Cortical function as experienced by a neurosurgeon Kathryn

Cortical function as experienced by a neurosurgeon Kathryn Holloway, MD Prof of Neurosurgery

Techniques of Cortical Mapping I Lesional Studies - Correlation of functional deficit with autopsy or Gyral Anatomy on structural imaging studies II Electrocorticography (1) Awake craniotomy (2) Implantation of cortical grid with extraoperative monitoring III Functional Imaging f. MRI PET IV MEG magnetic source imaging correlated with MRI

Lesional Studies

Speech areas as defined by lesional studies

Dominance • In 95% of population the left hemisphere is dominant • Essentially “all” right handed patients with a normal brain are left dominant • A small portion of left handed individuals are right or mixed dominant for speech • Dominance can be assessed by anesthetizing one hemisphere via an intracarotid amytal injection

Types of aphasia • Wernickes u u Posterior dominant temporal lobe extending around the angular gyrus into the parietal lobe Loss of comprehension Speech tends to be fluid but without content They are relatively unaware of their deficits • Broca’s u u Dominant inferior frontal gyrus Preserved comprehension Word generation ability (speech & written ) lost Patients very aware of deficit and are frustrated

Traditional speech areas Broca‘ s Wernicke s

Speech • Can, in fact, block naming as well as comprehension in the dominant temporal lobe (Wernicke’s area) • However if there is a comprehension deficit, the lesion is in the dominant temporal lobe • Severe speech production problems without any comprehension problems will be reliably localized to the dominant inferior frontal gyrus

Left temporal lobe bleed

Hematoma in Broca’s area

Names of gyri and corresponding Brodman areas

The primary visual cortex is identified on a mid-saggittal cut showing the calcarine fissure

Visual Cortex Visual cortex

Brodman #’s & Gyri names

G. S. - History 25 year old RH WM working in Poland Onset of right visual field obscurations followed by right homonymous hemianopsia One seizure consisting of a light in the right visual field associated with altered sensation in the right hand

G. S. - Exam No weakness Right homonymous hemianopsia

Right inferior quadrantanopsia

Area of destruction in visual cortex by bleed

Area of AVM, area of cortical destruction below this

AVM exposed by retracting brain to see medial surface of hemisphere Area of craniotomy Retracted parietal lobe Falx at midline

AVM exposed by retracting brain to see medial surface of hemisphere Retracted parietal lobe Saggital sinus, falx, midline

Postop angio shows no residual AVM Preresection angio Postresectio n angio

Damage to secondary association areas give less specific deficits

K. S. - History & Exam 39 year old RH WF Onset of seizures at age 2 Unresponsive to medication Developmentally delayed Normal examination

K. S. - Seizure Types Age 2 - episodes of blindness Age 8 – generalized tonic clonic seizures Teens – sees colors or micropsia or macropsia followed by unresponsiveness with a postictal aphasia Other seizures

Tumor in visual association areas

Patient’s representation of visual hallucinations

The motor/sensory strip can readily be identified on MRI imaging by noting the first vertical gyrus posterior to the horizontal frontal gyri

Precentral sulcus is most anterior vertical sulcus

Motor Sensory Cortex

Distribution of motor/sensory function along central sulcus is well known

F. R. - History 37 year old RH WF Gradual onset of headaches, right sided weakness New onset right sided jerking followed by generalized tonic clonic seizures

F. R. - Exam No aphasia Right sided facial weakness sparing forehead Right arm- spastic paresis Right leg – mild spasticity

MRI

Axial view

Saggital view

Exposure anterior ear Top of head posterio r

Cored and Delivered

Resection exposes frontal gyri Motor strip

F. R. - Postoperative Course Resolution of all deficits

In contrast speech and memory function can only be generally localized

Speech areas as defined by lesional studies

Traditional speech areas Broca‘ s Wernicke s

Speech areas in a population of 117 patients

R. B. - History 14 yo RH WM History of partial complex seizures since the age of 15 months EEG - Left mesial temporal lobe epilepsy with early lateral spread Uncontrolled on Primidone, Tegretol, Dilantin, Valproate, or Tranxene

R. B. - Physical Exam Normal

R. B. – Neuropsychological Evaluation Moderate dominant hemisphere damage

Mesial Sclerosis • Left hippocampus is shrunken and scarred • This is a frequent source of seizures that don’t respond to medication • The dominant temporal lobe is also the area of the brain responsible for verbal memory and speech

PROBLEM How much of this temporal lobe should be removed in order to cure his seizures and spare his speech and memory?

Dominance – Speech, memory & handedness • In 95% of population the left hemisphere is dominant • Essentially “all” right handed patients with a normal brain are left dominant • A small portion of left handed individuals are right or mixed dominant for speech • Dominance can be assessed by anesthetizing one hemisphere via an intracarotid amytal injection

R. B. - WADA Test Left hemisphere dominance Right hemisphere sufficient for memory

Seizure surgery 101 • Seizures are generally well treated with medication • Some seizures do not respond to medication and so are called intractable • Seizures arising from the medial temporal lobe are particularly likely to be intractable • The seizure focus can be surgically removed • This type of surgery requires a good understanding of speech and memory in order to preserve them

Extraoperating Mapping (MCV) Craniotomy under general anesthesia Silastric grid with evenly spaced electrodes is placed on the brain surface The “tails” of the grid are brought out through the skin The craniotomy is closed After recovery, the patient is transferred to the Epilepsy Monitoring Unit (EMU)

Grids, each silver disc can be individually stimulated

Epilepsy Monitoring Unit Electrode tails are connected to EEG machine which can record and stimulate Continuous video and EEG monitoring is carried out and recorded on tape During mapping sessions, individual electrodes are stimulated and responses are recorded on photo of brain taken at surgery

The stimulation of a small area of brain by the application of current to an electrode lying on the cortex can cause a positive or negative response

Negative response – a normal function is blocked eg. speech cortex Positive response – a normal function is elicited eg. motor cortex

Speech Mapping When eloquent cortex is stimulated a normal speech function is blocked for only the duration of stimulation Naming – the patient is shown flash cards of objects to name – there is a momentary inability to name Comprehension – the patient is given 2 part commands during stimulation to manipulate objects in front of him/her -Auditory or written commands can be used

Memory Mapping Stimulation during: 1. Speech – picture naming 2. Input – word on card 3. Storage – distractor 4. Retrieval – recall word

Fully mapped dominant temporal lobe

Craniotomy for placement of grids on left temporal lobe

Functional and spike maps anterior posterior

Postop MRI showing extent of resection

R. B. - Outcome • No complications • Seizures cured • Speech and memory preserved

Distorted anatomy or direct involvement of eloquent cortex requires mapping even in motor cortex

Motor/Sensory Mapping When eloquent cortex is stimulated: Motor – a movement is elicited Sensory – patient reports a tingling sensation The area of the body involved is reliably reproducible

The distribution of the areas of the body on the cortex is known as the homnculus

L. S. - History 39 year old RH BM – otherwise healthy Onset of seizures involving twitching of the right face and arm followed by aphasia Has new onset of mildly dysarthric speech

L. S. - Exam Dysarthric speech No anomia or difficulty repeating words or following commands Mild facial droop with no involvement of forehead Mild right sided pronator drift Right sided hyperflexia

LS - MRI scans

LS - cortex blanched in are of tumor

Motor cortex resection map

L. S. - Postoperative Course Dx – Anaplastic astrocytoma Received radiation therapy Mild right sided weakness which resolves within a month Seizure free on medication x 6 years No evidence of recurrence

Limbic and Cognitive Cortex • New areas of research and intervention • Requires fancier tools: f. MRI, PET, MRS • Info subject to change

Depression • Symptoms • Circuits • Treatment

Depression - Symptoms • Classic features - Anhedonia, negative mood, loss of energy, hopelessness, helplessness, attuned to the negative, positive tuned out • Vegetative symptoms -Change in sleep and eating • Cognitive changes u u u Slowed processing time Deficits in attention and concentration Deficits in working memory and executive fxn

Depression - circuitry • Depression consists of a relative overactivity of limbic subcortical circuits and underactivity of lateral frontal and parietal activity

Tradeoff between limbic and cortical circuits in healthy adults

Brodman #’s & Gyri names

Depression – PET scan • Decreased metabolism in u u u Lateral Prefrontal Cortex DLPFC BA 9/46 Anterior Cingulate Cortex ACC Anterior Insula • Increased metabolic activity u u Rostral Anterior Cingulate Cortex BA 24 in depressed patients who will respond to treatment but persists after successful RX Medial Prefrontal Cortex MPFC – subgenual ACC BA 25, not predictve of success but resolves with Rx Most work done by Helen Mayberg et al – full refs avail

mid. ACC – corr w severity – regulates affective attentional process Pregenu – predicts response –regulatory role in integrating emotion and cognition information Subgenu (not shown) – shows change in activity with successful rx

Depression – f. MRI cognitive • Measure activation of cortex with a task rather than a resting metabolic state • Evaluate working memory activation of the DLPC in depressed and controls • Some varied results but appears to show greater activation in order to achieve the same results as control subjects

Depression – f. MRI limbic • Depressed patients have an exaggerated response to sad or other negative faces that resolves with treatment • Increase amygdala, basal ganglia, and thalamus activation to negative faces in depression • Activation returns to control levels with successful treatment

Attenuation of the Neural Response to Sad Faces in Major Depression by Antidepressant Treatment A Prospective, Event-Related Functional Magnetic Resonance Imaging Study Cynthia H. Y. Fu, MD, FRCPC; Steven C. R. Williams, Ph. D; Anthony J. Cleare, MRCPsych; Michael J. Brammer, Ph. D;

Depression - treatment • Medication – enhance the serotonin system • Electroconvulsive therapy ECT • Surgical u u u Vagal nerve stimulation DBS – anterior limb of the internal capsule, nucleus accumbens, BA 25 subgenual ACC Cortical Stimulation of the DLPFC – Transcranial Magnetic Stimulation TMS or epidural cortical stimulation

The vagus nerve: pathway to the limbic system Studies have shown that vagus nerve stimulation affects serotonin and norepinephrine neurotransmitters and brain structures thought to be involved in mood regulation. 2, 3

Positron emission tomography data acquired St. Louis University, analyzed at Medical University of South Carolina (MUSC) Center for Advanced Imaging Research (CAIR) by Xingbao Li, MD; 6 patients for 3 months of VNS Therapy compared with baseline. P<. 05 for display, no significant decreases.

Deep Brain Stimulation can be used to modulate structure deep within the brain for depression as well as Movement Disorders Remember: Location, location

BA 25 subgenual ACC anterior limb of the internal capsule, nucleus accumbens

Cortical Stimulation not FDA approved • Transcranial Magnetic Stimulation TMS u u u Noninvasive Requires daily treatments for 3 -5 weeks Unknown duration • Epidural Cortical Stimulation ECS u u u Invasive, fully implanted, similar to DBS system Continuous treatment Theoretically longterm or permanent

Cortical Stimulator

Thanks for your attention. Remember when studying for the exam, this lecture is meant as an illustration of your prior lectures on these topics!