William R Bauer M.D. , Ph.D. F.A.A.N.William R Bauer M.D. , Ph.D. F.A.A.N.

MEDICAL MOTION TECHNOLOGYMEDICAL MOTION TECHNOLOGY

NORTHERN OHIO NEUROSCIENCENORTHERN OHIO NEUROSCIENCE

ADVANCED NEUROLOGIC ASSOCIATESADVANCED NEUROLOGIC ASSOCIATES

NEUROSCIENCE UNIVERSITY OF TOLEDONEUROSCIENCE UNIVERSITY OF TOLEDO

Higher Cortical Dysfunction

Higher Cortical Function• Association cortices process raw sensory

signals into complex concepts that can be remembered and used to create new ideas that can be formulated into action.

• One example regarding auditory languageSound (sensory)WordSentence Combined with higher level processes such as

semantic representations

What is cognition?

• Ability to:

• Attend to external stimuli and internal motivation

• Identify the significance of the stimuli

• Make meaningful responses

• Association cortices are responsible for this complex processing

Knowledge: The convergence of language, perception, and memory

Language & naming

Visual systems & category-specific processing

Imagery/sensory memory

Overview

The clinical aspects of higher cortical function will now be reviewed based on anatomy and functional concepts provided to you by pervious lectures.

A. It will be shown that “pure” lesions of a single cortical functional region are uncommon & most often involve adjacent cortical regions.

B. Information will be given to help localize disease longitudinally & horizontally i.e. cortex, white matter, brainstem, peripheral nerve etc.

C. The most common causes of cortical dysfunction will be reviewed including:a. Infectious disease: viral, bacterial, fungal

b. Vascular disease: thrombosis, embolism, hemorrhage, A – V malformation, vasculitis, inflammation

c. Neoplasm: benign, malignant & metastic

d. Neurodegenerative: Alzheimer’s, non Alzheimer’s Huntington’s, toxic

e. Congenital: dysgenesis, cortical anomalies agyria etc.

f. Toxic/metabolic: poison’s, thyroid, diabetes

g. Trauma: open, closed head injury, missiles

I. Effects of Frontal Lobe DiseasesA. Effects of unilateral frontal disease, either left or right:

1. Contralateral spastic hemiplegia

2. Slight elevation of mood, increased talkativeness, tendency to joke, lack of tact, difficulty in adaptation, loss of initiative

3. If entire prefrontal, no hemiplegia; grasp & suck reflexes may be released

4. Anosmia with involvement of orbital parts

B. Effects of right frontal disease:1. Left hemiplegia

2. Changes as in A:2-4

C. Effects of left frontal disease:1. Right hemiplegia

2. Motor speech disorder with agraphia, with or without apraxia of the lips and toungue

3. Loss of verbal associative fluency

4. Sympathetic apraxia of the left hand

5. Changes as in A:2-4

D. Effects of bifrontal disease:1. Bilateral herniplegia

2. Spastic bulbar (pseudobulbar) palsy

3. If prefrontal, abulia or akinetic mutism, lack of ability to sustain attention & solve complex problems, rigidity of thinking, bland affect & labile mood, & varying combinations of grasp & sucking, decomposition of gait, & sphincteric incontinence.

Frontal lobe injuries• Hypothalamus and limbic systems remain intact

– Mediate biological drives (thirst, hunger) and emotions (fear, anger)

• Hypothalamus and limbic system (including the cingulate gyrus and amygdala) send large number of projections to the frontal lobes

• Frontal lobe networks fuse biological drives and impulses with the knowledge of how to satisfy them.

• Fusion = leads to development of goal-oriented behavior.

• Frontal lobes project to motor systems enabling motivational states to initiate overt behavior.

• Intact frontal lobes – resist immediate biological drives to satisfy long-term

goals

• Injured frontal lobes– Regulation of drives is lost

• A farmer suffered a frontal lobe injury in a car accident. When he became hungry, he wanted food immediately. If he did not get food, he became abusive toward his wife. Also, the farmer knew that if he wanted food in the winter, he had to plant in the summer. Instead he sat on the sofa and watched television.

LACK OF TOO MUCH OFApathetic indifference vs. explosive emotional liabilityAkinesia (lack of voluntary movement) vs. HyperactivityEnvironment-bound vs. DistractibilityPerseveration vs. ImpersistenceMutism vs. ConfabulationDepression vs. ManiaHyposexuality vs. Hypersexuality

Frontal Lobe Syndromes:

dorsolateral medial

orbitofrontal

Frontal Lobe Function: 3 Regions

dorsolateral

Impairment of Dorsolateral Frontal

• Reduced working memory

• Increased dependence upon environmental stimuli

– “stimulus-bound” behavior: utilization behavior

• Difficulty shifting sets

orbitofrontal

Orbitofrontal function

• Reward value of stimuli; Emotional value of information

• Regulate (inhibit or facilitate) actions triggered by drives and appetites

• Regulate social behavior

Medial:initiation of action

Impairment of Medial Frontal Lobe

• Impaired initiation of movement = akinesia

• Impaired initiation of other activities

– Abulia (lack of motivated behavior)

– Apraxia of speech (left hemisphere)

Consequences of Dorsolateral frontal damage

• Utilization behavior• Perseveration • Reduced word fluency (loss of systematic

search for words) • Impaired ability to use environmental

information to guide behavior• Poor planning• Poor work performance

Consequences of Orbitofrontal damage

• Reduced capacity to use internal stimuli to guide behavior– Reduced decision-making ability– Poor social skills

• Witzelsucht (inappropriate jocularity)

• Inappropriate sexual advances

• Poor impulse control

– Poor sense of self

II. Effects of Temporal Lobe Disease

A. Effects of unilateral disease of the dominant temporal lobe:1. Homonymous upper quadrantanopia2. Wemicke’s aphasia3. Amusia (some types)4. Impairment in tests of verbal material presented through the auditory sense5. Dysnomia or amnesic aphasia

B. Effects of unilateral disease of the non-dominant temporal lobe:1. Homonymous upper quadrantanopia2. Inability to judge spatial relationships3. Impairment in tests of visually presented nonverbal material4. Agnosia for sounds & some qualities of music

C. Effects of disease of either hemisphere:1. Auditory delusions of hallucinations2. Psychotic behavior (aggressivity)

D. Effects of bilateral disease:1. Korsakoff amnestic defect- (hippocampal formation)2. Kluver-Bucy syndrome

a. Apathy and plasticityb. Increased sexual activity

3. “Sham rage”

Lesions of temporal association cortices

• Agnosia– Greek for “not knowing’– Different from neglect – Patient’s are able to acknowledge the presence of the stimuli, but cannot

identify it

• Anosognosia– Denial of illness– The term first coined by Babinski in 1914

• Prosopagnosia– Prosop = Greek for faces– Inability to recognize faces– Ability to identify other objects and subtle shape differences might be

unaffected. Also persons might still be recognized by voice, body shape and gait.

AnosognosiaDenial of illness:

• “Why are you here?”

AnosognosiaDenial of illness:

• Focal lesion explanation – anosognosia results from damage to the right

parietal lobe.

• Anosognosia is more common after right rather than left hemisphere stroke

– right 28% - 85%– left 0% -17%

M. Jehkonen, M. Laihosalo, J. Kettunen (2006)

Acta Neurologica Scandinavica 114 (5), 293–306.

AnosognosiaDenial of illness:

• 58% of right hemisphere strokes denied their hemiplegia early after stroke, and refused to admit to any weakness in their left arm. Cutting (1978)

• Mild– Acknowledge disability, but indifferent

• Moderate– Acknowledge disability, but underestimate the severity or minimize

the effects– paralyzed left arm and leg just a little weak

• Severe– Disavow existence of major disabilities – claim to perform activities clearly beyond abilities

Prosopagnosia

• Prosop = face; a = without; gnosis = knowledge

• Despite a total inability to recognize faces overtly, prosopagnosics can

– discriminate facial identity (Bauer, 1984)– facial familiarity (Tranel and Damasio, 1985)

• Prosopagnosics show normal interference in – name classification tasks (“Is Brad Pitt a politician or an actor?”)– when a face from a different semantic category is presented

(DeHaan et al 1987)– These data suggest they can extract information from faces that is

not in their verbal report

Prosopagnosia

• Lesions– Can be bilateral or unilateral– Well documented cases in unilateral right

hemisphere (DeRenzi, 1986, Benton 1990, Michel 1989, Landis 1986)

– Occipitotemporal projection system– Functional interface between visual association

cortex and temporal lobe

Language function: Using neuroimaging to test hypotheses

CJ Price, J Anat 2002

III. Effects of Parietal Lobe Disease

A. Effects of unilateral disease of the parietal lobe, right or left:1. Cortical sensory syndrome & sensory extinction, or total hemianesthesia with large acute, white matter lesions

2. Mild hemiparesis, unilateral muscular atrophy in children

3. Homonymous hemianopsia (incongruent) or visual inattention, and sometimes anosognosia, neglect of ½ of the body & of extrapersonal space (seen more with right than left parietal lesions)

4. Loss of opticokinetic nystagmus to one side

B. Effects of unilateral disease of the dominant parietal lobe (left hemisphere in right-handed patients); additional phenomena include:

1. Disorders of language (especially alexia)

2. Gerstmann syndrome

3. Tactile agnosia (bimanual astereognosia)

4. Bilateral ideamotor & ideational apraxia

C. Effects of unilateral disease of the nondominant (right) parietal lobe:1. Topographic memory loss

2. Anosognosia & dressing apraxia. These disorders may occur with lesions of either hemisphere, more frequently with nondominant lesions

Lesions of parietal association cortices

• Neglect syndrome:– “Failure to report, respond or orient to novel or

meaningful stimuli presented to the side opposite a brain lesion, when this failure cannot be attributed to either (primary) sensory or motor deficits” (Heilman, 1979)

• Neglect may be:– Spatial – Personal

Lesions of parietal association cortices

• Spatial Neglect

– Neglect the hemispace contralateral to lesion

– Variously termed:• Hemispatial neglect• Visuospatial

agnosia• Hemispatial agnosia• Visuospatial neglect• Unilateral spatial

neglect

Line bisection

Cancellation task

Line bisection

Cancellation task

Line bisection

“Draw the face of a clock, put in all of the numbers and set the hands for 10 after 11”

Right parietal lobe attends to both left and right hemispace

Right hemisphere lesion = left neglect

Left hemisphere lesion = neglect not as severe

Neuroanatomy of spatial neglect• Anatomy of Spatial Neglect based on Voxelwise Statistical

Analysis: A Study of 140 Patients. Hans-Otto et al. :Cerebral Cortex, Vol 14(10), Oct 2004. pp. 1164-1172.

• Unselected 7 year sample of 140 consecutively admitted patients with right hemisphere strokes.

• 78/140 had spatial neglect (62 did not show the disorder)

• Results – Individuals with spatial neglect showed significantly more

damage in ……– right superior temporal cortex– insula, putamen, caudate nucleus

Lesions of parietal association cortices

• Personal Neglect

Fail to dress or groom left side of body.

Run into doorways on left side.

Left paralyzed limb hangs over wheelchair arm.

2) Aprosodia

Experience of emotion is mediated by the limbic system, but the appreciation of others’ emotions and expression of emotion mediated by the right hemisphere.

– Expressive aprosodia

– Receptive aprosodia

Lesions of parietal association cortices

Functional neuroimaging of the language network

One to many, many to oneCJ Price, J Anat 2002

Functional neuroanatomy• Attention• Language• Knowledge• Imagery• Memory

– States ‘of mind’ (and body)– Adaptation/plasticity– Language; visual processing; mental imagery

• How our brains integrate types of information to develop concepts; how previous experience affects processing of new information

Linguistic access to specific types of knowledge

Damasio H, Nature 1996

Recovery of language function after stroke: Mapping plasticity in the human brain

Fernandez B, Stroke 2004

1 year after stroke

1 month after stroke

Plasticity: Many levels of scale in both time & space

IV. Effects of Disease of the Occipital Lobe

A. Effects of unilateral disease, either right or left:1. Contralateral (congruent) homonymous hemianopsia, which may be central (slitting the macula) or

peripheral; also homonymous hemiachromatopsia2. Irritatible lesions-elementary (unformed) hallucinations

B. Effects of left occipital disease:1. Right homonymous hernianopsia2. With deep white matter or splenium of the callosum lesions, alexia & color naming defects are seen3. Object agnosia

C. Effects of right occipital disease:1. Left homonymous hemianopsia2. With more extensive lesions, visual illusions (metamorphopsias) & hallucinations; more frequent with right

than left lesions3. Loss of topographic memory & visual orientation

D. Bilateral occipital disease:1. Cortical blindness (pupils reactive) Anton’s Syndrome2. Loss of perception of color3. Prosopagnosia4. Balint syndrome

Knowledge: The convergence of language, perception, and memory

Language & naming

Visual systems & category-specific processing

Imagery/sensory memory

Localization of function in the nervous system: Functional networks

5 major brain systems subserving

cognition and behaviorLeft perisylvian language networkParieto-frontal network for spatial attentionOccipitotemporal network for object/face recognitionMedial temporal/limbic network for learning & memoryPrefrontal network for attention & comportment

Visual processing: Two pathwaysDorsal (Occipito-parietal): Object & object feature recognition

Disorders:

visual object agnosia

prosopagnosia

achromatopsia

Ventral (Occipito-temporal): Visual recognition of spatial location

Disorders: optic ataxia, ocular apraxia, simultanagnosia (Balint’s); constructional apraxia, akinotopsia

Visual processing streams: Confirmation of hypotheses using neuroimaging

Ungerleider LG, PNAS 1998

Visual processing: Attention influences which stream is used

Ungerleider LG, PNAS 1998

Visual object recognition: Distinct but overlapping functional areas

Haxby JV, Science 2001

Visual object recognition: Faces & places

Kanwisher N, Science, 2006

Visual perception & imagery

Ganis G, Cog Brain Res 2004

Naming vs. recognition: Networks for conceptual knowledge

Damasio H, Cognition 2004

Object-specific naming deficits Object-specific recognition deficits

Lesion studies of the language network:Disconnection syndromes

Alexia without agraphia

Geschwind N & Kaplan E, Neurology, 1962

V. Non Dominant Hemisphere

• Spatial relationships

• Constructional apraxia

• Topographic agnosia

• Prosopagnosia

• Simultanagnosia

• Visual Neglect

Disconnection Syndromes:• Conduction aphasia

• Sympathetic apraxia in Broca’s aphasia

• Pure word deafness

What are we doing with our brains at this moment?

• Feeling your chair

• Squirming (moving)

• Watching

• Listening

• Remembering

• Paying attention

• Sleeping

• Feeling anxious

• Feeling hungry

• What happens when you ask a question?

• Learning

? Are you able to…….• See and eat the food from the left side of your

plate?

• Dress the left side of your body?

• Laugh at a sarcastic joke?

• Understand why people are crying at a funeral?

Are you able to…….• Recall these numbers in 2 minutes?

• 2195488

Are you able to…….• Recognize the face of someone you previously

met? Like this person…

Are you able to…….• Recognize the face of someone you previously

met?

What were those numbers?

Imagine for one minute what it would be like to have difficulty with any of

those life skills.

And that is what it would be like to have an impairment of higher cortical function.

And now imagine what it would be like for family members to live with

you.

And the impact on your studies, future profession, social life.

Knowledge: The convergence of language, perception, and memory

Language & naming

Visual systems & category-specific processing

Imagery/sensory memory

CONCLUSIONS• Cortical Dysfunction/Disease-complex processes

• Understanding based on anatomy, physiology, pathology

• Elucidation with History, Examination, Laboratory Testing

• Further insight with M.R.I., f-M.R.I., s-M.R.I., sp-M.R.I.,

• PET, SPECT, C.T., Angiography, Biopsy, C.S.F., EEG,

• EMG, ENG, Evoked potentials-(A,S,V.), Discography, C.T. myelography, Sleep, Thermography and U.S.

• NONE of above supersedes the Patient-Doctor Bond

I Thank you for your Attention !!

Mesulam MM, Phil Trans R Soc London, 1999