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 brad.dickerson@mgh.harvard.edu

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

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

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

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

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

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.

Heteromodal association cortex Mesulam, Principles, 1985

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

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

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

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

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

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

Hickok & Poeppel model of language processing

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

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

Visual processing: Two cortical pathways

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

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)

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

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

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

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

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

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

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

Attentional network Mesulam M, 1981

fMRI detects attentional network Mesulam et al, 1999

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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). 

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

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

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

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

Brain anatomy

Brain anatomy

Brain anatomy: white matter Medial Lateral

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: http://www.thehumanbrain.info 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)