PHYS 5 - From Tool Use to Playing Piano: Higher Order Motor Functions PDF

Pag. 1 a 19 PHYS 5 - FROM TOOL USE TO PLAYING PIANO: THE HIGHER ORDER MOTOR FUNCTIONS “To move things is all that mankind can do, and for this task the sole executant is a muscle, whether it be whispering a syllable or felling a forest.” – Charles Sherrington Sherrington’s metap...

Pag. 1 a 19 PHYS 5 - FROM TOOL USE TO PLAYING PIANO: THE HIGHER ORDER MOTOR FUNCTIONS “To move things is all that mankind can do, and for this task the sole executant is a muscle, whether it be whispering a syllable or felling a forest.” – Charles Sherrington Sherrington’s metaphor means that, even if you are thinking complex cognitive behaviours, our behaviour is a sequence of motor acts in which each act requires a sequence of muscles. For example, grasping food to put it near the mouth for eating entails three separate acts: -​ reach the food -​ grasp it -​ put it near mouth Motor outputs are neural commands that act on the muscles, causing them to contract and generate movement. This is done by the corticospinal tract and the primary motor cortex (pyramidal neurons). These outputs are derived from integrated multisensory inputs. In this case, the parietal-premotor pathways are responsible for sensory-motor transformation. 1.​ Different types of information are needed to move In order to move, need different types of information are needed: -​ extrinsic information internal representation of things around us: our sensory environment. This includes the world around us, both objects and other people. Hearing, smell, taste, touch, and vision can all trigger a specific behaviour. -​ intrinsic information 2 kinds: o​ kinematic = the information on the movement parameters o​ kinetic = the information on the force generated and muscle unit needed The extrinsic and intrinsic information must be integrated together. 2.​ Grasping a cup of coffee – Part I To accomplish the volitional task of grasping a cup of coffee, the motor system must solve 3 problems: 1)​ Space localisation = localise the cup in the space 2)​ Physical properties = extract the specific physical properties of the cup 3)​ Current status = translate the physical properties into a motor act  Pag. 2 a 19 Kinematics is the information on the movement parameters. The various brain operations required to plan and guide arm movements are implemented in part by interconnected populations of neurons in the primary motor cortex, premotor cortex, and the parietal cortex. This is allowed due to the dorsal stream. 3.​ Historical aspects Experiment Injecting a retrograde tracer into a monkey’s lateral funiculus of the spinal cord at upper cervical levels means injecting the corticospinal tract with said tracer: the retrograde tracer runs back up, such that the soma of the axons injected become stained. Results The areas stained were Area 5 and the parietal lobe. About 60% frontal lobe and 40% parietal lobe. Until 1950, the studies on brain control of movements (how the brain achieves muscle contraction) came from properties and studies on the primary motor cortex and pre-motor areas. In 1976, there was a paradigm shift. Mountcastle (who discovered the columnar organization of the cortex) started recording activity from the posterior parietal cortex. He found a class of neurons that were activated only by active movements of the monkey; none of them were activated by any form of stimulus delivered passively. The discharge of many parietal neurons highly depends on the goal of the behaviour. Neurons discharge strongly when a monkey: -​ reaches to grasp an object -​ searches for an object in a box -​ manipulates an object with its hand However, they are much less active when the monkey makes other arm and hand movements. From this, we can deduce that these neurons discharge only when the monkey explores the environment and tries to grasp objects placed in the peripheral space. This is a sign that the parietal cortex is related in the movement and activity. In 1995, four famous scientists started to investigate the properties of the parietal cortex and pre-motor cortex: how did the brain translate visual information into a motor act like grasping and movement: -​ G. Rizzolati investigated the role of pre-motor areas in non-human primates -​ H. Sakata investigated the role of parietal areas in non-human primates -​ M. Jannerod investigated the role of parietal and pre-motor areas in humans -​ M. Arbib made a computation model Based on their findings, these four scientists proposed that the dorsal stream and its recipient parietal areas form into 2 distinct functional systems: -​ the dorso-dorsal stream (d-d stream)  Pag. 3 a 19 -​ the ventro-dorsal stream (v-d stream) 4.​ Dorsal stream The dorsal stream can be subdivided into two subcomponents: the dorso-dorsal stream and the ventro-dorsal stream. a.​ Dorso-dorsal stream The dorso-dorsal stream is formed by: -​ area V6 (main dorso-dorsal extrastriate visual node) -​ areas V6A and MIP of the superior parietal lobule (i.e. the middle parietal areas). It is involved in online action control. Damage to the dorso-dorsal stream leads to optic ataxia. b.​ Ventro-dorsal stream The ventro-dorsal stream is formed by: -​ area MT (main ventro-dorsal extrastriate visual node) -​ visual areas of the inferior parietal lobule. It is involved in action organisation (like the dorso-dorsal stream), but also plays a crucial role in space perception and action understanding. The image shows the architectonic subdivisions of parietal and premotor areas.  Pag. 4 a 19 5.​ Grasping a cup of coffee – Part II a.​ Space localisation Space localisation is crucial for reaching movements. The planning of a reaching movement is usually defined as the neural process by which the location of an object in space is translated into an arm movement that brings the hand into contact with the object. The Superior Parietal Cortex Uses Sensory Information to Guide Arm Movements Toward Objects in Peripersonal Space Recent evidence in non-human primates support the idea that there are many spatial maps located in the parietal and pre-motor cortex involved in different space representation. The inferior parietal and ventral pre-motor cortex contain representations of the peripersonal space. The VIP-F4 circuit is the ventral part of the intraparietal sulcus that has reciprocal connections with F4. The neurons in this circuit have properties of both areas and are called polymodal neurons. Polymodal neurons in the parietal and pre-motor cortex respond to both tactile and visual stimuli (visuo-tactile neurons) within receptive fields that are spatially in register. This suggests that the visual receptive fields are not defined by the location of the visual stimulus on the retina, as in most neurons in the visual cortex, but are anchored to specific parts of the individuals body. Experiment In the first case, touching areas of the arm of a monkey with its eyes closed, showed neurons discharging. In the second case, keeping the eyes open but, instead of touching, only hovering close to the same areas of the arm, the neurons discharged in the same way. Results The neurons discharging in the same way without the need to see suggests that the visual receptive fields are not defined by the location of the visual stimulus on the retina (as in most neurons in the visual cortex) but are anchored to specific parts of the individual’s body. F4 neurons discharge also during arm, neck, face, and wrist movements. This shows that, since F4 is a pre-motor area: there are more motor information in the F4 neurons than in the VIP neurons. The superior parietal cortex uses sensory information to guide the arm movements towards objects in the peripersonal space.  Pag. 5 a 19 This cortex has a multisensor integration that guides the movement toward/in the peripersonal space: there is an integration between joint and limb position with respect to the body. This integration creates a body schema that provides fundamental information for the proprioceptive guidance of arm movements. Neurons in the parietal reach area encode target localisation in eye-centred coordinates and respond before movement onset. They receive efferent motor signals and were active before the touch of the specific object: this shows that a motor signal sent to this area, encodes the movement, as a type of forward control. Forward control allows a continuous online update of movement based on the motor program. This is necessary for a correct trajectory of the movement (i.e. the adjustment of the trajectory of the arm during a reaching movement): the brain must integrate the current position of the arm with the wanted position of the arm. Pre-motor and primary motor cortex formulate more specific motor plans about intended reaching movements. Neurons in area PMd (F2) contribute to sensorimotor transformation that provide increasingly detailed information about the desired spatial kinematics and kinetic details of the movements. Experiment The monkey was trained to move the arm in different areas. Results Independent of side, the neuron was directionally tuned with preference for rightward arm movements. The neurons were strongly active and directionally tuned toward the lower targets when the  Pag. 6 a 19 contralateral arm is used but only during the execution phase. They were essentially inactive when the ipsilateral arm is used. In summary, neurophysiological studies have provided support for the general hypothesis that reaching involves neuronal processes that implement a sequence of transformations between sensory input and motor input. Lesion of the dorso-dorsal stream: the case of optic ataxia. (https://www.youtube.com/watch?v=BkOb9FR5Lgk) b.​ Physical properties Grasping an object requires sensory information about its physical properties. At the same time as neural populations in several areas of the parietal and precentral cortex are controlling the reaching movement to bring your hand into proximity with a coffee cup, neural populations in several other overlapping and adjacent parietal and precentral areas are preparing the hand to grasp and lift the cup. Reaching requires translation of spatial information into arm trajectory. Grasping requires translation of the object’s physical features into a grip. Gibson used a specific name regarding this transformation: affordances. By definition, an affordance is all the features that afford specific opportunities for action. In the case of grasping a cup of coffee, visual affordances need to be translated into a specific movement.  Pag. 7 a 19 Neurons in the inferior parietal cortex associate the physical properties of an object with specific motor acts. The image shows the three types of AIP neurons and the conditions in which they discharge. The cortical processes that extract the affordances of observed objects and associate them with specific actions begin in the lateral and rostral part of the inferior parietal cortex: especially in the AIP and PFG areas. There are three types of grasping neurons in the AIP: Motor dominant neurons Visuomotor neurons Visual dominant Discharge during grasping of Discharge during grasping of Discharge during grasping of an object in light (full vision) an object in light (full vision) an object in light (full vision) Discharge during grasping of Discharge during grasping of Do NOT discharge during an object in dark conditions an object in dark conditions grasping of an object in dark conditions Do NOT discharge when you Discharge when you just see just see the object (fixation) the object (fixation) Discharge when you just see the object (fixation) Focus on the motor act of Link between visual grasping these neurons are information and required Focus on the visual more present in the motor act information pre-motor area anatomically connected to AIP  Pag. 8 a 19 The activity of neurons in the inferior parietal cortex is influenced by the purpose of an action. We often perform similar motor acts for different purposes: we pick up a cup of coffee to drink it or to wash the cup. The motor act of grasping is the same, but the objective is different. The activity of neurons in the ventral pre-motor cortex correlates with motor acts. Functional mapping of area F5 based on electrical stimulation shows that this area contains representations of hand and mouth movements that overlap considerably. About 20% of the cells in F5 are called as canonical neurons. These are neurons with visual-motor properties, which are similar to the properties of AIP motor neurons. They discharge for object fixation, but they show a strong selectivity for specific objects.  Pag. 9 a 19 As it can be seen in the figure above, the ring-shaped object, in both fixation and grasping condition, evoke a higher firing rate with respect to other objects such as cube, cone, or sphere. This discharge reflects the preference of the object both during observation and grasping. The congruence between visual and grasping preference signifies how to interact with the object. The discharge of neurons in F5 is correlated with the specific goal of the action rather than just encoding the kinematic and kinetic aspect of the movement. In the experiment below, there is a monkey that is grasping the food with a precision grip. The neuron discharges a lot even when the monkey grips with the ipsilateral hand. However, the same neuron doesn’t fire during the whole-hand grip. It discharges significantly less during whole hand prehension whether with the contralateral hand or the ipsilateral hand. The organization of area F5 allows the object affordances extracted by the anterior intraparietal lobe to be associated with appropriate motor actions. So, there aren’t only visuo-motor neurons with that selectivity, but there are also motor dominant neurons with huge selectivity for specific objects that constrain specific type of grip. Not all the primates are able to perform grasping with the opposition of thumb and index finger, because this grip is allowed by the huge expansion of the corticospinal tract, which is not present in all primates. Not all the monkeys can perform this movement, not even after training. In alternative, they perform side grasp, which is easier than the precision grasp in terms of freedom degree.  Pag. 10 a 19 6.​ Goal of Action Another aspect of F5 neurons relates to the encoding of the goal of the action. Experiment The monkey was trained by performing grasping with a specific tool. The monkey was trained to use two types of pliers: -​ normal pliers, which are grasped and gripped like A (it is similar to human gripping movement) -​ reverse pliers, in which the goal is the same but the movement that has to be performed is the opposite, so there is a release movement rather than a closing movement. Results For most of the neurons in F5, the firing rate doesn’t disentangle the two conditions. Independently by the mechanical aspect of the movement (release or grasp), what is encoded by the neurons was the final goal independent from the kinetic and kinematic aspect of the movement required and constrained by the type of the specific tool. If you remove the pliers, and let the monkey grasp the object, the grasping neurons will discharge in a similar way with respect to the normal and reverse pliers. The different types of muscular activity can be seen in EMG activity. Here, there are different muscle synergies in reverse pliers with respect to the normal pliers: -​ Normal pliers require an activation recorded from extensor digitorum, which is the intrinsic muscle of the hand and involved in the opening the fingers during approaching -​ Reverse pliers have a different muscle activity than normal pliers and hand grasping But the neurons don’t distinguish this condition. The hypothesis is that those neurons encode the specific goal of the action rather than their kinetic and kinematic aspect. What happens if we make a reversible chemical lesion in F5? Normally, the movement of the monkey should be performed in 400 milliseconds. (the monkey is very fast with respect to humans). If muscimol, which is a GABAergic substance, is injected, there will be a lessened activity of neurons, causing a temporary lesion on that area. Therefore, the monkey is not able to complete the movement correctly  Pag. 11 a 19 within 400 ms, but it takes more than 1 second and many times the monkey isn’t able to grasp the object. The movement was not affected per se, but what was affected was the shaping of the hand with respect to the object. Similar effect can be evoked in AIP, with the injection of similar substances into AIP. The case of the motor apraxia (https://youtu.be/B0Hp8bZxNH0) Even though the monkey was able to correctly perform reaching, it cannot coordinate the grasping. Patients with optic ataxia mis-reach the object. All of this information from the dorso-dorsal stream and from the dorso-ventral stream need to be embedded in a complete motor command in the primary motor cortex to be delivered to the corticospinal tract, directly to alpha motor neurons. 7.​ Functional Organization of Primary Motor Cortex The properties of neurons in M1 were discovered by Edward Evarts, who is one of the first neurophysiologist recording single neuron properties from primary motor cortex during specific hand-arm movement of the monkey. Experiment Train the monkey to grasp a manipulandum with a fixed writs and ask the monkey to rotate the tool in different conditions. This rotatory movement can be done with weight that assists the movement or can be performed with weight in the opposite phase with respect to the movement, even though it requires a higher muscular recruitment. Results Depending on the kinematics, what differentiates the firing rate is the presence of huge muscle recruitment. It was one of the first features of the primary motor neurons related to the kinetic aspect of the movement: muscle recruitment.  Pag. 12 a 19 Several years later, in 1983, Georgopoulos discovered not only the kinetic aspect of the movement are encoded in the primary cortex, but also the direction of the movement. In this case, the direction of the movement is the kinetic aspect. Experiment Same experiment performed in the primary motor cortex. The monkey was trained, starting from the centre to grasp the different degree of the manipulandum around the centre. Results There are neurons that discharge better in specific movement direction. If we make a summation of this firing rates for a thousand neurons in the primary cortex, a population vector can be produced, which corresponds closely to the actual movement direction. So, the firing rates are transformed into vectors. There are millions of neurons encoding for slightly different directions. If we merge all of these, there is a population of neurons enable to encode all the possible directions of movement. Another aspect that allows to investigate the kinetic and kinematic together in the primary motor cortex was the introduction of the technique spike-triggered averaging, in which the primary motor cortex was specifically stimulated. This stimulation was triggered by muscle activity in the end during specific grasping movement. This technique allows to correlate the muscle activity with discharge of single upper motor neurons and to discover the presence of muscle field theory. A given cortical motor neuron facilitate the activity of a number of different muscles, called as muscle field, rather than single muscle. Single motor neurons in the primary motor cortex contact several motor neurons pool in the spinal cord, meaning that several muscle fields can be modulated by huge number of neurons. Rather than individual muscle activity, movements are encoded by the activity of cortical motor neurons. That was one of the first evidence that the primary motor cortex can integrate both kinetic and kinematic aspect of the movement. M1 receives strong input from premotor cortex, also dorsal premotor cortex but also from F5. To understand the influence of F5 activity in the output of primary motor neurons, a conditioning test has been done. It’s found out that if F5 is stimulated before stimulating M1, you can modulate the muscle activity, particularly the intrinsic muscle of the hand. So, the F5 activity can modulate the activity of M1.  Pag. 13 a 19 M1 activity can be modulated based on information that emerge during sensory motor integration. Fagg & Arbib tried to picture out the role of the parietal premotor circuit and the influence on the primary motor cortex in a computational modelling. In dorsal-ventral stream the information coming from the features of an object are extracted by AIP neurons. Based on the intention (whether you want to move the cup or you want to bring the cup to the mouth), an information is put out. This information of intention is sent to F5. F5 can select the premotor scheme to be sent to the primary motor cortex, which will send this info finally through the corticospinal tract at the motor neurons in the spinal cord. Other areas contribute to the shaping of the activity of F5 that comes from premotor areas and prefrontal cortex. 8.​ Supplementary Motor Cortex The supplementary motor cortex that is located in the medial wall is composed of: -​ SMA (F3) -​ pre-SMA (F6) In this cortex, there are neurons that encode a sequence of movements rather than a specific movement. Experiment The monkey was trained to perform a push, turn, and pull actions in different orders by using a joystick. Results SMA neurons, in table A, encode this sequence starting before the push phase. The neurons were silent during the turn and the pull. But the order of pull and turn is changed, the same neuron doesn’t fire in the push phase. This means that the neuron encodes for a specific sequence of movement. In B, the neuron discharges after pull action, then it stays silent after push and turn. In the right side, if the push action is performed before pull, the neuron doesn’t fire.  Pag. 14 a 19 These are the evidence that neurons in the supplementary motor cortex encode movement sequences. Also, while driving a car, this kind of neurons contribute to learning and executing movement sequences. Another aspect of the supplementary motor complex is the readiness potential, which was first discovered in SMA. The readiness potential is an EEG evoked potential, recorded at the scalp, so there is no need to put an electrode inside the brain. When you are waiting to move, your brain, in particularly supplementary motor area, start to depolarize their activity. The activity will increase and when the action is performed, there will be a dramatic dropdown of the potential. This kind of physiological marker is associated to the movement initiation. Therefore, SMA is the part that contributes to movement initiation. 9.​ Neurological Disorders Affect the Initiation and Suppression of Voluntary Behaviour Lesion of SMA can have complex and behavioural outcomes: -​ Akinesia - loss of self-initiated arm movements -​ release phenomena: o​ as eco-apraxia o​ alien hand syndrome o​ anarchic hand syndrome - result in involuntary hand movement. 10.​Planning Action The premotor areas are not only involved in motor action but involved also in planning action (programming the movement). This is an activity that precedes the movement and muscle contraction. There are a lot of areas that encode this information e.g., the prefrontal areas encode the rule governed behaviour, such as a gambling task. To perform the task properly, the rules should be known. The premotor area is also important in learning motor skill and social behaviour. If there are testing neurons in the dorsal premotor cortex, during specific match-to-sample tasks, where the monkey was trained to perform a specific movement, different movements can be observed if the sensory signal matches or non-matches with the previous one. Experiment The monkey is presented a sample, then entered a delay period. After the delay period, the test picture is shown to the monkey. Depending on the test picture, which may match or nonmatch, the monkey performs two different movements.  Pag. 15 a 19 Results In nonmatch rule, the neurons discharge differently than the match rule, especially during the delay period, in which the monkey has to keep memory of the sample picture to match it with the test picture. There are neurons in the ventral premotor cortex that are effective in the delay period that is the period that precedes the movement. That happens also for the neurons in the ventral premotor cortex, but here, the match-to-sample task is not performed with the visual pictures, but with a stimulus delivered at different frequencies of oscillation. Depending on the second stimulus, whether it is same with the first stimulus or not, the monkey has to perform two different actions. There is a huge discharge of neurons during the delay period before the second stimulus and the movement. It means that the monkey and the neurons were encoding and keeping info that was necessary to match the second stimulus correctly. The sensory motor system and the parietal premotor network are involved in the coding action performed by others. Similar to object affordances, the same concept can be translated into a social context and social affordances can be created. Not only an object can be translated in adequate actions, but also the behaviour of others is important in regulating one’s own actions. For example, in the picture below, the monkey was observing another monkey bringing food, so the monkey is observing the action and the object. The information of the object that  Pag. 16 a 19 has been observed and the action should be merged in order to understand what the other is doing. 11.​Mirror Neurons In 1996, a special class of neurons was discovered. These neurons are a special class of visual motor neurons discovered in F5 and were called mirror neurons. They discharge when the monkey was performing an act, grasping, and also discharge in the same way when the monkey was watching someone else performing the same motor act. According to the direct matching hypothesis, the observation of the action of other activates the motor circuits responsible for similar motor actions by the observer. This activation of motor circuits would provide a link between the observed actions and the observer’s stored knowledge of the nature, motives, and consequences of his own corresponding actions. These neurons are tested in many conditions. In the first graph, the monkey was performing the grasping action and the mirror neurons fire. However, if you put a plexiglass to cover the object and to hide the last part of the action but the monkey knows that there is an object behind the glass, the mirror neurons still fire. If you put plexiglass and there is no object behind it and the monkey knows that there is no object, the mirror neurons don’t fire. 12.​Intention Understanding Mirror neurons were not only discovered in the ventral premotor cortex, but also in the inferior parietal lobe. In this case, in the parietal lobe there are neurons that disentangle between the grasping that has been performed for bringing the food to the mouth or bringing the food and putting the food in a box.  Pag. 17 a 19 So, there are neurons that, even for the same motor act, can disentangle between the different movement intentions. There are type of mirror neurons that can disentangle this aspect by watching the action performed by others. In the experiment below, the monkey was just observing. The mirror neurons fire during a grasping to eat movement. They fire significantly less when the grasping was performed to move the food to a container. This study indicated that this mirror neuron activity can allow you to understand the intention of the others in a motorial way. Just watching the visual information can trigger and allow the same pathway that is triggered during this pathway to understand what the other is doing. For this reason, it is motorically implicit, so it is an autonomic process. The mirror neurons are the evidence for direct matching hypothesis. For strange or complex actions, prefrontal cortex is used with mirror neurons, but for simple actions this direct mechanism immediately matches the other’s motor action into your own motor system, which allows you to understand what the other is doing. 13.​Mirror Network The mirror network in monkeys is shown in A, while the mirror network in humans is shown in B. In monkeys, the main areas in which the mirror neurons have been discovered are aIPS, PF/PFG, F5, and M1 (the mirror neurons in M1 are different). The functional magnetic resonance allows to study the same circuit in humans. Humans also have a homolog circuit, meaning that they are functionally corresponding. Recently, it has been shown that the mouse and rat also have the same network.  Pag. 18 a 19 There is some differentiation between primate and human primate, but it is very phylogenetically coherent. Probably there is some fitness in this kind of activity that allow humans to survive in the environment. For example, in the case of boxing, one’s reaction time and your movement should be coordinated: one must move in order to avoid getting hit, and to do that, one has to understand in a very fast way what the other is doing. The mirror neurons are also present in our limbic area which is involved in encoding and producing emotions. Therefore, this system may be a part of a mechanism that allows humans to empathize automatically. If you empathize too much, one’s behaviour cannot be a useful help, leading to physiatry. 14.​Extended Mirror Neuron Network Mirror neurons are not located just in PFG and F5, but they are spread in other brain areas, for example, in presupplementary motor area, there is a mirror-like activity. Luca Bonini extended the role of the mirror network: the classic mirror area in inferior parietal lobe is connected with prefrontal and middle frontal cortex, but it is also connected with subcortical structures such as basal ganglia. The mirror neurons are present in F5. In F5, the mirror neurons not only discharge when the monkey is looking at the action, but they also discharge when the monkey is expecting an action, but the action doesn’t result in the expected movement. There are execution mirror neurons that discharge during the observation of movement but also there are mirror neurons that discharge during inaction, when the actors refrain their own action. In pre-SMA, there is a mirror-like activity that can disentangle between self-action and other’s action. There are also mirror neurons that discharge both during self-action and during observation of other’s action. Therefore, Bonini classified these neurons as self-type neurons, other-type neurons, and self-other type neurons. These mirror neurons are involved in brain-body system in a loop with our environment. Our environment can be very complex, so the information should be filtered to produce movement and action that are required by our brain-body system.  Pag. 19 a 19 The way in which one is performing an action can be information to put out brain-body system in a continuous loop with the environment. In schizophrenia, the external environment cannot be put in a continuous loop with one’s one body and the body is considered foreign with respect to the environment.