1. Overview of cognitive systems
Bradford C. Dickerson, M.D. Associate Professor of Neurology, Harvard Medical School Department of Neurology Massachusetts General Hospital Martinos Center for Biomedical Imaging

2. Localization of function in the nervous system: Cytoarchitecture
K. Brodmann,
1909

3. Cortical neuroanatomy Convergence of scales of analysis
Investigators are using sophisticated technology to bring together cytoarchitectural and MRI-based topographic mapping:
The Jülich–Düsseldorf atlas
Eickhoff, Amunts, Zilles

4. Cortical neuroanatomy Monkey-human expansion
Comparison of cortical surface area of humans vs. macaques showing areas of greatest expansion in orange-red
Courtesy of David Van Essen

5. Cortical neuroanatomy Postnatal-to-adult expansion
Comparison of cortical surface area of human infants vs. young adults showing areas of greatest expansion in yellow-orange
Hill J et al., PNAS, 2010

6. Cortical neuroanatomy Age-related cortical atrophy
Comparison of cortical thickness in older cognitively normal adults vs. young adults showing areas of greatest age-related cortical thinning in yellow-orange
McGinnis & Dickerson, Brain Topography, 2013

7. Heteromodal association cortex Evolving concepts
Von Bonin & Bailey (1940s/50s)
Geschwind (1965)
Pandya & Kuypers (1969)
Jones & Powell (1970): The most obvious regions of convergence are in the depths of the superior temporal sulcus (probably the homologue of areas 39 and 40 in man), at the frontal pole, and in orbito-frontal cortex of the frontal operculum.
Mesulam (1998): The unique role of these areas is to bind multiple unimodal and other transmodal areas into distributed but integrated multimodal representations. Transmodal areas in the midtemporal cortex, Wernicke’s area, the hippocampal– entorhinal complex and the posterior parietal cortex provide critical gateways for transforming perception into recognition, word-forms into meaning, scenes and events into experiences, and spatial locations into targets for exploration.

8. Heteromodal association cortex
Mesulam, Principles, 1985

9. Cortical hubs: Areas with connectivity to many other areas
Buckner et al., Neuron 2009

10. Localization of function in the nervous system: Functional networks
5 major brain systems subserving
cognition
Left perisylvian language network
Occipitotemporal network for object/face recognition
Medial temporal/limbic network for learning & memory
Parieto-frontal network for spatial attention
Prefrontal network for executive function & comportment
From Mesulam MM, Brain, 1998

11. Localization of function in the nervous system: Functional networks
5 major brain systems subserving
cognition
Left perisylvian language network
Occipitotemporal network for object/face recognition
Medial temporal/limbic network for learning & memory
Parieto-frontal network for spatial attention
Prefrontal network for executive function & comportment
From Mesulam MM, Brain, 1998

12. Lesion studies of the language network: The major nodes
CJ Price, J Anat 2000
Broca’s (production)
Wernicke’s (comprehension)

13. Lesion studies of the language network: Disconnection syndromes
CJ Price, J Anat 2000
Alexia without agraphia
Geschwind N & Kaplan E, Neurology, 1962

14. Functional neuroimaging of the language network
CJ Price, J Anat 2000
CJ Price, J Anat 2002

15. Hickok & Poeppel model of language processing

16. Large-scale Language Network
fMRI task activation A B
Resting state fcMRI C
PPA atrophy

17. Localization of function in the nervous system: Functional networks
5 major brain systems subserving
cognition
Left perisylvian language network
Occipitotemporal network for object/face recognition
Medial temporal/limbic network for learning & memory
Parieto-frontal network for spatial attention
Prefrontal network for executive function & comportment
From Mesulam MM, Brain, 1998

18. Visual processing: Two cortical pathways

19. Visual processing streams: Confirmation of hypotheses using neuroimaging
Ungerleider LG, PNAS 1998

20. Visual object recognition: Lesion studies
It is well known from studies of patients with lesions that visual agnosias may be specific to certain categories of information (e.g., faces – prosopagnosia; tools, etc)

21. Visual object recognition: Faces, places, etc
Kanwisher N, Science, 2006

22. Visual object recognition: Faces
In monkeys, fusiform face area was localized with fMRI; electrodes were placed in FFA
Tsao D et al., Science, 2006

23. Visual object recognition: Faces
Electrophysiologic data indicated that neurons in FFA were selectively (not specifically) activated to faces
Tsao D et al., Science, 2006

24. Visual perception & imagery
Generally similar activations with somewhat weaker activations in early visual cortices
Ganis G, Cog Brain Res 2004

25. Localization of function in the nervous system: Functional networks
5 major brain systems subserving
cognition
Left perisylvian language network
Occipitotemporal network for object/face recognition
Medial temporal/limbic network for learning & memory
Parieto-frontal network for spatial attention
Prefrontal network for executive function & comportment
From Mesulam MM, Brain, 1998

26. Localization of function in the nervous system: Functional networks
5 major brain systems subserving
cognition
Left perisylvian language network
Occipitotemporal network for object/face recognition
Medial temporal/limbic network for learning & memory
Parieto-frontal network for spatial attention
Prefrontal network for executive function & comportment
From Mesulam MM, Brain, 1998

27. Attention
Attention involves a “flexible interplay among intense concentration, inhibition of distractibility, and the ability to shift the center of awareness from one focus to another according to inner needs, past experience, and external reality. The object of attention is not always a sensory event in extrapersonal space but also can include trains of thought or even sequences of skilled movements.”
–Mesulam Ann Neurol 1981

28. Attentional network
Mesulam M, 1981

29. fMRI detects attentional network
Mesulam et al, 1999

30. Attention can modulate activity in other brain regions
Mesulam MM, Phil Trans R Soc London, 1999

31. Visual processing: Attention influences which stream is used
Visual stimuli were identical but subjects were asked to attend to different features
Ungerleider LG, PNAS 1998

32. State vs “channel” functions
Attention modulates the processing of specific sensorimotor, memory-related, or emotional features
In addition to attention, states (of mind/brain and body) also exert a modulatory influence
Sleep/arousal
Needs (e.g., hunger)
Mood
“Channels”
Unimodal sensorimotor systems
States modulate function of “channel” systems

33. The limbic system directs heteromodal cortex toward relevant information
Amygdala and insula, and also fusiform cortex, were more active when hungry individuals viewed food objects
No such state-related effects were seen for tools
LaBar KS, Behavioral Neuroscience 2001

34. Localization of function in the nervous system: Functional networks
5 major brain systems subserving
cognition
Left perisylvian language network
Occipitotemporal network for object/face recognition
Medial temporal/limbic network for learning & memory
Parieto-frontal network for spatial attention
Prefrontal network for executive function & comportment
From Mesulam MM, Brain, 1998

35. Insula, ACC, frontoparietal regions
Nelson et al Brain Str Func 2010

36. Contemporary models of attention
Top-down control
Stimulus-driven control
Corbetta, Patel & Shulman, Neuron, 2008

37. Contemporary models of attention
Corbetta, Patel & Shulman, Neuron, 2008

38. Brain regions activated in response to pain
Apkarian AV, Bushnell MC, Treede RD, Zubieta JK, 2005

39. Empathic pain perception: shared circuits
Green: feeling your pain
Red: watching your spouse feel pain
Shared pain: areas representating the meaning of pain
Your own pain: areas localizing pain
Singer T et al., Science 2004

40. The “Salience” system
Seeley WW et al., J Neurosci 2007

41. Testing attention Verbal Continuous performance task
Raise your finger every time I say the letter “A”
Sequencing/mental alternation
Letters/numbers
Months of year/days of week

42. Testing high-level visual abilities
Trail Making Test
A: Visual scanning, visuopsychomotor speed
B: Visual executive (alternating sequences)
Clock drawing, other drawing
Visual perceptual
Complex scenes
Overlapping figures
Letter cancellation, line bisection
Visual exploration in the office
Visually guided reaching
Oculomotor control

43. Clinical implications & testing
If warranted, consider going beyond MMSE & clock to include focused testing of domains described here
Attention
Visual perceptual skills
Drawing skills
Praxis (imitation & use)
Calculation
Writing, reading
Object recognition/naming

44. Patient J.H. male, age 61, right handed
J.H. is a former high school history teacher who stopped working at age 61 in part due to “problems remembering the lesson material.” In hindsight remembers first being concerned when the bell rang and he couldn’t figure out the time on the classroom clock.
He reports difficulty finding his way in his neighborhood, using machines at the gym. Has trouble losing objects in his house and sometimes not seeing them “when they’re right in front of me.”
He also has difficulty thinking through the steps of a problem and completing tasks.

45. Patient J.H. male, age 61, right handed
Could draw simple shapes  (square, circle), difficulty with intersecting pentagons, overlapping squares 
Line bisection marks were placed to the left of center. 
Omissions were more prominent on the left side of a letter cancellation task (19 left omissions, 13 right omissions). 
He could identify single letters, but was unable to identify any letters  when they overlapped. 
When asked to verbally describe a narrative scene, he produced a good description of the right hand side of the page, but
 failed to attend to the elements on the left side of the page.  
Calculations were impaired (11+8 = 14, 17‐ 4 = 14; 8x7 = 54). 

46. Patient J.H. male, age 61, right handed

47. Imaging Findings: Patient J.H. male, age 61, right handed

48. Imaging Findings: Patient J.H. male, age 61, right handed
Mild global atrophy with enlarged ventricles
Significant caudal parietal cortical thinning (R > L)
Lesser bilateral hippocampal and associated medial temporal cortex atrophy

49. Thank you!

50. Brain anatomy Dorsal (superior) Caudal Rostral (posterior) (anterior)
Ventral (inferior)

51. Brain anatomy

52. Brain anatomy

53. Brain anatomy: white matter
Medial
Lateral

54. How to learn neuroanatomy
Look at scans
Atlases & texts
Paxinos & Mai textbook & atlas, H Damasio cortical atlas, Ono sulcal/gyral atlas
Schmahmann & Pandya white matter text
Online Mai atlas:
Papers on specific systems by major authors
Pandya D et al, Zilles K et al., Petrides M, Van Essen D, Mesulam M (From sensation to cognition, 1998)