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Live Discussion Transcript


Posted 6 August 2010

E-mail discussion
Printable version

Live Discussion: Language and Schizophrenia

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Attendees/Participants

Megan Boudewyn, University of California, Davis
Rochelle Caplan, University of California, Los Angeles
Beatrice Chakraborty, University of Pittsburgh
Carlos Cortes, University of Maryland
Alex Cohen, Harvard Medical School
Michael Compton, Emory University School of Medicine
Michael Covington, University of Georgia
Tali Ditman, Massachusetts General Hospital/Harvard Medical School
James Goss, University of Chicago
Peter Foltz, Pearson Knowledge Technologies
Martin Harrow, University of Illinois College of Medicine
Hakon Heimer, Schizophrenia Research Forum
Michael Kiang, McMaster University
Gina Kuperberg, Massachusetts General Hospital and Tufts University
Maya Libben, Harvard Medical School
Sean Morrison, Louisiana State University
Margaret Niznikiewicz, Harvard Medical School
Mark Rosenstein, University of Colorado Institute for Cognitive Science
Dean Salisbury, McLean Hospital, Harvard Medical School
Raechel Steckley, University of California, Davis
Stuart Steinhauer, University of Pittsburgh
Debra Titone, McGill University
Cynthia Wible, Harvard University
Victoria Wilcox, Schizophrenia Research Forum

Note: Transcript has been edited for clarity and accuracy.


Hakon Heimer
Let's start off by having all the people in the "room" introduce themselves. I'm Hakon Heimer, editor of the Schizophrenia Research Forum. I would like to introduce and thank our chat leader, Debra Titone.

Debra Titone
Hi, everyone. My name is Debra Titone, and I'm an associate professor in the Department of Psychology at McGill University.

Gina Kuperberg
I'm Gina Kuperberg. Just one thing: Before launching into our discussion, I’d just like to thank Deb for initiating this forum and also congratulate her on the recent birth of her new daughter. It’s pretty incredible that you’re here with us, Deb, at this exciting time. Congratulations!

Debra Titone
Gina, you're too kind!

Dean Salisbury
Ditto to Gina's comment. Thanks, Deb.

Raechel Steckley
Hi, I'm Raechel Steckley, third-year graduate student in Tamara Swaab's lab at UC Davis.

Dean Salisbury
Dean Salisbury, McLean Hospital, Harvard Medical School.

Victoria Wilcox
Hi, all. I'm Victoria Wilcox, a writer and editor with SRF.

Michael Kiang
Hi, I'm Michael Kiang, an assistant professor in the Department of Psychiatry and Behavioural Neurosciences at McMaster University. Congratulations, Deb!

Debra Titone
It's my pleasure to do this!

Michael Covington
Hello, I'm Michael Covington, a computational linguist at the University of Georgia.

Tali Ditman
Hi. I'm Tali Ditman, a research fellow at Massachusetts General Hospital/Harvard Medical School. Congrats, Deb!

Stuart Steinhauer
Stuart Steinhauer, Biometrics Research Program, University of Pittsburgh-Psychiatry and VA Pittsburgh.

Rochelle Caplan
I am Rochelle Caplan, Semel Institute, UCLA. Hi, everyone.

Carlos Cortes
Carlos Cortes, MPRC-University of Maryland. Hi!

Cynthia Wible
I am Cindy Wible, and I do functional imaging at Harvard.

Peter Foltz/Mark Rosenstein
Hi, everyone. Peter Foltz and Mark Rosenstein here. We are researchers at Pearson Knowledge Technologies, and also Peter is with the University of Colorado Institute for Cognitive Science.

Martin Harrow
I’m Martin Harrow, professor, University of Illinois College of Medicine.

Debra Titone
Thank you all for joining us! I also thank Hakon for suggesting that we do a Live Discussion on Language, Communication and Schizophrenia, which is the topic of a Special Issue of the Journal of Neurolinguistics due in print this May. I am pleased to see that many of the authors are present here, and others doing important work of relevance to schizophrenia, language, and communication.

Hakon Heimer
In our usual informal spirit, and because I can't find my carefully prepared preliminary comments, I'll just say that it was awfully nice for Debra to do this Special Issue just so we could have a live discussion on the topic. ::laugh

Debra Titone
I would like to start our discussion by suggesting that we break the hour into three 20-minute segments, which reflect the natural groupings of papers in the Special Issue. These consist of: 1) history/background/relevant populations of study relevant to language, communication, and schizophrenia, 2) recent cognitive neuroscience approaches that hold the most promise for illuminating the cognitive and neural bases of language and communication disorder in schizophrenia, and 3) how can the field better work towards translating this knowledge to helping people with schizophrenia improve communication abilities and the quality of their social interactions?

So let’s start our discussion of topics relevant to the first segment on history and relevant populations. A possible point of discussion (but please feel free to raise others): As mentioned in Debbie Levy’s paper, the study of language, communication, and schizophrenia really began as a debate between the notion of thought versus language disorder in schizophrenia. Is there still value in maintaining this theoretical distinction? Have we now come to an understanding of language and schizophrenia that makes this distinction obsolete or untenable?

Rochelle Caplan
Regarding Deb's point, this is very important. I agree the time has come to clarify the notion so that thought disorder will not only be considered a clinical symptom but also embody the linguistic and higher-level linguistic and cognitive deficits associated with thought disorder.

Raechel Steckley
Debra, for those of us who aren't experts on schizophrenia, could you explain briefly the difference between thought and language disorder?

Debra Titone
Raechel, there has historically been this distinction in the schizophrenia field as to whether the disordered language output seen in schizophrenia is something specific to language or general to thought (now known as cognition).

Dean Salisbury
Raechel, well, that's the crux of the argument. Is it the Whorfian hypothesis of language being thought, or is there a distinction between thought and language?

Stuart Steinhauer
Regarding thought versus language: The concept of language seems so basic, yet thought encompasses much more—imagination, daydreaming (thus a link to delusions—and not necessarily, but possibly, hallucinations)—yet expression is essentially tied to language production, and errors in communication often underlie the assumption of cognitive or “thought” pathology. I find that the distinction is worth maintaining.

Dean Salisbury
Stuart, I agree with your point. Intuitions, symbols, many things in thinking are not necessarily verbal, but we all must put them into words and not just to communicate.

Debra Titone
This thought/language distinction drove a lot of research in the early days, but to me, it seems to be moot in the day and age of cognitive neuroscience, when we know that cognitive functions are not encapsulated in any one module.

Gina Kuperberg
Deb, I do think that there is some value in maintaining a theoretical distinction between thought and language when you take language to incorporate things like phonology. But perhaps a less useful distinction is one between thought and semantics.

Debra Titone
Gina, you make an excellent point, that there are some aspects of language processing that are specific to language processing functionally (e.g., phonology, syntax, although even syntax might be related to sequencing ability).

Stuart, you also make an excellent point in that we must continue to distinguish between the content of language/thought and the form of language/thought.

Martin Harrow
In regard to speech versus thought, our evidence is that people with schizophrenia who say strange things also behave strangely in other ways (Harrow et al., 2003).

Gina Kuperberg
So, just to continue this argument, building on Martin's point, the fact that thought disorder co-occurs with disorganization in the real world suggests to me that similar representations and processes may go awry in both domains. Stuart, I absolutely agree that there is still an important distinction to be drawn between form and content of thought.

Peter Foltz/Mark Rosenstein
I like to think of language as the result of a number of cognitive functions. In that sense, though, when we look at language, we are looking at the output of those cognitive functions.

Gina Kuperberg
Peter, we are looking at the output of many cognitive functions but not simply their sum. Language is unique to humans. I think that there has been a tendency in the schizophrenia literature to say that patients have disordered semantics; patients have disordered working memory and executive function; therefore, we can “explain” language dysfunction.

Debra Titone
Gina, yes, language seems to bring together a unique array of cognitive operations (some of which are functionally specific to language). Thus, it is not appropriate to say that one cognitive operation (e.g., executive function) underlies/subsumes all of it.

Peter, I agree. It is noteworthy that people are now beginning to investigate the kinds of specific cognitive operations that co-vary with "language" impairment. Several papers in the Special Issue touch on this.

Michael Covington
Debra and others, it could be argued that speaking is the number one creative planning task that people face every day. Even the most ordinary people very commonly have to say things they've never said before. And one of the most obvious things that goes wrong with language in schizophrenia is the failure of discourse planning and plan execution. To what extent have people demonstrated experimentally that there is similar breakdown in other kinds of task planning?

Debra Titone
Michael, I would argue that some of the work in the memory literature, on relational memory in particular, is somewhat similar in that there it is necessary for people to abstract away novel relations among encountered stimuli to make sense of them. This would have to happen for specifically encountered stimuli and thus exhibits some amount of generativity.

Gina Kuperberg
Michael C., there is a lot of “clinical” evidence that patients show behavioral disorganization, but there are not all that many experimental studies exploring its neurocognitive underpinnings. Tatiana Sitnikova has carried out some work looking at patients' ability to comprehend real-world events (using silent video clips) and has found some commonalities in deficits shown by patients with behavioral and verbal disorganization (Sitnikova et al., 2009).

Dean Salisbury
Gina, I think of language as reflecting a model system for examining a cross-domain neurophysiological deficit in schizophrenia. It's precisely because language is so complex that it is so affected. But the constituent operations that are reflected in language abnormalities are likely to be aberrant in other domains and modalities.

Gina Kuperberg
Yes, Dean, I agree!

Michael Kiang
Michael, many schizophrenia patients appear to have a fairly pervasive deficit in planning sequences of actions necessary for real-world function and thus need varying degrees of functional assistance. These deficits are associated with impairment on more formal neuropsychological tests of planning/sequencing (see, e.g., Semkovska et al., 2004), so it's interesting to consider how related this is to deficits in discourse planning.

Debra Titone
Another possible point of discussion in this segment is that often people who do not study schizophrenia, but who do study language, are dismissive of studies involving schizophrenia because of the many confounding variables (e.g., medication status often being the most salient). Is there a better way to study language (and general cognitive dysfunction) relevant to schizophrenia that minimizes some of these well-founded concerns?

It seems that the many ways of doing this (studying first-episode patients, unaffected relatives, schizotypy, and childhood-onset schizophrenia) each has its pros and cons. What is the theoretically and methodologically most rigorous way to proceed given the very real pros/cons of each approach?

Martin Harrow
Deb, remember when normal people speak they also have complicating factors influencing what they say.

Debra Titone
Martin, absolutely! It seems to me that people with schizophrenia have difficulty exactly with the elements of language that normals under stress have difficulty with. So are they qualitatively or quantitatively different?

Michael Compton
Debra, one way to minimize many of these confounds is to study young, treatment-naive, first-episode psychosis patients.

Debra Titone
Michael, but don't first-episode studies have their limitations (e.g., it’s unclear whether people ultimately are diagnosed with schizophrenia)? I certainly like the corpus approach, which is represented in the Special Issue by Elvevåg and colleagues (Elvevåg et al., 2010).

Michael Compton
Debra, yes, they have their limitations, but it's one way to control for the effects of medications and chronicity.

Dean Salisbury
Michael Compton, it is difficult to get drug-naive first hospitalized patients. I run a pretty large study of first hospitalized subjects, and nearly all need to be acutely treated for ethical reasons. So, you're right, but usually at best you can get acutely medicated subjects. The issue with prodromes is the relatively low conversion rate, and with psychometrically-defined schizotypy, the issue is face validity: Is psychosis a continuum—like being just a little pregnant—or is it categorical? I think what we see is an aberrant mode of a complex system that "well" brains do not enter.

Gina Kuperberg
Deb, I guess the classic symptom-oriented approach goes some way to address confounds—that is, by comparing patients with and without thought disorder, but matched on overall illness severity and medication. The problem is that it's not “only” patients with thought disorder who show language deficits.

Stuart Steinhauer
Gina, that is an astute point; deficits are seen in relatives of schizophrenia patients, in some limited data on “high-risk” children, and less so when schizotypal personality disorder is not associated with a family history of schizophrenia. They show some improvement (at least for the ERP N400) for patients who are medicated versus those who are unmedicated.

Michael Covington
Debra, regarding ways to minimize confounding factors, I think the root of the problem is that linguistics is full of confounding factors. But there are 2 ways to proceed: 1) define specific language-generation tasks, and 2) use methods of corpus linguistics to study large samples of speech.

Hakon Heimer
Hello, James Goss and Sean Morrison. Welcome to the chat. If you don't mind, please introduce yourselves.

James Goss
I am a graduate student who studies gesture and language in schizophrenia.

Sean Morrison
Thanks, Hakon. I'm Sean, a doctoral student at Louisiana State University currently studying schizophrenia spectrum disorders.

Gina Kuperberg
Michael, I really do agree that recent computational approaches based on large corpora are important in characterizing language output in schizophrenia, such as the use of a Latent Semantic Analysis (LSA), which provides a measure of the co-occurrence between words in discourse (Landauer and Dumais, 1997), as described by Brita in the Special Issue (Elvevåg et al., 2010). They are an important extension of attempts to describe and systematically quantify thought disorder in the 1960s and 1970s using a Cloze Analyses and Type:Token ratio. Brita showed in a previous study that LSA measures correlate well with thought disorder (Elvevåg et al., 2007). They are not difficult to use (once you have patients’ transcribed speech), and I think provide valuable measures.

Michael Covington
Gina, exactly right. LSA is one approach to detecting topic change or topic drift. I want to look at a lot of other characteristics of speech that can be measured by computer, such as idea density (important in Alzheimer's) and syntactic complexity.

Peter Foltz/Mark Rosenstein
Gina, thanks. Yes, our approach has been to use large corpora (which unfortunately are hard to get) to try to "discover" some of the important semantic, statistical, and syntactic differences between patients, controls, and well siblings. We think there is a lot of potential in looking at a range of features of changes in language in these populations.

Michael Covington
Debra and others, I hope we can use language analysis to detect milder forms of thought disorder, detect prodromal cases, assess people who seem to be doing well on medication, and detect relapse.

Michael Kiang
Michael C., the work by Elvevåg et al. in the Special Issue (Elvevåg et al., 2010) using LSA approaches is also promising because it suggests excellent sensitivity to differences between some of the groups mentioned—e.g., unaffected relatives of schizophrenia patients, which traditional linguistic analysis methods may not have been able to differentiate.

Michael Covington
Michael Kiang, yes, I'm familiar with Brita's work. It is indeed very promising.

Raechel Steckley
Regarding methods, it seems we could adopt approaches used in other schizophrenia research—that is, to compare different types of schizophrenia patients (for example, medicated versus unmedicated). Correlational analyses may provide information about whether these groups seem to vary significantly on different aspects that we are interested in looking at. Furthermore, examining patients and their first-degree relatives has shown that some aspects are similarly impaired in relatives, and so this may be an approach to adopt as well.

Gina Kuperberg
Right, Michael and Michael, these computational methods have enormous potential for assessing whether language disorders in schizophrenia are quantitatively or qualitatively different from those in schizotypy.

Michael Covington
I'm a computational linguist and would be glad to team up with people who want to implement things.

Peter Foltz/Mark Rosenstein
Michael K., we do think that the LSA approach is more sensitive to more subtle language differences that may not be detected either by word counting methods or by clinicians just reading transcripts. We are able to see differences both in form of the language as well as the semantics.

Michael Kiang
Michael C. and Peter, indeed, it would be interesting to develop some standardized assessments to elicit language production. Perhaps they could be applied to larger populations across sites.

Peter Foltz/Mark Rosenstein
Michael K., I agree. We have tried a number of different ways to elicit language from patients, but so far have no standardized way of obtaining it. One key is collecting enough data to know which language elicitation methods will give the greatest degree of information about what we want to find.

Gina Kuperberg
Michael K., people have used TAT pictures to elicit language production, right?

Michael Kiang
Gina, yes. TAT is a good example.

Dean Salisbury
Michael Kiang, TAT? Thematic apperception task?

Michael Kiang
Dean, Thematic Apperception Test. Subjects are asked to describe a drawing of a scene.

Michael Covington
Gina and Michael K., yes, TAT pictures have been used, but if anything, there was too much variation. In a project with the University of Maastricht, we used simpler, cartoon-like drawings. I've been thinking of using still photos. It turns out that checking the completeness of the description (how many of the things in the picture are mentioned) is a useful measure.

Stuart Steinhauer
Regarding TAT, Michael, I would remind everyone about the Thought Disorder Index developed by Phil Holzman and Debbie Levy, just for this purpose, which also has been of great use with relatives. However, it is extremely labor intensive in analysis, a plague of the difference in studies of language production versus language comprehension (the latter is more often studied in psychophysiological approaches).

Dean Salisbury
Stuart, great minds think alike! The thought disorder index (Deb Levy's group) is a meaningless stimulus (inkblot) where subjects describe what they see. So, it’s useful for examining language output in the lack of a meaningful stimulus.

James Goss
Having subjects narrate cartoons is a good way to elicit discourse and control for the content. This also helps with the issue of affective reactivity in speech.

Peter Foltz/Mark Rosenstein
We have also used simple tasks that most everyone would be familiar with, such as, "Tell me the story of Cinderella" or "Tell me how you do your laundry."

Debra Titone
Another interesting point, which may be related to the next segment: Given the comments made by Gina Kuperberg and Stuart Steinhauer, what is the best way to think about schizophrenia with respect to language and communication? Is it most like adult syndromes involving damage to specific neural circuits, or is it more akin to a developmental language disorder (e.g., dyslexia, as written about previously by Ruth Condray [Condray, 2005])? Does the choice of an analogy change the way we ask questions and approach our understanding of language disorder in schizophrenia?

Gina Kuperberg
Deb, moving on to your next point about whether language disorders in schizophrenia should be conceived as more analogous to developmental communication abnormalities or those that result from brain lesions: Both, I think, but perhaps more the former.

Dean Salisbury
Gina, I would argue that it is probably a genetically determined late neurodevelopmental disorder, but in one sense, that leads to cortical derangement, which is "lesion-like."

Debra Titone
Gina, I tend to agree, and in fact, it seems to me that there may be a great opportunity in tracking language milestones in high-risk groups as a means of early identification (e.g., pushing on the reading/dyslexia connection more).

Michael Kiang
Debra, or applying some of the aforementioned methods of language analysis to speech samples from these high-risk groups.

Stuart Steinhauer
Debra, one of the models that has worked well in understanding both the link among apparently divergent (loose) associations and the physiological findings for decreased semantic association is the notion that semantic networks are poorly accessed among schizophrenia patients. They fail to narrow the network, thus not recognizing associated constructs while at the same time providing linkages to distally related meanings as shown both in speech and ERPs (also in some of Dean’s and others’ experimental findings).

Gina Kuperberg
Deb, Stuart et al., I think that useful links can be seen not only with dyslexia (which is specific to the written modality), but with communication and language disturbances in autism spectrum disorders (especially high-functioning autism, where you really see discourse-level impairments).

Rochelle Caplan
Gina, that is an important point, but the discourse impairments in high functioning children with autism are not like those in children with schizophrenia unless the autistic children also have psychosis, which does occur.

Debra Titone
Gina/Michael Kiang/Stuart, I agree; there are large literatures on developmental conditions like pragmatic language disorder (different from autism), and I often wonder whether such conditions might be related to the kinds of communication disturbances seen in schizophrenia.

Martin Harrow
Gina, the differences between schizophrenia and others are not just developmental, since before an episode most people with schizophrenia spoke normally, and after an episode many will again speak normally.

Dean Salisbury
Martin, precisely, but I argue that even in the patients that seem the least thought-disordered (via language output), constituent deficits in semantic memory processes exist.

Michael Covington
Debra et al., regarding pragmatic disorders: Yes. Arguably, formal thought disorder is a pragmatic disorder, a very severe one.

Michael Kiang
Martin, do you think it is possible that, with some of these methods like LSA, we could pick up subtle disturbances in patients who clinically appear to speak "normally"?

Peter Foltz/Mark Rosenstein
Michael K., it depends on what is defined as appearing to speak "normally." LSA-based approaches can pick up on some features that humans may not detect. Humans are very good at automatically making inferences and filling in gaps when they hear conversation, while LSA may detect that there are those gaps.

Rochelle Caplan
It is important to also note that about 25 percent of children with schizophrenia have in their history autism-like symptoms but not the full-blown syndrome.

Gina Kuperberg
Rochelle, I'd be interested to hear more about the differences. Obviously, high-functioning autism children don't necessarily have thought disorder. But are there not commonalities in “comprehension” impairments as well as some discourse-level language production problems? Have there been direct comparisons? It just strikes me from looking at this literature that there are similarities.

Debra Titone
Rochelle, it is clear that people studying adult schizophrenia in regard to language need to know more about the childhood-onset literature.

Peter Foltz/Mark Rosenstein
A general question to all: Are there any longitudinal studies of language that have looked at language before schizophrenia and then during?

Rochelle Caplan
The Rapoport group (Gochman et al., 2005) looked at IQ but not at language longitudinally.

Debra Titone
Peter Foltz, not that I know of. That would be incredibly illuminating. The only studies I'm aware of have looked retrospectively at reading ability, and reading was looked at specifically because scholastic records are somewhat readily available.

Martin Harrow
We have looked at schizophrenia, thinking longitudinally, and after the first break some still show language pathology, but less, and others show normal language.

Stuart Steinhauer
Regarding developmental studies, longitudinal studies have long suffered several problems, as notably illuminated by Erlenmeyer-Kimling’s studies (e.g., Erlenmeyer-Kimling and Cornblatt, 1987; Erlenmeyer-Kimling et al., 2000) of offspring of schizophrenic parents (primarily mothers). The difficulty is that so few will develop a full-blown disorder, even with inclusion of schizotypal personality disorder.

Hakon Heimer
All, somewhat off-topic, but are any measures of language being, or should they be, entered in the "endophenotype sweepstakes" especially for the purpose of genetic association studies?

Debra Titone
Hakon, ah, the important question! I wonder if semantic priming would qualify, although the studies out there are so variable. I'm encouraged by a recent set of papers by Gina and Michael Kiang showing how the task really matters in regard to priming.

Gina Kuperberg
Dean and Martin, really important points that language problems exist even in patients without thought disorder: I think that few of us would argue that the inspiration for most of the language studies that we carry out in schizophrenia has been the phenomenon of “thought disorder.” But, although thought-disordered language output is seen in only a subset of patients with schizophrenia, in many of our studies, abnormalities have been observed both in patients with and without clinical evidence of thought disorder at the time of testing. The idea that the study of language might give insights into schizophrenia as a whole was originally proposed by Bleuler; he saw “loosening of associations” as a basic cognitive disturbance that could explain multiple features of the disorder (Bleuler, 1911/1950). But it does raise several important questions about the link between these psycholinguistic abnormalities and the clinical phenomenon of thought disorder itself: 1) Is “thought disorder” the clinical manifestation of “extreme” language disturbances—i.e., does it lie on a continuum? 2) Is there an additional abnormality necessary to produce thought disorder (e.g., automatic overactivity within the semantic associative network that appears to be relatively specific for thought disorder)? 3) How does an overreliance on stored semantic associations affect language production? This, after all, is how thought disorder is clinically assessed and quantified. But, to date, almost all of our studies measure language comprehension.

Dean Salisbury
Hakon, Deb Levy is examining TDI scores, as they argue it is expressed very highly in unaffected relatives.

Debra Titone
Dean, you're correct, too. TDI performance holds a lot of promise as well, and the details are in Debbie Levy's Special Issue article (Levy et al., 2010)!

Gina Kuperberg
Deb and Dean, TDI and other rating scales are useful. But I think more promising are computational methods like LSA, which are very objective and relatively easy to quantify.

Hakon Heimer
All, do the practitioners of "big genetics" show any interest?

Michael Kiang
Hakon, for something like the N400, one approach to determining an endophenotype would be to determine what sort of paradigm results in the largest effect size between individuals with schizophrenia and normal individuals. As Deb mentioned, so far the results have been quite variable, likely because the exact stimuli and tasks have been different across studies.

Michael Covington
Gina and others, apart from Elvevåg's article (Elvevåg et al., 2010), is there a more detailed description somewhere of how LSA is being used to study schizophrenia? I'm familiar with it as a technique for judging whether texts are about the same subject. Making the leap from there to assessing schizophrenic language is what I'm not sure I understand all the details of.

Peter Foltz/Mark Rosenstein
Michael C., we have one other paper on using LSA to study schizophrenia (cited in the paper in the Special Issue), and there are a number of other papers on use of LSA for other types of language assessment. We have not done much other work (yet) in the clinical area.

Debra Titone
Hakon, I think that Debbie Levy and her colleagues have some interesting findings.

Gina Kuperberg
Michael K. and Hakon, I think that there's a real danger in using measures like the N400 as endophenotypes without paying close attention to the specific experimental paradigm. N400 modulation can be increased, decreased, or the same in patients, depending on the precise neurocognitive processes you're indexing.

Debra Titone
Another possible point of discussion here: Much of the work out there pertaining to language and schizophrenia relies heavily, if not exclusively, on neural measures of processing—ERP, fMRI, etc. However, as shown in at least two papers of the Special Issue (e.g., Froud et al., 2010; Salisbury, 2010) and others in the literature, often neural measures show impairment where macro-behavior (i.e., actual linguistic or communicative performance) does not. The reverse may often happen as well.

Gina Kuperberg
Deb, that's true and related to my previous (long) point about the relationship between clinical thought disorder and behavioral and neural measures of language.

Debra Titone
This leads to questions about the theoretical and practical utility of identifying distinctions in behavior versus the neural bases of behavior. Thus, given that there are many ways of identifying “impairment” using various cognitive neuroscience approaches, how are we to most fruitfully proceed? And of course, how do we reconcile the often many conflicting findings about language impairment in schizophrenia?

Gina, is there a good work-around for this? My suggestion is that measures of behavior (either collected simultaneously or not) are essential for understanding neural measures, although often behavior is not reported, or diverges from the conclusion drawn by neural measures.

Gina Kuperberg
Deb, there are certainly discrepancies in the literature but not as many as one would think if one takes into account specific paradigms (e.g., the differences in semantic priming abnormalities in schizophrenia depending on whether the paradigm or task biases towards controlled or automatic processing).

Stuart Steinhauer
Debra, regarding neural “markers,” I would argue that the lack of an obvious behavioral correlate when there is a strong physiological marker is exactly the strength of the neurophysiological or perhaps biochemical endophenotype approach—that we can find an aspect of the disorder that is revealing even though not readily apparent. I would also qualify that not all “markers” are necessarily what are restrictively considered endophenotypes, since they could also be related to the presence of the disorder and not merely associated with other family members. This is not a new concept and goes back several decades.

Dean Salisbury
Right on, Stu.

Michael Kiang
Gina and Hakon, I agree completely with Gina that the issues related to paradigm need to be related further. Another challenge with potential use of N400 or language-related tasks as endophenotype would be how to control for different levels of language experience/exposure, as most widely-used "endophenotypes" to date use lower-level stimuli.

Debra Titone
Stuart, that's one possible interpretation, but occasionally neural measures show no difference and behavior does. I don't think it's as cut and dried as neural measures are more sensitive.

Stuart Steinhauer
Deb, on neural measures—no argument on the last—but if the neural measures fail to reflect a clear disturbance, we are at the least looking at the wrong measures. ERPs are good at very quick decision events, and MRI shows blood flow or oxygenation - but when you are making a discrete decision, for instance, about the next decision to make in the Wisconsin Sorting Task, we don't necessarily know when that happens, much less the right measure to be assessing. Similarly, we are constricted by the currently available tools, but certainly they are better than what existed before 1965.

Debra Titone
Stuart, I agree. Behavioral measures have come a long way, too.

Gina Kuperberg
Deb, I think that behavior, ERPs, and fMRI data yield complementary measures and that we need all of these to make full sense of what's going on. We cannot directly translate one measure on to the other and assume they will correlate. This completely ignores their differing time scales.

Dean Salisbury
As behavior (I include as behavior neurophysiology—EEG, fMRI) gets more complex, like RT, comprehension, or language output, it becomes more variable within and between patients. There are myriad factors that influence the final overt output. By fractionating these behaviors into simpler events, there should be a relative decrease in variability. So, as we zero in on more basic physiological operations, we should be able to find tighter links between behavior and brain.

Debra Titone
Another possible comment for discussion, which nicely segues to the third topic of discussion: How do cognitive neuroscience studies of schizophrenia make a difference in patients’ lives? Perhaps stated somewhat differently, how can the field optimally translate knowledge about language and communication impairment to helping people with schizophrenia?

Michael Covington
Deb, by developing practical tests to detect prodromes, relapses, etc.

Debra Titone
Michael Covington, yes, absolutely! It would be nice to see more of this done. It seems that one way this would be possible would be to improve communication abilities and increase the quality of their social interactions with family and friends—that is, make this knowledge available to those devising social skills interventions and the like. I know that a number of people here may focus specifically on social skills training.

Michael Covington
Deb, that is a very good idea; the better we understand the communication deficits, the better someone might be able to devise training to enable patients to work around them.

Debra Titone
Michael Covington, yes, one of the papers in the Special Issue focused exactly on social skills training.

Gina Kuperberg
Deb, I don’t think that it's just cognitive neuroscience measures of language that can be used to make a difference in patients' lives. I do think that the absence of language-specific remediation approaches incorporated into cognitive rehabilitation programs in patients with schizophrenia is a glaring gap in the literature. As we’ve discussed, this is relevant not only for patients who show clinical evidence of thought disorder, but for all of our patients. Impairments in the ability to express thought clearly through language are seen not only in patients clinically characterized as being thought disordered, and many patients show subtle but clear higher-order comprehension abnormalities. There are a number of theoretically motivated approaches that draw upon affective and social neuroscience, but these do not tend to incorporate verbal language.

Rochelle Caplan
In terms of treatment, I agree with Gina; language is not incorporated into the social skills training programs and is really essential.

Peter Foltz/Mark Rosenstein
Deb, another way is to be able to provide more sensitive measures that could detect changes earlier or faster, or potentially to provide better, more focused diagnoses.

Michael Kiang
Deb, efforts to ascertain diagnostic and prognostic indicators would be helpful (e.g., can these measures distinguish individuals with a first episode of psychosis who will go on to develop schizophrenia versus not?) Also helpful are the efforts to correlate particular neurophysiological abnormalities with particular clinical symptoms (e.g., Gina's work on N400 and fMRI abnormalities and disorganized speech; see Kreher et al., 2008; Kuperberg et al., 2007) or real-world functional outcome.

Gina Kuperberg
All, in view of all these direct potential clinical applications, there is so little work being done on language in schizophrenia compared to other cognitive domains. Why is this?

Debra Titone
Peter Foltz and others, yes, I think that if language researchers did more of this (i.e., connecting basic research on language and schizophrenia to patients’ lives), this area would be rightfully elevated as a dominant approach (touching on Gina's point about there not being a whole lot of work on language relatively speaking).

Martin Harrow
It is hard to improve language disorder when we do not really understand some of the multiple factors that lead to it.

Gina Kuperberg
Martin, right, but we do have some handle on this, no?

Debra Titone
To all, how might we make what is known about language and schizophrenia more accessible to clinicians as well? Is there practical value in doing this?

Dean Salisbury
Deb, I absolutely agree that the detection of subtle language changes may help detect incipient acute episodes of psychosis, but I am not sure that there is a direct therapy to be devised from studies of language, if the language disorder truly reflects a pan-domain, ubiquitous brain deficit. If it relates to a general imbalance between glutamate and GABA, which changes the response field properties of neurons, then one must develop some sort of basic medication intervention to treat the whole brain. This disorder may preferentially affect secondary/tertiary cortical areas due to differences in cortical architecture, but still reflect a ubiquitous defect. So, I am not sure that targeting language for treatment is the right thing to do.

Debra Titone
Dean, but yet, targeting communication abilities is exactly what social skills training does (often quite successfully). Surely we have something to contribute?

Victoria Wilcox
Dean, is it necessarily true that even though the language deficits might stem from biochemical imbalance, that treatment can do nothing to improve behavior?

Dean Salisbury
Victoria, yes, I agree with your point, but I am not sure if it will actually help the disease rather than train a coping strategy. Of course, it's important to have a coping strategy or better means of functioning. I was thinking more of the disorder itself.

Gina Kuperberg
Dean, I agree and disagree. Obviously, medication is needed. But targeted communication approaches have had success in other equally ubiquitous and complex developmental disorders like autism. It's not obviously treating the underlying cause or mechanisms, but it targets a real-world deficit that can significantly impair functioning.

Rochelle Caplan
Making language more accessible to clinicians is very important both from a diagnostic perspective and from a treatment perspective. Clinicians have very little understanding for language and come to conclusions regarding clinical symptoms that might actually reflect the linguistic deficits rather than "other" psychotic symptoms.

Gina Kuperberg
Deb, education is needed. And not just of psychiatrists and psychologists who are familiar with schizophrenia, but also all those speech and language pathologists out there who have little idea that schizophrenia is a disorder characterized by language and communication impairments.

Michael Kiang
From a clinician's point of view, it seems evident that even subtle deficits in language production and comprehension affects patients' function in the real world occupationally and socially. Being able to characterize and measure these deficits precisely, and to treat them not only pharmacologically but potentially with skills remediation, would be extremely valuable.

Maya Libben
Deb, returning to the previous comment regarding the lack of longitudinal studies investigating language function/dysfunction, I think clinicians would benefit very much from a clearer understanding of how language in schizophrenia may or may not suffer impairment over time in order to target interventions at different stages of clinical onset.

Rochelle Caplan
Helping clinicians understand how language is used to express symptoms of schizophrenia and providing this information to linguists and psychologists is necessary for a better understanding of the clinical expressions of the disorder.

Debra Titone
Maya and Rochelle, clearly, this is an area in need of further investigation!

Rochelle Caplan
I agree; it should lead to targeted treatments for these patients.

Dean Salisbury
Maya, does the CBT you're developing here focus on positive symptoms, or does it also try to proactively treat issues of communication?

Debra Titone
Maya, this sounds like a very promising line of work to develop.

Rochelle Caplan
The CBT approach would be very helpful for patients with thought disorder and linguistic deficits but would need to be designed taking these deficits into consideration, since this treatment approach uses language as the medium.

Maya Libben
Dean, ultimately any kind of work on positive symptoms has to involve language and communication at some level. Much of the CBT work that we do is focused on effectively communicating experiences of the positive symptoms (e.g., hearing voices) to practitioners in a way that can be clinically relevant.

Gina Kuperberg
In other fields (e.g., rehabilitation of stroke patients), there has been interest in the development of theoretically-informed and neuroscience-guided cognitive remediation programs that will ameliorate verbal deficits and lead to improvements in real-world function. In developing such programs, the most important questions revolve around the level of cognition that should be targeted. Should we be focusing on bottom-up automatic stages of neural processing using elemental stimuli, or top-down mechanisms that integrate multiple sources of information using real-world stimuli? If we take a two-pronged approach and target both automatic and integrative mechanisms, should these be treated independently, or should we be incorporating exercises and stimuli that force maximal interactions between the two? Will the use of abstract tasks and stimuli generalize to improving cognition in real-world settings, or should remediation programs incorporate real-world stimuli such as conversation, text, and depictions of real-world events?

Stuart Steinhauer
The neurophysiological approach has been excellent at dealing with comprehension but poor in dealing with language production and generation. Some value may exist in studies looking at effects of recurrent feedback systems (e.g., Ford et al., 2007) in evaluating how early components of ERPs, including responses to the patient’s own speech, have particular properties that could inform the basis of future efforts to modify speech production.

Debra Titone
It appears that the hour is now drawing to a close. Thank you all for your very interesting contributions to the discussion. And thanks to Hakon for organizing this! I hope that it was as exciting and informative for everyone as it has been for me. Any final words? Where should we go next (in a sentence or less, please)?

Hakon Heimer
Florence?

Debra Titone
Ooh, Florence for sure, but I mean intellectually!

Raechel Steckley
Thank you very much for providing such a unique and interesting opportunity.

Gina Kuperberg
Thank you, again, Deb, for organizing this! My final words: more work on language and schizophrenia, both in terms of mechanisms and implications for treatment, and more lobbying to NIMH to support it. :)

Rochelle Caplan
It is important to develop treatment approaches. This would be of benefit to patients.

Michael Kiang
Thank you, Hakon and Deb, for organizing this very stimulating discussion!

Rochelle Caplan
Thanks to Deb and Hakon for all the work!

Margaret Niznikiewicz
Hello, I am entering late since I thought the symposium was at 1 pm. I guess I will read the notes.

Debra Titone
Hi Margaret; nice to "see" you.

Peter Foltz/Mark Rosenstein
Thanks for the very interesting conversation. Where should we go? We'd like to see more corpora of patient language data to be able to do more studies of language changes and differences as well as to keep on developing more sensitive computational analyses of different aspects of language.

Michael Covington
Corpora would be most welcome.

Debra Titone
Peter Foltz and Michael Covington, of course! I personally hope to see more of this, and more easily accessible analytic methods available for corpus studies.

Dean Salisbury
I have a large corpus of digital clinical interviews. They might be available if we could de-identify them appropriately.

Michael Covington
Dean, transcribed or audio?

Dean Salisbury
Digitized recordings of the speech, interviewer, and patient. My colleague Shirley Portuguese in Israel is working with a MIT group to do analyses of the speech, but I suspect they could be used for other purposes. I am working on transcribing them, thinking of making them into a text actually.

Michael Covington
Dean, that sounds extremely useful. Don't let me forget this :)

Dean Salisbury
Cool.

Margaret Niznikiewicz
That is actually a very interesting idea.

Dean Salisbury
There are also first-episode patients and chronically ill patients.

James Goss
Dean, is there video or only audio?

Dean Salisbury
James, ah, we erased the video per IRB time limit. What a shame!

Michael Kiang
Michael C, Peter, and others, if you are looking for specific language samples elicited from patients, I would be happy to try to help in collecting these.

Peter Foltz/Mark Rosenstein
Michael K., we are always interested in working with others if you have good data, and we can try new methods on the data.

Michael Kiang
Peter, that sounds good. I look forward to getting in touch and discussing with you further what might be useful.

Dean Salisbury
Thanks, all. Thanks, Deb, for graciously inviting me to contribute! Perhaps we should set up a symposium for next year on these issues?

Debra Titone
Dean, absolutely!

Dean Salisbury
If anyone wants to set up a symposium, send me suggestions for places. Perhaps more clinically oriented places would be fruitful, given the last thread of the discussion.

Michael Kiang
Dean et al., definitely, if we can connect the research to treatment, this will make it more relevant to the larger field!

Margaret Niznikiewicz
I think setting up a symposium that would really cut across different methodologies and populations relevant for language in schizophrenia would be very interesting.

Gina Kuperberg
I think that it would be great to set up a symposium. I think that it would be nice to make it cross-disciplinary, including not only schizophrenia researchers but a few people from communication sciences who have experience in applications to other disorders. Bye, everyone, and thanks again!

Debra Titone
Thanks, all; I must go now. Best wishes.

Dean Salisbury
OK all, thanks again, and feel free to contact me if you’d like to follow up.

Hakon Heimer
Bye, all, and thanks.

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