Functional anatomy of Frontal lobe

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

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

2. Outline 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

3. Increased with Evolution……

4. Frontal Lobe 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. Frontal Lobe - Sulci & Gyri 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)

7. Anatomy of Frontal Lobe

8. Functional Anatomy of Frontal Lobe 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 area Premotor area Prefrontal area B6 B4 Supplementary motor area (medially) Brodmann area

9. Functional Anatomy of Frontal Lobe

10. Functional Anatomy of Frontal Lobe

11. Frontal Lobe Primary Motor area Premotor area Anterior Premotor Ventral anterior Premotor Orbital frontal cortex Lateral Prefrontal cortex Dorsolateral Venteromedial prefrontal cortex Lateral frontopolar Venterolateral

12. Functional Anatomy of Frontal Lobe 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. Functional Anatomy of Frontal Lobe 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. Functional Anatomy of Frontal Lobe Motor cortex Primary Premotor Supplementary Frontal eye field Broca’s speech area Prefrontal cortex Dorsolateral Medial Orbitofrontal

15. Functions Associated with Prefrontal Cortex Executive function Thinking Judgment Social Curiosity Motivation Attention Sequencing

16. Functions Associated with Lateral Prefrontal cortex 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

17. Memory & Frontal Lobe

18. Theories of Frontal Lobe Function 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. 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

20. 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 returns but it is non-spontaneous

21. 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

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

23. 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

24. 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 ’

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. 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

27. 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

28. 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

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

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

31. Neurotransmitter connection 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).

32. Neurotransmitter connection 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).

33. Functional Frontal Lobe Anatomy Five ‘frontal subcortical circuits’ (Cummings,‘93) Motor Oculomotor Dorsolateral prefrontal Lateral orbitofrontal Anterior cingulate

34. Functional Frontal Lobe Anatomy ‘Frontal subcortical circuits’ Thalamus DM & CM nuclei Frontal cortex Striatum Caudate & Putamen Globus Pallidus & Substantia Nigra

35. 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 VL Globus Pallidus VL, VA, CM Thalamus Hypo-thalamus

36. Frontal subcortical Circuits: 2. Oculomotor Circuit Voluntary scanning eye movement Independent of visual stimuli Frontal Eye Field Central Caudate DM Globus Pallidus Substantia Nigra VA, MD Thalamus

37. 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 DL Caudate DM Globus Pallidus Substantia Nigra VA, MD Thalamus

38. Frontal subcortical Circuits: 4. Lateral Orbitofrontal Circuit 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

39. Frontal subcortical Circuits: 5. Anterior Cingulate Circuit Abulia, akinetic mutism Anterior Cingulate Gyrus Ventral Striatum RL Globus Pallidus Substantia Nigra MD Thalamus

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

41. 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

42. Frontal Lobe when affected cause 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

43. Frontal Lobe when affected cause 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

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

45. 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

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

47. 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 Frontal Lobe Syndromes

48. Attention and memory Inattentiveness Defect in working memory Defect in sequencing, perseverance Frontal Lobe Syndromes

49. 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 Frontal Lobe Syndromes - Tests

50. 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) Frontal Lobe Syndromes - Tests

51. Language Broca’s / non-fluent aphasia Prefrontal/ transcortical motor aphasia Language-motor dissociation Akinetic mutism Frontal Lobe Syndromes - Tests

52. 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” Frontal Lobe Syndromes - Tests

53. 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

54. “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.” Wisconsin Card Sorting Test

55. Trail Making Test A C 1 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” Trial making Tests

56. 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” Stroop Color and Word Tests

57. 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” Tower of London Tests

58. 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

59. 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

60. 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 Diseases Commonly Associated With Frontal Lobe Lesions

61. Tumors Gliomas, meningiomas subfrontal and olfactory groove meningiomas: profound personality changes and dementia Multiple Sclerosis Frontal lobes 2 nd highest number of plaques euphoric/depressed mood, Memory problems, cognitive and behavioral effects Diseases Commonly Associated With Frontal Lobe Lesions

62. Degenerative diseases Pick’s disease Huntington’s disease Infectious diseases Neurosyphilis Herpes simplex encephalitis Diseases Commonly Associated With Frontal Lobe Lesions

63. Psychiatric Illness – proposed associations Depression Schizophrenia OCD PTSD ADHD Diseases Commonly Associated With Frontal Lobe Lesions

64. Frontal Lobe Syndromes – Summary Personality and emotional changes Reflect prefrontal lesions Role of Dopamine and Norepinephrine Trauma > vascular, tumors

65. References Netter’s atlas of Neuroanatomy (Google Images) The Human frontal Lobe – functions and Disorders; Millers BL, Cummings JL, 2007, 2 nd 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, 1 st Ed, Oxford, 2002 , NY, USA

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