A Guided Tour of the Brain: A Guided Tour of the Brain: Understanding the Functional Understanding the Functional NeuroanatomyNeuroanatomy of Dementiaof Dementia

Jason Jason KanzKanz, PhD, ABPP, PhD, ABPPMarshfield ClinicMarshfield Clinic--Eau ClaireEau Claire

OutlineOutline

Overview of Overview of neuroanatomyneuroanatomy What is What is ““functionalfunctional”” neuroanatomyneuroanatomy?? NeuroanatomyNeuroanatomy in dementia?in dementia?

Gross AnatomyGross Anatomy

Frontal Lobe

Temporal Lobe

Parietal Lobe

Occipital Lobe

Cerebellum

Gross AnatomyGross Anatomy--MidlineMidline

Corpus Callosum

Cingulate Gyrus

Frontal Lobe

Cerebellum

Parietal Lobe

Occipital Lobe

Brain Stem

LandmarksLandmarks

Sylvian Fissure

Central Sulcus

LandmarksLandmarksLongitudinal Fissure

Central Sulcus

Structural Imaging MethodsStructural Imaging Methods

CT ScanCT Scan MRI ScanMRI Scan

–– T1 T1 –– T2T2–– FLAIRFLAIR–– DWI/ADCDWI/ADC Not going to talk a lot about these hereNot going to talk a lot about these here

Brain CTBrain CT•Bone-white

•CSF-dark

•Gray matter lighter than white matter

MRI CutsMRI CutsCoronal Sagittal

Axial or Transverse

MRI sequencesMRI sequences

T1 T2 FLAIR

T1 axial cutT1 axial cutFrontal lobe

Occipital lobe

Cerebellum

Caudate Putamen

Insular cortex

Anterior Commissure

T2 axial cutT2 axial cut--a bit lowera bit lower

Brain Stem

hippocampus

Temporal Lobe

Eyeball

SagittalSagittal CutCut--MidlineMidline

Frontal lobe

Corpus callosum

Cerebellum

Occipital Lobe

Coronal FLAIRCoronal FLAIR

hippocampus

Temporal lobe

Lateral ventricle

Functional Functional NeuroanatomyNeuroanatomy

A bit of historyA bit of history–– Paul Paul BrocaBroca/Karl /Karl WernickeWernicke–– PhineasPhineas Gage caseGage case–– Genesis of modern neuropsychologyGenesis of modern neuropsychology Localization of function by employing behavioral Localization of function by employing behavioral

teststests——in other words, looking at a personin other words, looking at a person’’s s cognitive function and dysfunction. cognitive function and dysfunction. One proviso: One proviso: though cognitive capacities are though cognitive capacities are

somewhat localizable, there is also widespread somewhat localizable, there is also widespread activation of numerous brain regions.activation of numerous brain regions.

Some Some generalgeneral basicsbasics

In the brain (cerebrum):In the brain (cerebrum):–– Anterior is associated with action/behaviorAnterior is associated with action/behavior–– Posterior is associated with sensation/ Posterior is associated with sensation/

perceptionperception Like the spinal cord Like the spinal cord

–– Left side of brain controls right side of bodyLeft side of brain controls right side of body–– Right side of brain controls left side of bodyRight side of brain controls left side of body Unlike the spinal cordUnlike the spinal cord

MoreMore general basicsgeneral basics

Left side tends to be associated with Left side tends to be associated with verbal functionsverbal functions

Right side tends to be associated with Right side tends to be associated with nonverbal functions.nonverbal functions.

Behaviors the Brain controlsBehaviors the Brain controls

MovementMovement SensationSensation Learning/memoryLearning/memory Language productionLanguage production ComprehensionComprehension Visual perceptionVisual perception Visual integrationVisual integration Constructional skillsConstructional skills

Executive functionsExecutive functions Emotional regulationEmotional regulation SleepSleep BreathingBreathing OKOK——all behaviors all behaviors

controlled by the controlled by the brainbrain

CerebellumCerebellumInvolved in:

1. Motor programming, coordination, postural regulation

2. Cognitive

1. Executive functions-abstract reasoning, verbal fluency, & planning

2. Memory and Learning

3. Spatial abilities

4. Attention/processing speed

5. Emotional regulation

*See with alcohol intoxication

ThalamusThalamus1. Loss of tactile sensation or

thalamic pain syndrome

2. Memory impairments-anterograde and retrograde

3. Disturbance of time sense

4. Lack of appreciation of deficit

5. Problems with concept formation/executive functioning

6. Emotional flattening/lack of spontaneity or drive

*May see involvement of the thalamus with Wernicke-Korsakoff syndrome

Basal GangliaBasal Ganglia1. Made up of caudate,

putamen, globus pallidus

2. Cognition to action-generally characterized by abnormal movements at rest.

3. Procedural memory

4. Trouble with cognitive flexibility

5. Left sided-can produce language disturbance

6. Can produce dramatic personality changes

*Huntington’s disease, Parkinson’s Disease, Wilson’s Disease

Limbic SystemLimbic System--AmygdalaAmygdala1. Involved in emotional

processing and learning

2. Hypersexuality

3. Diminished aggression

4. Processing of fear expressions-both perceiving and experiencing

*Kluver-Bucy Syndrome

Limbic SystemLimbic System--HippocampusHippocampus1. Highly interconnected brain

structure

2. Very important in memory formation

3. Somewhat modality specific—right: spatial, left: verbal

Occipital LobesOccipital Lobes1. Blindsight-loss of vision, but may be

responsive to visual stimuli

2. Anton’s syndrome-denial of blindness

3. Visual agnosia

4. Prosopagnosia

5. Numerous other visual disorders

6. Possible visual field cuts

Parietal LobesParietal LobesEither side:

1. Constructional defects

2. Short-term memory defects

3. Apraxia-ability to perform purposeful movements

4. Disrupted guidance of movements

Left side:

1. Fluent aphasia

2. Loss of semantic features of language

3. Disruption of reading, writing, math

4. Gestural defects

5. Gerstmann syndrome (R/L disorientation, acalculia, agraphia, impaired finger localization)

Right Side:

1. Constructional defects

2. Dressing apraxia

3. Sensory neglect

4. Lost appreciation of facial expressions

Temporal LobesTemporal LobesLeft Side:

1. Aphasia

1. Posterior-fluent

2. Anterior-Anomia

2. Verbal memory functioning (medial)

3. Odor Perception

Right Side:

1. Amusia

2. Trouble organizing plans

3. Nonverbal memory functioning (medial)

*Though hippocampus involved in processing newly learned info, it seems that temporal cortex is involved in housing old information.

Also:

1. Emotional disorders

2. Visual field cuts

Frontal LobesFrontal Lobes1. Movement, coordination/planning of

movement

2. Language production-nonfluent aphasia

3. Executive functioning-the brain’s supervisor

4. Verbal fluency

5. Online processing of information-working memory-divided attention

6. Emotional dampening/abulia

7. Impulse control, behavioral regulation

8. Odor discrimination

9. Frontal amnesia-not memory problem per se, but inability to spontaneously generate an answer

10.May be florid confabulation

Frontal Lobes, continuedFrontal Lobes, continued

Apathy, carelessness, and poor judgmentApathy, carelessness, and poor judgment Diminished abstract reasoning capacity, Diminished abstract reasoning capacity,

concrete tendenciesconcrete tendencies Perseveration/behavioral rigidityPerseveration/behavioral rigidity Defective selfDefective self--monitoring, selfmonitoring, self--awarenessawareness Problems starting tasks, stopping tasksProblems starting tasks, stopping tasks

White MatterWhite Matter•Connects regions of the brain together

•Can be associated with problems in in attention and diminished processing speed

Typical radiology report Typical radiology report

It seems that every radiology report for It seems that every radiology report for dementia care reads: dementia care reads: ““Age related Age related cerebral atrophy. Small vessel ischemic cerebral atrophy. Small vessel ischemic disease typical for age. Clinical correlation disease typical for age. Clinical correlation recommended.recommended.””

What are we supposed to do with that?What are we supposed to do with that?

Function + structureFunction + structure

Beware the imaging biasBeware the imaging bias--McCabe and McCabe and Castel (Cognition, 2008) demonstrated Castel (Cognition, 2008) demonstrated that having a picture of a brain rendered that having a picture of a brain rendered findings more credible. findings more credible.

Mechanic analogyMechanic analogy We need the structure/function correlationWe need the structure/function correlation We will spend the rest of the time looking We will spend the rest of the time looking

at at neuroanatomyneuroanatomy, cognition, and specific , cognition, and specific dementias.dementias.

AtrophyAtrophy Reflects the loss of brain tissueReflects the loss of brain tissue——cortical, subcortical, or cortical, subcortical, or

deep.deep.–– May lose cortical cell bodies with associated axonal May lose cortical cell bodies with associated axonal

degeneration.degeneration.–– Selective atrophy of the white matter following perivascular Selective atrophy of the white matter following perivascular

small vessel insults.small vessel insults.

(potentially) reversible atrophy (potentially) reversible atrophy –– AlcoholismAlcoholism–– Anorexia/StarvationAnorexia/Starvation–– ChemotherapeuticsChemotherapeutics–– DehydrationDehydration–– MarijuanaMarijuana–– RadiationRadiation–– Steroid useSteroid use

Cerebral (supratentorial) AtrophyCerebral (supratentorial) Atrophy Alzheimer diseaseAlzheimer disease Frontotemporal dementiaFrontotemporal dementia PickPick’’s diseases disease CruetzfeldCruetzfeld--Jakob diseaseJakob disease ParkinsonParkinson’’s diseases disease Multisystem atrophyMultisystem atrophy Progressive Supranuclear PalsyProgressive Supranuclear Palsy CorticalCortical--basal ganglionic degenerationbasal ganglionic degeneration Lewy Body DementiaLewy Body Dementia AIDSAIDS MultiMulti--infract dementia (vascular dementia)infract dementia (vascular dementia) Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis

AlzheimerAlzheimer’’s diseases disease--behaviorallybehaviorally

Progressively worsening Progressively worsening anterogradeanterograde memory, memory, eventually joined by retrograde memory and no eventually joined by retrograde memory and no benefit from remindersbenefit from reminders

LaterLater–– Diminished abstracting capacity/executive dysfunctionDiminished abstracting capacity/executive dysfunction–– AnomiaAnomia–– ApraxiaApraxia–– Constructional deficitsConstructional deficits–– AphasiaAphasia

Relatively preserved motor/sensory functionsRelatively preserved motor/sensory functions

AlzheimerAlzheimer’’ss--brain changesbrain changes

Arnold, et al. (1991). Cerebral Cortex.

•A 1991 study at the University of Iowa examined the accumulation of plaques and tangles in the Alzheimer’s brain, finding a preponderance of accumulation in the ventromedial (entorhinalcortex) and anterior temporal lobes.

•Disease progression tends to progress from entorhinal cortex, to hippocampus, to cortex.

•As mentioned earlier, the hippocampus and medial temporal cortices are essential in laying down new memories.

Hippocampal atrophyHippocampal atrophy

Advanced AlzheimerAdvanced Alzheimer’’ss•Global atrophy

•Hippocampus is gone.

SensorimotorSensorimotor sparingsparing

Frontotemporal DementiaFrontotemporal Dementia Atrophy primarily affecting frontal and/or Atrophy primarily affecting frontal and/or

temporal lobestemporal lobes–– 3 types: 3 types:

frontal variant (40%)frontal variant (40%) semantic dementia (40%)semantic dementia (40%) progressive nonfluent aphasia (20%)progressive nonfluent aphasia (20%)

Differentiation from DAT difficultDifferentiation from DAT difficult–– May show more frontotemporal atrophy in frontal May show more frontotemporal atrophy in frontal

variantvariant–– Semantic dementia may show atrophy of temporal Semantic dementia may show atrophy of temporal

pole and inferolateral gyripole and inferolateral gyri–– Progressive nonfluent aphasia may show perisylvian Progressive nonfluent aphasia may show perisylvian

atrophyatrophy

Cortical atrophy in FTDCortical atrophy in FTD

Frontal variant behaviorallyFrontal variant behaviorally

Generally begins with personality changeGenerally begins with personality change–– DisinhibitionDisinhibition–– Mood changesMood changes–– PerseverationPerseveration–– Coarsening of behaviorCoarsening of behavior–– *ask if they are craving more sweets*ask if they are craving more sweets

Progresses to dementiaProgresses to dementia

Frontal variantFrontal variant--MRIMRI

Semantic DementiaSemantic Dementia--behaviorally behaviorally

Difficulty generating familiar wordsDifficulty generating familiar words Often a loss of semantic knowledgeOften a loss of semantic knowledge However, speech remains fluentHowever, speech remains fluent Trouble recognizing familiar facesTrouble recognizing familiar faces

Semantic DementiaSemantic Dementia--MRIMRI

NonNon--fluent primary progressive fluent primary progressive aphasia aphasia

Hesitant, effortful speechHesitant, effortful speech Trouble producing speechTrouble producing speech Person eventually becomes mutePerson eventually becomes mute May have difficulty swallowingMay have difficulty swallowing May make May make paraphasicparaphasic errors in speecherrors in speech anomiaanomia

PNFA MRIPNFA MRI

Pick diseasePick disease

Characterized by memory loss, confusion, Characterized by memory loss, confusion, speech dysfunction, social coarsening, speech dysfunction, social coarsening, apathy and apathy and abuliaabulia

Imaging shows anterior temporal lobe Imaging shows anterior temporal lobe predominance + inferior frontal lobe predominance + inferior frontal lobe changes.changes.

Pick DiseasePick Disease

Posterior cortical atrophyPosterior cortical atrophy

Characterized byCharacterized by–– Changes in vision (complain they need new Changes in vision (complain they need new

glasses)glasses)–– Difficulty recognizing faces and objectsDifficulty recognizing faces and objects–– Diminished spatial awarenessDiminished spatial awareness–– Trouble perceiving colorTrouble perceiving color–– Problems with writingProblems with writing–– Problems with skilled movementsProblems with skilled movements

PCAPCA--MRIMRI

Vascular DementiasVascular Dementias Multiple areas of white matter infarctionMultiple areas of white matter infarction

–– Hypodense on CTHypodense on CT–– Hyperintense on T2 and FLAIR MRIHyperintense on T2 and FLAIR MRI

Severe deep gray matter lacunar diseaseSevere deep gray matter lacunar disease BinswangerBinswanger’’s diseases disease

–– May exclusively involve white matterMay exclusively involve white matter

CADASILCADASIL–– Severe lacunar diseaseSevere lacunar disease–– Subcortical white matter ischemic changesSubcortical white matter ischemic changes

Vascular DementiaVascular Dementia--behaviorallybehaviorally

Stepwise deteriorationStepwise deterioration Problems with memory, but often retained Problems with memory, but often retained

recognitionrecognition Problems with abstract reasoning/ Problems with abstract reasoning/

executive functioningexecutive functioning Notably slowed processing speed, Notably slowed processing speed,

diminished attentiondiminished attention Affective changesAffective changes--depression, anger, depression, anger,

pseudobulbarpseudobulbar affectaffect

Vascular diseaseVascular disease--MRIMRI

LacunarLacunar InfarctsInfarcts--deep gray matterdeep gray matter

Normal Pressure HydrocephalusNormal Pressure Hydrocephalus

Wet, wacky, and wobbly. Wet, wacky, and wobbly. Enlarged ventriclesEnlarged ventricles——particularly temporal particularly temporal

horns. horns. Only 50% of patients improve clinically Only 50% of patients improve clinically

after shunting.after shunting. Expansion of lateral ventricles leads to Expansion of lateral ventricles leads to

strains on white matter and clinical strains on white matter and clinical symptoms.symptoms.

Normal Pressure HydrocephalusNormal Pressure Hydrocephalus

TransependymalTransependymal FlowFlow

Deep Gray Matter DisordersDeep Gray Matter Disorders HuntingtonHuntington’’s diseases disease WilsonWilson’’s diseases disease ParkinsonParkinson’’s Diseases Disease

HuntingtonHuntington’’s diseases disease Selective atrophy of the caudate nucleiSelective atrophy of the caudate nuclei

–– Frontal horns of lateral ventricles are dilated Frontal horns of lateral ventricles are dilated and rounded. and rounded.

–– Frontal atrophy may be presentFrontal atrophy may be present–– Increased signal intensity in the globus Increased signal intensity in the globus

pallidus and putamen may appearpallidus and putamen may appear

HDHD--BehaviorallyBehaviorally

In HD, there tends to be changes in:In HD, there tends to be changes in:–– CognitionCognition: Memory, including procedural : Memory, including procedural

memory, executive functioning, processing memory, executive functioning, processing speed.speed.

–– BehaviorBehavior: : disinhibitiondisinhibition, depression, apathy, depression, apathy–– MovementMovement: Motor restlessness and chorea: Motor restlessness and chorea

HD imagesHD images

Wilson DiseaseWilson Disease CTCT

–– Atrophy of caudate and brainstemAtrophy of caudate and brainstem–– Hypodense basal ganglia and thalamiHypodense basal ganglia and thalami

MRIMRI–– hyperintensehyperintense signal in deep gray mattersignal in deep gray matter–– T1 may show bright hypothalamiT1 may show bright hypothalami–– T2 may show symmetric increased T2 may show symmetric increased

abnormalities in outer rim of putamen, abnormalities in outer rim of putamen, thalami, and globus pallidusthalami, and globus pallidus

WilsonWilson’’s Diseases Disease--behaviorallybehaviorally

Movement disorderMovement disorder--dystoniadystonia, chorea, , chorea, tremor, or parkinsonismtremor, or parkinsonism

Personality changePersonality change--labilitylability, , disinhibitiondisinhibition, , bizarre behaviorbizarre behavior

Perhaps psychosisPerhaps psychosis May produce dementia over timeMay produce dementia over time

Wilson Disease MRIWilson Disease MRI

Recommended ResourcesRecommended Resources

Neuroradiology: The Requisites, Yousem& Grossman

Neuroanatomy Through Clinical Cases, Blumenfeld

The Mental Status Examination in Neurology, Strub & Black