Neuroanatomy & neuropsychiatric aspects of Frontal Lobe

PresentorDr. Anant Kumar Rathi

GuideDr. D. K. Vijayvergia

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:

• 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

• Gyri – Elevated ridges “winding” around the brain.

Longitudinal Fissure

Transverse Fissure

Sylvian/Lateral Fissure

Central Sulcus

Specific Sulci/Fissures:

* 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– Premotor– Supplementary motor– Frontal eye field– Broca’s speech area

Prefrontal cortex– Dorsolateral – Medial – Orbitofrontal

Functional Frontal Lobe Anatomy

Lateral sulcus/Sylvian fissure

Central sulcus

Motor speech area of Broca

Frontal eye field

BA 44, 45

BA 9, 10, 11, 12

BA 8

Primary motor areaPremotor area

Prefrontal cortex

BA 6,8 BA 4

Supplementarymotor area(medially BA 6)

• 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 behavior, intentional preparation for movement; procedural memory

• 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• Broca’s speech area BA 44, 45

– Input: wernicke’s 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; akinetic-abulic syndrome & mutism

Prefrontal Cortex• Dorsolateral prefrontal cortex BA 9 and the lateral aspect of

10 and most of area 46– 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

Bedside 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

• Formal neuropsychological tests may be 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 won’t 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

Executive syndrome(Baddely & Wilson)

Features not unique to frontal lobe pathology

Lack of one to one correspondence b/w behavior &

location of lesion

• 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 one’s 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 lesionsBad 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

– Pick’s disease– Huntington’s 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

Increase resting rCBF in anterior cingulate region

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 mental functioning

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 symptoms1. Prefrontal cortex (command center)2. Caudate nucleus3. Globus pallidus

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 &

viscerosensory symptoms• Often misdiagnosed as psychological seizures

• 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

• 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

To conclude