KuperbergLab_logo

@ Martinos Center and Tufts University

Principal Investigator: Gina R. Kuperberg, M.D., Ph.D.

Department of Psychology, Tufts University and Department of Psychiatry, Massachusetts General Hospital

What is...

What is schizophrenia?

Schizophrenia is a severe neuropsychiatric disorder that affects 1% of the world’s adult population. Clinically, schizophrenia is characterized by positive symptoms: thought disorder, verbal hallucination and delusions, as well as by negative symptoms including lack of motivation and an inability to show emotion (blunting of affect). Cognitively, patients with schizophrenia show deficits in executive, emotional, memory and language function. Neuroanatomically, schizophrenia is characterized by widespread structural and functional abnormalities that affect multiple brain regions.

References

  1. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. (4th Rev ed.)(1990). Washington, DC: American Psychiatric Press.

    The diagnostic criteria for schizophrenia and other psychiatric disorders.

  2. Frith, C. D. (1992). The Cognitive Neuropsychology of Schizophrenia. Hove, UK: Lawrence Erlbaum Associates. [Amazon.com]

    An excellent introduction to the cognitive neuropsychology of schizophrenia. A very reader-friendly book.

  3. Kuperberg, G., & Heckers, S. (2000). Schizophrenia and cognitive function. Curr Opin Neurobiol, 10(2), 205-210. pdf

    An overview about schizophrenia and different aspects of higher cognitive function

  4. http://www.schizophrenia.com/szfacts.html

    A great resource for facts about schizophrenia

  5. Cohen, J. D. and D. Servan-Schreiber (1992). "Context, cortex, and dopamine: a connectionist approach to behaviour and biology in schizophrenia." Psychological Review 99(1): 45-77.

    A model that serves as an excellent introduction to conceptualizing how clinical, cognitive, and neurochemical dysfunction in schizophrenia may be linked.

  6. David, A. S. (1999). "Auditory hallucinations: phenomenology, neuropsychology and neuroimaging up-date."  Acta Psychiatrica Scandinavica 99 (Suppl.395): 95-104.

    A review about auditory hallucinations.

  7. Garety, P. A. and D. Freeman (1999). "Cognitive approaches to delusions: a critical review of theories and evidence." Br J Clin Psychol 38(Pt 2): 113-54.

    A review about delusions.

[Top of page]

What is language dysfunction in schizophrenia?

Language dysfunction is central to the main symptoms of schizophrenia: delusions, verbal hallucinations and thought disorder. Language cognitive deficits may be more severe than other cognitive deficits in schizophrenia and have been identified in children at risk for schizophrenia as well as in patients in their first episode of psychosis. Language in the brain is mediated within a temporal-prefrontal network that is known to show structural and functional abnormalities in schizophrenia.

References

  1. Kuperberg, G., & Caplan, D. (2003). Language dysfunction in schizophrenia. In R. B. Schiffer, S. M. Rao & B. S. Fogel (Eds.), Neuropsychiatry (2 ed., pp. 444-466). Philadelphia: Lippincott Williams and Wilkins. pdf

    A review about all aspects of language dysfunction in schizophrenia.

  2. Kuperberg, G. R., P. K. McGuire, et al. (1998). "Reduced sensitivity to linguistic context in schizophrenic thought disorder: Evidence from online monitoring for words in linguistically-anomalous sentences." Journal of Abnormal Psychology 107: 423-434. pdf

    An illustration of a cognitive psycholinguistic approach to studying thought disorder and sentence processing in schizophrenia. 

  3. Spitzer, M., U. Braun, et al. (1993). "Indirect semantic priming in schizophrenic patients." Schizophrenia Research 11: 71-80.

    One of the first papers to examine indirect relationships between single words to examine semantic memory structure and function in schizophrenia.

[Top of page]

What is thought disorder?

Thought disorder, or thought ‘disorganization’, is a symptom of schizophrenia. It is most commonly manifest in language (e.g. speech or writing) that is difficult to make sense of. Some people think that that thought disorder is a specific problem of language. Others think that it is a more general problem in semantics (meaning) that also leads to problems in making sense of non-verbal events around us.

References

  1. Kuperberg, G., & Caplan, D. (2003). Language dysfunction in schizophrenia. In R. B. Schiffer, S. M. Rao & B. S. Fogel (Eds.), Neuropsychiatry (2 ed., pp. 444-466). Philadelphia: Lippincott Williams and Wilkins. pdf

    Includes an overview of the ways thought disorder has been traditionally defined.

  2. Andreasen, N. C. (1979a). Thought, language and communication disorders. II. Diagnostic significance. Archives of General Psychiatry, 36, 1325-1330.
  3. Andreasen, N. C. (1979b). Thought, language and communication disorders: I. Clinical assessment, definition of terms, and evaluation of their reliability. Archives of General Psychiatry, 36, 1315-1321.

    Two classic papers describing the phenomenology of thought disorder.

[Top of page]

What is cognitive neuroscience?

Cognitive neuroscience is the study of how cognitive or thought processes take place in the human brain. Cognitive processes are defined as the specific psychological steps that are required to perform a particular task. An understanding of cognitive neuroscience is essential to develop and test cognitive and neurobiological models of neuropsychiatric disorders such as schizophrenia.

References

[Top of page]

What is multimodal imaging?

Multimodal neuroimaging is the use of more than one technique to give different types of information about the human brain. Functional MRI can tell us about where in the human brain various cognitive processes occur. Event-related potentials (ERPs) and magneto-encephalography (MEG) give us excellent information about the time-course of brain activation during cognition. By combining these different techniques, we can achieve both good spatial and temporal resolution.

References

  1. Kuperberg, G. R. (2003). EEG, ERPs, MEG and multimodal imaging: Applications in Psychiatry. In S. Rauch & D. Doughtery (Eds.), Psychiatric Neuroimaging: A Primer for Clinicians: American Psychiatric Press. pdf

    A basic introduction to different types of imaging techniques and how they can be combined.

  2. Dale, A. M., & Halgren, E. (2001). Spatiotemporal mapping of brain activity by integration of multiple imaging modalities. Curr Opin Neurobiol, 11(2), 202-208.

    An excellent overview of how imaging techniques can be combined.

  3. Dale, A. M., Liu, A. K., Fischl, B. R., Buckner, R. L., Belliveau, J. W., Lewine, J. D., et al. (2000). Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity. Neuron, 26(1), 55-67.
  4. Marinkovic, K. et al. (2003). Spatiotemporal dynamics of modality-specific and supramodal word processing. Neuron 38, 487-97.

    Two examples of how fMRI has been combined with MEG to construct spatiotemporal maps giving insights into the dynamics of word and semantic processing in the brain.

[Top of page]

What is fMRI?

FMRI (functional magnetic resonance imaging) is a technology that allows us to take pictures of brain activity.  Unlike standard MRI scans, which only show the structure or shape of the brain, fMRI actually shows which areas of the brain are maximally activated or functioning while performing a specific task such as moving fingers, reading, remembering or feeling certain emotions. No radiation is involved: fMRI makes use of the fact that more blood flow and more oxygen goes to the parts of the brain that perform the task than the parts of the brain that don’t perform the task.

References

  1. Human Brain Function, J Ashburner, K Friston, W Penny http://www.fil.ion.ucl.ac.uk/spm/HBF2/Contents.html
  2. The Basics of MRI, Joseph P. Hornak, Ph.D. http://www.cis.rit.edu/htbooks/mri

    Two books about MRI and fMRI.

  3. Dale, A.M. & Buckner, R.L. Selective averaging of individual trials using fMRI. Human Brain Mapping 5, 329-340 (1997).
  4. Buckner, R. Event-related fMRI and the hemodynamic response. Human Brain Mapping, 6,, 373-377 (1998).
  5. Dale, A.M. Optimal Experimental Design for Event-Related fMRI. Human Brain Mapping 8, 109-114 (1999).
  6. Burock, M.A., Buckner, R.L., Woldorff, M.G., Rosen, B.R. & Dale, A.M. Randomized event-related experimental designs allow for extremely rapid presentation rates using functional MRI. Neuroreport 9, 3735-3739 (1998).
  7. Friston, K.J., Zarahn, E., Josephs, O., Henson, R.N. & Dale, A.M. Stochastic designs in event-related fMRI. Neuroimage 10, 607-19. (1999).

    The classic papers describing event-related fMRI (FIR analyses).

  8. Dale, A. M., B. Fischl, et al. (1999). “Cortical surface-based analysis. I. Segmentation and surface reconstruction.” Neuroimage 9(2): 179-94.
  9. Fischl, B., M. I. Sereno, et al. (1999). “Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system.” Neuroimage 9(2): 195-207.
  10. Fischl, B., M. I. Sereno, et al. (1999). “High-resolution intersubject averaging and a coordinate system for the cortical surface.” Hum Brain Mapp 8(4): 272.

    The papers by Dale and Fischl describing cortical surface-based analysis

  11. http://www.functionalmri.org/

[Top of page]

What are ERPs: event-related potentials?

Event-related potentials (ERPs) are a measure of the electrical activity generated by the brain during tasks such as reading. When averaged together, the electrical activity to specific stimuli appears as waves whose onset, amplitude and offset can be measured in milliseconds. Thus, event-related potentials give excellent temporal resolution for determining the time course of brain activity to cognitive processes.

References

  1. Rugg MD, Coles MGH (1997): Electrophysiology of Mind, Vol 25. Oxford: Oxford University Press.
  2. http://neurocog.psy.tufts.edu/images/erp.htm

    Excellent introductions to ERPs.

  3. Garnsey SM (1993): Event-related potentials in the study of language: An introduction. Language and cognitive processes 8:337-356.

    An excellent introduction to ERPs: how they are defined and some of the ambiguities and controversies about how to analyze them. Other articles in this special issue of LCP are also excellent.

  4. Picton TW, Bentin S, Berg P, et al (2000): Guidelines for using human event-related potentials to study cognition: recording standards and publication criteria. Psychophysiology 37:127-52.

    A good overview of a variety of different ways of conducing ERP analysis and rigorous publication criteria.

  5. Donchin E, Coles MGH (1988): Is the P300 component a manifestation of context updating? Behavioral and Brain Science 11:355-372.

    The classic review about the most common non-language-related ERP component - the P300.

  6. Kutas M, Hillyard SA (1980): Reading senseless sentences: Brain potential reflect semantic incongruity. Science 207:203-205.
  7. Kutas M, Hillyard SA (1984): Brain potentials during reading reflect word expectancy and semantic association. Nature 307:161-163.

    Two classic papers that first described the N400 ERP component in sentences.

  8. Bentin S, McCarthy G, Wood CC (1985): Event-related potentials, lexical decision and semantic priming. Electroencephalography and Clinical Neurophysiology 60:343-355.
  9. Rugg MD (1985): The effects of semantic priming and word repetition on event-related potentials. Psychophysiology 22:642-647.

    Two classic papers about the N400 in word-pair priming paradigms.

  10. Federmeier KD, Kutas M (1999): A rose by any other name: long-term memory structure and sentence processing. Journal of Memory and Language 41:469-495.
  11. Kutas M, Federmeier KD (2000): Electrophysiology reveals semantic memory use in language comprehension. Trends Cogn Sci 4:463-470.

    A couple of papers about what the N400 tells us about interactions between semantic memory and sentence processing .

  12. Osterhout L, Holcomb PJ (1992): Event-related potentials elicited by syntactic anomaly. Journal of Memory and Language 31:785-806.

    One of the first papers that described the P600 ERP component.

  13. Coulson S, King J, Kutas M (1998): Expect the unexpected: Event-related brain responses to morphosyntactic violations. Language and Cognitive Processes 13:21-58.
  14. Osterhout L, Hagoort P (1999): A superficial resemblence does not necessarily mean you are part of the family: counterarguments to Coulson, King and Kutas (1998) in the P600/SPS-P300 debate. Language and Cognitive Processes 14:1-14.

    The debate about whether the P600 ERP component is just another P300 component.

  15. Kuperberg GR: Neural mechanisms of language comprehension: Challenges to syntax. Brain Research (Special Issue) 2007; 1146:23-49. [pdf]
  16. A review of the semantic P600 and a conceptualization of language processing into distinct but interactive neural streams.

  17. van Berkum JJ, Brown CM, Hagoort P (1999a): Early referential context effects in sentence processing: evidence from event-related brain potentials. Journal of Memory and Language 41:147-182.
  18. van Berkum JJA, Hagoort P, Brown CM (1999b): Semantic Integration in Sentences and Discourse: Evidence from the N400. Journal of Cognitive Neuroscience 11:657-671.

    Two papers using ERPs to examine different aspects of discourse processing. 

  19. Van Berkum JJ (In press): The neuropragmatics of 'simple' utterance comprehension: An ERP review. In: Sauerland U, Yatsushiro K editors. Semantic and Pragmatics: From Experiment to Theory. [pdf]
  20. A great review of language ERPs, specifically in relation to discourse processing.

  21. Nieuwland MS, Van Berkum JJ (2008): The neurocognition of referential ambiguity in language comprehension. Language and Linguistics Compass, Vol. 2, June 2008.
  22. A review of studies by Nieuwland and van Berkum examininng co-reference using ERPS.

  23. Kutas M, Van Petten C, Kluender R (2006): Psycholinguistics electrified II: 1994-2005. In: Traxler M, Gernsbacker MA editors. Handbook of Psycholinguistics, second edition. New York: Elsevier, pp 659-724. [pdf]
  24. A great general review on ERPs engaged during language comprehension.

[Top of page]

What is MEG?

Magnetoencephalography (MEG) is a brain imaging method that measures magnetic fields on the scalp that are generated by brain activity. While it does not allow us to pinpoint the exact location of activity in the brain, it provides very detailed information about the timing of this activity.  This makes it a good complement to fMRI which provides more precise information about location.

References

  1. Hari, R., Levanen, S., & Raij, T. (2000). Timing of human cortical functions during cognition: role of MEG. Trends Cogn Sci, 4(12), 455-462.

    An overview of how MEG can be used to study cognition

  2. Eulitz, C., Eulitz, H., & Elbert, T. (1997). Differential outcomes from magneto- and electroencephalography for the analysis of human cognition. Neurosci Lett, 227(3), 185-188.

    Insights into how MEG and EEG can give different types of information about brain function.

[Top of page]