CORTICAL-SUBCORTICAL NETWORKS AND A DUAL TIERED MODEL OF COGNITION – THEORY AND PRACTICE LFK www.hostzone.com/koziol
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