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Hand motor control of the brain

Hand motor control of the brain


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I was watching a documentary (don't remember the name or the URL to the documentary) but they stated that the brain is layered and that each new layer is placed on top of the last. So the most primitive part of the brain that sends a signal to move the fingers actually has no way of moving just one, but in fact sends a message to just open and close the hand. That message is then passed on to a newer part of the brain that then filters it into individual finger movements.

I would like to know if this is true and how is the newer layer of the brain able to take an open-close message and identify what finger to move.

This sounds like a strange way for the brain to work; as I'm typing this message out at 86wpm, how is my brain doing such a complex task of moving all my fingers from an open-close message?


Hand motor control of the brain - Biology

The defining characteristic of the somatic nervous system is that it controls skeletal muscles. Somatic senses inform the nervous system about the external environment, but the response to that is through voluntary muscle movement. The term “voluntary” suggests that there is a conscious decision to make a movement. However, some aspects of the somatic system use voluntary muscles without conscious control. One example is the ability of our breathing to switch to unconscious control while we are focused on another task. However, the muscles that are responsible for the basic process of breathing are also utilized for speech, which is entirely voluntary.


1. Introduction

In 2030, nearly one in five U.S. residents is expected to be 65 or older. This age group is projected to increase to 88.5 million in 2050, more than doubling the current number (38.7 million, US Census data). With advanced age comes a decline in sensorimotor control and functioning. These declines in fine motor control, gait and balance affect the ability of older adults to perform activities of daily living and maintain their independence. The causes of these motor deficits are multi-factorial, with central nervous system declines and changes in sensory receptors, muscles and peripheral nerves playing a role.

Advances in neuroimaging techniques have contributed greatly to our understanding of the aging brain. The impact of age-related brain differences on cognitive function has been studied extensively in recent years, and this topic has been reviewed elsewhere (cf. Cabeza, 2001 Li et al., 2001 Park & Reuter-Lorenz, 2009 Raz et al., 2007). The literature on age-related differences in neural control of movement has not developed as quickly, but numerous studies have been conducted to date (cf. Harada et al., 2009 Heuninckx et al., 2005, 2008 Hutchinson et al., 2002 Mattay et al., 2002 Naccarato et al., 2006 Riecker et al., 2006 Ward & Frackowiak, 2003). The results thus far point to some parallels in aging of the motor and cognitive systems, but also hint at areas of divergence. The purpose of the current article is to provide a comprehensive review of age-related differences in brain structure, function, and biochemistry, with particular reference to their impact on motor performance in older adults. We advance the hypothesis that motor control becomes more reliant on central mechanisms with age, including prefrontal and basal ganglia systems (for supporting evidence see sections 3.3 and 4). Engagement of these structures likely reflects increased reliance on cognitive control mechanisms for older adults, in compensation for age-related sensorimotor declines (see Figure 1 ). Paradoxically, the prefrontal structures that support cognitive control show the largest age-related differences (see section 3.1 for evidence), potentially leading to further compromises in motor control.

“Supply and demand” framework applied to age-related changes in the neural control of movement. Older adults increasing rely on cognitive brain processes for motor control (𠇌ognitive demand”) due to structural and functional declines in the motor cortical regions (MC), cerebellum, and basal ganglia pathways, coupled with reduced neurotransmitter availability. At the same time attentional capacity and other relevant cognitive resources (𠇌ognitive supply”) are reduced due to differential degradation of the prefrontal cortex (PFC) and anterior corpus callosum (CC). Young Adults (YA) Older Adults (OA).

Note: we use the term 𠇌ognitive” here in a general sense to represent attention, working memory, visuospatial processing, and other functions contributing to motor control.


Neural pathways for cognitive command and control of hand movements

A piece of fruit—a raisin—swings on a stick in front of a monkey (Fig. 1). He likes raisins he wants this one. He stretches out his arm, opens his hand with the fingers spread wide apart, and tries to capture it he misses (bursts B and D). He tries again, this time successfully (burst F). He grabs the raisin, pulls it off the stick, brings it to his mouth, and eats it. Delicious! What happens in the brain when the animal performs these actions? The chart above the images in Fig. 1 tracks responses of a neuron recorded in lateral area 5 bordering the intraparietal sulcus, a subregion of the posterior parietal cortex (PPC) originally studied by Mountcastle et al. (1, 2), and described as a hand-manipulation “command neuron” engaged in purposeful actions of the hand: reaching and grasping an object of behavioral interest.

(Upper) Burst analysis of neural responses to spontaneous reaches and attempted grasps of a raisin on a stick moving through the workspace. The green burst trace marks intervals when firing rates are one SD greater than the mean during the 3-min analysis period. Firing rates are highest as the animal reaches toward the raisin and attempts to grasp it (bursts B, D, and F), and decay when the hand withdraws to a rest position. (Lower) Frame-by-frame tracings of the hand kinematics, gaze direction, and target location in digital video clips recorded simultaneously with neural responses. Same neuron as in figures 4–7 of Gardner et al. (30).

Mountcastle et al. (1) proposed that these regions of the PPC, …receive afferent signals descriptive of the position and movement of the body in space, and contain a command apparatus for operation of the limbs, hands, and eyes within immediate extrapersonal space. This general command function is exercised in a holistic fashion. It relates to acts aimed at certain behavioral goals and not to the details of muscular contraction during execution. These details are, on this hypothesis, made precise by the motor system, for which it is well suited by virtue of its powerful mechanisms for specifying movement exactly.

However, no anatomical substrate was defined in that report beyond “the motor system.”

In PNAS, Rathelot et al. (3) use a state-of-the-art neuroanatomical pathway tracing to demonstrate a direct pathway from lateral area 5 to interneurons of the spinal cord, providing an efficient, rapid route for modulating hand and arm movements during goal-directed behaviors. These authors harnessed bacterial toxins and viruses to label the biological circuits that implement the command functions originating from the PPC, providing a wiring diagram that complements the traditional voluntary movement pathways from area 5 to corticomotoneuronal fiber tracts to motoneurons (4 ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ –13).

Rathelot et al. (3) take the reader, step-by-step, through the pathway from the PPC to action. First, they placed microelectrodes into lateral area 5, where Mountcastle et al. (1) had recorded “command” neurons, and evoked grasping type movements of the thumb and fingers following trains of electrical pulses delivered by the electrodes. Grasping movements were evoked from both the anterior bank of the intraparietal sulcus (area PEip), as well as the adjacent cortical surface caudal to the S1 hand area (area PE).

To determine the anatomical projection targets of these physiologically identified zones, Rathelot et al. (3) injected lateral area 5 with cholera-toxin subunit B (CTb), a highly sensitive anterograde tracer molecule. CTb uptake into neurons is mediated by absorptive endocytosis when it binds to monosialoglycoside GM1 in neuronal membranes, and is actively transported bidirectionally within the neuron, retrograde (back toward the cell soma and dendrites) and anterograde (forward along the axon to the synaptic terminals) (14, 15). Rathelot et al. (3) demonstrate that anterograde transport of CTb produces dense labeling of axon terminals in the medial dorsal horn of the spinal cord from C2 to T2. This region is populated by spinal interneurons that receive somatosensory input from mechanoreceptors in the hand (16) many of them also participate in reflex pathways to hand motoneurons. The descending corticospinal projection from area 5 is contralateral and excludes the ventral horn where motoneurons reside. The pathway from area 5 is disynaptic and does not excite motoneurons directly.

In a second series of experiments, Rathelot et al. (3) injected rabies virus into specific hand muscles to delineate the circuitry of anatomical projections to their spinal motoneurons. In previous studies, these authors and others demonstrated retrograde transneuronal transport of rabies virus from hand muscles to motoneuron pools of the spinal cord, and subsequently to corticomotoneuronal cells of the primary motor cortex (13, 14, 17 ⇓ –19). Multiple levels of retrograde transneuronal transport depend upon the survival time after viral injection. Rathelot et al. (3) demonstrate that short survival times labeled the cell somas of specific motoneurons as well as those of interneurons in laminae IV–VIII. Moreover, there was much overlap between the retrogradely virus-labeled interneurons projecting to specific hand motoneurons and the anterogradely labeled nerve terminals from the CTb injections from area 5. These data indicate that descending projections from area 5 modulate activity of motoneurons innervating hand muscles through a disynaptic pathway mediated by last-order interneurons in the medial dorsal horn.

Longer survival times labeled third-order transneuronal projections from the cerebral cortex to the virus-injected hand muscles. These regions include the primary motor cortex (M1), several regions of the premotor cortex, and importantly, layer V of lateral area 5. The retrograde label in areas PE and PEip overlapped the anterograde projection sites demonstrated in the CTb and microstimulation experiments. Moreover, the density of transsynaptically labeled neurons in the PPC was substantially greater when rabies virus was injected into distal muscles of the hand, than into proximal muscles of the elbow and shoulder. Retrogradely labeled corticospinal neurons from lateral area 5 were only about half as frequent as those in M1, but nearly 1.5 times more numerous than those in the dorsal premotor cortex.

Rathelot et al. (3) conclude that the “lateral region within area 5 has corticospinal neurons that are directly linked to the control of hand movements” and that “a localized region within the posterior parietal cortex has” a more direct “route to access motor output” than pathways from premotor areas. Their data clearly fit Mountcastle’s view of a command function for the PPC (1, 2).

It is significant that the descending area 5 projections demonstrated by Rathelot et al. (3) terminate on interneurons, not motoneurons, thus modulating the excitability of motoneuron pools. Terminating on motoneurons would simply confer a direct motor role on the PPC. Instead, by terminating on interneurons that activate specific motor pools, PPC cells may rev up the engine or slow it down, enabling facilitation or inhibition of specific actions. Additionally, by terminating on interneurons in a somatosensory projection zone, as demonstrated by Rathelot et al., PPC neurons may enhance relevant sensory inputs, and suppress or gate irrelevant, distracting signals when subjects engage in purposeful acts.

The 1975 Mountcastle et al. paper (1) was a game-changer, a paradigm shift in neuroscience, because it demonstrated that it was possible to study higher functions of the brain in nonhuman primates (topics such as intention, attention to sensory events, motor planning, and decision-making), and to analyze spontaneous complex behaviors under subjective control of the animal. The report also debunked the idea that the PPC was a higher-order sensory-association area in which several modalities converged on individual neurons. The actions described in the 1975 report and illustrated in Fig. 1 combine visual tracking of an object and proprioception of hand and arm actions during reach and grasp, with motor behaviors needed to accomplish the goal of acquisition of an unpredictable target swinging in space.

Is the role of the PPC sensory, motor, or a combination of these functions? When an animal explores its environment with its hands or eyes, it is seeking some information or trying to acquire a desired object, such as food. These actions persist until the goal is achieved. Sensory feedback confirms subjective expectations or alters actions to achieve that goal.

Later studies from other neurophysiologists using trained tasks clearly established that PPC neurons in areas 5 and 7 are engaged in planning goal-directed movements of the hand, arm, and eyes to obtain a reward, and provide relevant sensory feedback concerning achievement of task goals (20). These functions are anatomically segregated into specific subregions of the PPC. Medial areas, such as the medial intraparietal area and the “parietal reach region,” are engaged by reaching to cued targets in the workspace (21 ⇓ ⇓ ⇓ ⇓ –26) lateral cortical regions surrounding the intraparietal sulcus (area 5 and the anterior interparietal area) signal the hand postures used to grasp specific objects (27 ⇓ ⇓ ⇓ –31) and areas of the medial wall of the hemisphere integrate arm and hand movements with visual signals (32, 33). Motor plans and sensory attention are transformed into action by parietal interconnections with relevant premotor areas of the frontal lobe. The Rathelot et al. report (3) demonstrates a new pathway: direct parietal connections to spinal interneuron pools, enabling modulation of spinal circuits for goal-directed actions of the hand and arm, supplementing the more traditional direct frontal motor pathways.


Brain mapping study suggests motor regions for the hand also connect to the entire body

Mapping different parts of the brain and determining how they correspond to thoughts, actions, and other neural functions is a central area of inquiry in neuroscience, but while previous studies using fMRI scans and EEG have allowed researchers to rough out brain areas connected with different types of neural activities, they have not allowed for mapping the activity of individual neurons.

Now in a paper publishing March 26 in the journal Cell, investigators report that they have used microelectrode arrays implanted in the brains of two people to map out motor functions down to the level of the single nerve cell. The study revealed that an area believed to control only one body part actually operates across a wide range of motor functions. It also demonstrated how different neurons coordinate with each other.

"This research shows for the first time that an area of the brain previously thought to be connected only to the arm and hand has information about the entire body," says first author Frank Willett, a postdoctoral fellow in the Neural Prosthetics Translational Laboratory at Stanford University and the Howard Hughes Medical Institute. "We also found that this area has a shared neural code that links all the body parts together."

The study, a collaboration between neuroscientists at Stanford and Brown University, is part of BrainGate2, a multisite pilot clinical trial focused on developing and testing medical devices to restore communication and independence in people affected by neurological conditions like paralysis and locked-in syndrome. A major focus of the Stanford team has been developing ways to restore the ability of these people to communicate through brain-computer interfaces (BCIs).

The new study involved two participants who have chronic tetraplegia--partial or total loss of function in all four limbs. One of them has a high-level spinal cord injury and the other has amyotrophic lateral sclerosis. Both have electrodes implanted in the so-called hand knob area of the motor cortex of their brains. This area--named in part for its knoblike shape--was previously thought to control movement in the hands and arms only.

The investigators used the electrodes to measure the action potentials in single neurons when the participants were asked to attempt to do certain tasks--for example, lifting a finger or turning an ankle. The researchers looked at how the microarrays in the brain were activated. They were surprised to find that the hand knob area was activated not only by movements in the hand and arm, but also in the leg, face, and other parts of the body.

"Another thing we looked at in this study was matching movements of the arms and legs," Willett says, "for example, moving your wrist up or moving your ankle up. We would have expected the resulting patterns of neural activity in motor cortex to be different, because they are a completely different set of muscles. We actually found that they were much more similar than we would have expected." These findings reveal an unexpected link between all four limbs in motor cortex that might help the brain to transfer skills learned with one limb to another one.

Willett says that the new findings have important implications for the development of BCIs to help people who are paralyzed to move again. "We used to think that to control different parts of the body, we would need to put implants in many areas spread out across the brain," he notes. "It's exciting, because now we can explore controlling movements throughout the whole body with an implant in only one area."

One important potential application for BCIs is allowing people who are paralyzed or have locked-in syndrome to communicate by controlling a computer mouse or other device. "It may be that we can connect different body movements to different types of computer clicks," Willett says. "We hope we can leverage these different signals more accurately to enable someone who can't talk to use a computer, since neural signals from different body parts are easier for a BCI to tease apart than those from the arm or hand alone."

This work was supported by the Office of Research and Development, Rehabilitation R and D Service, Department of Veterans Affairs, the Executive Committee on Research of Massachusetts General Hospital, NIDCD, NINDS, Larry and Pamela Garlick, Samuel and Betsy Reeves, the Wu Tsai Neuroscience Institute at Stanford, the Simons Foundation Collaboration on the Global Brain, the Office of Naval Research, and the Howard Hughes Medical Institute.

Cell, Willett et al. "Hand Knob Area of Premotor Cortex Represents the Whole Body in a Compositional Way" https://www.cell.com/cell/fulltext/S0092-8674(20)30220-8

Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit: http://www. cell. com/ cell. To receive Cell Press media alerts, contact [email protected]

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Anatomy and Functions of the Pons

The pons is one of the smallest parts of the brain at only 2.5cm in length, but, especially since it’s a part of the brainstem, it is involved in a great many processes that run the central and peripheral nervous systems.

Cranial Nerves

The pons is vital to the central and peripheral nervous system – a major reason for this being its connections to several cranial nerves including the trigeminal, abducens, facial, and vestibulocochlear nerves.

In the center of the pons is an indentation, or line, called the basilar groove (also where the basilar artery is located). All of the cranial nerves originate from the same side of the basilar groove, with the exception of the trigeminal nerve.

Because of its abundance of nerve connections, the pons is involved in many nervous system functions ranging from sensory to motor functions. The trigeminal nerve is the largest cranial nerve and earns its name from its three branches: the ophthalmic, maxillary, and mandibular nerves.

This collection of nerves controls sensory information gathered from organs of the face and the motor control of chewing.

The abducens controls the movement of the eye, facial nerve controls the expressions of the face (therefore controls the relay of neuronal signals from the brain to all of the fine muscles in the face – that is a lot to manage!) and the sense of taste and the vestibulocochlear regulates the equilibrium and auditory sensations.

All of the cranial nerves associated with this structure emerge from the ventral surface of the pons.

Even if we were to stop here, it is clear that the functionality of the pons is wide-reaching. But, it doesn’t stop there!

Other External Anatomical Features of the Pons

The same area from which these cranial nerves emerge is distinguished by a bulge formed by a structure called the transverse pontocerebellar fibers. This bundle of nerves connects to the cerebellum and constitutes the main afferent source of neuronal information to the cerebellum.

A large portion of the information sent via the pontocerebellar fibers concerns the planning and execution of fine movements, specifically, movements of the arm, forearm, and hand. These fibers wrap around the remainder of the brainstem.

An important landmark to take note of is the pontomedullary junction: this is marked by the angle between the inferior region of the pons and the superior boundary of the medulla oblongata.

The floor of the fourth ventricle constitutes the dorsal surface of the pons, along with that of the medulla oblongata. A few more structures can be identified in this region of the pons including the medial eminence, which marks the midline of the dorsal surface, the facial colliculus, a bulge formed by the fibers of the facial nerves that loop around the nucleus of the abducens, and the stria medullaris, a bundle of nerves belonging to the fourth ventricle.

Another landmark to help you identify the pons is called the cerebellopontine angle, where the cerebellar flocculus (a small part of the cerebellum involved in motor control), the ventricular choroid plexus, and the facial and vestibulocochlear nerves surround the foramen of Luschka (structures that link the fourth ventricle to the cerebellopontine cistern, another space into which cerebrospinal fluid can pool).

Internal Anatomy of the Pons

The pons is recognized as having two major divisions: the ventral pons and the tegmentum (different from the tegmentum of the midbrain.) The ventral pons is home to the pontine nuclei, structures that are responsible for the coordination of movement. These nuclei travel from the pons across the midline and form the middle cerebellar peduncles as they make their way to the cerebellum.

The tegmentum of the pons is considered to be the older region of the pons evolutionarily (meaning that this structure was present in the ancestors of humans and other vertebrates that have a pons as a part of their nervous system).

The tegmentum forms a part of the reticular formation, a network of nerves that extend from the medulla oblongata and connect to the spinal cord and thalamus.

Pontine Nuclei

These nuclei are a part of the pons that is concerned with motor activity. They are among the largest nuclei informing the cerebellum and provide some of the most important neuronal transmissions. The pontine nuclei are informed primarily by the cerebral cortex and project to the cerebellar hemispheres.

Reticular Formation

The reticular formation is a complex collection of nerve fibers and cell bodies that are comprised of both ascending and descending nerve tracts. Nuclei within the reticular formation are involved with the production of neurotransmitters, and associated with several cranial nerves, controlling both sensory and motor functions with the descending tracts and arousal and consciousness with the ascending tracts.

The neurotransmitters produced by the reticular formation are connected with many parts of the central nervous system and regulate many types of activity in several different areas of the brain. This reticular formation is related to the production of dopamine, the release of serotonin, production of acetylcholine, and more. All of these hormones and neurotransmitters are related to sensory perception, motor control, and behavioral responses to various stimuli.

Nerve Tracts That Pass Through the Pons

There are four major nerve tracts that pass through the pons to control the sensory, autonomic, and voluntary functions of the body.

Corticospinal Tract

The corticospinal tract (CST), also known as the pyramidal tract, comprises part of the descending nerve tracts that emerge from the pons into the spinal cord and into the peripheral nervous system. There are about 1 million nerve fibers that make up the CST, each of the transmitting neuronal information at speeds of 60m/s!

The CST travels through the corona radiata (a sheet of white matter) and posterior limb of the internal capsule to terminate in the brainstem. Once it reaches the brainstem, one of the structures it passes through, of course, is the pons. The CST controls many motor functions including spinal reflexes, and the most notable of the voluntary movements are the voluntary distal movements.

Corticobulbar Tract

This is a descending neuronal pathway responsible for innervating several of the cranial nerves, controlling the muscles in the face, tongue, jaw, and pharynx.

The cranial nerves that are supplied by the corticobulbar tract include the trigeminal nerve (controls the process of chewing), facial nerve (controls muscles of the face), accessory nerve (specifically control the sternocleidomastoid and trapezius muscles), and the hypoglossal nerve (controls tongue muscles).

Medial Lemniscus Tract

The nerve tract is part of a greater pathway called the dorsal column-medial lemniscal pathway, which is responsible for the transmission of sensory information related to fine tactile sensation, detection of vibrations, and proprioception (awareness of the position of certain body parts).

Spinothalamic Tract

The spinothalamic tract works along with the medial lemniscus tract to create one of the most important pathways of the nervous system, responsible for transmitting information regarding sensation.

Neuronal signals related to pain, temperature, and touch are relayed to the somatosensory region of the hypothalamus through this nerve tract. In total, the spinothalamic tract is composed of four sub-tracts: the anterior spinothalamic tract, lateral spinothalamic tract, spinoreticular tract, and spinotectal tract.


Learning fine motor coordination changes the brain

Summary: Study identifies a population of neurons in an area of the midbrain, called the red nucleus, that alter when fine motor skills are learned. The more an action is practiced, the stronger the connections between these neurons become.

Source: University of Basel

When we train the reaching for and grasping of objects, we also train our brain. In other words, this action brings about changes in the connections of a certain neuronal population in the red nucleus, a region of the midbrain. Researchers at the University of Basel’s Biozentrum have discovered this group of nerve cells in the red nucleus. They have also shown how fine motor tasks promote plastic reorganization of this brain region. The results of the study have been published recently in Nature Communications.

Simply grasping a coffee cup needs fine motor coordination with the highest precision. This required performance of the brain is an ability that can also be learned and trained. Prof. Kelly Tan’s research group at the Biozentrum, University of Basel, has investigated the red nucleus, a region of the midbrain that controls fine motor movement, and identified a new population of nerve cells which changes when fine motor coordination is trained. The more that grasping is practiced, the more the connections between the neurons of this group of nerve cells are strengthened.

The red nucleus, a little investigated region of the brain

Grasping is a skill that can be trained and improved, even in adults. For muscles to perform a movement correctly, brain commands must be transmitted through the spinal cord. The red nucleus, which, over the years, has received little attention in brain research, plays an important role in fine motor coordination. Here the brain learns new fine motor skills for grasping and stores what it has learned.

Our fine motor skills such as grasping are steered by the red nucleus, a region of the midbrain. The image is credited to University of Basel, Biozentrum.

Kelly Tan’s team has now investigated the red nucleus in more detail in the mouse model and analyzed its structure and neuronal composition. “We have found that this brain region is very heterogeneous and consists of different neuron populations,” says Giorgio Rizzi, first author of the study.

Improved fine motor skills through plastic changes in the brain

The research team has characterized one of these neuron populations and demonstrated that learning new grasping movements strengthens the connections between the individual neurons. “When learning new fine motor skills, the coordination of this specific movement is optimized and stored in the brain as a code,” explains Tan. “Thus, we have been able to also demonstrate neuroplasticity in the red nucleus.”

In a further step, the team now wants to investigate the stability of these strengthened nerve cell connections in the red nucleus and find out to what extent they regress when the learned fine motor movements are not practiced. The findings could also provide new insights into the understanding of Parkinson’s disease, in which affected individuals suffer from motor disorders. The team hopes to find out whether the neuronal connections in the red nucleus have also changed in these patients and to what extent fine motor training can restrengthen the neuronal network.

Source:
University of Basel
Media Contacts:
Heike Sacher – University of Basel
Image Source:
The image is credited to University of Basel, Biozentrum.


Understanding the control of instinctive behaviour

Dr. Cornelius Gross, Deputy Head of Unit and Senior Scientist at EMBL, recently gave a seminar at SWC on how animals produce and control fear behaviours. I caught up with him to learn more about his research on instinctive behaviours.

How do you define instinctive behaviour?

People often use the terms “instinctive” or “innate” to describe behaviours that are not learned, i.e. behaviours you already know how to do for the first time. Instinctive behaviours are important for promoting the survival of your genes and thereby your species.

What role is the hypothalamus thought to play in the expression of instinctive behaviours?

The hypothalamus is an ancient part of the brain whereas other areas, such as the cortex and forebrain, are very recent evolutionary additions. As such, the hypothalamus is able to respond to sensory inputs, form internal states and induce motor outputs.

According to the evolutionary neurobiologist Detlev Arendt, the hypothalamus was formed by the fusion of two ancient neural nets:

  • a neuroendocrine system that responded to light and secreted factors into the main body cavity – ancestor of the modern midline neuroendocrine nuclei
  • a motor system that controlled contractile tissue to produce basic behavioral patterns – ancestor of the medial and lateral hypothalamus that control instinctive behaviors

The hypothalamus is sometimes mistakenly called the “reptilian” brain in reality it dates back to before the appearance of the first bilaterian organisms and is perhaps better termed the Ur-brain. A lot of current work focuses on trying to understand how the hypothalamus encodes internal motivational states that drive instinctive behaviour, and although its basic architecture was clarified already 30 years ago, how it controls behaviour it still pretty much a mystery.

Why does emotion often accompany instinctive urges in humans?

The question of emotion is a prickly issue. Strictly speaking, only humans have emotions as, by definition, they have to be conscious and reportable in some way. However, we know that areas of the brain that control behaviours associated with emotions like fear and sexual desire in humans are highly conserved across many species and so the presumption is that animals also have emotion-like states, which we call internal states or motivational states.

You might ask why we don’t just respond to threatening stimuli by running away without feeling the emotion of fear. This strategy might be effective for an animal that repeatedly encounters the same threat and has a standard, fixed response pattern. This happens in humans for example when we trip and our hands automatically rise to protect our face. However, emotional behaviours are typically elicited by living, autonomous stimuli that are unpredictable.

To survive animals need to integrate information about a threat to guide the activation of a repertoire of predetermined instinctive behaviours, both to select the most appropriate response and to keep the predator guessing about its intentions. One can argue that such an integration-selection task is better served by the activation of an internal state that encodes threat intensity and that empowers a variety of behavioural responses. It is not clear, however, whether internal states are really the best way to drive instinctive behaviour, or whether this brain architecture is just an evolutionary relic that was useful to our ancestors.

One idea is that emotions in humans are the result of our conscious detection of these internal states. As our cortex has developed, our capacity for self-awareness of our internal states has increased to the point where we are often able to feel and report them. In my opinion, a major goal of emotional behaviour research is to discover methods to increase awareness of our internal states and reduce the suffering they impart.

How much is currently known about the brain regions that support instinctive responses?

The basic architecture of the system – the brain regions involved and their connections – was worked out in the 1980s and 90s using classic anatomical methods. At the moment we are in a second phase of discovery where we are applying new genetic tools – optogenetics, pharmacogenetics, and neural activity imaging – to identify the individual cell-types involved and see how the microcircuitries in each structure works.

At the completion of this discovery phase will should understand how you go from sensory input to motor output and how information is encoded and transformed at each synapse along the way. With this information we will be able to make computational models that will help us predict the performance of these circuits and will lead us to new hypotheses about how their work that can be tested by further experiments. I was excited to see how the Sainsbury Wellcome Centre is perfectly placed to contribute to this marriage between experimental and computational neural circuit approaches.

A future phase will focus on plasticity and how the circuits can be adapted, and exploring how the process can be targeted by drugs, such as small molecules that can selectively block regions or cell types or modulate their computational capacity to mitigate behaviours. We are still a long way away from translating this work to humans, but there is great potential in targeting the instinctive behavioural system to treat psychiatric disorders because the suffering associated with these illnesses is overwhelmingly caused by pathological excess or insufficiency in these behaviors.

Why are we so far away from translating this research to humans?

For one, if you look at the human literature nobody talks about the hypothalamus and behaviour. The hypothalamus is very small and can’t be readily seen by human brain imaging technologies like functional magnetic resonance imaging (fMRI). Also, much of the anatomical work in the instinctive fear system, for example, has been overlooked because it was carried out by Brazilian neuroscientists who were not particularly bothered to publish in high profile journals. Fortunately, there has recently been a renewed interest in these behaviors and these studies are being newly appreciated.

Are animals able to control instinctive behaviours?

Yes, we observe that animals dramatically adapt their instinctive responses depending on their environment. For example, animals can become more avoidant of other animals, a form of social fear, if they are bullied by other animals and this avoidance can last for weeks even if the animal is not further bullied.

We have some ideas of how this plasticity works. Cortical structures that record past experiences are able to reach into the brain regions that control the production of instinctive fear behaviour and suppress them. And we have found that these circuits are conserved in primates, so it is very likely that humans use them as well to suppress avoidance behavior.

We also know that the capacity to control instinctive behaviours increases around adolescence when humans begin to interact with peers and presumably need to regulate their instincts so as to balance their immediate needs with those of the group.

How are instinctive behaviours connected to psychiatric disorders?

If you talk to psychiatrists about the things that bother their patients most, they often say it is the negative symptoms such as aggression, fear, and lack of pleasure. Even if we don’t know the origin of the disorder, if we could block the relevant instinctive drive, we could probably help these people. A drug that selectively ramped down aggression, for example, even if it did not improve cognitive symptoms, could be very useful in autism or schizophrenia.

Even if we could target negative behaviour, would people still experience negative feelings?

It would depend on where you intervene between the sensory input and motor output. Of course, this is a big question in humans as we have so much access to our internal states and we don’t really know at what part along the pathway the emotions are getting monitored.

Work in mice and rats suggests that the emotional part is coming from a connection between the medial hypothalamus and cortex that goes via the mid-line thalamus, but in humans this may be different as there may be more connections that we don’t know about. For example, humans could have access to very early sensory information with emotional content, and blocking this could be much more complex than in mice and rats.

What techniques do you currently use in the lab and what are the main research challenges you face?

We use the full range of neural circuit and molecular manipulation and monitoring tools adapted to behaving mice. Many of these are new and truly revolutionary, but we still need more selectively ways to subtly up and down modulate synaptic connections without altering endogenous neural firing activity.

This is because our current tools are still very crude as they globally activate or suppress cells, essentially breaking the circuit. Ideally, you want to leave the circuits intact and tweak their computational properties up or down, increasing or decreasing the gain to see what happens.

Another advance that is desperately needed is the ability to record from thousands or even millions of neurons simultaneously across many brain regions. This will allow us to see brain states encoded in a distributed manner and understand how the brain works as a single organ.

At the same time we need to go down to the sub-cellular level and understand the cell biological mechanisms of circuits. I think we will find that there is a lot of divergence from the standard models about how neurons work. This work will require electron microscopy as synapses lie beyond the resolution of light microscopy, and new tools will be needed like genetically-encoded EM-visible dyes and sensors.

About Dr. Cornelius Gross

Dr. Cornelius Gross is Group Leader, Senior Scientist, and Deputy Head of the Epigenetics & Neurobiology Unit at the European Molecular Biology Laboratory (EMBL) in Rome since 2003. His research aims to understand the neural circuit mechanisms controlling instinctive behaviors, with a special focus on fear and anxiety.

Dr. Gross was raised in the United States and received undergraduate training in biophysics at the University of California, Berkeley and then pursued doctoral research at Yale University studying transcriptional regulation by homeodomain factors with William McGinnis. Dr. Gross then joined the group of René Hen at Columbia University as a postdoctoral fellow where he discovered a developmental role for serotonin in determining life-long anxiety-related behavior and identified the serotonin receptor responsible for the therapeutic effects of antidepressants.

In his early work at EMBL he showed how deficits in serotonin autoregulation can cause sudden infant death syndrome and how serotonin moderates the impact of maternal care on anxiety traits in adulthood. His laboratory is currently focused on characterizing hypothalamic and brainstem circuits that regulate social and predator fear and understanding the role of microglia in determining the wiring of behavioral circuits during development.

In 2013 he was awarded an Advanced Grant from the European Research Council (ERC) to study social and predator fear circuits in the brain. Earlier in his career Dr. Gross served for two years as a science teacher at a public high school in New York City, where he gained an appreciation of the benefits and challenges of communicating science to a lay audience. He is married with three children and lives in Rome, Italy.


How the Motor Cortex Works

The different sections of the motor cortex control different aspects of movement. For example, the premotor cortex is responsible for planning movement, and the primary motor cortex is in charge of executing that movement.

The primary motor cortex is arranged in such a way that different parts of the cortex control different parts of the body. However, not every part has equal amounts of brain matter devoted to it.

Complex movements that require more precise control take up larger amounts of space in the brain than simple motions do. For example, a significant portion of the motor cortex is devoted to finger movements and facial expressions, while a smaller portion of the brain is responsible for leg motions, since these movements are less precise.

This fact explains why many stroke patients struggle with fine motor control or facial paralysis. Because those motions are controlled by a larger portion of the motor cortex, they have a much higher likelihood of becoming damaged during a stroke.

On the other hand, with leg control, only a small amount of brain matter controls it. So a stroke must occur in that small area in order to affect the leg.


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Watch the video: Πώς μπορούμε να αναπτύξουμε νέους νευρώνες στον εγκέφαλο. TED (September 2022).


Comments:

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