Language its development and pathologies Isabelle Rapin Pediatric

Language, its development and pathologies Isabelle Rapin Pediatric Neurology Seminar, Dec. 4, 2013 No conflict of interest

Tools to investigate brain basis of behavior § § § § § Behavioral observation, neuropsychology Brain lesions, diseases Inhibitory r. TMS (transient virtual focal lesions) Histology (incl. focal gene expression) Structural imaging: CT, MRI, DTI (connectivity) Metabolism: PET (glucose, metabolites, transmitters) ↑ blood flow during task : f. MRI (BOLD) Electrophysiology: EEG, ERP Magnetoencephalography

Some advantages/drawbacks of these tools § § § All: group data, comparisons, baseline problem Electrophysiology/MEG: real time data EEG/ERP: good time, poor spatial resolution MEG: realtime, subcortical data, expensive and not widely available f. MRI: reasonable spatial but not time resolution. Most require cooperative subj. , but advantage of clever experiments. PET: radiation, etc.

Language in the brain

What is language? § In the individual: A computational system between thought and an acoustic signal (Hickok, 2006) § Among people: A shared medium to transmit information

Multiple language modalities (all: sensory → code/grammar → motor) § § § § § Oral – speech Written – reading, writing Gestural – Sign Somatosensory - Braille Mathematical notation Chemical, genetic symbols, etc. Musical notation Dance notation Blue prints Etc. , etc.

Levels of language § Phonology - sound units of language § Grammar/syntax - word order, word markers [morphemes], grammatical [closed class] words § Semantics - interface of (known) words – lexicon - to meaning § Pragmatics - communicative intent, verbal, non-verbal (prosody, gestures)

Steps in language processing Input (sensory) Decoding Output (motor) Higher order processing Encoding

Steps in language processing § § § Input: sound to language (phonetics) Decoding input: phonological form + lexical/semantic information Comprehension/programming: grammar, sentence. Working verbal memory, executive skills, attention… Programming output: lexical item + phonological form Output: motor, i. e. , speech, other language modalities

Classic view: Language areas in the left hemisphere

Classic view: Language connectivity: left hemisphere Peoppel et al. , 2012

Current view of language in the left hemisphere Dorsal stream Ventral stream Map sound to articulation Map sound to meaning Gow 2012

Language Processing Circuitry § § § Primary auditory cortex (Heschel gyrus) ↔ Post. sup. temporal gyrus/sulc. (Wernicke) Ventral lexicon (post. middle temp. gyr. ↔ temporal pole (semantic hub) Ventral stream ↔ inf. frontal (Broca) Dorsal lexicon (inf. parietal, supramargin. gyr. ) Dorsal stream ↔ premotor cortex and ↔ Broca (phonological loop, rehearsal – work. memory)

Schematic of language processing: current view 4. 3. . 1 2. 5. 3. 4. Hickok 2009

Functional language processing: dorsal and ventral streams ATI A BA Ant. temporal lobe PM Premotor cortex Broca area SMG Supramarginal gyrus AUD Auditory cortex Spt Syvian parietal (Left only STG Superior temporal gyrus MTG/ITG Middle/inferior temporal gyrus Hickok 2009

Interhemispheric language processing § § § Audition –sound → phonetic: bilateral Dorsal pathway -- phoneme and articulation: left Ventral pathway – map sound to meaning: left >> right Map words to thoughts (syntax, sentence): bilateral distributed network Map communicative intent (pragmatics): right

Lateralization of phonologic tasks (meta-analysis of neuroimaging studies) Left Right Vigneau et al. , 2011

Lateralization of lexical semantic tasks (meta-analysis of neuroimaging studies) Left Right Vigneau et al. , 2011

Lateralization of syntax, sentences (meta-analysis of neuroimaging studies) Vigneau et al. , 2011

Interfaces of language with short term/working memory § § § Auditory buffer (aud. assoc. cortex) ↔ Prefrontal cortex ↔ perirhinal cortex, hippocampus ↔ temporal cortex (working memory + episodic-semantic memory) (ventral stream + fornix & mammillo/ thalamic cingulate connections) Ventral interconnects dorsal stream (articul. ) Child & Benarroch, Neurology Nov. 19, 2013 Battaglia et al. , Neurosci. Biobehav. Rev. 2012

Language development

Hearing is present in utero § Cochlea is full size by the end of the second trimester § Infant hears in utero, e. g. , mother’s heart beat, borborygmi, voice § Hearing acuity good and testable at birth, matures during the first year § Latency of obligatory auditory ERPs decreases with maturation

Sequence of language development § Phonology: at birth, function of language exposure → bilingual advantage § Pragmatics: at birth § Semantics: starts at ~6 months § Syntax: by ~ 2 years § Reading: starts at preschool

Stages of language development § § § Neonate – hears speech sounds relevant to all languages, hones the ones heard, loses others ~ 1 year -- Single word holophrastic utterances ~ 18 -24 mos. – start of 2 word utterances, mostly rote echoes ~ 24 -30 mos. – 2 word utterances increase, become individualized, start of grammatic rules ~ 3 -4 years – sentences of increasing complexity Fully mature syntax -- → ~age 10 yrs or more

Semantic development § Infants develop awareness of permanence in the face of transformation (sounds, moving faces, objects, movements, own body parts) § Infants associate speech sounds with permanent stimuli § By 1 year: they understand some words, point to say “gimme” or “look”, may have a few meaningful words

Syntactic development § Starts at the 2 word stage, usually around 2 years § Two word stage usually starts when toddler has some 50 words in lexicon § Sentences with articles, pronouns, and, later, morphologic markers, usually established by 3 years § Very complex syntax not achieved until well into the school years

Are late talking toddlers at risk for specific language impairment? Courtesy: D. Thal

Normal Variability produced in relation to number of words understood by 12 to 16 -month-old children at the 10 th, 50 th, and 90 th percentile on the Mac. Arthur Communicative Development Inventories Number of words produced § Number of words understood

Variability in normal development § Range of word produced by typicallydeveloping girls on the Mac. Arthur Communicative Development Inventories (Fenson, Dale, Reznick, Thal, Bates, Hartung, Pethick, & Reilly, 1993)

When to worry (1) § Questionable hearing at any age, including at birth, refer to audiology § No reciprocal eye gaze/dialog at any age § No pointing by 1 year § No comprehension of speech ≥ 1 year § No turning when called by name ≥ 15 months § < 10 words at 18 mos § No 2 word phrases at ≥ 2 years

When to worry (2) § Unintelligible to parents at 2 years § Unintelligible to strangers at 3 years § Language not communicative, e. g. , talks to no one in particular § Abnormal features of speech: echolalia, scripts, pedantic vocabulary, aberrant prosody (e. g. , robotic, singsong), selective mutism § Any loss of language milestones (including communicative gestures)

Useful clinical language tools § Mac. Arthur Development Communicative Inventories. n n n L. Fenson et al. Paul Brookes, 1993 For kids < 30 months. Infant and verbal toddler versions Parents collect the data on comprehension, production and use Extremely well standardized in multiple languages § Early Language Milestone Scale. J. Coplan, Pro. Ed 1987, n n n ELM-2 2012 For kids < 3 years. Scored by observer. Quick Format similar to the Denver ELM-2: also for older DLD kids, , uses a kit

DEVELOPMENTAL LANGUAGE DISORDERS (DLDs) a. k. a. SPECIFIC LANGUAGE DISORDERS (SLIs) or DYSPHASIAS

Differential diagnosis of inadequate language development § § § Hearing loss Specific language disorder (dysphasia) Intellectual deficiency Autism Selective mutism (recording of normal speech required!

2 types of information the child neurologist needs to make a specific behavioral language diagnosis § § The familiar input – processing – output brain pathway Levels of language encoding

Steps in language processing Input (sensory) Decoding Output (motor) Higher order processing Encoding

Levels of language encoding (1) § Phonology – speech sounds n n phonetics – segmental prosody – suprasegmental § Grammar n n syntax (word order) morphology (word endings, etc. )

Levels of language encoding (2) § Semantics – meaning of utterances n n lexicon – word dictionary in brain meaning of connected speech § Pragmatics – conversational language n n verbal – turn taking, referencing, etc. nonverbal – facial expression, gestures, body posture, prosody

Associated deficits (frequent!) § Oromotor deficits (pseudobulbar palsy, etc. ): n n § Intellectual deficiency: n § does not cause specific language disorders Autism: n § frequent in dysfluent children with verbal dyspraxia and those with mixed receptive/expressive disorders but do not “cause” the language disorder intellectual deficiency & lack of drive to communicate = inadequate explanations for the language disorder Selective mutism: n must have recording of allegedly “normal” speech at home

Types of dysphasia § “Pure” expressive (comprehension OK, pragmatics OK, affects only phonology ± syntax) Ø Ø § Mixed expressive/receptive syntax + semantics ± pragmatics) Ø Ø § fluent but phonology very impaired (phonologic programming -- PP) dysfluent or mute (verbal dyspraxia -- VD) comprehension ≥ expression (phonologic-syntactic or MER) no comprehension = verbal auditory agnosia (verbal auditory agnosia VAA) Higher order processing Ø Ø (affect phonology + (semantics ± pragmatics) word finding deficit dysfluent, immature syntax (lexical syntactic -LS) fluent, verbose, comprehend less than they can say, use scripts. Most often in Asperger-type children (semantic pragmatic --SP)

DLD proposed syndromes § SP § LS § PP § VD § MER/PS § VAA semantic/pragmatic lexical syntactic phonologic programming verbal dyspraxia mixed expressive receptive or phonologic syntactic verbal auditory agnosia

Work-up, Prognosis

Standard Work-up of DLD Preschooler § § § § Physical/neurologic evaluation: syndrome? Family history Formal hearing evaluation unless phonology is 100% OK Rarely need for EEG, imaging, genetics (several genes now known) unless for research Refer to speech pathology (and psychology) Refer to preschool (more effective than speech Rx alone) Follow-up needed: most speak but later problems likely (see Rutter 1881, Aram, 1984 Beichtman 1996, etc. )

Potential Outcome Predictors in Developmental Language Disorders • • • . Gender Not ethnicity Bilingual exposure? Family income Parental education Ear infections • First degree relatives with history of w Learning/reading disability w Speech or language disorders w Neurological disorders • Use of gestures • # of words understood • # of words produced

Course of language development in DLD/SLI § Classification is not stable Ø More children move out of or into the category than remain in it between 3 an 5 years of age (Silva) § Children with delays in comprehension and production are at greater risk for continued “delay” than those with normal comprehension (Bishop, Silva, Tallal) § Younger children at start of intervention tend to have a better prognosis (Bishop, Silva, Tallal) Donna J. Thal Ph. D.

Course of development in DLD § 5 ½ y. DLD with normal language scores: likely to remain in the normal range on such tests (Bishop) § However, lower phonological processing scores likely n half read below age level, at 15 years of age (Stothard et al. , 1998)