Frontal subcortical circuits, case scenario and quiz

1. Frontal Subcortical Circuits
And Their Assessment
Presenter:-
Dr Zuber Ali Quazi
Senior Resident
Department of Neurology
GMC Kota

2. Introduction
• The Frontal lobes can be divided into three major regions
a. Primary Motor Cortex,
b. Premotor And Supplementary Motor Cortices,
c. Association Cortices Comprising The Prefrontal Lobes
• The Prefrontal lobes is structurally divided into four areas:
1. Superior Medial Prefrontal Cortex, which includes the Anterior Cingulate
Cortex;
2. Lateral Prefrontal Cortex
3. Orbitofrontal Cortex
4. Frontal Poles.

3. Frontal Subcortical circuits
The 5 frontal-subcortical circuits
1. Motor circuit originating in the motor cortex and pre-motor cortex
2. Oculomotor unit originating in the frontal eye fields
3. Dorsolateral Prefrontal circuit------ Executive function
4. Anterior cingulate circuit------Motivation
5. Orbitofrontal circuit ---- Impulse control and social behavior.
MOTOR CORTEX
PREFRONTAL
CORTEX

4. The Frontal subcortical circuit has 4 components and is schematically represented as:-

5. ventralis
lateralis
ventralis
anterior,
pars
magnocellularis
medialis dorsalis,
pars multiformis
ventralis
anterior, pars
parvocellularis
medialis
dorsalis, pars
multiformis
medialis
dorsalis,
pars
magnocellularis
ventralis anterior,
pars
magnocellularis
medialis dorsalis,
pars multiformis
medialis
dorsalis,
pars
magnocellularis
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 1986;9(1):357–381.
doi:10.1146/annurev.ne.09.030186.002041.

7. Behavioral Syndromes Associated With Dysfunction of the Motor Circuits
Poor organization strategies
Poor memory search
strategies
Stimulus-bound behavior
Environmental dependency
Impaired set-shifting and
maintenance
Emotional incontinence
Tactlessness
Irritability
Undue familiarity
Antisocial behavior
Environmental dependency
Mood disorders (depression,
lability, mania)
Obsessive-compulsive
disorder
Impaired motivation
Akinetic mutism
Apathy
Poverty of speech
Psychic emptiness
Poor response inhibition
DLPFC OFC
ANTERIOR
CINGULATE CIRCUIT
Bradley and Daroff’s Neurology in Clinical Practice, 8th edition

8. Disruption of the orbitofrontal circuit
Bradley and Daroff’s Neurology in Clinical Practice, 8th edition

9. DLPFC –Subcortical circuit
•Principally involved in
•ATTENTION and EXECUTIVE FUNCTIONS.
•These functions include the:-
•Ability to Shift Sets,
•Organize & Solve Problems
•Abilities of Cognitive Control
•Working Memory

10. • The circuit includes the
• Dorsolateral head of the caudate,
• Globus pallidus interna,
• Parvocellular aspects of the mediodorsal and ventral anterior thalamic
nuclei.
• Dysfunction in this circuit
• Environmental dependency syndromes
• Slowed information processing,
• Memory retrieval deficits,
• Mood and behavioral changes
• Poor organization and planning,
• Mental inflexibility,
• Working memory deficits.
E.g., Vascular dementias, PD, and HD
DLPFC –Subcortical circuit

11. DLPFC
Bedside tests:
1. Is the patient able to make an appointment and arrive on time?
2. Is the patient able to give a account of current problems and the reason for the being
brought to hospital? Is there evidence of thought disorder?
3. Digit span, days of the week or months of the year backwards.
4. Controlled oral word association test (COWAT): the patient is asked to produce as many
words as possible, in one minute, starting with F, then A, then S. (Benton, 1968).
Other categorical fluency tests naming animals, fruits and vegetables (Monsch et al, 1992).
Normal >10
Abnormal <8
Common errors include :- perseveration (repeating words), inappropriate words.

12. Alternating hand sequences.
One example is that 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.
Another example is that the backs of the hands are both placed downwards,
but one hand is clenched and the other is open, then the patients is asked to
close the open hand and open the closed hand, and keep reversing the posture
of the hands as rapidly as possible.
A final example is that the 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 (the fist which first tapped twice now taps only once).

13. Similarities (conceptualization)
In what way are they alike?”
Banana and a Orange
Table and a Chair
Tulip, a Rose, and a Daisy
Score: only category responses (fruits, furniture, flowers) are considered
correct.
i. Three correct: 3
ii. Two correct: 2
iii. One correct: 1
iv. None correct: 0
Site:- Left Perisylvian Prefrontal regions

14. Motor Luria test
The examiner performs alone three times with his left hand the series of
Luria “fist–edge–palm.”
The examiner performs the series three times with the patient, then says to
him/her: “Now, do it on your own.”
• Score:-
six correct consecutive series alone: 3
At least three correct consecutive series alone: 2
Fails alone, but performs 3 correct consecutive series with examiner: 1
Cannot perform 3 correct consecutive series even with the examiner: 0

15. Conflicting instructions
“Tap twice when I tap once.”
• To be sure that the patient has understood the instruction, a series of three trials is run:
1-1-1.
 “Tap once when I tap twice.”
• To be sure that the patient has understood the instruction, a series of three trials is run:
2-2-2.
• The examiner performs the following series: 1-1-2-1-2-2-2-1-1-2.
 Score:-
No error: 3
One or two errors: 2
More than two errors: 1
Patient taps like the examiner at least four consecutive times: 0

16. Environmental Autonomy
• “Do not take my hands.”
• The examiner is seated in front of the patient. Place the patient’s
hands palm up on his knees. Without saying anything or looking at
the patient, the examiner brings his hands close to the patient’s and
touches the palms of both the patient’s hands
• If the patient takes the hands, the examiner will try again after asking
him/her: “Now, do not take my hands.”
Score:-
Patient does not take the examiner’s hands: 3
Patient hesitates and asks what he/she has to do: 2
Patient takes the hands without hesitation: 1
Patient takes the examiner’s hand even after he/she has been told
not to do so: 0

17. OFC–subcortical circuit
• Mediates Empathy, Civil and Socially Appropriate Behavior.
• It pairs Thoughts, Memories, and Experiences with corresponding Visceral And
Emotional States.
• Medial OFC -----Reward processing and behavioral responses.
• Lateral OFC ----- External, sensory evaluations including decoding punishment.
• Anterior subregions process the reward value for more abstract and complex
secondary reinforcing factors such as money.
• Posterior areas -------concrete factors such as touch and taste.
• Posteromedial OFC ------evaluating the emotional significance of stimuli

18. • Site:-
• Ventromedial caudate
• Mediodorsal aspects of the globus pallidus interna
• Medial ventral anterior and inferomedial aspects of the magnocellular
mediodorsal thalamus.
• Classic personality change experienced by “Phineas Gage” following injury of his
left medial prefrontal cortex by a metal rod in a construction accident, is
associated with impulsivity, disinhibition, irritability, aggressive outbursts, socially
inappropriate behavior,and mental inflexibility
• E.g.,
 Persons with bilateral OFC lesions may manifest “theory of mind” deficits.
 Schizophrenia, depression, OCD, FTD, HD
 Other condition that may affect are:- head trauma, rupture of anterior communicating
aneurysms, and subfrontal meningiomas.
OFC–subcortical circuit

19. 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. Stroop test
4. Go/ No-Go test
OFC

20. Stroop Test
Examines the ability of the patient to inhibit responses.

21. “Tap once when I tap once.”
• To be sure that the patient has understood the instruction, a series of three trials is run:
1-1-1.
“Do not tap when I tap twice.”
• To be sure that the patient has understood the instruction, a series of 3 trials is run: 2-2-
2.
• The examiner performs the following series: 1-1-2-1-2-2-2-1-1-2.
 Score:-
No error: 3
One or two errors: 2
More than two errors: 1
Patient taps like the examiner at least four consecutive times: 0
Go–No Go test

22. ACC and its subcortical connections
• Motivated behavior
• Conflict monitoring
• Cognitive control
• Emotion regulation. Subgenual and region rostral to the genu of the
corpus callosum with reciprocal amygdala
connections
· Cognitive Functions And
Behavioral Expression of
Emotional States
Dorsal ACC regions are
interconnected to lateral and
mediodorsal prefrontal regions
The Ability To Pursue and Regulate
Goal-oriented Behavior

23. • Site:-
• Nucleus Accumbens/ Ventromedial Caudate
• Ventral Globus Pallidus
• Ventral Aspects Of The Magnocellular Mediodorsal Thalamic Nuclei
• Ventral Anterior Thalamic Nuclei.
• Lesion:-
• Amotivational syndromes (apathy, abulia, akinetic mutism)
• Cognitive impairments including poor response inhibition, error detection,
and goal-directed behavior.
• E.g., AD, FTD, PD, HD, head trauma, brain tumors, cerebral infarcts, and
obstructive hydrocephalus.
ACC and its subcortical connections

24. Trail Making test A Trail Making test B
Sensitive to energization deficits
Assesses Visuomotor attention and
scanning.
Task setting and Monitoring errors

25. Trail Making Test

26. Sample Questions to Probe Each Cognitive Domain

27. Sample Questions to Probe Each Cognitive Domain

28. Sample Questions to Probe Each Cognitive Domain

29. Case Scenario

30. A 62-year-old man presented for evaluation of a 3-year history of new behavioral symptoms. He had become less
hard-driving in his work as an attorney, accepting fewer cases and taking longer to close them. Although he had
always been a diligent gardener, he left the yard unattended despite his wife’s encouragement. He became less
systematic when attempting to repair broken household fixtures or plan even short trips. His emotional range
diminished; he remained agreeable, almost malleable, and warm toward his wife, but his conversations with her
lacked depth. Spontaneous speech slowly diminished but was otherwise intact. He often repeated questions or
asked for clarification about recent events.
On examination, motor function was spared. His Mini-Mental State Examination (MMSE) score was 21/30.
Neuropsychological testing revealed executive deficits, especially in processing speed, generativity, and response
switching, as well as poor delayed verbal recall and spared visuospatial function. MRI revealed severe left-
predominant medial and dorsolateral frontal atrophy with conspicuous sparing of the anterior temporal lobe and
posterior brain regions but marked left hippocampal atrophy

32. Differences between various types of FTD
Puppala GK, Gorthi SP, Chandran V, Gundabolu G. Frontotemporal Dementia – Current Concepts. Neurol India 2021;69:1144-52.

33. QUIZ

34. Q. Impulse control and social behavior is the function of which of the
following circuit?
1. Premotor-subcortical circuit
2. Orbitofrontal circuit
3. DLPFC circuit
4. Anterior Cingulate circuit

35. Q. The ability to pursue and regulate goal-oriented behavior, i.e.,
Cognitive control is mediated by :-
1. Orbitofrontal subcortical circuit
2. Dorsolateral prefrontal subcortical circuit
3. Anterior cingulate subcortical circuit
4. Dorsolateral head of the caudate

36. Q. Reward processing and behavioral responses is mediated by :-
1. Lateral Orbitofrontal cortex
2. Medial Orbitofrontal cortex
3. Anterior cingulate subcortical circuit
4. Posteromedial Orbitofrontal cortex

37. Q. Evaluation of the emotional significance of stimuli is done by:-
1. Lateral Orbitofrontal cortex
2. Medial Orbitofrontal cortex
3. Anterior cingulate subcortical circuit
4. Posteromedial Orbitofrontal cortex

38. Q. Conceptualization is mediated by which region of the brain?
1. Anterior cingulate subcortical circuit
2. Left Perisylvian area
3. Right Perisylvian area
4. Lateral Orbitofrontal cortex

39. Q. Obsessive-compulsive disorder is related to dysfunction of which of
the following circuits?
1. Orbitofrontal subcortical circuit
2. Dorsolateral prefrontal subcortical circuit
3. Anterior cingulate subcortical circuit
4. Dorsolateral head of the caudate

40. References
• Bradley and Daroff’s Neurology in Clinical Practice, 8th edition
• Continuum Journal
• Brazis, Paul W. Localization in clinical neurology.
• Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally
segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci
1986;9(1):357–381. doi:10.1146/annurev.ne.09.030186.002041.
• Puppala GK, Gorthi SP, Chandran V, Gundabolu G. Frontotemporal Dementia –
Current Concepts. Neurol India 2021;69:1144-52.
• Michael Hoffmann, "The Human Frontal Lobes and Frontal Network Systems: An
Evolutionary, Clinical, and Treatment Perspective“ International Scholarly
Research Notices, vol. 2013.

41. THANK YOU