human, brain, frontal lobe, function, neurology, psychiatry, higher brain function

1. Presenter
Dr. Anusa A M
First year MD PG
1st August 2012
Hon. Chairperson
Dr. KUMANAN MD DPM,
Professor
Dr. KARTHIKEYAN MD, DPM,
Assistant Professor

2.  Anatomy & Functional anatomy of frontal lobes
 Neurotransmitters in the frontal lobes
 Circuits of the frontal lobe and deficits
 Testing prefrontal cortical function
 Common causes of frontal lobe syndromes
 References

4.  Largest of all lobes
 Sagitally : ~1/3 / hemisphere
 3 major areas in each lobe
 Dorsolateral aspect
 Medial aspect
 Inferior orbital aspect

5. 1, 2, 3 = primary sensory cortex
4 = motor cortex
5, 7 = secondary sensory cortex
6 = supplementary motor area (medial) and premotor cortex (lateral)
8 = frontal eye fields
9/46 = dorsolateral prefrontal cortex
10 = frontopolar cortex
11, 12 = orbitofrontal areas
17 = primary visual cortex
18, 19, 20, 21, 37 = secondary visual cortex
24, 32 = anterior cingulate cortex
41 = primary auditory cortex
22, 42 = secondary auditory cortex
39 = angular gyrus, part of Wernicke's area
40 = supramarginal gyrus, part of Wernicke's area
44/45 = Broca's Area
47 Ventrolateral prefrontal cortex
(13, 14, 15, 16, 27, 49, 50, 51 - monkey only)

6. Surface Division Separated by & B Number
Superolateral Prefrontal
Superior frontal gyrus (4l, 6l, 8l) · Middle frontal
gyrus (9l, 10l, 46)
Inferior frontal gyrus: 11l · 47-Pars orbitalis · Broca's
area (44-Pars opercularis, 45-Pars triangularis)
Superior frontal sulcus · Inferior frontal sulcus
Precentral Precentral gyrus · Precentral sulcus
Medial/inferior Prefrontal
Superior frontal gyrus (4m, 6m) · Medial frontal
gyrus (8m, 9m)
Paraterminal gyrus/Paraolfactory area (12) · Straight
gyrus (11m) · Orbital gyri/Orbitofrontal
cortex (10m, 11m, 12) · Ventromedial prefrontal
cortex (10m) ·Subcallosal area (25)
Olfactory sulcus · Orbital sulci
Precentral Paracentral lobule (4) · Paracentral sulcus
Both
Primary motor cortex (4) · Premotor cortex (6) · Supplementary motor
area (6) · Frontal eye fields (8)

8. 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
Supplementary
motor area
(medially)
Brodmann area

11.  Primary Motor area
 Premotor area
 Anterior Premotor
 Ventral anterior Premotor
 Orbital frontal cortex
 Lateral Prefrontal cortex
▪ Dorsolateral
 Venteromedial prefrontal cortex
▪ Lateral frontopolar
▪ Venterolateral

12. Broadman's
area
Anatomical
descriptions
Cortical type Functional region
4 Primary Motor
Cortex
Primary Motor Motor
6 Premotor Primary Motor (caudal);
Unimodal motor (Roustral)
Premotor
44 Pars opercularis Unimodal motor Premotor
8 Motor
association
cortex
Unimodal motor (caudal);
heteromodal (rostral)
Premotor
46 Dorsolateral
Prefrontal cortex
Heteromodal Prefrontal -
dorsolateral
9 Superior
Prefrontal cortex
Heteromodal Prefrontal -
dorsolateral
10 Inferior
prefrontal cortex
Heteromodal Prefrontal -
dorsolateral

13. Broadman's
area
Anatomical descriptions Cortical type Functional region
45 Pars triangularis Heteromodal Prefrontal - ventrolateral
47 Pars orbitalis Heteromodal Prefrontal - ventrolateral
11 Lateral orbitofrontal
cortex
Heteromodal Prefrontal - orbitofrontal
12 Medial orbitofrontal
cortex
Heteromodal (Rostral);
Paralimbic (Caudal)
Prefrontal - orbitofrontal
32 Medial frontal cortex Heteromodal (Rostral);
Paralimbic (Caudal)
Paralimbic (medial, frontal)
24 Anterior cingulate Paralimbic Paralimbic (medial, frontal)
25 Paraolfactory region Paralimbic Paralimbic (medial, frontal)

14.  Motor cortex
 Primary
 Premotor
 Supplementary
 Frontal eye field
 Broca’s speech area
 Prefrontal cortex
– Dorsolateral
– Medial
– Orbitofrontal

15.  Executive function
 Thinking
 Judgment
 Social
 Curiosity
 Motivation
 Attention
 Sequencing

16.  Selective attention
 Working memory
 Preparatory set
 Monitoring
 Temporal organization of behavior, speech, and reasoning
 Distractibility, Perseveration, Dis-inhibition
 Novelty, Uncertainty, Choice
 Emotional Coloring of Action, Experience, and Decision
Making
 Significance, Context and Ambiguity
 Switching Perspectives and Mental Relativism

18.  Single-process theories
 Damage to a single process or system is responsible for a number
of different dysexecutive symptoms
 Multi-process theories
 Frontal lobe executive system consists of a number of
components that typically work together in everyday actions
(heterogeneity of function)
 Construct-led theories:
 Most,if not all, frontal functions can be explained by one construct
(homogeneity of function) such as working memory or inhibition”
 Single-symptom theories
 A specific dysexecutive symptom (e.g., confabulation) is related
to the processes and construct of the underlying structures

19.  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

20.  Supplementary motor
 Input : Cingulate gyrus, thalamus, sensory &
Prefrontal cortex
 Output : Premotor, primary motor
 Function : Intentional preparation for
movement; Procedural memory
 Lesions : Mutism, akinesis; speech returns but
it is non-spontaneous

21.  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

22.  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 & commands
movement (saccades)
 Lesion : Eyes deviate ipsilaterally with destructive
lesion & contralaterally with irritating lesions

23.  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

24.  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’

25. Schematic illustrating the connections of the VS. Blue arrows=inputs; gray arrows=outputs; Amy=amygdala;
BNST=bed nucleus stria terminalis; dACC=dorsal anterior cingulate cortex; Hipp=hippocampus; hypo=hypothalamus;
MD=medio-dorsal nucleus of the thalamus; OFC=orbital frontal cortex; PPT=pedunculopontine nucleus; S=shell;
SNc=substantia nigra, pars compacta; STN=subthalamic nucleus; Thal=thalamus; VP=ventral pallidum; VS=ventral
striatum; VTA=ventral tegmental area; vmPFC=ventral medial prefrontal cortex

26.  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

28.  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

30.  Dopaminergic tracts
 Origin:
▪ ventral tegmental area in midbrain
 Projections:
▪ Prefrontal cortex (mesocortical tract) and to limbic
system (mesolimbic tract)
 Function:
▪ Reward; motivation; spontaneity; arousal

31.  Norepinephrine tracts
 Origin:
▪ Locus ceruleus in brainstem and lateral brainstem tegmentum
 Projections:
▪ Anterior cortex
 Functions:
▪ Alertness, arousal, cognitive processing of somatosensory info

32.  Serotonin tracts
 Origin:
▪ Raphe nuclei in brainstem
 Projections:
▪ Number of forebrain structures
 Function
▪ Minor role in prefrontal cortex; sleep, mood, anxiety,
feeding

33. BS-ACh, brain stem cholinergic cell groups; DRN, dorsal raphe nuclei; MRN, median raphe nuclei; NBM, nucleus basalis of Meynert;
VTA; ventraltegmental area; 5HT, 5-hydroxytrytamine (serotonin).

34. BS-ACh, brain stem cholinergic cell groups; DRN, dorsal raphe nuclei; MRN, median raphe nuclei; NBM, nucleus basalis of Meynert;
VTA; ventraltegmental area; 5HT, 5-hydroxytrytamine (serotonin).

36.  Five ‘frontal subcortical circuits’
(Cummings,‘93)
1. Motor
2. Oculomotor
3. Dorsolateral prefrontal
4. Lateral orbitofrontal
5. Anterior cingulate

37.  ‘Frontal subcortical circuits’
Thalamus
DM & CM
nuclei
Frontal
cortex
Striatum
Caudate &
Putamen
Globus
Pallidus &
Substantia
Nigra

38.  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
VL Globus
Pallidus
VL, VA, CM
Thalamus
Hypo-
thalamus

39.  Voluntary scanning eye movement
 Independent of visual stimuli
Frontal
Eye Field
Central
Caudate
DM Globus
Pallidus
Substantia
Nigra
VA, MD
Thalamus

40.  Executive functions: motor planning, deciding which stimuli to
attend to, shifting cognitive sets
 Attention span and working memory
Lateral
Prefrontal
DL
Caudate
DM Globus
Pallidus
Substantia
Nigra
VA, MD
Thalamus

41.  Emotional life and personality structure
 Arousal, motivation, affect
 Orbitofrontal cortex: consciousness
VM
Caudate
DM Globus
Pallidus
Substantia
Nigra
VA, MD
Thalamus
Infero-
lateral
prefrontal
Orbito-
frontal

42.  Abulia, akinetic mutism
Anterior
Cingulate
Gyrus
Ventral
Striatum
RL Globus
Pallidus
Substantia
Nigra
MD
Thalamus

43. Corticostriatal Loops
Alexander, Delong, and Strick, 1986

44. Frontal Lobe Syndromes
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, had profane
speech, failed to execute his plans

45.  Puerile (Childish)
 Profane (Disrespectful)
 Slovenly (Sloppy)
 Facetious (Teasing)
 Irresponsible
 Grandiose
 Irascible (Irritable)
 Lost spontaneity, curiosity & initiative
 Apathetic blunting of feeling, drive, attentive power, behavior.
 Erosion of foresight, judgment, insight
 Inability to delay gratification or experience remorse.
 Impairment of abstract reasoning, hypothesis generation,
creativity, problem solving, and mental flexibility

46.  Jumped to premature conclusions
 Excessively literal
 Loss of orderly planning and sequencing of complex
behaviors
 The ability to attend to several components
simultaneously
 Flexibly alter the focus of concentration
 Capacity for grasping the context and gist of a complex
situation
 Resistance to distraction and interference
 Ability to follow multistep instructions
 Inhibition of immediate but inappropriate response
tendencies
 Ability to sustain behavioral output without
perseveration

47. Frontal Lobe Syndromes
 Emotional make-up and personality
 Abstraction and judgment
 Attention and memory
 Language

48. Frontal Lobe Syndromes
 Emotional make-up and personality
– May be the only manifestation
– Apathy / euphoria / labile mood
– Decreased drive / poor impulse control
– Abulia; akinetic mutism
– Pseudobulbar palsy; Opercular syndrome
– Best assessed with Hx from family / friends &
observation

49. Frontal Lobe Syndromes
 Abstraction and judgment
– Cognitive functions undisturbed
– Concrete thinking
– Diminished insight
– Defect in planning / executive control

50.  Tests of abstraction and judgment
– Interpret proverbs (e.g.“the golden hammer opens
iron doors”)
– Explain why conceptually linked words are the
same (e.g. coat & skirt)
– Plan & structure a sequential set of activities (“how
would you bake a cake?”)
– Insight / reaction to own illness

51.  Attention and memory
– Inattentiveness
– Defect in working memory
– Defect in sequencing, perseverance

53.  Tests of attention and memory
– Alternative sequence (e.g. copying MNMN)
– Go/no-go:
–”tap once if I tap twice, don’t tap if I tap once”
–“tap for A”
–read 60 letters at 1/sec; N: < 2 errors

54.  Tests of attention and memory cont’
– Digit span
– “repeat 3-52; 3-52-8; 3-52-8-67..” N: >5
– Visual grasp: “look away from stimulus”
– Recency test
–“recall sequence of stimuli / events”
– Imitation (of examiner) / utilization (of objects
presented)

55.  Language
– Broca’s / non-fluent aphasia
– Prefrontal/ transcortical motor aphasia
– Language-motor dissociation
– Akinetic mutism

56.  Language tests
– Thurstone / word fluency test (“recite as many
words beginning with ‘F’ in 1 min as you can,
then with ‘A’, ‘S’”); N: >15
– Repetition (Broca’s vs transcortical)
– “Ball”
– “Methodist”
– “Methodist episcopal”
– “No if’s end’s or but’s”
– “Around the rugged rock the ragged rascal ran”

57. Frontal Lobe Syndromes - Tests
 Formal Tests
– 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

58. “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.”

59. Trail Making Test
A
C1
2
7
3 D
5 B
4
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”

60. 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”

61. 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”

62. 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

63.  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

64.  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

65.  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

66.  Degenerative diseases
– Pick’s disease
– Huntington’s disease
 Infectious diseases
– Neurosyphilis
– Herpes simplex encephalitis

67.  Psychiatric Illness – proposed associations
– Depression
– Schizophrenia
– OCD
– PTSD
– ADHD

68.  Personality and emotional changes
 Reflect prefrontal lesions
 Role of Dopamine and Norepinephrine
 Trauma > vascular, tumors

69.  Netter’s atlas of Neuroanatomy (Google Images)
 The Human frontal Lobe – functions and Disorders; Millers BL, Cummings JL, 2007,
2nd Ed, Guilford Publisher, NY, USA (Google books)
 Burruss JW, Hurley RA, Taber KH et al. Functional Neuroanatomy of the frontal lobe
circuits. Radiology 2000;214:227-230 (Open access)
 Stuss DT, Knight RT. Principles of frontal lobe function, 1st Ed, Oxford, 2002, NY, USA