The document provides an overview of frontal lobe disorders, including: - The functional anatomy and neurotransmitters of the frontal lobes. - Frontotemporal dementia, which selectively attacks the frontal and temporal lobes. - Frontal lobe syndromes, which can cause changes in personality and behavior. - Frontal lobe epilepsy, characterized by seizures arising from the frontal lobes. - The relationship between the frontal lobes and schizophrenia, depression, and other conditions.

1. FRONTAL LOBE
DISORDER
Moderator: Dr.
Saradhi

2. 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

3. Complexity of the Brain
… one hundred trillion synapses
in a single human brain
organized into exquisitely complex circuits…
responding to experience, drugs,
disease, and injury…

4. 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.

5. 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.

6. 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.

7. 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

8. FUNCTIONAL FRONTAL LOBE ANATOMY
Premotor area Primary motor area
B6 B4
Central sulcus
Supplementary
motor area
(medially)
Frontal eye field
B8
Prefrontal area
B 9, 10, 11, 12
Lateral sulcus/
Sylvian fissure
Motor speech
area of Broca
B 44, 45

9. FUNCTIONAL FRONTAL LOBE ANATOMY
Motor cortex Prefrontal cortex
 Primary – Dorsolateral
 Premotor
– Medial
 Supplementary
– Orbitofrontal
 Frontaleye field
 Broca‟s speech area

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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‟

16. 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

17. 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

18. 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

19. NEUROTRANSMITTERS
 Norepinephrine tracts
 Origin:locus ceruleus in brainstem and lateral
brainstem tegmentum
 Projections: anterior cortex
 Functions: alertness, arousal, cognitive
processing of somatosensory info

20. NEUROTRANSMITTERS
 Serotonin tracts
 Origin:raphe nuclei in brainstem
 Projections: number of forebrain structures
 Function: minor role in prefrontal cortex; sleep,
mood, anxiety, feeding

21. FUNCTIONAL FRONTAL LOBE ANATOMY
 Five „frontal subcortical circuits‟
(Cummings,„93)
1. Motor
2. Oculomotor
3. Dorsolateral prefrontal
4. Lateral orbitofrontal
5. Anterior cingulate

22. FUNCTIONAL FRONTAL LOBE ANATOMY
 „Frontal subcortical circuits‟
Globus Pallidus
Striatum & Thalamus
Frontal Caudate &
cortex Substantia
Putamen Nigra

23. FRONTAL SUBCORTICAL CIRCUITS:
1. MOTOR CIRCUIT
Globus
SMA, Pallidus
Hypo-thalamus
Premotor,Mo Putamen
tor
Thalamus
 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

24. FRONTAL SUBCORTICAL CIRCUITS:
2. OCULOMOTOR CIRCUIT
Globus
Frontal Eye Pallidus
Central Thalamus
Field
Caudate
Substantia
Nigra
 Voluntary scanning eye movement
 Independent of visual stimuli

25. FRONTAL SUBCORTICAL CIRCUITS:
3. DORSOLATERAL PREFRONTAL CIRCUIT
Globus
Lateral Pallidus
Caudate Thalamus
Prefrontal
Substantia
Nigra
 Executive functions: motor planning, deciding which stimuli to
attend to, shifting cognitive sets
 Attention span and working memory

26. FRONTAL SUBCORTICAL CIRCUITS:
4. LATERAL ORBITOFRONTAL CIRCUIT
Infero-lateral
Globus
prefrontal
Pallidus
Caudate Thalamus
Substantia
Orbito-frontal
Nigra
 Emotional life and personality structure
 Arousal, motivation, affect
 Orbitofrontal cortex: consciousness

27. FRONTAL SUBCORTICAL CIRCUITS:
5. ANTERIOR CINGULATE CIRCUIT
Globus
Anterior
Ventral Pallidus
Cingulate Thalamus
Gyrus Striatum
Substantia
Nigra
 Abulia, akinetic mutism

28. Frontal Lobe Syndromes
The 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

29. 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.

30. 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.

31. 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.

32. 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.

33.  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.

34. 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.

35. 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.

36. 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.

37. 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

38. DIFFERENTIAL DIAGNOSES
Absence Seizures
Periodic Limb Movement Disorder
Psychogenic Nonepileptic Seizures
REM Sleep Behavior Disorder
Somnambulism (Sleep Walking)
Temporal Lobe Epilepsy

39. 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.

40. 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.

41. 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.

42. Testing for Frontal lobe
function
– 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

43. 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.”

44. Trail Making Test
5 B
A 4
6
1 C
2
3 D
7
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”

45. Stroop Color and Word Tests
RED BLUE ORANGE YELLOW
GREEN RED PURPLE RED
GREEN YELLOW BLUE RED
YELLOW ORANGE RED GREEN
BLUE GREEN PURPLE RED
“Please read this as fast as you can”

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

47. 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

48. 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)

49. 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

50. 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

51. Diseases Commonly
Associated With Frontal Lobe
Lesions
 Degenerative diseases
– Pick‟s disease
– Huntington‟s disease
 Infectious diseases
– Neurosyphilis
– Herpes simplex encephalitis

52. Diseases Commonly
Associated with Frontal Lobe
Lesions
 Psychiatric Illness – proposed associations
– Depression
– Schizophrenia
– OCD
– PTSD
– ADHD