12.006 Im-Bolter, N., Johnson, J., & Pascual-Leone, J. (2006). Processing limitations in children with specific language impairment: The role of executive function. Child Development, 77(6), 1822-1841. Indefrey, P., & Levelt, W. J. ( 2004). The spatial and temporal signatures of word production components. Cognition, 92 (1)(2), 101-144. Jacquemot, C., & Bachoud-Lévi, A. C. (in revision). Striatum and language processing: Where do we stand ? Jacquemot, C., & Bachoud-Lévi, AC. (2019). CATEX: Modulation of executive demand in language Processing (Institut National de la Protection Industrielle Patent No. eSoleau DSO2019017223). Jacquemot, C., Dupoux, E., & Bachoud-Levi, A. C. (2007). Breaking the mirror: Asymmetrical disconnection between the phonological input and output codes. Cogn Neuropsychol, 24(1), 3-22. https://doi.org/10.1080/02643290600683342 Jacquemot, C., Dupoux, E., Decouche, O., & Bachoud-Levi, A.-C. (2006). Misperception in sentences but not in words: Speech perception and the phonological buffer. In COGNITIVE NEUROPSYCHOLOGY (Vol. 23, Issue 6,. PSYCHOLOGY PRESS. https://doi.org/10.1080/02643290600625749 Jacquemot, C., Dupoux, E., Robotham, L., & Bachoud-Levi, A. C. (2012). Specificity in rehabilitation of word production: A meta-analysis and a case study. Behav Neurol, 25(2), 73-101. https://doi.org/10.3233/BEN-2012-0358

Disclosure of interest

The authors report no conflict of interest. LG's deficit with a Z-score below 1.96 (outside the 95% confidence interval) is indicated with * and below 2.58 (outside the 99% confidence interval) with **, except for LG's WAIS normative scores for which the WAIS score interpretation is reported [START_REF] Wechsler | WAIS-III -Échelle d'intelligence de Wechsler pour adultes[END_REF]. Table 2: Dissociation of LG's performance in language as a function of executive load.

Conditions of the language comprehension and production tasks are classified according to the executive resources they require to be performed (low or high executive load). We reported LG's score, as well as a Z-score of LG's performance in each condition and the statistical difference (two tailed probability) between LG's standardized scores for low and high executive language conditions compared to controls using the Revised Standardized Difference Test (RSDT, [START_REF] Crawford | Point and interval estimates of effect sizes for the case-controls design in neuropsychology: Rationale, methods, implementations, and proposed reporting standards[END_REF]. Effect sizes (ES) for the difference between LG and controls (Z-DCC) and 95% Bayesian Credible Interval (CI) are also reported.

LG's pattern of performance fulfils the criteria of dissociation between low and high executive conditions for each of the language tasks.