Brain imaging and neuropsychology. Glyn Humphreys

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1 Brain imaging and neuropsychology Glyn Humphreys

2 There now exist a wide range of brain imaging techniques structural and functional Was is the impact of these techniques on clinical understanding and practice, and what are some of the issues in using imaging data from patients?

3 What we learn from structural imaging - understanding neuropsychological disorders - predicting outcome What we learn from functional imaging - understanding neuropsychological disorders - understanding recovery of function

4 Structural imaging Different techniques - Subtraction/lesion overlap - Voxel-based morphology/voxel-based lesion-symptom mapping - Diffusion tensor imaging (DTI) & fibre tracking of lesions

5 Lesion-symptom studies Broca (1861) patient Tan Problem of single cases

7 Lesion- symptom mapping in neglect N=7 Does this reflect the localisation of the syndrome? The issue of anatomical constraint N=7

8 It is the difference in lesions, relative to controls, that is critical N=7 N=4 Result indicates that neglect and extinction may be functionally and anatomically independent

9 Lesion overlap procedures very often depend on lesion delineation by skilled clinician Lesion delineation typically does not take account of degenerative changes which may be functionally important Other approaches (e.g., VBM) do not require lesion delineation but operate by testing statistically for correlations between the intensity of each voxel and the behavioural measure

10 Development of semi-automated procedures Crinion et al. (2007)

11 Gillebert, Humphreys & Mantini (2014)

12 The Apples test in BCoS attempts to separate out egocentric and allocentric deficits

13 Egocentric neglect spatial errors on 1 side of page

14 Allocentric neglect asymmetric false alarms based on missing a target on one side of each object

15 Relation between the behavioural deficits: DEPARTMENT OR OFFICE TITLE No behavioural correlation between the 2 forms of neglect EDIT IN TITLE MASTER (VIEW MENU) Poor behavioural correlation

16 Voxel-based morphological analysis (VBM) Looks at the correlation between the image change and the behaviour The assessment operates across a range of patients need variation in the data

17 VBM analysis correlation between image intensity changes and magnitude of behavioural deficit (age, gender, handedness, motor deficit co-varied) [Chechlacz et al., Cog. Neuro. 2010] Distinct neural correlates of the two forms of neglect, along with some regions where damage can generate both deficits

18 In contrast to the regions of distinct cortical damage, the two forms of neglect are associated with common regions of white matter damage Supported by DTI analyses using fractional anisotropy to track specific fibre paths

19 DTI imaging the inferior longitudinal and the inferior fronto-occipital fasciculi

20 Problems fibre tracking when patients have large lesions Problems crossing fibres Solutions? Use of mapping from the spared hemisphere (Catani group)

21 (a) Lateralisation index links to performance (b) Group classification links to performance (c) Gender effects

22 Issues of co-occurring, multiple deficits Attempts to derive common factors e.g., using PCA

23 Corsi Block Tapping Test (Corsi, 1972; Lezak, 1995)

24 Principal Component Analysis PCA analysis - to probe for common (shared) and distinct (dissociated) functional RIGHT components underlying different visuospatial deficits LEFT

25 Component 1 Right TPJ Right IPL (angular/supramarginal) Right MTG extending into MOG Role for spatial encoding component but not isolated to neglect Use of structural imaging for looking at functional recovery

26 3 months 9 months Lesions predictive of different recovery profiles of neglect

27 Not all initial lesions associated with neglect are predictive of chronic neglect Chronic neglect associated with damage to angular gyrus, superior temporal gyrus and basal ganglia Maybe able to use such analyses to help predict which patients should require most rehabilitation resources

28 What about functional brain imaging? Most would argue that functional brain imaging might be most useful if tasks were chosen on the basis of being deficient in the patient For example, carrying out functional brain imaging of reading in a patient with a reading problem However it can also be very useful to study patients on the tasks they CAN do Example 1: Visual extinction Example 2: Visual agnosia

30 Easy task = colour at fixation Hard task = letter at fixation Change in activity, easy to hard Activation in both the lesioned and non-lesioned hemispheres under low load (B & C) Reduced activation, confined to the lesioned hemisphere, under high load (low load > high load, D) Veulleumier et al. (2005)

31 Drop in brain activity in undamaged visual cortex, when the patient is engaged in a difficult task elsewhere in the field Evidence for interactivity in neural processing Parietal cortex supports visual processing in visual cortex Example 2 visual agnosia

32 Use of fmri to probe the neural processes supporting local and global shape perception Here we examine two agnosic patients with selective impairments in responding to local and global aspects of form

33 HJA bilateral ventral occipito-temporal Poor local response SA- bilateral dorsal occipital Poor global response

34 1100 Local interference 900 RT (ms) Respond global 1000 Controls 800 HJA 700 SA SA poor global 1100 D salient 1000 Respond local 900 RT (ms) Global interference T salient Controls 800 HJA 700 SA HJA poor local 400 T salient D salient

35 fmri data: extra-striate regions of interest HJA SA Mean BOLD change (%) Enhanced local response Enhanced global response 0.4 Global Local C (dorsal) C (ventral) HJA (dorsal) SA (ventral)

36 Results indicate that brain regions may be interactive E.g., decreased local processing in the ventral extrastriate cortex increases the response to global shape in the dorsal extrastriate cortex Implications for cognitive neuropsychology we should not assume that brain lesions simply reduce activity rather activation can be changed

37 Conclusions Brain imaging analyses can add new information about interactivity between visual areas supporting intermediate vision Mechanisms of recovery of function

38 Posner-cueing expt., in acute and chronic stages Relative activity in left and right parietal regions in the two stages

39 Changes in parietal activity mirrored in visual cortex

40 AH: 51 year old patient Left posterior cerebral artery stroke Alexia (letter by letter reading) Problems in picture naming, word finding, naming faces Here, we examined whether we could effect a functional recovery by a reading programme, and whether we could measure the neural substrates of any recovery

41 12 months post lesion AH Reading RT (ms) HF LF Word length 15 months post lesion AH Reading RT (ms) HF LF Word length 9

42 Training: letter matching task, with the level of difficulty staggered - normal font - rotated font - changed font

43 4000 HF (15) LF (15) HF (19) LF (19) 3000 RT 2000 (ms) Word length

44 Other functions showed little recovery Picture naming /76 25/ /76 Not generalised recovery but reading specific

45 Words > falsefonts (p<0.05 corrected) AH (2003 & 2004) AH & Controls AH 2003 > Controls AH 2004 > 2003 Left hemisphere Right hemisphere

46 Red: AH > Controls Yellow: 2004>2003 Functional recovery here linked to take over of left hemisphere function in homologous right hemisphere

47 In sum Structural brain imaging can help distinguish different functional disorders It can also be useful for predicting functional recovery Functional brain imaging informs us about interactivity in brain processes Functional brain imaging can be informative about the mechanisms of functional recovery

2 Neurons. 4 The Brain: Cortex

2 Neurons. 4 The Brain: Cortex 1 Neuroscience 2 Neurons output integration axon cell body, membrane potential Frontal planning control auditory episodes soma motor Temporal Parietal action language objects space vision Occipital inputs