Center for Language and Brain in Moscow, Russia

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Center for Language and

Brain in Moscow, Russia

EMCL+ Internship Report

Elise Oosterhuis (s2624680)

Supervisors:

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Introduction

As part of the Erasmus Mundus Master in Clinical Linguistics, I did an internship during the fourth semester of this Master’s program. For the internship, I went to the Center for Language and Brain at the International Research University Higher School of Economics in Moscow. I chose this research environment because it is a research center and the place offered many learning opportunities for me. I did a three-month internship at the same institute two years ago. I really enjoyed conducting research in the Center and I learned a lot about conducting research and acquired new skills. I experienced the Center as very friendly and I had good relations with the head of the lab, prof. dr. Olga Dragoy, and with my colleagues. Another reason why I chose this research environment was that I could join an interesting research project in which we would look at the lesion location of people with aphasia and compare the outcomes to the predictions made by the Russian neuropsychologist Alexander Luria. I could practice previously learned skills (lesion delineation), develop these skills, and learn new skills. Furthermore, the Center for Language and Brain was an interesting internship place for me, because it offered opportunities to learn from the expertise of the Center’s researchers.

The institute

The Center of Language and Brain was grounded on the first of April 2018. The Center’s aim is to study language in the brain in adults, children, and in clinical groups, by implementing several research methods and technologies. Prof. Dr. Olga Dragoy is the head of the Center and Dr. Svetlana Malyutina is the deputy director. Furthermore, the lab consists of research fellows and many research assistants. The Center also offers possibilities for Bachelor students to join the Center and conduct research. In 2018, the lab received a large grant offered by the Russian Federation, which allowed them to start new projects to study language disorders. There is also a baby lab available for testing young children. The room was painted with child-friendly images by the lab members themselves!

Before 2018, the Center was called “Neurolinguistics laboratory” which was established by Prof. Dr. Olga Dragoy in 2013. Over the years, the lab grew rapidly and, nowadays, covers many research areas in the field of linguistics:

2 • Psycholinguistics

• Speech Pathology

• Child Language and Acquisition • Bilingualism

• Language and Aging

The several research areas are covered by projects investigating, among others, reading mechanisms in healthy people, first-language acquisition of mono- and bilingual children with normal language development and children with neurodevelopmental disorders, bilingualism in adults, and changes in language processing related to healthy aging. The research area “Speech Pathology” covers, among others, language mapping during awake brain surgery for removing tumors while leaving as much functional brain tissue intact as possible. To conduct these projects, the Center has access to several research techniques, such as a range of neuroimaging and brain stimulation techniques (functional Magnetic Resonance Imaging, magnetic- and electroencephalography, diffusion tensor imaging, and different brain stimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation), eye tracking, and several behavioral methods. Many projects already led to publications in well-known research journals, such as “Cortex” and “Brain and Language”. In addition, many members of the Center regularly attend international conferences and scientific meetings, such as the ANT Neuromeeting, Science of Aphasia, and the European Workshop on Cognitive Neuropsychology. The Center for Language and Brain also has a big impact on society through its research outputs. A good example is the research on the developmental reading disorder “dyslexia”, which did not receive much recognition in Russia before. One of the Center’s researchers, Svetlana Dorofeeva, invested much of her resources in conducting research in this area and to raise awareness for dyslexia. There is definitely more attention now for dyslexia. The Center even developed a test, the ZARYA, to assess language development and is able to diagnose phonological deficits in dyslexia (https://www.hse.ru/en/neuroling/cla_zaria/).

Besides the many research projects, the Center organizes lab meetings on Thursday’s called “neurothursday” during which other lab members or student assistants present their research. The Center regularly invites researchers from outside the institute, such as prof. Alfredo Ardila. There is also an academic writing group on Thursday’s in which we get the possibility to give and receive feedback on written research output, such as articles and abstracts. Lastly, the Center organizes the annual Summer Neurolinguistics School, which covers different research

3 topics each year. This year, the topic of the summer school was “Experimental Linguistics in Less-studied Languages”. As interns, we had the opportunity to attend this summer school for free.

Main Research Project

As an intern at the Center, I joined a large research project. In September, we agreed that my main research activity would concern the participation in the Great Luria Project. This very large research project was started by the Center and concerns the aphasia syndromes proposed by the Russian neuropsychologist Alexander Romanovich Luria (1902-1977). The aim of the project was to delineate the lesions of many patients with left single hemispheric lesions and to overlay these lesions to test Luria’s predictions with regard to the lesion locations underlying the aphasia syndromes. The project also involved reading about Luria’s work and his ideas. In addition, the project aims to report Voxel-Lesion Symptom-Mapping (VLSM) analyses. This method requires to indicate which brain areas are lesioned by delineating the lesion (i.e. mapping). In this way, we can determine more precisely which brain areas are involved in particular language functions (Bates et al., 2003). In order to conduct such analyses, we have to follow several steps:

1. Preprocessing of MRI images, in which we manually orient the images to the anterior and posterior commissures of the brain.

2. Reconstructing the lesion, in which we indicate which brain voxels are lesioned in the patient.

3. Normalization of all brains, in which we convert the reconstructed lesion masks onto a brain template so that the lesion masks can be overlaid.

4. Correcting lesion boundaries, in which we check and correct the normalization of lesion masks.

5. Lesion overlay, in which we make an overlay mask with all the patients' data and obtain descriptive statistics about the lesion location.

6. Subtraction analysis, in which we subtract the lesion overlay of a group of patients without the syndrome from the lesion overlay of patients with the syndrome.

7. VLSM analysis, in which we correlate the lesion overlay with different behavioral tasks. I had the possibility to connect my thesis to this project. Therefore, I chose one aphasia syndrome on which I would focus and about which I would write my thesis. I read up on the

4 Russian aphasia types and I found acoustic-mnestic aphasia very interesting (see “outcomes” for a description of this aphasia syndrome). The idea was that I would reconstruct the lesions of all patients with that aphasia type. In addition, I reconstructed lesions of approximately half of the participants that joined the project so far. Besides reading up on my aphasia syndrome, I read more about Luria’s work and his ideas. Luria wrote several books that are also translated to English. I read “Higher Cortical Functions in Man” (1980), “Traumatic Aphasia” (1970),

and “The Working Brain” (1973), in order to understand his ideas, which I will present in the

next section. I joined the VLSM project from the very start, so in October, and the project is currently ongoing.

Before starting my internship, I only had some skills concerning the first stages of the VLSM procedure, namely the MRI preprocessing steps and the lesion reconstruction. During my internship, I developed these skills further and I learned to do a lesion overlay and obtain descriptive statistics. We used different software programs for the procedure. We used the software SPM121 _{in MATLAB R2018a}2 _{to preprocess the raw MRI files. We also used}

MATLAB to set thresholds for our lesion overlay masks. We used ITK-SNAP3 _{for our lesion}

delineations. Lastly, we used MRIcron4 _{for visual inspection of the lesion overlay masks, to}

obtain the descriptive statistics about the voxel count and proportion for the lesioned brain regions, and to create figures of the lesion overlay masks (see Figure 1, p.8). One of the aims of our internship was to learn the complete VLSM procedure, including subtraction analysis and the VLSM analysis. We will learn the last two skills at the end of my internship period (mid-August, 2019). In my opinion, I was able to gain and apply the necessary knowledge and skills in order to be able to complete the lesion overlay procedure successfully. I am very grateful for our supervisor Yulia Akinina, who checked all our lesion reconstructions, gave us tips and feedback, and taught us the VLSM procedure.

Unfortunately, VLSM does not allow us to look at the underlying brain connections. However, it is generally known that underlying white matter tracks are often damaged after stroke and involved in language impairments. We did not implement this method in our research project because the period of our internship was too short, unfortunately. However, we have learned to reconstruct white matter tracks during a short course. In this course, we had to search

1 _{SPM12 version 7219; https://www.fil.ion.ucl.ac.uk/spm/}

2 _{MATLAB® version R2018a; https://nl.mathworks.com/products/matlab.html}

3 _{ITK-SNAP version 3.8; http://www.itksnap.org/pmwiki/pmwiki.php}

4 _{Neuroimaging Tools and Resources Collaboratory (NITRC), MRIcron version 2;}

5 for information about the major language tracts and methods on how to draw them. Afterwards, we tried to draw them ourselves. I found the course very interesting and instructive and I hope that I will be able to use and develop this skill in future research projects.

Research Outcomes: Luria’s view

In his books, Luria argued that “the ‘localization of symptoms’ is of great use to the clinic, but it is reasonable to suggest that functions disturbed may be based on much broader brain mechanisms” (Luria, 1970, p.16). According to Luria, higher cortical functions, such as language, are not localized in specific brain areas but instead, comprise many brain areas that each contribute to a complex functional system. Luria had the unique opportunity to carry out his investigations because of World War II in 1941-1945 (Glozman, 2007). Many soldiers suffered from head injuries inflicted by bullets, resulting in focal brain damage and, in many cases, language impairments. Luria called these language impairments “traumatic aphasia”. Bullet wounds often lead to small, focal lesions and happen before cognitive functions are affected by old age (Luria, 1970). Luria investigated the range of symptoms observed in patients with traumatic aphasia, which led him to define several aphasia syndromes, among which acoustic-mnestic aphasia. The main characteristic of acoustic-mnestic aphasia is word-finding difficulties, which can be identified with a naming task and during spontaneous speech (Akuthina, 2016; Luria, 1970). Apart from word-finding difficulties, there is a disturbance in the repetition of series of phonemes, series of words, and long sentences (Akuthina, 2016; Luria, 1965, 1973, 1980; Luria, Sokolov, & Klimkowski, 1967). Language comprehension is relatively unimpaired. Luria predicted that the inferior temporal gyrus (ITG) and medial temporal gyrus (MTG) are damaged in these patients (Akhutina, 2016; Luria, 1971; Luria, 1970).

Research Outcomes ~ Great Luria Project

During my internship, I gained a lot of skills and knowledge in the areas: knowledge and insight, communication, academic judgment, academic skills, and application of knowledge and insight. The area knowledge and insight with regard to the field of linguistics. I read many older studies about aphasia and localization but also more recent studies which implement modern neuroimaging techniques. Older studies in the 19th and 20th century focused very much on localizing cognitive functions on specific brain areas. Alexander Luria came with a different theory, which proposed that many different brain areas are part of a more complex functional system. Following damage to one brain area can result in many different symptoms

6 since the functional system is disrupted. Nowadays, studies use modern neuroimaging techniques to answer questions about the brain. Many researchers tried to localize cognitive functions using these techniques and found that cognitive functions are indeed not localized in just one brain area but comprise several brain areas that together function as a system.

In addition, several language processing models were proposed. In my thesis, I discussed the model for language production and comprehension (Roelien, 2011), which is a box-and-arrow representation of how we perceive, comprehend, and produce words and sentences. With the use of this model, we can pinpoint the underlying deficit in language disorders, such as those in aphasia. Of course, there are many different models and theories presented in the literature but I chose this model because it is backed up by many studies and proven to be helpful in finding the underlying deficit in aphasia. However, I had some trouble in interpreting the model correctly in the beginning. With reading the literature and with the help of my supervisors, I was able to understand and interpret the model. We proposed that the underlying deficit of acoustic-mnestic aphasia lays in the access to the Phonological Output Lexicon, which is a store for phonological word-forms. Following this idea, we looked at modern neuroimaging studies to find which brain areas are involved in access to the Phonological Output Lexicon. Based on previous studies suggesting a role of left superior temporal gyrus (STG) and left supramarginal gyrus (SMG), we were wondering whether Luria’s predictions about the underlying neuroanatomical substrate of acoustic-mnestic aphasia were right. We used lesion overlays to test Luria’s predictions (lesion in the left ITG and left MTG).

The lesion overlay method in the fifteen participants with acoustic-mnestic aphasia revealed significant overlap of common brain areas in a maximum of nine patients. Figure 1 shows the overlay of all the patients diagnosed with acoustic-mnestic aphasia. In almost half of the patients with acoustic-mnestic aphasia, the left MTG seems to be affected to some extent. The left ITG was often mildly affected or even spared. In most patients, the left STG and the left SMG were unaffected. Also, the putamen and insula of the left hemisphere were often affected. We also visually inspected the lesion overlay of the group of patients without acoustic-mnestic aphasia and found that the putamen and insula are often affected in this group as well. In addition, we inspected the lesion overlay of the patients with a pure acoustic-mnestic syndrome (N=9). We found common overlap in the left MTG but not in the left ITG, left STG, or left SMG. Also, the left STG was almost entirely spared in the patients with a pure acoustic-mnestic aphasia syndrome. Furthermore, we looked at the affected brain regions in each patient

7 individually and found that the predicted brain areas by Luria (i.e. left ITG and left MTG) are not always affected in all the patients with acoustic-mnestic aphasia. Interestingly, in one patient, only subcortical areas were affected, without any cortical area being involved. Hence, our findings are partly in line with Luria’s predictions. Mainly the left MTG is damaged in patients with acoustic-mnestic aphasia. The left ITG is sometimes affected. Furthermore, the left STG and left SMG do not seem to be the underlying neuroanatomical substrate of acoustic-mnestic aphasia. As last step, we decided to take a closer look at two single cases with pure acoustic-mnestic aphasia: i) one case which was in line with Luria’s predictions, and ii) one case which suffered from a lesion in a location not proposed by Luria. This investigation is still ongoing and therefore not presented here.

Figure 1. Lesion overlay of fifteen patients with acoustic-mnestic aphasia in the axal, sagittal,

and coronal plane respectively.

So, I learned about more theoretical approaches by using theoretic language models and basing our predictions on these models, and about the use of more modern techniques, such as VLSM. In my opinion, theory and more modern neuroimaging techniques complement each other beautifully. I also believe that theories and models are necessary to base our research

8 hypotheses on and to be able to explain and discuss our findings. My internship really helped me to realize this. Also, I read many studies in which linguistics, cognitive science, neurology, and psychology met. The disciplines cognitive science and neurology are necessary when talking about cognitive functions and the brain. In addition, psychology is more focused on the behavioral aspect of cognitive functions, and linguistics is focused on specifically the language aspects of cognitive functions and often explained by theoretical models.

To give an example, Alexander Luria proposed that the underlying deficit in acoustic-mnestic aphasia was a deficit in auditory-verbal short-term memory. This is more a psychological approach, but from a linguistic point of view, we can explain the deficit by looking purely at language processes. Following this view, we proposed that the underlying deficit is in the access of the Phonological Output Lexicon. However, literature on both views was necessary to understand more about the underlying deficit. Literature on neurology and cognitive neuroscience helped us determining and predicting the underlying neuroanatomical substrates. There was still a lot more to learn and I do not feel that my knowledge in these areas is completely up-to-date. This topic is so elaborate that it will probably take a life-time to be an expert in this area. Therefore, I really needed to restrict myself to the focus of the study, namely acoustic-mnestic aphasia. I found it quite difficult to stay within the boundaries of this focus and to read literature that was closely related to the topic. I learned to use websites, such as Web of Knowledge and PubMed to restrict my searches. However, I feel that I should stay within the boundaries more and apply techniques, such as outlines, better.

Additional academic activities

The Center for Language and Brain organizes many events. When possible, I joined the talks on Thursdays and other organized talks. I also joined the academic writing meetings, in which we discussed written work from other staff members and we had the possibility to send in our own work. We commented on the writing style, the general structure, and even content when necessary. I gained skills in reviewing and commenting on written texts and also implement general comments in my own written work. Personally, this was very useful to me since I had some struggles structuring my thesis. The academic writing group gave me tips for and new insights in my writing. As an extension of the academic writing meetings, we had the possibility to follow the workshop “Literature Review and Publication Process” organized by the Higher School of Economics, Moscow. It was a three-hour workshop in which we talked about different kinds of literature research, making a literature overview with notes, and about

9 organizing our literature review. Also, we briefly discussed the process of publishing our own work. We talked about journal jargon, selecting a journal before writing, and really write for that journal by also citing literature that was published in the same journal. It was very interesting and useful and I will definitely implement some tips in my future work. My literature review was already finished by this time, so I could not apply any of these tips in my work but I am sure that the tips will be very useful in my future academic writing work.

In collaboration with the neurosurgeons of the National Medical Surgery Pirogov Center, the Center for Language and Brain organized a two-day conference about neurosurgery named

"Awake Surgery of Eloquent Brain Areas: Classic Approaches and Innovations". The Centers

organized a range of talks about awake surgery in patients with brain tumors. There were speakers from the Pirogov Center and the Center for Language and Brain, and also international speakers. I attended a few talks about language testing during awake brain surgery, which was a nice addition to the knowledge I obtained during the course “Language Testing during Awake Brain Surgery” in Groningen during my second semester. The talks were given by Prof. Dr. Roelien Bastiaanse, Prof. Dr. Olga Dragoy, and by a research assistant of the Center for Language and Brain, Andrej Zyryanov. They presented about the importance of and norms for linguistic tests during awake surgery, the development of a Russian test battery for language testing during awake surgery, and pre- and post-operative language outcomes and brain plasticity in the case of language function.

As mentioned before, the Center also organized the annual summer school in July. This year the theme was “Experimental Linguistics in Less-studied Languages”. I was involved in some organizational tasks before the start of the summer school. Together with another intern, we created a document with all the necessary information on the route to the university, lunch and dining options in the area close to the university, and some practical information. In addition, I showed the way to the summer school venue to one of the guest speakers. I also participated in the summer school by attending several lectures. I enjoyed helping out with these small tasks and to get more insight into the organization around a summer school. I also enjoyed most of the lectures. It was not entirely my field of interest but it was certainly a good opportunity to refresh my knowledge in theoretical linguistics and its application to experimental studies.

The Implementation of Previous Learned Skills

EMCL+ is a research Master’s and thus a large focus was on the cycle of conducting research. The internship offered me the opportunity to practice several competencies and skills

10 that I have acquired during my Master’s program. The academic writing course by Prof. Dr. Irina Sekerina thought me, among others, how to create a writing habit, how to formulate sentences and structure paragraphs and texts, and how to be consistent and coherent. To be honest, I did not practice to create a writing habit since I had days on which I only reconstructed lesions and other days which I completely attributed to my literature review, including a lot of literature reading. Creating a writing habit is useful in the daily writing of parts of any academic text. In this way, we can avoid what I have been doing (i.e. devoting whole days to one particular task instead of doing a bit of each task during the day). I noticed that creating a writing habit is not easy at all and does not always work in practice. That does not take away the fact that I still want to create such habit because it keeps you on track with your writing and makes it less difficult to sit down and actually write. The other competencies Sekerina taught us during her class were very useful and I could practice them. Among others, during the academic writing meetings, I could pay attention to the structure of paragraphs, whether they contained a key sentence on which the writer elaborated, but also whether the person wrote in paragraphs of similar length and not too short (i.e. only three sentences). In addition, I practiced the use of these style competencies in my own written work and reviewing my own texts. Not only Irina’s course taught me skills in writing. During the whole Master’s program, we had to write academic texts and I implemented and practiced the feedback during my internship in my written work. This also included searching for relevant research articles and understanding what was written.

Besides academic writing, EMCL+ taught us how to understand and analyze statistical data using R. Since the analyses we used for the VLSM procedure differ from what we learned, I could not practice these skills as much as I had wanted to. I mainly learned a new kind of analysis, which was also very educating of course. Yulia Akinina taught us these new analyses and she also told us about data fraud and the whole publication process. This added to my already existing knowledge.

During a previous internship, I had already learned how to preprocess MRI images and reconstruct lesions, although I was still at a very beginner’s level. This internship provided me with a lot of practice which allowed me to develop my skills further. I noticed that I can reconstruct lesions much faster and that I can also distinguish better between healthy and damaged brain tissue. In addition, I learned a lot about recognizing different brain areas and structures, and also non-stroke induced lesions in MRI scans, such as white matter disease and Virchow-Robin Spaces. VLSM is not only preprocessing MRI images and reconstructing lesions, but also normalizing the images to a standard template, conducting analyses, and

11 writing down a method and result section for this method. I never wrote a method and result section for a study in which we used MRI but Yulia Akinina provided us with good guidance regarding these sections. Thus, I learned how to preprocess MRI data, how to overlay lesion masks and obtain descriptive statistics from this data, how to write down a method and result section for such study designs, and what (not) to include in these sections. I still have to learn more since we have not learned the subtraction and VLSM analysis yet. We will learn these skills in the coming weeks.

Conclusion

I really enjoyed my time in Moscow and at the Center for Language and Brain. Our colleagues were very nice and always willing to help us out and to teach us new skills. I enjoyed the environment in which people have knowledge in different research areas. I am very thankful to the Center to have offered me an opportunity to learn particular skills concerning MRI data. This is not possible in every internship environment. I want to take this opportunity to thank prof. dr. Olga Dragoy for offering and arranging this internship position, for the opportunity to join in the Great Luria Project, and for her insights and suggestions during the project. I also would like to thank Yulia Akinina for all the skills she taught us and for the time she took to inspect our work and give us feedback. I would like to thank Roelien Bastiaanse for her feedback on my written work. Last but not least, I would like to thank all the colleagues of the Center for Language and Brain for their kindness, help, and good conversations. They really contributed to my good time during the internship.

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References

Akhutina, T. (2016) Luria’s classification of aphasias and its theoretical basis, Aphasiology

30(8), 878-897, DOI: 10.1080/02687038.2015.1070950

Bastiaanse, Y.R.M. (2011). Afasie. Houten: Bohn Stafleu van Loghum.

Bates E., Wilson S.M., Saygin A.P., Dick F., Sereno M.I., Knight R.T., & Dronkers N.F.. (2003). Voxel-based lesion-symptom mapping. Nature Neuroscience, 6(5), 448-50. Glozman, J.M. (2007). A.R. Luria and the history of Russian neuropsychology. Journal of the

History of the Neurosciences, 16(1-2), 168-80.

Luria, A.R. (1965). Aspects of aphasia. Journal of the Neurological Sciences, 2(3), 278-287. doi:10.1016/0022-510X(65)90112-7

Luria, A.R. (1970). Traumatic aphasia : Its syndromes, psychology and treatment. Berlin: De Gruyter Mouton.

Luria, A.R. (1971). Memory disturbances in local brain lesions. Neuropsychologia, 9(4), 367-375. doi:10.1016/0028-3932(71)90001-7

Luria, A.R. (1973). The working brain : An introduction to neuropsychology. New York: Basic books.

Luria, A.R. (1980). Higher cortical functions in man (2d ed., rev. and expanded. ed.). New York: Basic Books.

Luria, A.R., Sokolov, E.N., & Klimkowski, M. (1967). Towards a neurodynamic analysis of memory disturbances with lesions of the left temporal lobe. Neuropsychologia, 5(1), 1-11. doi:10.1016/0028-3932(67)90046-2