Goals, Executive Control, and Action: Principles of the Frontal Lobe

Quotes and Case Studies: Phineas Gage

The Case of Phineas Gage (JM Harlow, 1868/1998):
- Description of personality after injury: ‘He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires … A child in his intellectual capacity and manifestations, he has the animal passions of a strong man … His mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage’.’
- Mechanism of injury: The passage of an iron bar through the head.

1.0 Introduction

Evolution of Understanding:
- Historically, the frontal lobes were known as the ‘silent lobes’ because they were not easily linked to simple, defined functions, unlike the busy sensory processes in other lobes.
- Over time, they came to be understood as the ‘organ of civilization’ due to their importance in cognition.
- The concept of executive control is intimately linked to frontal lobe function, though there are caveats:
  - Not all frontal lobe functions fall under executive control.
  - Not all executive control functions are subserved exclusively by the frontal lobes.
Anatomical Divisions of the Prefrontal Cortex (PFC):
- Lateral: The side region.
- Medial: The midline region.
- Ventral: The bottom region.
- Dorsal: The top region.
- The Inferior Lateral Sulcus: This major horizontal fold separates the lateral division into dorsal and ventral halves.

2.0 Phylogeny and Ontogeny

Evolutionary Expansion:
- The prefrontal cortex has expanded significantly over mammalian and primate evolution.
- An enlarged prefrontal cortex is a distinctively human and primate feature.
Comparative Neuroanatomy (Brodmann, 1909):
- Proportion of total cortex accounted for by the prefrontal cortex:
  - Humans: $29\%$
  - Chimpanzees: $17\%$
  - Macaques: $11.5\%$
  - Cats: $3.5\%$
- Exception in Marine Mammals: While whales and dolphins possess large brains, expansion occurred in the parietal cortex rather than the frontal cortex.

3.0 Function Overview

Difficulty of Definition: Frontal lobe functions do not have a single, ready-to-label definition.
Primary Roles of the Prefrontal Cortex:
- Forming goals and objectives.
- Devising a plan of action required to attain those goals.
- Selecting needed cognitive skills for plan implementation.
- Coordinating skills and applying them in the correct order.
- Evaluating actions as success or failure relative to original intentions.

4.0 A Closer Look at Frontal Lobes

Mapping via Brodmann Areas:
- Definition is based on neuron types and typical connections within each area.
- The prefrontal cortex is comprised of Brodmann areas: $8$ , $9$ , $10$ , $11$ , $12$ , $13$ , $44$ , $45$ , $46$ , and $47$ .
- Lateral View Areas: $8$ , $9$ , $10$ , $11$ , $44$ , $45$ , $46$ , and $47$ .
- Mid-sagittal View Areas: $8$ , $9$ , $10$ , $11$ , and $12$ .
Subcortical Projections and Integration:
- The dorsomedial thalamic nucleus serves as a point of convergence and the ‘summit’ of integration occurring within specific thalamic nuclei.
Connectivity for Motor Control:
- The prefrontal cortex is directly connected with every distinct functional unit of the brain.
- Three lateral frontal regions (prefrontal, premotor, and motor cortices) form a motor hierarchy.
- These regions are interconnected with the thalamus, basal ganglia, and cerebellum via recurrent axonal loops essential for motor control.
- Specific Thalamic Nuclei involved:
  - CM: Central median nucleus.
  - MD: Mediodorsalis nucleus.
  - VA: Anteroventral nucleus.
  - VL: Ventrolateral nucleus.
Diffusion Tensor Imaging (DTI) Insights:
- Tractographs suggest massive connectivity, particularly to Brodmann area $10$ .
- Ipsilateral connections: Vertical fibers (red and dark) show connections within the same hemisphere.
- Inter-hemispheric connections: Many fiber tracts travel across the corpus callosum to connect the two hemispheres.
- Midsagittal DTI views identify fiber bundles in the prefrontal cortex (often color-coded green in mapping).

5.0 A Closer Look at Frontal Lobe Function

Traditional Perspective on Executive Systems:
- Linked to motor functions, actions, and plans.
- Two broad types of cognitive operations:
  1. Formulation and Guidance: The ability to guide behavior via internal representations (plans).
  2. Adaptive Switching: The capacity for ‘switching gears’ when unexpected events occur.
Mental Flexibility:
- Definition: The capacity to respond rapidly to unanticipated environmental contingencies.
- Assessment Task: A subject must extract rules to place a round object in the correct location.
  - Trials 1 and 2: Subject follows a rule, receives feedback that it is correct.
  - Trial 3: Rule changes (e.g., object belongs in a different location).
  - Clinical finding: Patients with frontal lobe damage struggle to ‘switch gears’ in these tasks.
Executive Control and Social Maturity:
- Volitional control is not innate; it emerges gradually during development.
- It is considered a central ingredient of social maturity.
- Orbitofrontal Cortex Development: Early mother-infant interaction is critical for its development during the first months of life.

6.0 Neuroimaging the Executive Brain

Core Research Areas: Investigators use PET and fMRI to study four broad cognitive operations:
1. Attention and perception.
2. Working memory.
3. Executive function.
4. Motor control.
Methodological Caveat: Prefrontal cortex involvement is intricate and overlapping. Processes like paying attention, making decisions, and holding items in memory are active simultaneously. Careful study design is required to disentangle these processes (e.g., isolating attention from working memory).
Attention and Perception:
- Task Example: Identifying the gender of faces and pressing buttons.
- Brain Regions:
  - V1: Visual cortex activation for sensory processing.
  - FFA: Fusiform face area activated for human face recognition.
  - Frontal Lobes: Control processes of paying attention, making decisions, and motor execution (pressing buttons).
- Posner’s Networks: Dr. Michael Posner identified networks for:
  - Alerting to a stimulus.
  - Orienting to a stimulus.
  - Maintaining executive control.
Working Memory:
- Definition: The ability to keep something in mind for a limited time.
- Relation to Attention: Can be described as an ‘inward directed voluntary attention system’.
- Fuster’s Meta-analysis (2008):
  - Visual working memory: Early stages activate visual cortex, moving forward to frontal areas in later stages (stages $2$ - $6$ ).
  - Verbal working memory: Early stages activate the temporal lobe, moving forward to frontal areas in later stages (stages $2$ - $6$ ).
  - Overlap: Frontal lobe areas are active in both visual and verbal tasks, while sensory regions (occipital for visual, temporal for verbal) remain active throughout trials.
- Perception-Action Cycle: The continued activation of sensory regions suggests ‘reverberating re-entry’ of information between sensory and motor regions.
Executive Function and Motor Control:
- Tower of London Task: A puzzle requiring multiple steps and planning. It activates the Dorsolateral Prefrontal Cortex (DLPFC).
  - Research shows increased DLPFC activity in subjects who find the task difficult (Morris et al., 1993).
- Anterior Cingulate Cortex (ACC - BA 24):
  - Hypothesized to have an inhibitory effect on the frontal lobes.
  - Aids voluntary attention by inhibiting distractions.
  - Functional Distinction: Bush et al. (2000) showed the ACC has differing activations for cognitive tasks vs. emotional tasks.
Decision Making and Rule Adoption:
- Veridical Decision-Making: Simple decisions with one correct solution (e.g., remembering a phone number).
- Adaptive Decision-Making: Complex daily decisions with no single correct answer. Requires resolving ambiguity and maintaining flexibility.
- Wisconsin Card Sorting Test (WCST):
  - Tests rule adoption and mental flexibility.
  - Cards sorted by color, number, or shape.
  - Rules change mid-game without telling the subject; they must learn via trial and error.

7.0 Frontal Lobe Dysfunction

The Fragile Frontal Lobes:
- The frontal lobes act as a ‘bottleneck’ or point of convergence for damage anywhere in the brain.
- There is a reciprocal relationship; frontal injury produces ‘ripple effects’ across the whole brain.
Dorsolateral Syndrome (Symptoms):
- Perseverative Behavior: Inability to initiate behavior, or inability to terminate/change a behavior once started.
- Field-Dependent Behavior: High distractibility. Patients perform actions simply because objects are present (e.g., drinking from an empty cup, putting on someone else’s jacket, scribbling on a table).
- Mental Rigidity: Inability to change mental state or problem-solving approaches.
- Flat Affect: Emotionless voice and facial expression.
Orbitofrontal Syndrome (Symptoms):
- Disinhibition: Patients are behaviorally and emotionally disinhibited.
- Emotional Instability: Affect alternates between euphoria and rage.
- Poor Impulse Control: Impaired ability to inhibit the urge for instant gratification.
- Lack of Concern: Violation of social taboos or legal prohibitions without concern.
Non-Focal Disorders Associated with Prefrontal Dysfunction:
- Schizophrenia.
- Tourette’s syndrome.
- Attention Deficit (Hyperactivity) Disorder (AD(H)D).
- The Attentional Loop: A circuit combining frontal, brainstem, and posterior cortex. Breakdowns anywhere in this loop can cause attention deficits.

8.0 Organizing Principles of the Frontal Lobes (Fuster, 2008)

The entire frontal lobe cortex is devoted to the representation and production of action at all biological levels.
The neuronal substrate for producing an action is identical to its representation.
Hierarchical Organization of Substrate: Elementary actions are at low levels (orbitofrontal and motor cortex); complex/abstract actions are in the lateral prefrontal cortex.
Hierarchical Organization of Function: Simpler functions exist within and serve more global functions.
Anterior-Posterior Gradient: Organization is based on the level of abstraction of the action.

9.0 Towards a Unified Theory of Executive Control

Modular View: Suggests ‘fractionating’ functions by modality (vision vs. audition), language (linguistic vs. non-linguistic), or object/space (what vs. where).
Gradient View: Suggests organization in heteromodal association cortices is interactive, distributed, and not modular.
Conclusion: The choice between modular and gradient views remains a subject for future research.