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Language systems in the brain across the life span

Maria Luisa Gorno-Tempini, MD, PhD

University of California, San FranciscoMemory and Aging Center

Language Neurobiology LaboratoryDyslexia Center

In right-handed individuals language is a left brain function

In 25% of left handers, language is bilateralIn 5% of left handers, language is right-sided

Different brain networks sustain specific language functions in healthy subjects

Reading and writing

Semantics and word comprehension

Sounds and speech

Aphasia is defined as an acquired language deficit due to brain lesion

Lesion models to study Aphasia: Stroke Anatomy of lesion follows the vasculature

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Primary Progressive Aphasia (PPA): Selective degeneration of language systems

Logopenic PPA

Semantic PPA

Non-fluent PPA

Lesion models to study Aphasia: PPAAnatomy of lesion follows brain connections

Variants of PPA linked to underlying patterns of atrophy caused by different toxic proteins

Nonfluent variant = FTD-Tau

Semantic variant = FTD-TDP

Logopenic variant = AD-Amyloidtau

1. Comprehension and semantic network

Semantics and comprehension

Semantic PPA

What is semantic memory?

• Semantic:

• Episodic:

PHONE

JUSTICE

OBAMA

Tulving, 1972

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Pathways to “understanding”

INTEGRATION:SEMANTICS

OUTPUT

spoken word

written wordSound

VISUAL ANALYSIS

ACOUSTIC ANALYSIS

♪♪

MATERIAL SPECIFIC ENCODING

MATERIAL SPECIFIC ENCODING

Spoken words or written words?The contribution of functional neuroimaging

read vs. repeat

read repeat

repeat vs. read

Visual Temporal lobe: faces or written words

written word

What happens if these areas are lesioned?

“Auditory” Temporal Lobe: WORDS

• Lesion posterior portion of the superior temporal gyrus/sulcus results in language comprehension deficits and

Wernicke’s aphasia (1874)

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Viasual temporal lobe: prosopagnosia and visual dyslexia

R

Pathways to “understanding”Auditory stimuli Visual stimuli

Spoken name Bill Clinton

Integration ?

When the semantic network lesioned:Semantic PPA

• Progressive difficulty naming and recognizing objects and understanding words

buryyachtflanneltailwolf

snitehancehoachsmode

islandweddingchickencolonel

When semantic network is lesioned:Surface dyslexia

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Two interacting reading systems

• Phonological dyslexia: errors in “decoding non-words (words that do not exist) most common in developmental dyslexia

WHOLE-WORD PROCEDUREusing semantics:

Irregular LFSUBLEXICAL

PROCEDURE using phonic rules: regular

words, non-words

lexicalWritten word

sub-lexical

lexical

sounds

sub-lexical

Semantics“YACHT”“CHOIR”

“MUST”“tine”

2. Sounds (phonological) network

Logopenic PPA

Children use this network when they first learn to read, when they “sound out”, less after words are memorized

• Segments words and sentences into their phonological (sounds) components

• Translates letters/words into sounds and vice versa for reading and spelling

Vision to sounds and phonological “loop” network

Logopenic patients have Alzheimer’s disease.Why does it look different?

59 yo F

63 yo M

60 yo F

56 yo F

MRI PET-FDG

norm

0

2.0

PET-PIB

DVR

0

2.5

Rabinovici et al., Annals Neurol 2008

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Anatomical changes in lvPPA

Developmental dyslexia

Network covariance in fcMRI

Developmental vulnerability? Increased frequency of dyslexia in logopenic PPA patients

Miller Z et al., Brain 2014

3. Sounds to articulation and grammar networks

Highly connected system for fast feedback and adjustment

Non-fluent PPA

• Segment words into phonemes, holds them in a rehearsal system and then translates them into movements

• Speech is the most fine-tuned motor control system

Sounds to speech: articulation

Often the first symptom in diseases of the motor system

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•Speech hesitant, effortful, with sound distortions and substitutions (AOS)

•Agrammatism in production and •comprehension

Non-fluent/Agrammatic variant PPA(or progressive nonfluent aphasia)

Example of speech errors

boy

kite

Agrammatism in production

The is ing

fly

a

Agrammatism in production

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Summary

• Highly specialized left-hemisphere for language

• Many interactive language systems and networks

• Individual differences in these networks will influence how one learns, writes, reads and interprets language

• Differences in development influence how neurological diseases present in adulthood

Thank youCurrent Lab members:

• Maria Luisa Mandelli• Misha Pakvasa• Zachary Miller• Kevin Shapiro• Peter Pressman• Isabel Hubbard• Marita Mayer• Miguel Santos• Eduardo Caverzasi• Jenny Ogar

• Edoardo Spinelli

• Bruce Miller• Bill Seeley • Gil Rabinovici• Nina Dronkers

Funding: NINDS R01 NS05915, NIA P01 AG019724, NIDCD, French Foundation

Grammatical system

• Grammar is the system of rules that allows us to construct sentences

• Syntax and morphology

• Patients with grammatical deficits omit “functor” words, have trouble with verbs and, when severe, speak in single words (nouns)

Grammar Network

Connected to executive functioning system for working memory, inference, attention