NEUROANATOMY & NEUROPSYCHIATRIC ASPECTS OF FRONTAL LOBE

CONTENTS
Anatomy of frontal lobe
Neuroanatomy

Functional anatomy

Motor cortex Prefrontal cortex

Neurotransmitters
Frontal lobe syndromes Disease associated with frontal lobe lesions

Psychiatric illnesses
Frontal lobe epilepsy Frontal lobe & memory

Cerebral Features:
Gyri Elevated ridges winding around the brain. Sulci Small grooves dividing the gyri
Central Sulcus Divides the Frontal Lobe from the Parietal Lobe

Fissures Deep grooves, generally dividing large regions/lobes of the brain

Longitudinal Fissure Divides the two Cerebral Hemispheres Transverse Fissure Separates the Cerebrum from the Cerebellum Sylvian/Lateral Fissure Divides the Temporal Lobe from the Frontal and Parietal Lobes

Specific Sulci/Fissures:
Central Sulcus Longitudinal Fissure

Sylvian/Lateral Fissure Transverse Fissure

* Note: Occasionally, the Insula is considered the fifth lobe. It is located deep to the Temporal Lobe.

CEREBRUM - THE LARGEST DIVISION OF THE BRAIN.

IT IS DIVIDED INTO TWO HEMISPHERES, EACH OF WHICH IS DIVIDED INTO FOUR LOBES

Cerebral Cortex - The outermost layer of gray matter making

up the superficial aspect of the cerebrum

Functional Frontal Lobe Anatomy

Phylogenetically youngest part of brain Located deep to the frontal bone of the skull Largest of all lobes
SA: ~1/3 / hemisphere

3 major areas in each lobe

Dorsolateral aspect Medial aspect Inferior orbital aspect

FRONTAL LOBE
Motor cortex Primary motor

Prefrontal cortex
Dorsolateral Medial Orbitofrontal

Premotor
Supplementary motor Frontal eye field Brocas speech area

Functional Frontal Lobe Anatomy

Premotor area
BA 6,8

Primary motor area

BA 4

Supplementary motor area

(medially BA 6)

Central sulcus

Frontal eye field

BA 8

Prefrontal cortex
BA 9, 10, 11, 12

Motor speech area of Broca

BA 44, 45

Lateral sulcus/ Sylvian fissure

 Prefrontal area consist of paralimbic (anterior cingulate gyrus & posterior orbitofrontal) and high order association cortex (dorsolateral convexity & anteromedial surface) This area was considered silent

Prefrontal cortex

Functional regions of the left frontal lobe (lateral view)

functional regions of the right frontal lobe (medial view)

Motor Cortex
Primary motor cortex BA 4
Input: thalamus, BG, sensory, premotor Output: motor fibers to brainstem and spinal cord Function: executes design into movement Lesions:tone (spasticity); power; fine motor function on contra lateral side

 Bedside test : Motor strength of hand grip Motor speed on finger tapping

Diagnostically, poor performances suggest local lesions such as vascular or neoplastic pathology, or a generalized lesion such as a degenerative disease.

Motor Cortex
Premotor cortex BA 6
Input: thalamus, BG, sensory cortex Output: primary motor cortex Function: sensorimotor integration, stores motor programs; controls coarse postural movements Lesions: moderate weakness in proximal muscles on contralateral side, spasticity, grasp reflex, buccofacial apraxia, inability to make use of sensory feedback in the performance of smooth movements

Bedside test :-

1. Sensorimotor abilities are tested by asking the patient touch each finger to the thumb in succession as rapidly as possible (Watch for speed and dexterity) 2. Apraxia can be tested by asking the patient to "blow a kiss" and to demonstrate the use of a shovel.
Poor performance carries the diagnostic implications

MOTOR CORTEX
Supplementary motor area medial aspect of BA 6

Input: cingulate gyrus, thalamus, sensory & prefrontal cortex

Output: premotor, primary motor Function: involved in motivated behavior, initiation and goal directed intentional preparation for movement; procedural memory

behavior,

Lesions: transient transcortical motor aphasia (mutism), impairment in motor initiation (akinesis); impaired rapid alternating movements, grasp reflex, alien hand syndrome

MOTOR CORTEX
Frontal eye fields

BA 8 with some area of 9 & 6

Input: parietal / temporal (what is target); posterior / parietal cortex (where is target) Output: caudate; superior colliculus; paramedian pontine reticular formation Function: selects target and commands movement (saccades) Lesion: eyes deviate ipsilaterally with destructive lesion and contralaterally with irritating lesions

Bedside test:-

1. Ask the patient to follow the movement of a finger from left to right and up and down.
2. Ask the patient to look from left to right, up and down (with no finger to follow). Note inability to move or jerky movement .

MOTOR CORTEX
Brocas speech area BA 44, 45 Input: wernickes area Output: primary motor cortex Function: speech production (dominant hemisphere); emotional melodic component of speech (non-dominant) Lesions: motor aphasia; dysprosody (monotonus speech) Speech is sparse, slow, hesitant, disturbance of rhythm and articulation, difficulty in word finding, wrong words are chosen & often mispronounced, perseveration, agrammatism

Pt recognize his mistakes & tries to correct them but becomes impatient
Phrase length is small :- telegraphic language Writing is also affected with speech, but comprehension is preserved

PREFRONTAL CORTEX
Orbital prefrontal cortex

BA 10 & 11

Connections: temporal, parietal, thalamus, GP, caudate, SN, insula, amygdala Part of limbic system

Function: It mediates empathic, civil and socially appropriate behavior, emotional input, arousal, suppression of distracting signals
Lesions: emotional lability, disinhibition, distractibility, hyperkinesis

Much of the personality change described in cases of frontal lobe injury is due to lesions in this area

BEDSIDE TESTS: 1. Does the patient dress or behave in a way which suggests lack of concern with the feelings of others or without concern to accepted social customs. 2. Test sense of smell - coffee, cloves etc. 3. Go/no-go Test- The patient is asked to make a response to one signal (the Go signal) and not to respond to another signal (the no-go signal) 4. The Stroop Test - Examines the ability of the patient to inhibit responses

PREFRONTAL CORTEX
Medial prefrontal cortex

Connections: temporal, parietal, thalamus, caudate, GP, substantia nigra, cingulate

Functions: motivation, initiation of activity Lesions: apathy; decreased drive/ awareness/ spontaneous movements; akineticabulic syndrome & mutism

PREFRONTAL CORTEX
Dorsolateral prefrontal cortex

area 46

BA 9 and the lateral aspect of 10 and most of

Connections: motor / sensory convergence areas, thalamus, GP, caudate, SN Functions: executive functioning include the integration of sensory information, the generation of a range of response alternatives to environmental challenges, the selection of the most appropriate response, maintenance of task set, sequential ordering of data, self-evaluation of performance and the selection of a replacement responses if the first applied response fails monitors and adjusts behavior using working memory Lesions: executive function deficit, apathy, aspontaneity and impoverished & stereotyped thought process

TESTS: 1. Is the patient able to make an appointment and arrive on time?

2. Is the patient able to give a coherent account of current problems

Digit span, days of the week or months of the year backwards Controlled oral word association test (COWAT): the patient is asked to FAS verbal fluency test - produce as many words as possible, in one minute, starting with F, then A, then S

 Alternating hand sequences :- one hand is placed palm upwards and the other is place palm downwards, and the patient is then asked to reverse these positions as rapidly as possible or Patient taps twice with one fist and once with the other, then after the rhythm is established, the patient is asked to change over the number of beats Patients with frontal lobe deficits usually perform poorly on these tests, often unable to follow relatively simple instructions

NECESSARY WHERE UNCERTAINTY REMAINS Commonly employed tests include Controlled Oral Word Association Test (Benton, 1968) and the Wisconsin Card Sorting Tests (Heaton, 1985)

Wisconsin Card Sorting Test

Please sort the 60 cards under the 4 samples (stimulus cards). I wont tell you the rule, but I will announce every mistake. The rule will change after 10 correct placements.

NEUROTRANSMITTERS
Dopaminergic tracts

Origin: ventral tegmental area in midbrain

Projections: prefrontal cortex (mesocortical tract) and to limbic system (mesolimbic tract)

Function: reward, motivation, spontaneity, arousal

NEUROTRANSMITTERS
Norepinephrine tracts

Origin: locus ceruleus in brainstem and lateral brainstem tegmentum

Projections: anterior cortex Functions: alertness, arousal, cognitive processing of somatosensory information

NEUROTRANSMITTERS
Serotonergic tracts

Origin: raphe nuclei in brainstem

Projections: number of forebrain structures Function: minor role in prefrontal cortex; sleep, mood, anxiety, feeding

 PREFRONTAL LESIONS cause prominent personality changes without loss of general intelligence, motor, sensory or memory functions FRONTAL LOBE SYNDROME
Frontal lobe syndrome

Features not unique to frontal lobe pathology Lack of one to one correspondence b/w behavior & location of lesion

Executive syndrome (Baddely & Wilson)

 A 45 year old man with b/l prefrontal strokes was found to have
Normal neurological examination

Slightly flattened affect

Lack of spontaneity, mental slowness Increased left sided motor tone

Neuropsychological testing normal intelligence & memory

Demoted at his managerial jobs d/t ineffective work habits Unable to adequately supervise children

Often lost his temper

Inattention Bad judgment

 CLINICAL PICTURE : varies among pts.

Individual features depends on Nature & time course of pathological process Lateralization Localization

Extent of involvement among subcortical & callosal

fibers Secondary effect of raised ICT

Kliest first suggested that components of frontal lobe syndrome may be related to specific regional involvement

 Orbital lesions cause : Disinhibition, failure to appreciate consequences of ones action, euphoria (effect on personality & social behavior)
Lesions of dorsolateral convexity cause : Apathy, aspontaneity, impoverished & stereotyped thought process Left prefrontal injury : loss of executive & planning function, depression, When supplementary/ premotor area affected : transcortical motor aphasia, impairment of rapid skilled manual movements Right prefrontal injury : left sided extinction & neglect, blunted or labile affect, impersistence, disinhibition, confabulation, alien hand sign

 Patients with classical frontal lobe syndrome usually have b/l lesions encompassing both orbital & lateral cortex Negative symptoms : Lack of initiative & spontaneity General diminution of motor activity (sluggish response)

Task are left unfinished

New initiatives are rarely undertaken Capacity to function independently in life is affected Cognition & intellect may remain unaffected Yet when vigorously urged or constrained by structural situation pt may function quite well

 Other pts may show positive symptoms Restless Hyperactive yet lack of goal directed behavior Mild euphoria Tendency to joke/pun State of excitement, pressured speech Overfamilarity Outburst of irritability Such changes are rarely sustained and when left to themselves these pts become inert & apathetic

 Social awareness & behavior Less concerned with consequences of his acts Loss of social graces Coarsening of personality Lack of normal adult tact & restraints Little concern about his future Fails to plan ahead, to carry out ideas Sexual disinhibition Pt usually has little insight into the changes

 Inability to plan & execute multistepped behavior is hallmark of prefrontal lesions Can manage simple one or two step command Evaluated by asking the pt & spouse, do things get started but not completed? Ask pt about planning a vacation, changing a tyre.

Test of sequential motor & visual patterns

Reciprocal coordination test Sequential motor test

Visual pattern completion task

 Wisconsin card sorting test : shift cognition sets Perseveration is another symptom of frontal lobe disorder but not pathognomic Concrete thinking or lack of abstraction
Proverb test Similarity test
Bifrontal lesions Bad judgment resulting from deficits affecting Planning & carrying out multistepped behavior, adaptation to new situation, understanding & reacting social cues

Lack of awareness, attentional deficits, understanding, sensitivity & communication skills

Family, relation, occupation problems

 Abulia : Poverty of thought action & emotion is common with large midline and b/l dorsofrontal lesion Abulia is characterized by loss of spontaneity & will power They comprehend the question, hesitate, delay respond, seem to ignore or give yes no answer Severely abulic pt do not speak unless spoken, do not move unless they are hungry or ready to void & may be incontinent Tidal waves of emotional & motor behavior (brief rage, irritability, hyperactivity) may emerge from tranquil sea of abulia (placid, apathetic, disinterested) Perseveration v/s abulia :- Random A test.

 Classical case reports The Case of Phineas Gage (Harlow 1868)

tamping iron blown through skull: L frontal brain injury excellent physical recovery dramatic personality change: no longer Gage:stubborn, lacked in consideration for others, unreliable, lacking in social skills, had profane speech, failed to execute his plans

 Utilisation behavior (Lhermitte 1986) Observed pt with frontal lobe lesion in complex everyday life situation

He noted lack of personal autonomy with an excessive dependence on social & physical environment (environmental dependency syndrome)
Decisions of pts actions were not made by themselves Social & physical environments issue the order to use them even the pt has neither idea or nor intend to use them

DISEASES COMMONLY ASSOCIATED WITH FRONTAL LOBE LESIONS

Traumatic brain injury
Gunshot wound
Closed head injury Contusions and intracerebral hematomas

Vascular disease
Common cause especially in elderly

ACA territory infarction

Damage to medial frontal area

MCA territory
Dorsolateral frontal lobe

ACom aneurysm rupture

Personality change, emotional disturbance

Frontal Lobe seizures

Tumors Multiple sclerosis

Degenerative diseases
Picks disease Huntingtons disease

Infectious diseases
Neurosyphilis Herpes simplex encephalitis

Psychiatric Illness proposed associations

Schizophrenia

Depression
ADHD OCD Antisocial personality disorder

SCHIZOPHRENIA
Symptoms can be aggregated in 3 broad clusters
(Liddle 1987)

1. Psychomotor poverty syndrome Affecting speech & movement, blunting of affect Decreased rCBF in left prefrontal & parietal cortex

2. Reality distortion syndrome Positive symptoms hallucinations & delusions Increase rCBF in left parahippocampal gyrus & contiguous area

3. Disorganization syndrome Thought disorder & inappropriate affect

FRONTAL LOBE & DEPRESSION

Depression is often a realistic reaction to misfortunes Requires the cognitive capacity to appreciate and thus feel depressed In consequence : Area of the brain mediating the depression may become excessively active Whereas yet another region of the cerebrum which is expressing the depression may become underactive Right frontal lobe demonstrated increased activity in response to negative moods Not only reductions in left frontal activity, but injuries to the left frontal lobe have been consistently associated with depression, "psycho-motor" retardation, apathy, irritability, and blunted

FRONTAL LOBE & ADHD

Executive functions of frontal cortex include:
Problem solving Attention Reasoning Planning

ADHD suffers usually have deficits in these functions Right frontal lobe is smaller in children with ADHD Problems in the circuit between three regions are the underlying mechanisms that cause ADHD symptoms 1. Prefrontal cortex (command center) 2. Caudate nucleus

FRONTAL LOBE & OCD

OCD could be due to abnormalities of the frontal lobe, basal ganglia, and cingulum

OCD is caused by problems in communication between the frontal lobe and basal ganglia
On PET Scan, OCD pt burned energy more quickly in the frontal lobe and cingulate pathway Abnormally low levels of serotonin found in people with OCD

FRONTAL LOBE & ALCOHOLISM

Prefrontal cortex has been linked to impulse control because damage to this region of the brain can lead to loss of inhibitions Two neurotransmitters, gamma-amino butyric acid (GABA) and dopamine are responsible for the loss of impulse control in those who consume alcohol Alcohol increases the amount of dopamine release and enhances the normal feeling of pleasure Alcohol co binds with GABA to GABA receptor and hyperpolarize the post synaptic neuron, so ability of the neurons in the frontal lobes to inhibit socially unacceptable behavior is reduced

FRONTAL LOBE EPILEPSY

IInd most common type of epilepsy Brief recurring seizures often while pt is sleeping 2 forms : Simple partial seizures : does not affect awareness & memory Complex partial seizures : affects awareness & memory

Symptoms : Physical/emotional aura of tingling, numbness, tension Fear expressed on face Tonic posturing & clonic movements Often misdiagnosed as psychogenic seizures

More specific symptoms depends on area of frontal cortex involved

 Supplementary motor area : somatosensory aura precedes tonic posturing which is u/l, asymmetrical Motor symptoms :- facial grimacing, complex automatism like kicking, pelvic thrusting

Vocal symptoms :- laughing, yelling or speech arrest

Primary motor cortex : jacksonian seizures that spread to adjacent area, often triggers to IInd round of seizures Usually tonic, myoclonic movements with speech arrest
Medial frontal, Cingulate gyrus, Orbitofrontal, Frontopolar region :
Short repetitive thrashing, pedaling, thrusting, laughing, screaming, crying Motor symptoms are accompanied by emotional feelings &

 Dorsolateral cortex : tonic posturing & clonic movements c/l head turning & eye deviation

Operculum : symptoms involve head & digestive tract as swallowing, mastication

Person is fearful, clonic facial movements & speech is often arrested

Diagnosis : EEG, MRI

Treatment : Medical : anticonvulsants as carbamazepine, phenytoin, gabapentine, lamotrigine, topiramate etc. Surgical : frontal lobectomy, multiple subpial transections, gamma knife radiosurgery, vagus nerve stimulator

Diet : ketogenic diet, high fat & low carbohydrate

FRONTAL LOBE & MEMORY

Focal frontal injury does not produce a severe amnesic disorder It can cause more subtle, yet definable, memory deficits in form of an impairment in the control of memory Prefrontal cortex appears to be crucial for the monitoring and control of memory processes, both at the time of encoding and at the time of retrieval Significant impairment was observed on tests of free recall (80% of studies), cued recall (50% of studies) and even on tests of recognition (8% of studies)

TO CONCLUDE
Frontal lobe forms about 1/3 part of each cerebral hemisphere Phylogenetically newest part Previously considered silent brain, but now found to produce variety of symptoms 2 major parts (a) precentral/motor cortex :- planning, execution & control of c/l body movements (b) prefrontal cortex :- emotion control center & home of our personality Bilateral prefrontal cortex lesion leads to frontal lobe sydrome

TO CONCLUDE
Left prefrontal cortex lesion :- psuedodepressive type Right prefrontal cortex lesion :- psuedopsychotic type Inability to plan & execute multistepped behavior is hallmark of prefrontal lesion Frontal lobe functions are deranged in schizophrenia, depression, ADHD, OCD, antisocial personality disorder, alcoholism etc. Frontal lobe epilepsy is often misdiagnosed as psychogenic seizures prefrontal cortex is crucial for control of memory during encoding & recall