W5: Cerebral Cortex

Learning objectives

• The hierarchical organisation of the motor systems

• cortical regions of the motor system

• topographic maps in the primary motor cortex

• the function of the primary motor cortex

• the functional roles played by the other main cortical motor areas

• neuroplasticity

Hierarchical sensory-motor organisation

organisation of the cerebral cortex

• red = primary motor cortex

• somatosensory cortex = involved in processing feedback from the muscles

• premotor regions = involved in action selection + planning (dorsal/ventral regions)

• dorsal (on top) vs ventral (lower)

• supplementary motor area (midline structure) = involved in action planning + sequencing

• dorsal lateral prefrontal cortex = decision making + early stages of motor control

cerebral cortex

• cortex forms the outer surface of the forebrain (AKA grey matter)

• 6 distinct layers (laminae)

• cortex covers the other sub-cortical forebrain structures (e.g. thalamus, hippocampus)

cortex: laminae

• inputs and outputs are layer specific

• layer 4 = key input layer

• 5 + 6 = key output layers

• 3 + 5 = have really large Betz cells = defining feature of primary motor cortex = critical for execution of voluntary movement

Betz cells

M1 (BA4) contains Betz cells in layer 5 (one of 2 output layers)

• Betz cell = large pyramidal cell

• they are in layer 5 (one of the two output layers of primary motor cortex)

Cortical Projections

• Betz cells - large pyramidal cells

• Project from motor cortex to spinal tract (cortical tract neurons)

• Only 5% project to motor-neurons + the rest reach spinal interneurons

• Betz cells also project to brain stem

Corticospinal tract

• Betz cells from the motor cortex initiate, regulate and control voluntary skilled movements

• Done bye innervating alpha + gamma motor neurons in the spinal cord

• Tract crosses at medulla, so limb movements are controlled by the contralateral motor cortex

Mapping the motor cortex

• Fritsch + Hitzig (1870): electrical stimulation in dog = mapping somatotopic motor representation

• somatotopic rep. = the diff parts of the primary motor cortex that send motor commands to diff parts of the body

• Penfield (1940): stimulated during surgery on epileptic patients

• Discovered electrical stimulation causes simple movements

• Map established

• hands + feet have largest areas = seems like the more fine motor control needed determines area size in primary motor cortex

Cortical motor maps

• another way of mapping primary cortex

• close mirror relationship between sensory + motor maps

• multiple maps: maps reflect sensory-motor specialization

• purple = motor cortex maps, orange = somatosensory cortex maps

Cortical motor maps are not very realistic

• research discovered a lot more overlap between representation of body parts than expected

• don’t know what this overlap means - could be how much the body parts have to work together for movement

Study: Effector maps might not be the only organisation principle within the motor cortex

• Study - fMRI studies

• Argue that there’s a parallel organisational scheme in primary motor cortex

• Replicated with lots of very large samples (inc. infants, animals etc)

• Found 2 regions

• Effector-specific connectivity regions are interdigitated with regions showing different connectivity, structure and function

• Inter-effector regions = show high connectivity to each other and to cingulo-opercular network

• Inter-effector regions become active during planning (instead of execution) + lack effector specificity

• still controversy over whether this is another premotor cortex

What is represented in the motor cortex: muscle or movements?

Electrical stimulation:

• Brief micro-stimulation (50ms) = simple movements + contractions of contralateral muscles

• Prolonged stimulation (500ms) = complex goal-directed actions

Findings show:

• There isn’t just a simple 1-1 mapping between motor cortex + muscle contractions

• the region also = represents complex goal-directed actions

What is represented in the motor cortex: precision grip + skilled use of fingers?

• study - invasive recording study in monkeys

• trained monkeys to execute 2 types of actions

  • precision grip = more fine control w diff fingers

  • power grip = apply brute force

• recorded muscle activity EMG (electromyography)

• similar activity in both movements

• more activity before + after in precision task

Primary Motor Cortex summary

• The PMC/M1 = a principal brain area involved in motor function + located in frontal lobe

• PMC defined anatomically as = the region of cortex that contains large neurons = Betz cells

• Betz cells send long axons down the spinal cord to synapse directly onto the alpha motor neurons in the spinal cord which connect to the muscles

• Somatotopic contralateral representation but far more integrated

• Size is based on precision/fine motor control not size of body part

• Unclear specifically what the M1 codes - but individual muscles and complex actions can be ‘stimulated’ = basc, it sends the signals needed for movement

• Motor cortical stroke = permanent loss of fine motor control

Frontal Eye Fields

• it is a region in frontal lobe (a bit anterior so in front of PMC + much smaller)

• basc its the equivalent of PMC for controlling eye movements

• brain imaging found in monkeys - similar to humans

• connects to occipital lobe + receives a lot of bottom-up input about visual surroundings

• connects to prefrontal cortex (specifically in dorsolateral prefrontal cortex)

• strong connection with superior sulcus (initiates eye movements)

• can modulate activity in eye movement

• antipsychotic task = classic task used to study control of eye movement

  • peripheral stimulus appears + tendency is to look towards = in this task you must do opposite (look away)

Secondary motor areas

• Supplementary motor area (SMA)

• Pre-motor

  • Dorsal PM (PMd)

  • Ventral PM (PMv)

• Posterior parietal cortex

Secondary Areas

• Very dense connections between sec. motor areas

• Heavily connected to primary cortex = leading to execution of actions

• SMA + PMC more involved in planning movements

• Brain imaging shows activation when imagining / planning sequence of movements - even if no action is performed

Posterior Parietal Cortex (PPC)

• Links frontal cortex (decision-making) with premotor (planning) areas.

• Receives info from sensory regions (visual, sensorimotor cortexes)

• Important for determining potential actions/goals given the environment (e.g. pick up coffee, continue working)

• Frontal cortex more critical = decision about which action to perform + secondary area = develop plan for that actions

Supplementray Motor Area (SMA)

• SMA now considered to be 2 areas:

  • SMA proper = learning

  • Pre-SMA = execution

• Postural stability

• Planning + executing complex sequential movements

  • e.g. Parkinson’s patients usually have decreased activity in sequencing tasks

• Initiation of internally generated movements (rather than stimulus driven)

Dorsal premotor (PMd)

• Important in preparation of movement

• Learning conditional actions (response to external cues/environmental signals)

  • Red traffic light = foot on brake

  • green = foot on gas

  • set related activity e.g. ready, set, go

Ventral premotor (PMv)

• Important for sensory guidance of movement - responsive to tactile, visual + auditory stimuli

• Visuomotor control during grasping

• Mirror neurons

PMv and Mirror Neurons

• First reported in ventral premotor cortex (PMv)

• MNs show similar activity when monkey makes a goal directed action + when the same action is observed or heard

• Thought to be important for learning through observation

• Also for understanding other people’s intentions

Neuroplasticity

• The ability of the brain to form + reorganise synaptic connections - esp in response to learning following injury

• This can occur in all areas of brain - very clear examples in PMC + motor sensory cortex

• Very pronounced in childhood + decreases as you get older

Changes in the somatotopic map

Sensory remapping = rapid changes in somatosensory (motor maps) evident after change in inputs training (new skill)

neuroplasticity: example from co-activation

• fusion from a lab that uses fMRI-

• simple tasks - asked to do things with fingers except thumb

• see where in the brain gets recruited

• looked at distance in brain space between these hand areas

• then index and middle finger glues together for 24 hrs = found changes in motor maps (became more similar)

neuroplasticity: example from amputation

• hand amputation

• amputees had similar maps to controls = no evidence of reorganisation of adjacent motor areas

• people born with only one hand = evidence that some of the face region starts to invade the hand area

Changes in maps reflect neuroplasticity

• Long term changes in function connectivity e.g. growth of neurons

• Branching (or pruning) of dendritic connections

• Neurons appear to ‘compete’ for space in cortex = unused cortex gets overtaken by other inputs

• Imaging of the living mouse brain shows changes (growth + pruning) in dendritic branches within hours / days of new task

Learning-based neural changes: synapse efficacy

Synapse enables one neuron to communicate with another

Pre-synaptic:

• Increase vesicle volume

• Increase availability of vesicles

• Increase release probability

Synaptic cleft:

• Reduce re-uptake mechanisms

• Reduce gap dimenstions

Post-synaptic:

• Increase receptor density / area

Growth:

• Make new synapses

Long-term synaptic plasticity

Specific times patterns of neuronal activity can = long-term synaptic changes:

• Long-term potentiation (LTP) =

  • is an activity-dependent persistent strengthening of synapses

  • these produce a long-lasting increase in signal transmission between 2 neurons

• Long-term depression (LTD) =

  • is an activity-dependent reduction in the efficacy of neuronal synapses

  • these produce long-lasting deceases in signal transmission between 2 neurons

Associative LTP induction

• NMDA channel is normally blocked by MG++

• Concurrent voltage change to drive out Mg

  • achieved by glutamate binding to nearby AMPA receptors

  • equivalent to stimulation with high freq electrical pulses

• Glutamate binds to NMDA + AMPA receptors

  • temporary change in shape of channel = opens up channel

  • calcium can enter through the open, unblocked NMDA channel

• Ca++ entry triggers intra-cellular signalling cascade which results in

  • migration of AMPA receptors from intracellular stores to the cell membrane

  • synthesis of more AMPA receptors

Key principles of LTP

Cooperatively:

• LTP requires simultaneous activation of large number of axons (due to large depolarisation)

Associative:

• When weak synaptic input is paired with strong + long depolarisation = can propagate + cause LTP at synapse with weak input

• If 2 neurons fire together (1 weak + 1 strong) then the strong one will allow the weak one to become stronger over time

Synapse specific:

• if particular synapse is not activated then LTP will not occur even with strong post synaptic depolarisation

Long Term Depression (LTD)

• First identified in hippocampus - thought to be a major component of motor learning in the cerebellum

• Cerebellar LTD involves a decrease in AMPA receptors - However, this is NOT NMDA-dependent

Measuring in humans: Transcranial Magnetic Stimulation

• A non-invasive method of measuring neuroplasticity

• Apply coil on scalp + deliver a brief pulse = causes electrical stimulation of underlying neuron

• Cells in PMC = cause involuntary muscle contractions

Measuring the somatotopic map with TMS

if you record muscle activity in the middle, index then little finger = you will find spots where simulation will induce activity