CORTICAL-SUBCORTICAL

NETWORKS AND A DUAL

TIERED MODEL OF

COGNITION – THEORY AND

PRACTICE

LFK

www.hostzone.com/koziol

Cortical and Subcortical

Structures

• The cortico-centric model

• The basal ganglia and cerebellum are often

presented as co-processors of movement.

• Neuropsychological test interpretation and

the horizontal organization of the brain.

• Lateralized hemispheric differences in

information processing.

• Anterior and posterior differences in

cognitive processing.

Squire, 2005

Kolb & Whishaw, 2008

Current Neuropsychological

Evaluation• Neuropsychology is very adept at measuring the

functioning of the medial temporal lobe memory system (posterior cortices)

• Neuropsychology is adept at assessing aspects of frontal system functioning, especially DLPFC processes

• Neuropsychology does not assess the ability to benefit from interacting with the environment;

different types of “memory” are not assessed - this is a huge drawback

Models of Cognition

• Perception-cognition/thought-movement

• First we perceive

• Then we think (about what to do)

• Then we act (we engage a motor program)

• But in “real life,” do things really work that

way?

Cisek, 2007

Movement, Cognition, and

Perception • Sometimes we perceive, think, and move

• Sometimes we perceive and move without thinking - we do things without conscious awareness, just because things need to be done

• Sometimes we move in order to perceive

• Movement is focal. Accepting this idea requires a different understanding of functional neuroanatomy

• We are born to move!

Vertical Brain Organization

• There are two vertically organized re-

entrant brain systems that interface the

cortex and the descending systems:

• The cortico-striatal system

• The cerebro-cerebellar system

NEW WORKSHOP TITLE

• THINKING OUTSIDE THE BOX!

• This requires a significant modification to the cortico-centric model of cognition and behavior

• If ontogeny recapitulates phylogeny, then is the cortico-centric model of neuropsychology inaccurate and misleading?

Frontal Cortex

Striatum

Globus Pallidus

Substantia Nigra

Thalamus

Chapter 1 Figure 1

Simplified version of Frontal-subcortical circuit

Cerebral Cortex

Pontine Nuclei

Cerebellar

Cortex/Dentate

Nucleus

Red

Nucleus

Thalamus

Chapter 1 Figure 2

Simplified version of Cerebro-cerebellar circuit

NEW WORKSHOP TITLE

• FOLLOW THE YELLOW BRICK ROAD

• If we follow the connectional profiles of vertical

brain organization, then the integrated functional

neuroanatomy that might be proposed by the

“Wizard of Oz” does not provide support for many

of the inferences that are derived from

neuropsychological tests

• What do our tests assess? What are we neglecting?

The Purposes of this Workshop

• To provide an understanding of the structure and function of the basal ganglia

• To provide an understanding of the structure and function of the cerebellum

• To provide an understanding of cortical-subcortical interactions

• To propose an anatomy of a dual tiered model of brain function

• To present this information in a practical way

Basal Ganglia SubdivisionsBasal ganglia

structure

Primary

subdivision

Secondary

subdivision

Tertiary

subdivision

Striatum Dorsal striatum

Ventral striatum

Caudate

Putamen

Nucleus accumbens Core

Shell

Septum

Olfactory tubercle

Globus pallidus External segment

Internal segment Outer portion

Inner portion

Ventral pallidum

Substantia nigra Pars compacta

Pars reticulata Pars lateralis

Subthalamic nucleus

Evolutionary Underpinnings

• A general evolutionary model – survival

through interaction with the environment

• Object recognition and object location

• Motor or action programs-what to do and

how to do it

• Intention programs-when to do it; when to

act

Intention Programs

• Knowing when to start a behavior

• Knowing when not to start a behavior

• Knowing when to persist with a behavior

• Knowing when to stop a behavior

Types of Processing

• Stimulus-based processing (this includes reflexes, habits, skills, and procedures)

• Higher-order processing

• We usually do things automatically, just because they need to be done

• If circumstances change, higher-order processing, cognitive control mechanisms allow for “adjustments”

Adaptive Advantages of

Stimulus-based Processing

• Simplicity of design

• Biologically cost effective

• High speed of reaction

• Exploitation of predictable features of the

environment

• Under the proper conditions, the behavior

always works

Disadvantages of Stimulus-based

Processing

• Limitations to the number of viable trigger stimuli

• Problems of competition between triggers

• Little or no spontaniety or autonomy

• No capacity to generate/synthesize new behavior under novel environmental conditions

• No ability to “move in order to perceive”

Higher-Order Processing

• Managing novelty and ambiguity

• Problem-solving – setting the context for

stimulus-based control

• Autonomy – programming goal-directed

behavior

Disadvantages of Higher-Order

Controls

• This system has one huge drawback – it is

SLOW!

• Stimulus-based control – a system which is

fast, accurate, efficient, but “dumb.”

• Higher-order control – a system which is

smart, extremely flexible and creative, but

slow.

The Frontostriatal System

• Nature’s response to adaptive pressure is the frontostriatal system

• Both systems coexist

• Both systems interact in order to learn and benefit from interacting with the environment

• Bonus – solutions to “novel” problem-solving situations can be automated for future application.

• Adaptation is characterized by alternating episodes of automatic processing with higher-order control

Ideal Higher-Order Control

Processing• Provide solutions in situations where stimulus-

based control is unable to do so or has failed.

• Allow for a “best guess” or extrapolation based upon aspects of stimulus input or context.

• Determine goal-directed action by synthesizing certain response links and inhibiting others.

• To automate solutions to previously “novel” situations for future application.This is the “heart” of the matter – operating on the basis of acquired associations

What Functions Do The Basal

Ganglia Serve?• The BG promote the learning of procedures,

habits, and cognitive skills-instrumental learning

• Highly specialized regions subserve movement, cognitive skills, and affective/emotional predispositions

• The linking of automatic movement with voluntary movement

• Intention (when) programs

• The BG are a selection mechanism

Phylogeny and the Basal Ganglia

• The forebrain components of the BG are well

conserved across vertebrates

• The Nucleus Accumbens and the Globus Pallidus

• The Caudate and the Putamen

• The Basal Ganglia and the Cortex

• The connectional profiles we will discuss are

phylogenetically very old.

• Implications for Executive Functions

A Major Evolutionary Trend

• The striatum always receives sensory input

from the largest and presumably most

important sensory region of the brain.

• In amphibians, inputs originate from the

dorsal thalamus.

• In reptiles, inputs originate from the ventral

area of the olfactory cortex.

• In mammals, striatal inputs invariably arrive from

the neocortex.

• In climbing up the phylogenetic scale, the striatum

receives more and more highly processed and

highly specialized sensory inputs.

• A major evolutionary trend is the progressive

involvement of the cortex in the processing of the

thalamic sensory information projected to the

striatum.

• Mammals always direct output from the

basal ganglia back to the thalamus and from

there, back to cortex, maintaining

segregated, parallel circuits.

• During the course of phylogenetic

development, the neocortex was slowly and

gradually grafted upon this system.

Why Is This of Critical

Importance?• The neocortex operates according to a principle of

excitation.

• A complex organism cannot function only according to principles of excitation

• The basal ganglia are the first and only region of the brain that are capable of massive and selective inhibitory control

• Cortical-basal ganglia interactions control the processes of excitation versus inhibition, enabling focused attention and behavior.

Interim Conclusions

• The basal ganglia have always played a critical role in executive control

• The basal ganglia assist in allowing the organism to make choices and decisions which are in the best interest of the organism as a whole.

• The basal ganglia continue to serve a critical role within the executive functioning system.

• The basal ganglia are the vertebrate brain solution to the selection problem

Basal Ganglia Input Structures

• Caudate

• Putamen

• Nucleus Accumbens

• These input structures receive direct

projections from nearly the entire cerebral

cortex

Graybiel, 2001

Matrix / Striosome Compartments

Basal Ganglia Intermediate

Structures

• Subthalamic Nucleus

• Globus Pallidus Externa

• Substantia Nigra Pars Compacta

• These nuclei project most heavily to other

basal ganglia nuclei

Basal Ganglia Output Structures

• Globus Pallidus Interna

• Substantia Nigra Pars Reticulata

• Ventral Pallidum

• These output nuclei send projections to the

thalamus (VA/VL/DM/IL), which project

back upon cerebral cortex

Cortical – Basal Ganglia Circuitry

Koziol & Budding, 2009

Salloway, Malloy, & Duffy,2001

Cortical – Basal Ganglia Circuitry

The Direct and Indirect Pathways

• Most cortical projections into the striatum

have two pathways

• The Direct Pathway

• The Indirect Pathway

• These pathways project to the Matrix

compartment

Springer, 2011

Springer, 2011

Parent & Cicchetti, 1998

The Hyperdirect Pathway

• The Subthalamic Nucleus – STN

• The Subthalamic/Hyperdirect Pathway

• Projections originate from frontal regions

• Quickly suppresses Thalamic activity

The Striosomal Pathway

• Projections originate primarily from

Orbitofrontal and Temporal limbic regions

• Project to the Striatal “Patches” or

Striosomes

• This pathway projects to the SNpc

Graybiel, 2001

Matrix / Striosome Compartments

Excitation and Inhibition

• The Cortex – primarily functions according

to principles of excitation

• The Basal Ganglia – a selection mechanism

that balances excitation with inhibition

• Without these pathways, the vertebrate

brain cannot decide/select what to attend do

and what to do!

Information Integration and

Learning

• The segregated, parallel connectional

profile explains how attention and behavior

can be sustained or maintained.

• However, we live in a constantly changing

environment in which attention and

behavior must be adjusted or changed to

meet the demands of the internal/external

environment as conditions develop.

• Parallel and segregated processing through

the identified circuits does not address this

critical issue.

• Information must flow between circuits for

generating new or changing previously

learned behaviors.

Basal Ganglia Integrative

Networks

• Cortico-striatal pathways are characterized by

focal, circumscribed, and topographically

organized projections

• However, there is some overlap between terminal

fields from these different functional regions.

• There are regions where focal projections from

cognitive and reward-related prefrontal areas

converge.

Graybiel, 2001

Matrix / Striosome Compartments

• Although the Gpi is also topographically

organized according to functional domains,

information integration occurs by

convergence at the borders between

functional domains.

• Within the Gpe, projection fibers extend

well into other functional domains besides

through the domain border areas.

• A striato-nigro-striatal projection system has also

been identified.

• This midbrain, SN system includes reciprocal

connections with cognitive, limbic/motivational,

and motor regions of the striatum.

• This establishes a mechanism for integrating

cognition and motivation for influencing motor

decision-making processes.

Haber, 2010

Cortical – Basal Ganglia Circuitry

• The thalamo-cortical pathway is not simply

a “relay station” for thalamus to activate

cortex.

• The thalamus has additional, non-reciprocal

connections projecting to nearly all cortical

layers, besides those parallel and segregated

regions from which the cortico-striatal

“loop” originated.

Haber, 2010

• Therefore, cognitive/associative,

motivational/reward, and motor control functions

are not discretely, distinctly, and completely

segregated within cortico-striatal networks.

• Specific integrative networks function in concert

with parallel circuitry.

• This allows for behavior to be focused and

maintained, as well as modified and changed, and

for new behaviors to be learned.

The Basal Ganglia and Working

Memory

• Working memory consists of two

contradictory demands

• Representations in working memory must

be robust

• Representations in working memory must

be flexible

• Working memory and motor programs

Cognitive Control

• Cognitive control is higher-order processing

• Working memory is cognitive control

• Cognition evolved and developed for the

purpose of controlling the motor system

• Child development is the process of

acquiring increasing control over the motor

system

Koziol & Budding, 2010

The BASAL GANGLIA AND

INSTRUMENTAL LEARNING

• The Basal Ganglia are an instrumental

learning system.

• Instrumental learning is based upon

Dopaminergic activity

• The roles of D1 and D2 in instrumental

learning – sensitivity to the reward-based

characteristics of the environment

DOPAMINE AND

INSTRUMENTAL LEARNING

• Tonic Dopaminergic levels

• D1 receptors and sensitivity to the positive reward characteristics of the environment

• D2 receptors and sensitivity to the negative reward characteristics of the environment

• Dopaminergic “spikes” versus “dips.”

• Dopaminergic activity also modulates movement

The Basal Ganglia in Human

Sequence Learning

• Learning a relative sequence of events across time

• Viewing 4 locations on a screen that correspond to

4 response keys

• Stimuli actually appear in a sequence

• Learning is measured by comparing reaction time

to sequenced versus random ordered presentations

• Head of caudate and anterior putamen

Categorization and Classification

• The ability to respond differentially to objects or events that belong to separate classes or categories is termed categorization

• This ability is absolutely essential for adaptation and survival

• Not all complex category learning tasks are the same

Types of Category Learning

• Unstructured categories (my passwords,

important phone numbers – MTL)

• Probabilistic learning

• Information-integration learning

• Rule-based category learning

Category Learning

• Category learning with feedback

• S’s view stimuli and learn which stimuli

belong in which category by trial and error

• PD and HD are impaired on classification

learning

• High levels of caudate activity are are found

on category learning tasks

Functional Specialization of

Striatal Regions• Learning about rewards involves the affective loop

(VS and OFC)

• Learning visual categories involves the visual loop

• Boday/Tail of CN demonstrate increased activity during correct classification, activity increased with time course of learning, and greater activity is exhibited in good versus poor learners.

• Head of CN demonstrates peak activity with positive feedback

Cortical-Striatal Interaction

• Does the cortex “teach” the striatum what to

do?

• Activity in the head of the CN peaks early

after the beginning of each new

task/problem and then drops.

• Activity in PFC reaches peak values later.

• Striatal activity preceeds frontal activity!

• These data are in agreement with theories

that suggest the striatum identifies the

behavioral context necessary for the frontal

lobe to select an appropriate strategy.

• The striatum is important for recognizing

the behavioral context and modulating

activity in the cortex.

Orbito-

Frontal

Anterior

Cingulate

Dorsolateral

Prefrontal /

Posterior

Parietal

Temporal

Cortex

Ventrolateral

Prefrontal

Premotor

SMA/

Somato-sensory

Ventral

Striatum

GPi SNr

Thalamus

Caudate:

Head

GPi SNr

Thalamus

Caudate:

Body TailPutamen

GPi SNr GPi SNr

Thalamus Thalamus

Motivational Executive Visual Motor

Parallel Corticostriatal Loops

AssociativeKoziol & Budding, 2010

Interim Summary

• Stimulus-based processes and higher-order

processes coexist and interact.

• The basal ganglia link automatic

movements with voluntary movements so

that behaviors are biologically adaptive.

• This linking includes translating sensory

input into motoric “what” and “when.”

• The basal ganglia place a situation in context and select behaviors/mobilize procedures according to that context.

• PFC sets goals and develops new stimulus-based programs when existing programs do not work.

• The basal ganglia operate on the basis of reward-based instrumental learning – acquired associations

• This has direct implications for neuropsychological testing.

Neuropsychological Evaluation

• Sequence learning is not assessed

• Instrumental learning is not assessed; information about a person’s sensitivity to the reward characteristics of the environment is not obtained

• The use of practice effect as a source of clinical information instead of practice effect as a source of error

CORTICAL-SUBCORTICAL

NETWORKS AND A DUAL

TIERED MODEL OF

COGNITION – THEORY AND

PRACTICE

Part II

LFK

www.hostzone.com/koziol

The Cerebellum – Structural

Divisions

The Cerebellum – Lobes and

Deep Nuclei

• The anterior lobes and posterior lobes are divided by the primary fissure

• The anterior and posterior lobe together form the corpus cerebelli

• A ventral view reveals the nodulus and flocculus which together are called the flocculondular lobe

• Deep cerebellar nuclei

The Cerebellum – Functional

Divisions• Vestibulocerebellum – involved in making

postural adjustments to vestibular stimulation

• Spinocerebellum – responsible for maintaining muscle tone, for coordinating the muscles involved in balance, for changes in posture, and for adapting motor programs for varying conditions, including walking and running

• Cerebrocerebellum – plays a role in learning new motor skills and in modulating non-motor, cognitive, and affective processing

Vascular System

Neocortex and Cerebellar

Infrastructure

Purkinje Cells, Unknown Source

What Does The Cerebellum Do?

• The cerebellum regulates neural signals in other

parts of the brain

• The cerebellum accomplishes this through “loops”

of interaction

• Copying the content of cortical working memory

• This allows the cerebellum to generate models of

what the brain wants to do so that behavior

becomes efficient

Cerebral Cortex

Pontine Nuclei

Cerebellar

cortex/Dentate

Nucleus

Red

Nucleus

Thalamus

Cerebro-cerebellar-thalamic

connections

• The circuits that connect the neocortex to the cerebellum are highly segregated (as are the circuits connecting the cortex and BG)

• The organization of mossy fiber inputs remain segregated in the granular layer

• Projections to/from the deep cerebellar nuclei are also highly specific and segregated

Prefontal Cortex

Paralimbic Cortex

Superior

Temporal

Sulcus

Parietal Cortex

CerebellumPontine Nuclei Thalamus

Fig. 5: Connections between the cerebellum and the neocortex Koziol, et al, 2010

Neocortex

B G

Cerebellum

Olive

(Model)

Koziol, 2007

Functions of the Cerebellum

• In the main, the cerebellum’s function is to refine the information it receives from the cortex

• It projects this modified or “corrected” neural signal (from the deep cerebellar nuclei) back to the primary point of origin of the circuit

• This “neural signal”represents the most efficient representation of the “behavior” in question

• This representation is then retained within the neocortex

• While the BG, through interactions with the neocortex, decide “when” to act by allowing the thalamus to release behavior, the cerebellum “teaches” the brain “how” to act within its specific circumstances.

• It performs this role through refining the rate, rhythm, and force of behavior

• It adjusts the amplitude of responses so that behavior is of appropriate “quality”for the given situation

The Organization of the

Cerebellum and Cognition

• The associative and paralimbic cerebro-

cerebellar circuits are the neuroanatomic

underpinning of the cerebellar contribution

to cognition, emotion, and autonomic

functioning.

• There are discretely organized anatomic

subunits that subserve functional

subsystems within the circuitry.

• Therefore, from an anatomic perspective,

the cerebellum is an integral module in the

distributed neural circuitry that subserves

sensorimotor, cognitive, autonomic, and

affective processing.

• The cerebellar cortex is anatomically

homogeneous

• Different regions of the cerebellum

modulate different functional domains.

• There is a topography of function within the

cerebellum that has an anterior-posterior

and a medial-lateral gradient.

Anterior-Posterior Gradient

• Sensorimotor functions are primarily mapped in

anterior regions.

• This is primarily within the anterior lobe in

lobules I-V with some representation in VIII and

IX.

• Cognitive and affective functions are represented

in the posterior hemispheres, in the vermal and

hemispheric components of VI and VII.

Medial-Lateral Gradient

• The vermis and fastigial nucleus are involved in

the mediation of autonomic and affective

regulation.

• The lateral cerebellar hemispheres and dentate

nucleus are involved in the regulation of

executive, visuospatial, linguistic, and

learning/memory functions.

• This anatomy predicts that regional involvement

should lead to focal deficits.

Additional Organizational

Features

• The cerebellum is topographically

organized

• Within the cerebellum, functions are

represented asymmetrically

• Information is processed within specific

microzones or microcomplexes – discretely

organized anatomic subunits/subsystems

From Movement to Thought

• For the brain, movement and thought are equivalent

• Once a movement or thought is “coded” within the neural circuitry of the brain, the brain will manipulate the input in the same way

• For the cerebellum, movement and thought are identical control objects

The Construction of Cerebellar

Models

• The uniformity of the cerebellum’s

infrastructure implies uniformity in the

processing of information, regardless of its

source of origin within the cerebral cortex

• How does the cerebellum perform its

operations within the context of the

circuitry that has been described?

• For the cerebellum to exert its influence, it needs to “know” what the neocortex has in mind and what it has decided to do

• Cortical cognitive control can be referred to as “working memory.”

• Working memory is modulated by interactions between the prefrontal cortex, posterior cortices, and the basal ganglia.

• Cerebro-cerebellar circuitry allows the cerebellum to “copy” the content of cortical working memory, or plans and intentions

• Sensory feedback is cortically based and it functions slowly

• For movement to be rapid, coordinated, and smoothly controlled, it cannot depend on sensory feedback alone.

• When the cerebellum copies the content of cortical

working memory, it develops a “model” that

contains all of the necessary motor, sensory

(sensorimotor), cognitive, and affective

information to perform the behavior in question.

• This is termed a Forward Model because the

model is based upon prediction or anticipation,

which by-passes direct cortical sensory feedback

• This short-cut, anticipatory control model

comprises the most efficient neuronal pathways

through which the repeated bodily movements can

be executed most quickly and precisely

• In essence, an internal model of what the brain

thinks it will do is based upon its storage of the

multiple episodes during which it has already done

so.

• As the movements are repeatedly executed

and as anticipatory, predicted “feedback” is

received from each instance, the cerebellum

has more information and becomes

increasingly accurate in its predictive

capacities

• The cerebellum uses these increasingly accurate predictions to inform successive executions of the behavior.

• This allows behavioral execution to become smoother and faster and allows the brain to store the most efficient representation of that behavior.

• This becomes the Inverse Model

Inverse Models

• Cerebellar models allow behavior to

become independent of cortical

control/cortical working memory input and

to rely less and less on sensory feedback

from the moving limbs for accuracy.

• With successful repetition, behaviors

governed consciously by cerebellar

feedforward models become automated

• As automaticity develops, it reflects the

development of cerebellar inverse models

• Inverse models permit rapid, coordinated,

highly skilled movement (and thought) to

occur at an unconscious level, outside of the

awareness of cortically based working

memory

The Cerebellum: Two

Fundamental Principles

• The cerebellum plays a critical in the initial acquisition and automation of new behaviors

• The cerebellum plays a critical role in adapting these learned, automated behaviors across various environmental settings

• These principles and dynamics appear to be at the heart of the UCT

Neocortex

B G

Cerebellum

Olive

(Model)

Koziol, 2007

Examples

• Neurodevelopment – “learning” to walk

• Playing sports – basketball, as the game

unfolds in “real time”

• Football – the well prepared quarterback

• Assembly work/moving furniture

• Cognition – problem-solving

• Motor and cognitive procedural learning

More Examples

• First responder professions

• US Airways flight landing in the Hudson

River

• Simple, daily routine tasks

• Approaches towards interpreting NP test

data

• The surgeon, etc., etc., etc…

Pathology: The Cerebellar Motor

Syndrome

• Dysmetria of the extremities – movements

become erratic in amplitude and size;

overshooting/undershooting

• Gait ataxia

• Eye movement abnormalities

• Speech

• Dysphagia

Cerebellum as a Modulator

• Possessing a normal cerebellum and disrupting function

• Never possessing much of a functional cerebellum

• Possessing a cerebellum with focal abnormality.

• Cerebellar pathologies can look different at various ages/stages of neurodevelopment

The Dual Tiered Model

• All domains of behavior can be conceptualized within a dual tiered model of brain function

• Neuroanatomic data support this conclusion in each and every domain that has been studied

• Without dual tiered systems, the vertebrate, and human, cannot function autonomously!

• If you cannot “automate,” you are as good as “dead.”

• All cognitive/behavioral pathology can be explained by a dual tiered model

A Simple Practical Framework

• Cortex – devises strategies and develops programs

• Basal Ganglia – selects and mobilizes procedures based upon context/links voluntary with automatic behavior (intention)

• Cerebellum – adapts cognition and behavior to the situation (rate, rhythm/timing,and force/amplification)

• This has implications for neuropsychological testing