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Schizophrenia

Schizophrenia. Stacy Zeigler. NIMH. Schizophrenia is a chronic, severe, and disabling brain disorder Affects 1.1% of the U.S. population age 18 and older in a given year.

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Schizophrenia

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  1. Schizophrenia Stacy Zeigler

  2. NIMH • Schizophrenia is a chronic, severe, and disabling brain disorder • Affects 1.1% of the U.S. population age 18 and older in a given year. • People with schizophrenia sometimes hear voices others don’t hear, believe that others are broadcasting their thoughts to the world, or become convinced that others are plotting to harm them.

  3. Symptoms develop in men- late teens or early twenties • women in the twenties and thirties, but in rare cases, can appear in childhood. • Hallucinations, delusions, disordered thinking, movement disorders, flat affect, social withdrawal, and cognitive deficits

  4. Brain Research Reviews (2009) • Superior temporal gyrus volume change in schizophrenia: a review on region of interest volumetric studies

  5. Superior temporal gyrus (STG) • Production, interpretation and self monitoring of language; implicated in AH • Superior temporal gyrus • 1 of 3 gyri in temporal lobe • Brain volume/structure change may be linked to a brain region

  6. Region of Interest (ROI) analysis • STG structural differences • Advantages: • Anatomical validity, definition of landmarks in native space and quantitative measures of voxels • Limitations: • Labor intensive and time consuming

  7. Studies considered • Published up to July 2008 as an article • Compared schizophrenia patients with healthy group • Data on volume of STG and its subregions • Used ROI volumetric method • Individuals with schizophrenia and related diagnoses • Early onset schizophrenia included • Follow-up included

  8. Details • 2771 subjects • 1444 patients • 1327 controls • 46 studies (5=follow up) • 11.8 to 72 years old • Male patients 3 times more than females • Illness duration= 0.44 to 23.3 years

  9. 24% of studies- no significant difference in STG volume and/or subregions between schizophrenic patients and controls • 43% unileratal effects in STG or subregional volume change • Reduced on left side of STG more reported • 37% bilateral reduction effect in STG or subregional volumes • 6 studies- mixed effects (unilateral/bilateral)

  10. Most showed reduced effect in STG or several subregional volumes • 43% of studies- unilateral reduction • More pronounced on left side • Left STG- substrate of auditory and language processing and may be related to common symptoms • The review support STG or its subregions as candidate region related to hallucinations

  11. Raij et al. (2009)-procedure • 11 subjects with AVH and able to rate subjective reality • Practiced task then entered fMRI scanner • Cylinder shaped response keys in both hands • Each beginning and each end • If no AVH in 18 sec rate the reality or loudness of latest AVH by moving cursor via response key

  12. Analysis of coupling • Tested coupling of IFG with other brain regions during AVH vs. non-AVH periods • One sample t test used to test the resulting contrast images for hallucination-related changes in the connectivity of IFG with other brain parts • Correlated contrast images with SRH across subjects

  13. Strength of AVH-related activation in the IFG correlated with the SRH • Correlation of SRH with coupling between left IFG and left auditory cortex strongest in Heschl’s gyrus • Bilateral IFG signals correlated strongly with SRH

  14. Brain (2008) 131: 3169-77 • Auditory Verbal Hallucinations Predominantly Activate the Right Inferior Frontal Area

  15. Method • 24 Subjects • Frequent AVH and frequent moments without AVH • Right handed • Antipsychotic meds during study • 17 males • 7 females • 18= schizophrenia • 3= schizo-affective disorder • 3= psychosis not otherwise specified

  16. Method- continued • Comprehensive Assessment of Symptoms and History (CASH) • Diagnosis • Edinburgh Handedness Inventory • The Positive and Negative Syndromes Scale (PANSS) • Symptom assessment • Psychotic Symptom Rating Scales- Auditory Hallucinations Rating Scale (PSYRATS-AHRS)

  17. Procedure • fMRI scans made continuously (8 min) • Patients squeeze balloon during AVH • Release when AVH subsided • Language activation measured (8 min) • Paced letter fluency task • Letter displayed on screen in front of them and patients silently generate word • Letters presented in 8 activation blocks • Each block= 30 sec • Each activation block- 10 different letters • 1 letter every 3 sec

  18. Procedure- continued • 2 more letter fluency trials • Patients generate words aloud • Used to measure behavioural performance while they were in the scanner • Activation maps via Philips Achieva 3 Tesla Clinical MRI scanner

  19. Procedure- continued • 3D PRESTO SENSE sequence • Fast scan sequence • Full brain coverage in .609 sec • Combines 3D PRESTO pulse sequence with parallel imaging (SENSE) in 2 directions using a commercial 8 channel SENSE • SENSE= parallel imaging technique using multiple receiver head coils • 800 3D PRESTO SENSE images aquired

  20. Data Analysis • Preprocessing • Reorientation and within-subject image realignment due to head motion • Comparing hallucinating and non-hallucinating periods • Squeezed balloon upon onset of hallucination • Stopped squeezing balloon when hallucinations stopped

  21. Data Analysis- continued • Letter fluency paradigm • Activation model created • Contrast activity when letter presented and rest periods • Following first level analyses, second level random- effects analyses conducted for both hallucination and letter fluency paradigm • Random effects group-wise conjunction analysis conducted • Identifies a ‘common processing component’ by finding area activated in independent subtractions

  22. Data Analysis- continued • Lateralization indices calculated using individual t-tests • Lateralization indices= difference in ‘thresholded’ signal intensity changes in L vs. R hemispheres divided by sum of ‘thresholded’ signal intensity changes • Mask created using AAL (anatomical automatic labeling) atlas • Differences in indices compared via paired sample t-test

  23. Data Analysis- continued • Pearson’s correlations used to assess associations between: • Subjective loudness of AVH and activation of Heschl’s gyrus • Number of voices and activation of superior temporal gyrus • Lateralization index of AVH and degree to which emotional content of AVH was scored as negative

  24. Results • Subjects chronically psychotic • PANSS score average= 73 • Average AVH several times/hour; lasting a few minutes • Hear voices inside and outside head (most) • Loudness- normal speaking • Most patients (18)- voices derogatory • 6 patients- voices more neutral

  25. PSYRATS-AHRS interview

  26. During the scan- balloon task • 18 hallucinations in 8 min • Duration- 20 sec • Total duration of hallucinations- 362 sec

  27. Letter Fluency Task • 96% correct performance • 8 of the 24 patients- AVH during language and during resting blocks

  28. fMRI • Group analysis- multiple brain regions activated • Most extended activation in right inferior frontal area • Right insula and Broca’s homologue • Highly significant activation • Left motor cortex and right cerebellum • Significant activation during AVH • Left insula, bilateral supramarginal gyri, right superior temporal gyrus • Not significantly activated during AVH • Broca’s area and left superior temporal gyrus

  29. Language Task • Extensive activation of Broca’s area and contralateral homologue (lesser degree) • both extending into insula, bilateral temporal area (superior and middle gyri), left more than right, anterior cingulate gyri • Masks (created with AAL atlas) overlaid on group results

  30. Group conjunction analysis • Several areas activated • Right inferior frontal gyrus (including Broca’a homologue) • Right dorsolateral prefrontal cortex (DLPFC) • Left insula and right anterior insula

  31. Lateralization • Mean lateralization index • -0.11 for hallucination paradigm • 0.14 for word generation task • Lower lateralization during AVH compared to word generation • Individual lateralization indices of hallucinatory activation not correlated to lateralization indices of word generation

  32. Lateralization- continued • No association with: • AVH loudness and Heschl’s gyrus activation • Number of voices and superior temporal gyrus • No difference in activation during AVH between individual with voices inside or outside head • More negative emotional content of voices associated with stronger lateralization of hallucinatory activation to right hemisphere

  33. AVH • AVH most extensive activation in right inferior frontal area (right insula and right homologue of Broca’s area) • Significant activation during AVH in superior temporal and supramarginal gyri (mostly right hemisphere), and left insula • Broca’s area or left superior temporal gyrus- no significant activation during AVH

  34. Word production task • Activitation of left inferior frontal area (Broca’s area and left dorsolateral prefrontal cortex) • Left insula, left superior and middle temporal gyri, anterior cingulate gyrus • Right side homologues activated, but to smaller degree • Activation during inner speech more extended compared to hallucinatory activity • Primarily results from difference in the applied paradigm

  35. Corrections • Number and duration of AVH differed • Variable and less extended activation • Conjuction analysis applied

  36. AVH vs. language production • AVH activate right homologues of language areas • Especially the insula and Broca’s area homologue • Normal language production activates frontal and temporal language areas in left hemisphere • Large inter-individual variability in lateralization of activity during AVH • Activation correlated with AVH negative emotional valence

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