CORTICAL-SUBCORTICAL

NETWORKS AND A DUAL

TIERED MODEL OF
COGNITION THEORY AND
PRACTICE

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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

Thalamus

Pontine Nuclei Red

Nucleus

Cerebellar
Cortex/Dentate
Nucleus
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 Subdivisions
Basal ganglia Primary Secondary Tertiary
structure subdivision subdivision subdivision
Striatum Dorsal striatum Caudate
Putamen
Ventral striatum 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
Natures 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
Matrix / Striosome Compartments

Graybiel, 2001
 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
Matrix / Striosome Compartments

Graybiel, 2001
 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.
Matrix / Striosome Compartments

Graybiel, 2001
 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
Ss 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.
 Parallel Corticostriatal Loops

Orbito- Dorsolateral Premotor

Temporal
Frontal Prefrontal / SMA/
Cortex
Ventrolateral Somato-
Anterior Posterior
Prefrontal sensory
Cingulate Parietal

Ventral Caudate:
Caudate: Putamen
Striatum Body Tail
Head

GPi SNr GPi SNr

GPi SNr GPi SNr

Thalamus Thalamus Thalamus Thalamus

Motivational Executive Visual Motor

Associative Koziol & 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 persons 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

Thalamus

Pontine Nuclei
Red
Nucleus

Cerebellar
cortex/Dentate
Nucleus
 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

Pontine Nuclei Cerebellum Thalamus

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

BG

Cerebellum

(Model)

Olive

Koziol, 2007
 Functions of the Cerebellum
In the main, the cerebellums 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 signalrepresents 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 qualityfor 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 cerebellums
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

BG

Cerebellum

(Model)

Olive

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