William R Bauer M.D., Ph.D. F.A.A.N. MEDICAL MOTION TECHNOLOGY NORTHERN OHIO NEUROSCIENCE ADVANCED NEUROLOGIC ASSOCIATES NEUROSCIENCE 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 language  Sound (sensory)  Word  Sentence  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 Diseases A.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 OFTOO MUCH OF Apathetic indifference vs.explosive emotional liability Akinesia (lack of voluntary movement) vs.Hyperactivity Environment-boundvs.Distractibility Perseverationvs.Impersistence Mutismvs.Confabulation Depressionvs.Mania Hyposexualityvs.Hypersexuality Frontal Lobe Syndromes:

dorsolateralmedial 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 quadrantanopia 2.Wemicke’s aphasia 3.Amusia (some types) 4.Impairment in tests of verbal material presented through the auditory sense 5.Dysnomia or amnesic aphasia B.Effects of unilateral disease of the non-dominant temporal lobe: 1.Homonymous upper quadrantanopia 2.Inability to judge spatial relationships 3.Impairment in tests of visually presented nonverbal material 4.Agnosia for sounds & some qualities of music C.Effects of disease of either hemisphere: 1.Auditory delusions of hallucinations 2.Psychotic behavior (aggressivity) D.Effects of bilateral disease: 1.Korsakoff amnestic defect- (hippocampal formation) 2.Kluver-Bucy syndrome a.Apathy and plasticity b.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.

Anosognosia Denial of illness: “Why are you here?”

Anosognosia Denial 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.

Anosognosia Denial 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 pp 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 one CJ 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 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 hemiachromatopsia 2.Irritatible lesions-elementary (unformed) hallucinations B.Effects of left occipital disease: 1.Right homonymous hernianopsia 2.With deep white matter or splenium of the callosum lesions, alexia & color naming defects are seen 3.Object agnosia C.Effects of right occipital disease: 1.Left homonymous hemianopsia 2.With more extensive lesions, visual illusions (metamorphopsias) & hallucinations; more frequent with right than left lesions 3.Loss of topographic memory & visual orientation D.Bilateral occipital disease: 1.Cortical blindness (pupils reactive) Anton’s Syndrome 2.Loss of perception of color 3.Prosopagnosia 4.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 behavior  Left perisylvian language network  Parieto-frontal network for spatial attention  Occipitotemporal network for object/face recognition  Medial temporal/limbic network for learning & memory  Prefrontal network for attention & comportment

Visual processing: Two pathways Dorsal (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 deficitsObject-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?

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