Language and the brain A Neuroimaging Perspective

Language and the brain a Neuroimaging Perspective Rita Barakat Neuroscience Graduate Program NSCI 539, Thursday February 2nd 2017

Brief Introduction to the Neuroanatomy of Language Talk about my work at the VA and thus far in my first two Rotations Feel free to stop me at any point if Im talking too fast/ if you have comments or questions! 1

How I came to care about language and the brain Worked as an employee without compensation (aka: volunteer with benefits) from May of 2015 until May of 2016, in Martinez, California. Met approximately thirty men and women (estimated average age of 65), more than half of whom had served in the United States Army, Navy and Marines. All of them suffered left hemisphere brain injuries of varying severity. Attempted to help them find alternative means of communicating with non-impaired individuals, so as to focus on their strengths while working on their weaknesses. Also collaborated with clinicians (mainly Speech Language Pathologists) and Neuropsychologists in order to help maximize therapies based on the neuroanatomical basis of the individual patients deficits.

The Researchers at the Center for Aphasia and Related Disorders, the Department of Veterans Affairs Medical Center in Martinez, CA, 2016.

Its one thing to learn about Neurological disorders in an academic setting, its an entirely other thing to witness these disorders in a clinical context (in-person)Learn a lot about how language works from what happens when it doesnt work 2

Why we should all care about the structural and functional basis of language Language distinguishes humans from all other species on earth (current consensus in the field) What are the social and clinical implications of disorders in language? Developmental language disorders, such as Dyslexia, are often difficult to diagnose early, and can have an incredible impact on a childs ability to attain literacy. Other developmental disorders may not be strictly language-related, such as Autism Spectrum Disorders (ASDs) or other social-cognitive conditions, but can nevertheless impact a childs ability to communicate. A significant percentage of individuals who suffer a stroke in the United States are left with some form of language deficit, ranging anywhere from a mild Dysphasia to complete Aphasia. These conditions are incredibly difficult to diagnose and even more so to treat.

Illustration of common methods and techniques for communicating with people with Aphasia, from the American Heart Association and the National Aphasia Association, 2016.

Language has a clearly-defined developmental origin, but the neurobiological basis for language still remains largely unexplored (where is it in the brain, what cells/ circuits contribute to it, etc.) Our lack of knowledge about the neurobiological and neuroanatomical basis of language makes treating disorders of language very difficult. 3

(Some) neuroanatomy of languageHistorically, language speech-motor and comprehension processing thought to be attributed to key cortical areas localized to the left temporal lobe:Brocas Area (Brodmann Areas 44 and 45), from the work of Pierre Paul Broca, attributed to speech-motor control Wernickes Area (Brodmann Area 22), from the work of Carl Wernicke, attributed to comprehensionWith the advent of more sophisticated neuroimaging tools (i.e. sMRI, fMRI, DTI, etc.), researchers have begun to look more closely at the role of white matter tracts that intersect these cortical areas in language processing: Arcuate Fasciculus Superior Temporal Gyrus (Superior Longitudinal Fasciculus) Middle Temporal Gyrus Inferior Temporal Gyrus (Inferior Longitudinal Fasciculus, Inferior Occipital-Frontal Fasciculus)Insula Cerebellum

Image showing Brocas and Wernickes areas in the left temporal lobe, taken from the National Institute on Deafness and other Communications Disorders web page on Aphasia.A tractography image showing the white matter tracts of reading in the left temporal lobe, Figure 2 from Ozernov-Palchik and Gaab, 2016.

Arcuate Fasciculus: White matter tract that links the two Language Centers (cortical areas), Brocas and Wernickes Area. Brocas Area towards the anterior arcuate, Wernickes towards the posterior arcuate. Also links together areas like the angular gyrus and the superior temporal gyrus (STG) Superior Temporal Gyrus: Contains Wernickes Area, responsible for auditory processing/ comprehension of spoken language Middle Temporal Gyrus: Exact role in language highly debated, but may play a role in word comprehension during reading Inferior Temporal Gyrus: Contains the Ventral Stream of visual processing, responsible for recognition of word-forms and numbers Insula: Exact role in language largely unknown, though based on lesion studies, as well as examination of patients with Primary Progressive Aphasia (PPA), found that severe deficits in language expression, but not necessarily comprehension, were linked to damage to the insular cortex Cerebellum: Recent research now covering the cerebellum, particularly the more evolutionariliy young cerebellum (cerebrocerebellum), potential role in cognition and language 4

How we process speech in adverse listening conditions: Rotation #1: dr. jason zevin, september 2016-november 2016Examining individual differences in continuous speech processing under adverse listening conditions, using fMRI.Hypothesize that distinct language-associated pathways, such as the superior temporal gyrus (STG), middle temporal gyrus (MTG), and inferior temporal gyrus (IFG) networks, can exhibit positive relationships with particular listening styles or strategies. For the future, would explore the possible error-feedback circuitry of the auditory cortex, a la mechanisms of the cerebellum, in the context of continuous listening and speech processing.

Noise Vocoded Speech:

Matt Davis, An Introduction to Noise Vocoded Speech, Cambridge University. Local Temporal Reversal:

Cross and Lalor, Journal of Neurophysiology, 2014.

Aimed to look at the different ways individuals (with diverse educational, social and cultural backgrounds) process language in adverse listening conditions (show samples, pray they work) Expect to see significant differences in BOLD signal (activity) measured in the superior temporal gyrus (STG)/ auditory cortex Ultimately, would like to cover other regions, including cerebellum, to see if theory on error-feedback processing as a means of continuous speech listening comprehension is valid in the auditory cortex, as well as cerebellum 5

Adverse Listening Conditions CONT.In addition to developing my skills with FSL (a broadly-used, freely-available software for fMRI data analysis), I also assisted in selecting and generating novel stimuli for our experimental design. In earlier trials, used SAT reading comprehension passages for stimuli, largely due to the benefit of having pre-written, standardized questions to test the participants understanding of the passage. Perhaps unsurprisingly, we found that these passages were non-translatable to a community population (did not account for the diversity in educational backgrounds), and were also rated largely unengaging.

Skipper and Zevin, , Figure 1, 2015.

Originally, slide read I got 99 problems, and selecting appropriate stimuli is definitely one of them (lol) Difficult task, in that interpretation of the differences in BOLD signal between subjects dependent on attention of each subject (were they attending to the stimulus, listening hard enough to actually glean information from the passage, despite ALC?) 6

Reading networks in children with dyslexia: Rotation #2: Dr. Kristi clark, november 2016-february 2017Examining differences in orthographic and phonological processing between non-impaired controls (matched for age, as well as reading-level) and children with Dyslexia. Correlating behavioral data (quantified in task performance) with structural and functional connectivity measures (sMRI, fMRI and DTI). Ultimately, aim to characterize the reading networks of children with Dyslexia in order to improve efficacy of therapeutic interventions. Continuing to develop my skills with functional imaging data analysis using FSL, as well as practicing statistical analysis of behavioral data.

Figure 1: The figure above shows the task design for the fMRI protocol. On the left, the Orthographic task (in which subjects choose the word that is spelled correctly) is shown; on the right, the Phonologic task (in which subjects choose the word that sounds correct) is shown.

Figure 2: The above figure displays a sample of the FEAT output (FSL) from co-registration of the high-resolution T1-weighted images to the four-dimensional functional image.

Shifting from auditory language processing to visual language processing Looking for differences (again, via BOLD signal) in children with Dyslexia on two tasks (Ortho and Phono) compared to age-matched and reading level-matched control subjects 7

Reading networks cont.

Figure 3: Preliminary Results examining Average Difficulty Level (ranging from 1-5) in both, the Orthographic and Phonological tasks for Control (Age-matched and Reading Level-matched) and Dyslexia subjects. No statistical analyses/ corrections have been run on these results.

Figure 4: Preliminary Results examining Average Reaction Time (in seconds) during correct trials in both, the Orthographic and Phonological tasks for Control (Age-matched and Reading Level-matched) and Dyslexia subjects. From the range of the data values between both graphs, it is evident that, overall, control subjects showed reduced reaction times in both tasks. No statistical analyses/ corrections have been run on these results.

Review preliminary results, and how I obtained them (also, apologize for the difference in scaling between the Dyslexia and Control figures!!) Overall, the general trend in performance and reaction time for both, the controls (lumped age-matched and reading level-matched) and Dyslexia subjects is the same, however, the scale/ magnitude is different; lower performance (quantified in the average difficulty level over all 60 trials in each task) in children with Dyslexia, and longer reaction time in children with Dyslexia, compared to control group(s). 8

Future research and goals For my future work, I would like to continue utilizing functional and structural imaging technologies as a means of better understanding how language is organized in the human brain. Attempt to examine white matter tracts/ regions not explored in more depth (i.e. the insular cortex, the cerebellum, etc.), using the aforementioned imaging techniques. Communicate with clinicians, physicians and communities at large to help solidify our understanding of the neurological basis of language, in the hopes of developing practical therapies for people who suffer from disorders of language.

Work with adult populations or adult databases of individuals who have suffered a traumatic brain injury or stroke and have language deficits? Heres to hoping participant recruitment wont cause me to have a 10-year long PhD

Want to select populations to study that have been overlooked, and/or are in great need of clinical help, without being overly-ambitious for a PhD projectWould like to work towards developing a standard of practice in understanding language, at least to a limit (based on current knowledge in the field); many of the problems in communicating what we know about communication with clinicians is a fundamental lack of clarity within our own field.

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Acknowledgements and referencesCenter for Aphasia and Related Disorders (Department of Veterans Affairs): Dr. Nina Dronkers and her team of Neuropsychologists and Clinicians, for inspiring my pursuit of a Ph.D. The participants and members of the Aphasia Support Group at the Martinez VA, without whom much of the findings Ive highlighted would not have been possible.Neuroscience Graduate Program (University of Southern California): Dr. Jason Zevin and his lab, for helping me immensely during my first rotation. Dr. Kristi Clark and her lab, for helping me immensely during my second rotation. The faculty, instructors and students in the Neuroscience Graduate Program, for giving me invaluable advice along the journey thus far. An incredible thank you toSelected References:

Baldo, Juliana V., Anala Arvalo, Janet P. Patterson, and Nina F. Dronkers. "Grey and White Matter Correlates of Picture Naming: Evidence from a Voxel-based Lesion Analysis of the Boston Naming Test." Cortex 49.3 (2013): 658-67. Dehaene, S., F. Pegado, L. W. Braga, P. Ventura, G. N. Filho, A. Jobert, G. Dehaene-Lambertz, R. Kolinsky, J. Morais, and L. Cohen. "How Learning to Read Changes the Cortical Networks for Vision and Language." Science 330.6009 (2010): 1359-364. Dikker, S., L. J. Silbert, U. Hasson, and J. D. Zevin. "On the Same Wavelength: Predictable Language Enhances Speaker-Listener Brain-to-Brain Synchrony in Posterior Superior Temporal Gyrus." Journal of Neuroscience 34.18 (2014): 6267-272. Ivanova, Maria V., Dmitry Yu. Isaev, Olga V. Dragoy, Yulia S. Akinina, Alexey G. Petrushevskiy, Oksana N. Fedina, Victor M. Shklovsky, and Nina F. Dronkers. "Diffusion-tensor Imaging of Major White Matter Tracts and Their Role in Language Processing in Aphasia." Cortex 85 (2016): 165-81. Pugh, Kenneth R., W. Einar Mencl, Bennett A. Shaywitz, Sally E. Shaywitz, Robert K. Fulbright, R. Todd Constable, Pawel Skudlarski, Karen E. Marchione, Annette R. Jenner, Jack M. Fletcher, Alvin M. Liberman, Donald P. Shankweiler, Leonard Katz, Cheryl Lacadie, and John C. Gore. "The Angular Gyrus in Developmental Dyslexia: Task-Specific Differences in Functional Connectivity Within Posterior Cortex." Psychological Science 11.1 (2000): 51-56. Wang, Xiaojuan, Jianfeng Yang, Jie Yang, W. Einar Mencl, Hua Shu, and Jason David Zevin. "Language Differences in the Brain Network for Reading in Naturalistic Story Reading and Lexical Decision." Plos One 10.5 (2015)

- Any Questions or Comments/ Suggestions? 10