FRONTAL LOBE DISORDER

Moderator: Dr. Saradhi

OUTLINE Introduction Functional anatomy of the frontal lobes Neurotransmitters in the frontal lobes Frontotemporal Dementia Frontal lobe syndrome Frontal lobe epilepsy Schizophrenia & Frontal lobe Depression & frontal lobe Testing prefrontal cortical function Common causes of frontal lobe syndromes

… one hundred trillion synapsesin a single human brainorganized into exquisitely complex circuits…responding to experience, drugs,disease, and injury…

Complexity of the Brain

Complexity of the Brain

As befits the 3-pound organ of the mind, the human brain is the most complex structure ever investigated by our science.

It is useful to think of the brain as containing six or seven component parts. The largest and most advanced part consists of the left and right cerebral hemispheres, which appear to be more or less symmetrical. They are covered with a layer of gray matter called the cerebral cortex. Each of the cerebral hemispheres has traditionally been divided into four "lobes," which are named after the bones of the skull that surround them: frontal, parietal, occipital, and temporal.

The frontal lobe is the largest and least understood, beginning at the front of the brain and reaching back to the central sulcus & laterely lateral sulcus. The area between the central and precentral sulci helps control body movements and is called the "motor area," while the remainder of the frontal lobe probably modulates various aspects of thinking, feeling, imagining, and making decisions.

FUNCTIONAL FRONTAL LOBE ANATOMY

Largest of all lobes SA: ~1/3 of each

hemisphere 3 major areas in each

lobe Dorsolateral aspect Medial aspect Inferior orbital aspect

FUNCTIONAL FRONTAL LOBE ANATOMY

Lateral sulcus/Sylvian fissure

Central sulcus

Motor speech area of Broca

Frontal eye field

B 44, 45

B 9, 10, 11, 12

B 8

Primary motor areaPremotor area

Prefrontal area

B6 B4

Supplementarymotor area

(medially)

FUNCTIONAL FRONTAL LOBE ANATOMY

Motor cortex Primary Premotor Supplementary Frontal eye field Broca’s speech

area

Prefrontal cortex– Dorsolateral – Medial – Orbitofrontal

MOTOR CORTEX

Primary motor cortex Input: thalamus, BG, sensory,

premotor Output: motor fibers to brainstem

and spinal cord Function: executes design into

movement Lesions:/ tone; power; fine motor

function on contra lateral side

MOTOR CORTEX Premotor cortex

Input: thalamus, BG, sensory cortex Output: primary motor cortex Function: stores motor programs; controls

coarse postural movements Lesions: moderate weakness in proximal

muscles on contralateral side

MOTOR CORTEX Supplementary motor

Input: cingulate gyrus, thalamus, sensory & prefrontal cortex

Output: premotor, primary motor Function: intentional preparation for

movement; procedural memory Lesions: mutism, akinesis; speech is non-

spontaneous

MOTOR CORTEX

Frontal eye fields Input: parietal / temporal (what is

target); posterior / parietal cortex (where is target)

Output: caudate; superior colliculus; paramedian pontine reticular formation

Function: executive: selects target and commands movement (saccades)

Lesion: eyes deviate ipsilaterally with destructive lesion and contralaterally with irritating lesions

MOTOR CORTEX Broca’s speech area

Input: Wernicke’s Output: primary motor cortex Function: speech production (dominant

hemisphere); emotional, melodic component of speech (non-dominant)

Lesions: motor aphasia; monotone speech

PREFRONTAL CORTEX Orbital prefrontal cortex

Connections: temporal,parietal, thalamus, GP, caudate, SN, insula, amygdala

Part of limbic system Function: emotional imput, arousal,

suppression of distracting signals Lesions: emotional lability, disinhibition,

distractibility, ‘hyperkinesis’

PREFRONTAL CORTEX Dorsomedial 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 Connections: motor / sensory

convergence areas, thalamus, GP, caudate, SN

Functions: monitors and adjusts behavior using ‘working memory’

Lesions: executive function deficit; disinterest / emotional reactivity; attention to relevant stimuli

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 info

NEUROTRANSMITTERS Serotonin tracts

Origin: raphe nuclei in brainstem Projections: number of forebrain structures Function: minor role in prefrontal cortex;

sleep, mood, anxiety, feeding

FUNCTIONAL FRONTAL LOBE ANATOMY Five ‘frontal subcortical circuits’

(Cummings,‘93)

1. Motor2. Oculomotor3. Dorsolateral prefrontal4. Lateral orbitofrontal5. Anterior cingulate

FUNCTIONAL FRONTAL LOBE ANATOMY

‘Frontal subcortical circuits’

ThalamusFrontal cortex

StriatumCaudate & Putamen

Globus Pallidus &

Substantia Nigra

FRONTAL SUBCORTICAL CIRCUITS: 1. MOTOR CIRCUIT

Supplementary Motor & Premotor: planning, initiation & storage of motor programs; fine-tuning of movements

Motor:final station for execution of the the movement according to the design

SMA,Premotor,Motor

Putamen

Globus Pallidus

Thalamus

Hypo-thalamus

FRONTAL SUBCORTICAL CIRCUITS: 2. OCULOMOTOR CIRCUIT

Voluntary scanning eye movement Independent of visual stimuli

Frontal Eye Field Central

Caudate

Globus Pallidus

SubstantiaNigra

Thalamus

FRONTAL SUBCORTICAL CIRCUITS: 3. DORSOLATERAL PREFRONTAL CIRCUIT

Executive functions: motor planning, deciding which stimuli to attend to, shifting cognitive sets

Attention span and working memory

Lateral Prefrontal Caudate

Globus Pallidus

SubstantiaNigra

Thalamus

FRONTAL SUBCORTICAL CIRCUITS: 4. LATERAL ORBITOFRONTAL CIRCUIT

Emotional life and personality structure Arousal, motivation, affect Orbitofrontal cortex: consciousness

Caudate

Globus Pallidus

SubstantiaNigra

Thalamus

Infero-lateral prefrontal

Orbito-frontal

FRONTAL SUBCORTICAL CIRCUITS: 5. ANTERIOR CINGULATE CIRCUIT

Abulia, akinetic mutism

AnteriorCingulate Gyrus

VentralStriatum

Globus Pallidus

SubstantiaNigra

Thalamus

Frontal Lobe SyndromesThe Case of Phineas Gage

tamping iron blown through skull: L frontal brain injury

excellent physical recovery dramatic personality change:

stubborn, lacked in consideration for others, had profane speech, failed to execute his plans

FRONTOTEMPORAL LOBE DEMENTIA Frontotemporal lobar degeneration (FTLD) is a

neurodegenerative disease that selectively attacks the frontal and anterior temporal regions.

FTLD occurs in 5–15% of patients with dementia and it is the third most common degenerative dementia, following only Alzheimer’s disease (AD) and dementia with Lewy bodies.

Typical age of onset is between 50 and 60 years, although FTLD can occur as early as the 20s and has been reported in the ninth decade.

FRONTOTEMPORAL LOBE DEMENTIA In contrast to AD, in which memory loss is usually

the first symptom, the initial symptoms of FTLD often involve changes in personality, behavior, affective symptoms, and language function.

Most patients with FTLD begin with language (left-sided cases) or emotional (right-sided cases) changes. The lack of insight seen in FTLD,leads patients to ignore or deny their deficits.

The core features of FTLD as defined by the Neary criteria (Neary et al., 1998) are early decline in social and personal conduct, emotional blunting, and loss of insight.

FRONTOTEMPORAL LOBE DEMENTIA The clinical onset is insidious, with a slow gradual

progression. Although the neuropsychiatric profile for patients with FTLD varies.

Behavior problems such as overeating, repetitive compulsive behaviors, apathy, and agitation and disinhibition, develop in the majority of these patients as the disease progresses.

The estimated duration of the illness is around 6–10 years.

SSRI improved a variety of psychiatric symptoms, including irritability, depression, repetitive behaviors, and hyperorality.

FRONTAL LOBE SYNDROMES The dorsolateral frontal cortex is concerned with

planning, strategy formation, and executive function. Patients with dorsolateral frontal lesions tend to have apathy, personality changes, abulia, and lack of ability to plan or to sequence. patients have poor working memory for verbal information (if the left hemisphere is predominantly affected) or spatial information (if right hemisphere lesion).

The frontal operculum contains the center for expression of language. Patients with left frontal operculum lesions may demonstrate Broca aphasia and defective verb retrieval, whereas patients with exclusively right opercular lesions tend to develop expressive aprosodia.

The orbitofrontal cortex is concerned with response inhibition. Patients with orbitofrontal lesions shows disinhibition, emotional lability, and memory disorders. Personality changes from orbital damage include impulsiveness, a jocular attitude, sexual disinhibition, and complete lack of concern for others.

Patients with superior mesial lesions typically develop akinetic mutism.

Patients with inferior mesial (basal forebrain) lesions tend to manifest anterograde and retrograde amnesia and confabulation. 

CAUSES Mental retardation Traumatic brain injury Brain tumors Degenerative dementias including Alzheimer

disease, dementia with Lewy bodies, Parkinsonian dementias, and frontotemporal dementias

Cerebrovascular disease Schizophrenia major depression  multiple sclerosis It is associated with blood alcohol level and occurs during

acute intoxication with many recreational drugs.

CLINICAL PICTURE Profound change in personality. Lack of initiation and spontanity. Response are sluggish. Occasionally patient are hyperactive and restless. Mood is often euphoric and out of keeping with

patients situation. Irritability and outbursts are common. Loss of finer senses. Judgements are impaired. Fail to plan and carry through ideas.

FRONTAL LOBE EPILEPSY Frontal lobe epilepsy is characterized by recurrent

seizures arising from the frontal lobes. Seizures may arise from any of the frontal lobe areas,

including orbitofrontal,dorsolateral, opercular, supplementary motor area, motor cortex, or cingulate gyrus.

In most centers frontal lobe epilepsy accounts for 20-30% of operative procedures involving intractable epilepsy.

No significant gender-based frequency. In a large series of cases, mean subject age was 28.5

years with age of epilepsy onset 9.3 years for left frontal epilepsy and 11.1 years for right frontal epilepsy.

CLINICAL PICTURE Patients with frontal lobe seizures may present with a

clear epileptic syndrome or with unusual behavioral or motor manifestations that are not immediately recognizable as seizures.

may be associated with facial grimacing, vocalization, or speech arrest.

seizures frequently preceded by a somatosensory aura. Complex behavioral events characterized by motor

agitation and gestural automatisms; viscerosensory symptoms and strong emotional feelings often described; motor activity and may involve pelvic thrusting, pedaling, or thrashing, often accompanied by vocalizations or laughter/crying; seizures often bizarre and may be diagnosed incorrectly as psychogenic

DIFFERENTIAL DIAGNOSESAbsence Seizures

Periodic Limb Movement Disorder

Psychogenic Nonepileptic Seizures

REM Sleep Behavior Disorder

Somnambulism (Sleep Walking)

Temporal Lobe Epilepsy

EXPRESSIVE APHASIA Expressive aphasia, known as Broca's aphasia caused by damage

or developmental issues in anterior regions of the brain, including the left posterior inferior frontal gyrus known as Broca's area (Brodmann area 44and Brodmann area 45).

Sufferers of this form of aphasia exhibit the common problem of agrammatism. For them, speech is difficult to initiate, non-fluent, labored, and halting. Similarly, writing is difficult as well. Intonation and stress patterns are deficient. Language is reduced to disjointed words and sentence construction is poor.

comprehensionis generally preserved, meaning interpretation dependent on syntax and phrase structure is substantially impaired.  Patients who recover go on to say that they knew what they wanted to say but could not express themselves.

Residual deficits will often be seen.

SCHIZOPHRENIA & FRONTAL LOBE some schizophrenic symptoms are found in frontal

lobe disorder, in particular that involving dorsolateral prefrontal cortex. Symptoms included are those of the affective changes, impaired motivation, poor insight. Evidence for frontal lobe dysfunction in schizophrenic patients has been noted in neuropathologic studies like EEG studies, in CT scan, with MRI, and in cerebral blood flow studies. Hypofrontality is documented in several studies using PET. These findings emphasize the importance of neurologic and neuropsychologic investigation of patients with schizophrenia.

DEPRESSION & FRONTAL LOBE  it has been found that the right frontal lobe demonstrated increased

activity in response to negative moods whereas left frontal activity decreases. repetitive transcranial magnetic stimulation of the right frontal lobe reduces depressive symptoms , whereas left frontal activity increase depression as demonstrated through functional imaging studies.

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. 

psychiatric patients classified as depressed demonstrate insufficient left frontal activation and arousal.

In severely depressed patients demonstrate insufficient activation and a significant lower integrated amplitude of the EEG evoked response over the left vs right frontal lobe.

– Wisconsin Card Sorting Test• abstract thinking and set shifting; L>R

– Trail Making• visuo-motor track, conceptualization, set shift

– Stroop Color & Word Test• attention, shift sets; L>R

– Tower of London Test• planning

Testing for Frontal lobe function

Wisconsin Card Sorting Test

“Please sort the 60 cards under the 4 samples. I won’t tell you the rule, but I will announce every mistake. The rule will change after 10 correct placements.”

Trail Making Test

A

C12

73 D

5 B4

6

Various levels of difficulty:1. “Please connect the letters in alphabetical order as fast as you can.”2. “Repeat, as in ‘1’ but alternate with numbers in increasing order”

Stroop Color and Word Tests

RED BLUE ORANGE YELLOW GREEN RED PURPLE REDGREEN YELLOW BLUE REDYELLOW ORANGE RED GREEN BLUE GREEN PURPLE RED

“Please read this as fast as you can”

Tower of London Tests

Various levels of difficulty:e.g. “Please rearrange the balls on the pegs, so that each peg hasone ball only. Use as few movements as possible”

Diseases Commonly Associated With Frontal Lobe Lesions Traumatic brain injury

– Gunshot wound– Closed head injury

• Widespread stretching and shearing of fibers throughout• Frontal lobe more vulnerable

– Contusions and intracerebral hematomas

Diseases Commonly Associated with Frontal Lobe Lesions Frontal Lobe seizures

– Usually secondary to trauma – Difficult to diagnose: can be odd (laughter, crying, verbal

automatism, complex gestures)

Diseases Commonly Associated With Frontal Lobe Lesions Vascular disease

– Common cause especially in elderly– ACA territory infarction

• Damage to medial frontal area– MCA territory

• Dorsolateral frontal lobe– Anterior Communicating artery aneurysm rupture

• Personality change, emotional disturbance

Diseases Commonly Associated With Frontal Lobe Lesions Tumors

– Gliomas, meningiomas – subfrontal and olfactory groove meningiomas: profound personality

changes and dementia

Multiple Sclerosis– Frontal lobes 2nd highest number of plaques– euphoric/depressed mood, Memory problems, cognitive and

behavioral effects

Diseases Commonly Associated With Frontal Lobe Lesions Degenerative diseases

– Pick’s disease– Huntington’s disease

Infectious diseases– Neurosyphilis– Herpes simplex encephalitis

Diseases Commonly Associated with Frontal Lobe Lesions Psychiatric Illness – proposed associations

– Depression– Schizophrenia– OCD– PTSD– ADHD

Thanks for your

patience