Basal ganglia disorders Flashcards
What is the basal ganglia and what does it do
The basal gangli are a cluster of interconnected neurons (a mass of grey matter) localised beneath the neocortex
It can be divided into
The Global pallidus :
- internus
- externus
It is responsible for motor control primarily
Ext
- motor learning
- executive functions and behaviours
- emotions
What is the Neuro anatomy of the basal gangli
Caudate nucleus
^ lateral to the lateral ventricle
Putamen
^ most lateral part of basal ganglia on axial/ coronal sections
Global GPi / GPe
- internus
- externus
^ located medial to the putamen
Subthalamic nucleus (STN)
^ located ventrally to the thalamus
Substantia Nigra (SN)
- pars compacta (SNc)
- pars reticulata (SNr)
^ large structure of the mid brain
What is the function of the basal ganglia
Input
Caudate and Putamen
Receive large number of inputs from the cortex
(Other, brainstem structures and thalamus)
Basal ganglia networks
Output
GPi and SNr
Outputs to the cortex via thalamus
Inhibitory to the thalamus/ cortex
Cycle
Input —> output = through basal ganglia network
Output —> input = through cortex
What is the Neuro chemistry of the basal ganglia
All structures are inhibitory (GABA) except STN
STN = excitatory (glutamate)
SNc (subthalamic nucleus pars compacta)
- release dopamine DA, a neuromodulator role is depended upon downstream receptors present.
Dopamine receptors: D1/5
- Gs coupled
- location: substantia nigra
- increases intercellular level of cAMP by activated adenylate cyclase (1)
Adenylate cyclase increase (5)
Dopamine receptors : D2/3/4
- Gi coupled
- location: striatum(2/3) amygdala (4)
- decreased adenylate cyclase (3/4), increased intercellular cAMP by activated adenylate cyclase (2)
What is the conceptual basis of basal ganglia physiology
Direct / Indirect pathways
Direct: excitatory (go)
- maintained message.
Indirect: inhibitory (stop)
- down regulated message.
Normal state - predominantly indirect
(Modulates the cortex)
What are the current concepts of basal ganglia concepts
New concept for the basal ganglia as domains)
Functional subdivisions:
Basal ganglia domains
1. Motor
2. Associative
3. Limbic/ emotional
^ maintain spatial topography
Circuits form a “message passing” network through the formation of “open non-reciprocal” and “closed reciprocal” spiral loops
Movement disorders of the basal ganglia
PD
- loss of dopaminergic neurons in the SNc a
- intraneuronal fibrillar aggregates mainly consisting of a-syn (lewy bodies)
HTT
- loss of GABAergic neurons of the basal ganglia
- caudate nucleus and putamen atrophy
Hemiballismus
- lesion in the contralateral STN
- ballismus, affecting 1 hemi body; left side
PD basal ganglia
- loss of dopaminergic neurons in the SNc
- loss of pigmented neurons
- intraneuronal fibrillar aggregates mainly consisting of a-syn (lewy bodies)
- profound reduction in dopamine structural concentration in PD patients
Clinical presentations
- bradykinesia (slowing/ fatigue of movement)
- rigidity
- resting tremor (BG, cortical loops and cerebello-thalamo-cortical networks)
Non-motor features
- low mood
- anxiety
- bladder problems
DBS target
- STN
HTT, basal ganglia
- loss of GABAergic neurons of the basal ganglia
- caudate nucleus and putamen atrophy (significant and progressive)
- enlarged ventricles due to atrophy, seen in prodromal HTT
- preferential loss of indirect pathway striatal neurons, resulting in hyperactivity of the direct pathway
Clinical presentations
- chorea (hyperkinetic)
- cognitive impairment
- psychiatric manifestations
Cognitive deficits
- processing speed
- sequencing
- distractibility
What are the different types of basal ganglia loops
Motor loop
- movement control
Oculomotor loop
- component of eye movement control
Lateral orbito-frontal loop
- control of social behaviour
Dorsolateral prefrontal loop
- control of executive function, planning, working memory
Anterior cingulate circuit
Basal ganglia pathology and movement
Hyperkinetic
- tremor (oscillating)
- dystonia (sustained)
- chorea
- myoclonus (jerking)
- tics
Akinetic
- Parkinsonism
- other
What is the sorting house vs clearing house model ?
“The basal ganglia at the same time focus the attention, emotional preparation and excitability on one single event by simultaneously suppressing and fading all other happenings and motivational objects”
- suppression of things we don’t want to or mean to do
Proposal of “selection function” of the basal ganglia
The basal ganglia has all the aspects of a clearing house that redirects samples of ongoing critical activity and facilitates (selects) one while suppressing all others
Basal ganglia literature implies “selection” that is implemented by selective disinhibition within the looped architectures that connect the basal ganglia with the cerebral cortex and brainstem structures
What is the rate model of the basal ganglia
Postulates that the basal ganglia process cortical inputs through parallel pathways from the striatum through to basal ganglia output nuclei and feed it back to the cortex via thalamic relay
Increase our dearest in firing rate of different basal ganglia outputs
- postulated to regulate basal ganglia output and behaviour
The rate model is an oversimplification
- direct and indirect pathways represent only a subset of connections within the basal ganglia which may be bidirectional
- connections may exist between the direct and indirect pathways
Additional
- hyperdirect pathway also protects from the cortex to the STN and suppresses movement
Which basal ganglia lesions are associated with movement disorders
Putamen (most direct involvement for movement)
-dystonia
Thalamus
-dystonia
-asterixis
- tremor
Subthalamus
- ballism
- chorea
What is the role of dopamine in the motor basal ganglia network
Direct pathway
- D1 has dopamine receptors, when they binds to sectio direct pathway it is activated
Indirect pathway
- D2 has dopamine receptors, when they bind, the indirect pathway is inhibited
The role of dopamine is to promote movement
The loss of sustained dopamine is to inhibit movement
What other roles are involved in PD basal ganglia
Oscillations :
Oscillatory signals subserve important functions (developing and mature brain)
5 frequency bands
Delta
Theta
Alpha
Beta
Gamma
Lots of beta oscillations in PD
- ‘idling rhythm’ , promoter of the motor status quo
- elevated beta may be an exaggerated promoter of status quo, causing rigidity and bradykinesia
- beta suppressed by levodopa and DBS, correlated with clinical improvement
What are goal directed and habitual control in PD
Actions may have goal directed and habitual components
- may be many sites at which output from the two systems converge (ex., cortical motor output and brainstem)
Ability to perform normal automatic, habitual components of actions (arm swinging, facial expression, gait pacing etc) is impaired
This ability is further aggravated when patients are required to engage in a goal directed activities.
In PD, loss of dopamine innervation from sensorimotor regions in the basal ganglia causes dysfunctional output signals from these territories and their associated networks (disoriented inhibitory output)
Presumably lots of function here, leads to reliance on goal directed control
What happens when you get trapped in goal directed control
Gradual replacement of autonomic control , by goal directed processing in patients with PD
Once action sequences become automatic, it is difficult to revert them to conscious volitional control
PD patients increasingly operate in goal directed control mode, and have difficulty in automatic action sequences
What are the possible mechanisms of dystonia and what symptoms do they present
Loss of inhibition
- hyperkinetic disorder
- mirror movements/ overflow (when move finger, other fingers may also move)
- agonist/ antagonist co-contractions - reciprocal inhibition impairment
Abnormal brain plasticity
- repetitive TMS and transracial direct stimulation (tDCS) modulates cortical excitability that outlasts the period of brain stimulation
- found in writing, cranial and cervical dystonia
Sensorimotor mismatch
- sensory tricks (touch point)
- impaired temporal and spatial discrimination threshold
- abnormal somatotopic organisation in focal hand dystonia
