Voluntary Movement and Motor Cortex Flashcards

Voluntary Movement and Motor Cortex

Introduction

• Voluntary movements are consciously willed behaviors involving the cerebral cortex.
• Understanding of voluntary movement neurophysiology has evolved significantly due to advances in recording from and manipulating neurons.
• Control over complex voluntary behaviors requires intricate coordination among millions of neurons.
• Basic discoveries in the past 100 years have provided insight into the control of voluntary movements.

Sources of Descending Input Driving Voluntary Movements

• Topographic organization of motor nuclei in the spinal cord is crucial for understanding voluntary movement control.
• Motor nuclei controlling hand muscles are located dorsolaterally in the ventral horn of the cervical spinal cord.
• Motor nuclei for proximal limb muscles are located ventromedially, and those for trunk/axial muscles are in the most medial portion.
• Descending pathways providing input to motor neurons for voluntary movements originate from:
  • Cortical areas: Brodmann’s areas 6 (premotor area), 4 (primary motor cortex), and somatosensory cortices (Brodmann’s areas 3a, 3b, 1, 2, 5).
  • Brainstem: Reticular formation and vestibular nuclei.

Descending Motor Pathways

• Two main descending pathways:
  • Medial Pathway:
    • Arises from brainstem nuclei (vestibular nuclei and reticular formation).
    • Descends primarily in the ventral column of the spinal cord.
    • Terminates in the medial aspects of the intermediate and ventral gray matter.
    • Commands upright posture and balance.
    • Integrates body movements and stabilization during whole limb movements.
    • Reticular formation activates central pattern generators for locomotion.
    • Receives cortical inputs (corticobulbar projections) for volitional control.
  • Lateral Pathway:
    • Originates from layer 5 neurons in primary motor cortex (M1, Brodmann’s area 4), premotor area (Brodmann’s area 6), primary somatosensory cortex (Brodmann’s areas 3a, 3b, 1, 2), and somatosensory association cortex (Brodmann’s area 5).
    • Axons form the pyramidal tract (corticospinal pathway).
    • Most axons (~90%) cross over to the opposite side at the pyramidal decussation in the medulla oblongata; the remaining 10% descend ipsilaterally.
    • Gives off collaterals to brainstem structures bilaterally.
    • Descends in the lateral column of the spinal cord.
    • Terminates in the lateral part of the ventral horn (controlling limb/hand/foot muscles) and in the intermediate/dorsal regions.
    • Direct excitatory synapses onto motor neurons exist only in higher primates, facilitating independent and flexible control over individual muscles, particularly for hand muscles.
    • Projections from the somatosensory cortex target interneurons to suppress reflexes that interfere with voluntary movements.

Lesion Experiments: Medial vs. Lateral Pathways

• Medial Pathway Lesions:
  • Severe postural deficits, inability to sit upright.
  • Impaired proximal limb movements.
  • Disability in locomotion.
  • Ability to perform fine finger movements when supported.
• Lateral (Corticospinal) Pathway Lesions:
  • Immediate ability to sit, stand, walk, run, and climb.
  • Inability to use extremities independently of total body movements.
  • Inability to pick up food with hands but can use them for clinging and climbing.

Rubrospinal Pathway

• Another descending pathway with features of both medial and lateral pathways.
• Arises in the red nucleus of the midbrain.
• Descends with corticospinal axons in the lateral column.
• Targets lateral aspects of the ventral horn.
• Relatively sparse in humans; its role may be supplanted by the expansion of the motor cortex and corticospinal pathways.

Topography of the Primary Motor Cortex

• Electrical stimulation of the cortex rostral to the central sulcus (Brodmann’s area 4) evokes different types of movements.
• Stimulation of the premotor area (Brodmann’s area 6) also produces movements but requires higher stimulus intensities.
• Leyton & Sherrington (1917) found that stimulation of M1 in apes produced movements of the leg, arm, hand, and face/mouth/tongue, mostly contralateral to the stimulation site.
• Eye movements were evoked by stimulating the frontal eye fields, rostral to M1.
• Penfield and Rasmussen (1952) used similar procedures on human patients to map the motor cortex as a homunculus, representing separate regions dedicated to controlling different body parts.

Evidence Challenging Somatotopy of M1

• Responses to M1 stimulation in anesthetized animals were unstable (Leyton & Sherrington, 1917).
• Finger movement sites in M1 were intermingled across a wide expanse, and movements of all fingers together were more common than individual digits (Penfield & Boldrey, 1937).
• The region of M1 evoking finger movements almost perfectly overlapped with that evoking shoulder, elbow, and wrist movements (Penfield & Boldrey, 1937).
• Neuroanatomical, electrophysiological, and imaging studies presented results incompatible with a strict partition of the motor cortex.
• Trans-synaptic labeling using rabies virus showed that cortical neurons controlling an individual muscle were distributed over the entirety of the “arm/hand” region of M1 (Rathelot & Strick, 2006).
• Individual corticospinal axons project to multiple motor nuclei (Shinoda et al., 1981), suggesting that such neurons enlist the activities of multiple muscles together.
• Individual neurons in the motor cortex frequently facilitate more than one muscle, including proximal and distal muscles (Fetz & Cheney 1980; McKiernan et al. 1998).
• Motor nuclei controlling intrinsic finger muscles have relatively independent inputs (Buys et al. 1986).

Output Arrangement of Motor Cortex

• Little topographic organization within M1, except for broad regions supplying the leg, arm, and head.
• Corticospinal neurons supplying a particular motor nucleus are distributed over a wide expanse of M1 and intermingled with neurons supplying other muscles (“many (locations)-to-one” organization).
• Single corticospinal neurons can project to multiple motor nuclei (“one-to-many” arrangement).
• Specific connectivity patterns across motor nuclei might underlie the assemblage of muscles into synergistic groups for elemental movements (Hockensmith et al. 2005; Schieber 1990).
• Co-activation of multiple muscles occurs even for simple finger movements (Wood Jones, 1941), such as synchronized activation of the extensor carpi ulnaris (ECU) when extending the thumb by the extensor pollicis brevis (EPB) muscle to counteract radial deviation.

Representation of Muscle Activity by Individual Corticospinal Neurons

• Edward Evarts pioneered recording from individual neurons in awake, behaving animals.
• Evarts (1968) distinguished between M1 neural activity associated with muscle activity vs. more abstract features of motor behavior (movement direction).
• Monkeys were trained to move a lever by flexing the wrist with varying loads and in configurations where wrist extensor activity was needed to control rotation.
• Evarts specifically targeted M1 neurons that send axons to the pyramidal tract (corticospinal neurons originating in layer 5).
• Corticospinal neuron activity was tested by stimulating the corticospinal pathway with an electrode in the medulla oblongata.
• Firing rates of pyramidal tract neurons in M1 code for the intensity of muscle contraction (and associated muscle force) needed to perform various tasks.

M1 Neurons Coding Movement Direction

• Activity in primary motor cortex may represent desired movements rather than muscle activities.
• Shen and Alexander (1997) trained monkeys to move a cursor on a computer screen using a joystick in standard and rotated configurations.
• Some M1 neurons encoded movement direction of the cursor, independently of the muscles or limb movements involved.
• Kakei et al. (1999) reported similar findings, dissociating movements from muscles.

Confronting Complexity in the Organization of the Motor Cortex

• The motor cortex is a complex system with millions of neurons, each receiving and sending thousands of synaptic contacts.
• Representation of the motor cortex can be likened to an artificial neural network.
• The strength of each synapse varies markedly.
• This architecture is used in artificial intelligence, where synaptic strengths are adjusted through trial, error, and plastic changes.

Neural Population Analyses

• Early attempts to consider neural populations were carried out by Humphrey et al. (1970), who found that combining firing rates could predict movement parameters.
• Georgopoulos et al. recorded hundreds of neurons in the motor cortex while monkeys made arm reaches to radially displaced targets.
• A typical M1 neuron showed increased activity after target illumination.
• Peri-stimulus time histograms (PSTH) show the response of neurons around the time the stimulus was presented or behavior instigated.
• Georgopoulos and colleagues calculated the average firing rate and fitted it with a sinusoidal curve to determine the preferred direction (PD) of movement for each neuron.
• The collective action of the active neurons prescribes the impending movements of the limb.
• Each neuron “votes” for the upcoming movement to be in its PD, with the strength of the vote related to the firing rate.
• Vector summation is performed among all the active neurons to produce a population vector (pv) that points close to the intended movement direction.
• Population vectors can be computed on finer time scales during a reach.
• Schwartz and colleagues applied population vector analysis to the activities of motor cortex neurons while monkeys traced complex figures on a touch screen.

Brain–Machine Interfaces

• Brain-machine interfaces (BMIs) use activity recorded from many neurons to predict intended behavior and control devices like computers or robotic arms.
• BMIs were first demonstrated in rats and monkeys in the early 2000s.
• Hochberg et al. (2012) and Collinger et al. (2013) implanted BMIs in the motor cortex of paralyzed human patients.
• Neural activity was used to predict the direction the patient desired to reach and grasp actions in real-time, allowing them to perform basic activities.

Summary

• Commands from the brain are conveyed to muscles via the medial and lateral pathways.
• The medial pathway originates from brainstem nuclei and acts on spinal circuits for posture, balance, and locomotion.
• The lateral or corticospinal pathway descends from layer 5 neurons in the cerebral cortex to target neurons in the spinal cord for limb, hand, and finger movements.
• M1 lacks clear-cut topographic organization, with neurons projecting to individual motor nuclei distributed across a wide expanse.
• Layer 5 neuron activity encodes muscle activation intensity, while other layers represent complex features of desired movements.
• Considering the collective action of neural populations deepens our knowledge and can be leveraged to aid paralyzed individuals.