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Introduction: Traumatic Brain Injury

Chris Rorden– Deficits associated with focal injury– Typical scanning modalities

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Describing cortex location

Brodmann Areas (BAs, 1909)Appearance of cortex under microscopeNot necessarily function

Arbitrary numbers are hard to remember

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Squirrels vs humans

squirrel brain– Surface of human brain

is grooved.– Surface of brain from

many animals is flat.– If we completely flattened

a squirrel brain, it would be the size of a stamp.

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Cortical folding

Cortical folding increases surface area.Ridges are called Gyri (singular = Gyrus)

– Greek gyros = circle, hence a coil of brain cortex

Valleys are called Sulci (singular = Sulcus).– Latin = a groove.

Gyri

Sulci

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Anatomy

Surface of human cortex and cerebellum is very folded– Flattened, each hemisphere 1100cm2

– Cerebellum is also 1100cm2

Crumpled shape hides size of cortex– Compare Folded/Unfolded (from Marty Sereno)

HumanChimpanzeeMonkey

Frontal Cortex (ch12)

Prefrontal cortex– Dorsolateral) (DLPFC):

Executive control, perseveration

– Oribitofrontal (OFC): Inhibition, personality, OCD

– Anterior Cingulate: Abulia, Apathy

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Hemispheres

Right Hemisphere Injury Associated with Neglect

‘Dominant’ Left Hemisphere Associated with Speech and Language

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Language Production

Broca’s Area (1861)Difficulty in speech productionLoss of ability to repeat speechComprehension intactFoot of 3rd frontal convolution

(BA 44)Left hemisphere (1865)

– Except left handers

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Language Comprehension

Wernicke’s Area (1874)Normal production (speech sounds and

fluent nonsense)Sounds okay if you do not know the patient’s

language (e.g. Chinese Wernicke’s aphasic would sound fine to me)

Unaware of deficitImpaired comprehensionLeft hemisphereSuperior temporal gyrus

(BA 42, 22)

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Wernicke’s prediction

Predicted two language centers:– Broca’s Area: speech articulation.– Wernicke’s Area: language comprehension.

Predicted 3rd Syndrome:– Disconnection syndrome– ‘Conduction aphasia’– Damage to

arcuate fasciculus

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Conduction aphasia

Can comprehend speechArticulation is intactDifficulty in repeating speechLesions in Temporal Parietal Junction that knock out

underlying white matterPatients with damage ONLY to the arcuate fasciculus

can still generate speech.– Why? Other pathways

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Wernicke-Lichtheim (1885) Schema

From auditory input (a) to motoric articulation of speech (m)

Broca’s Aphasia Wernicke’s

Aphasia

Concepts(Distributed)

Conduction aphasia

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Memory

Fornix (Squire’s Patient)

Mammillary body

(Korsakoff Patients)

Severe memory deficits seen with damage to Papez circuit.

Hippocampal formation - HM

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HM’s lesion

Corkin et al. (1997) bilaterally symmetrical

– medial temporal pole

– most of the amygdaloid complex

– most or all of the entorhinal cortex

– anterior half of hippocampal formation (dentate gyrus, hippocampus, and subicular complex)

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HM – severe anterograde amnesia

Anterograde amnesia – since lesion– Suggests encoding deficit

Retrograde amnesia – prior to lesion

1945 1950 1955

1/9/

1953

Mem

ory

anterograderetrograde

Limbic system

Memory and emotions tightly coupled.

Fear and reward

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Anatomy of t

Patients who spontaneously confabulate tend to have orbitofrontal damage (aka damage to the ventromedial PFC).

Frontal lobe injury

Personality Executive function, organization, problem

solvingSet switching - Perseveration

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The homonculus

Clear spatial mapping in gray and white matter.

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M1: movement

S1: sensation

Somatosensory Cortex

Woolsey and Wann (1976) examined plasticity of somatosensory cortex in mice.

Normally, cortical barrels topographic map of space.

If whiskers removed, mapping of remaining whiskers grows

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Phantom Limbs

MEG offers evidence of reorganization.– Patient lost one arm– When face is brushed, he experiences his old arm is touched. – Consistent spatial mapping of face to lost limb.– MEG reveals that arm and face encroach hand area

Figure below: arm hand and face regions in normal locations contralateral to intact arm, but arm and face representation have grown together contralateral to lost limb.

– For review Ramachandran and Hirstein (2000), Brain, 121, 1603-1630

ArmHandFace

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Is plasticity reversible?

Sirigu et al. (Nature Neuroscience, 4, 691-692).– CD lost both hands in 1996– Bilateral hand transplantation in 2000– Both M1 and S1 show elbow activity had taken over hand

area before graft.– After graft: hand area enlarges and elbow representation

shrinks.

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Thought experiment

What brain injury leads to visual field injury?

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Mapping Lesions

With MRIcron it is easy to trace injured area.We can create an overlay plot of damaged

region.For example: here are the lesion maps for 36

people with visual field defects:

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The problem with overlay plots

Overlay plots are misleading:– Highlight areas involved with task (good)– Highlight areas commonly damaged (bad)

Brain damage is not random: some brain areas more vulnerable. Overlay plots highlight these areas of common damage.

Solution: collect data from patients with similar injury but without target deficit.

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Value of control data

Solution: collect data from patients with similar injury but without target deficit:

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Statistical plots

We can use statistics to identify areas that reliably predict deficit

E.G. Damage that results in visual field cuts

Acute brain imaging

Structural and perfusion imaging techniques used at admission.– Designed to be fast, does not require conscious

patient.– In contrast, functional measures require

participation and typically have long duration (future lectures).

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CT versus MRI scans

CT– Clinically crucial:

Detect acute hemorrhageCan be conducted when MRI contraindicated

– Limited research potentialExposes individual to radiation

• Difficult to collect control data• Typically very thick slices, hard to normalize

Little contrast between gray and white matter MRIDifferent contrasts

(T1,T2, DWI)No radiation, so we

can collect thin slices if we have time.

Xrays and CT

single contrast mechanism: how well does tissue attenuate rays.

Air ~transparent, bone ~opaque, soft tissue ~translucent

The only way to influence Xray contrast is to change tissue. E.G. injection of radio-opaque Gd into bloodstream

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Analogy: overhead projector ~ Xray

CT: reconstructed from series of Xrays

CT Terms

Computerized Axial Tomography (CAT/CT) measured Xray attenuation.– Hyperintensity: Bright spot– Hypointensity: Dark spot– For CT (but not MRI) you can say

‘density’ instead of ‘intensity’– ‘W’/‘Window Width’ describes contrast

setting for display– ‘C’/’L’/‘Window Center’/’WindowLevel’

describes brightness setting for display

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Image Center/Width

How do we view an image that has higher resolution than our computer screen?

Panning changes the ‘image center’.– We will not see some of the

image.Zooming changes the ‘image

width’.– We may lose details.

Pan

Zoom

33 Intensity Center/Width (Brightness/Contrast)

Adjust brightness ‘window center’– E.G. range -64..124 makes muscles gray,

114..302 shows kidneys– C/W 30/188 vs C/W 208/188

Adjust contrast ‘window width’– E.G. range -64..124 shows muscles,

-400..596 shows full range.– C/W 30/188 vs C/W 98/996

CT intensity is calibrated (kidneys always ~208 Hounsfield units)

– Air -1000– Water 0– White Matter 25– Gray Matter 40– Bone 1000

Pan

Zoom

CT Perfusion

CT can be enhanced with a contrast agent.

For example, Gadolinium (Gd) injected into the blood stream.

Gd is radio-opaque.Can show areas of reduced,

delayed or slowed flow.Acute mismatch of perfusion

and injury shows tissue that can be salvaged.

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Major Cerebral Arteries

Injury not random: common patterns to stroke and TBI.

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CT Signs of TBI

Hematoma: pooled bloodContusion: swelling,

bruising.

EDH: epidural hematomaDAI: diffuse axonal injurySDH: subdural hematoma,SAH/IVH: subarachnoid

and intraventricular hemorrhage.

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Magnetic Resonance Imaging (MRI)

MRI uses strong magnetic field and radio signals to acquire image.

Analogy: Low energy state for compass needle is North, but tap briefly knocks out of alignment.

Likewise, hydrogen atoms align to field. Radio signal knocks them out of alignment, they echo radio signals while they return to alignment.

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Conventional MRI scans

T1 (anatomical): fast to acquire, excellent structural detail (e.g. white and gray matter).

T2 (pathological): slower to acquire, therefore usually lower resolution than T1. Excellent for finding lesions.

T1 T2

T2

T1 CSF

Bone

Air

Air

CSFWM GM

GM WM Fat

edema

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Lesion mapping: T1 vs T2

T1 scans offer good spatial resolution. T2 scans better for identifying extent of injury, but poor

spatial resolution. Solutions:

1. Acquire chronic T1 (>8 weeks)2. Acquire both T1 and T2, use T2 to guide mapping on T1.3. Acquire T2, map on normalized iconic brain (requires expert

lesion mapper).4. Aquire high resolution T2 image, use for both mapping and

normalization (e.g. 1x1x1mm T2 ~9min). Requires latest generation MRI.

Note: Many clinicians like FLAIR as it attenuates CSF. Lesion signal similar to T2. Normalization tricky (thick slices, no standard template).

T1

T2

FLAIR

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Imaging acute stroke

T1/T2 MRI and x-rays can not visualize hyperacute ischemic strokes.– Acute: Subtle low signal on T1, often difficult to

see, and high signal (hyperintense) on spin density and/or T2-weighted and proton density-weighted images starting 8 h after onset. Mass effect maximal at 24 h, sometimes starting 2 h after onset.

– Subacute (1 wk or older): Low signal on T1, high signal on T2-weighted images. Follows vascular distribution. Revascularization and blood-brain barrier breakdown may cause enhancement with contrast agents.

– Old (several weeks to years): Low signal on T1, high signal on T2. Mass effect disappears after 1 mo. Loss of tissue with large infarcts. Parenchymal enhancement fades after several months.

www.strokecenter.org/education/ct-mri_criteria/www.med.harvard.edu/AANLIB/

T2

CT

acute +3days

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Imaging Hyperacute Stroke

T1/T2 scans do not show acute injury. Diffusion and Perfusion weighted scans show

acute injury:– Diffusion images show permanent injury. Perhaps

good predictor of eventual recovery.– Perfusion scans show functional injury. Best correlate

of acute behavior.– Difference between DWI and PWI is tissue that might

survive. Diaschisis: regions connected to damaged areas show acute

hypoperfusion and dysfunction.Hypoperfused regions may have enough collateral blood

supply to survive but not function correctly (misery perfusion).

T2

DW

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Perfusion imaging

Allows us to measure perfusion– Static images can detect stenosis and

aneurysms (MRA)– Dynamic images can measure perfusion (PWI)

Measure latency – acute latency appears to be strong predictor of functional deficits.

Measure volume

– Perfusion imaging uses either Gadolinium or blood as contrast agent.Gd offers strong signal. However, only a few boluses

can be used and requires medical team in case of (very rare) anaphylaxis.

Arterial Spin Labelling can be conducted continuously (CASL). Good CASL requires good hardware.

MRI versus CT

MRI disadvantages:– Expensive– Slow to acquire– Poor bone contrast

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MRI advantages:– No ionizing radiation– Many contrast

modalities– Some acute

modalities

T2 vs SWI for micro-hemorrhage

Susceptibility weighted imaging shows venous blood useful for microbleeds, DAI

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Diffuse Axonal Imaging

SWI and GRE images of individual with DAI

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