Notes on Somatosensation

By and large, somatosenses or bodily sensations are mostly concerned with sensations that arise from stimulation of the skin of the body. Primarily referred to as touch sensation, this was later known to encompass more properties, e.g. pressure, vibration, warmth, and cold. When we interact with an object, we are usually aware of its many different attributes such as the shape, texture, plasticity, hardness, and temperature. One distinctive feature of touch is that it arises from specialized receptors distributed throughout the whole skin known as the mechanoreceptors. There are also specialized receptors within the muscles and joints that provide sensory feedback known as proprioception and kinesthesia. These sensors convey muscle length, change in length, and force (tension), allowing us to be aware of the limb location and movement without vision in space. Receptors encapsulating nerve endings are stimulus-specific and have their unique physiological properties. 

Historically, researchers have viewed the senses as generally subserving a primarily discriminative role (Mountcastle, 2005). Touch and proprioception are naturally related to motor control. Touch is also related to affective and social neuroscience, that is, how one feels and interacts with each other.

1. Peripheral receptors

Mechanoreceptors beneath the skin surface give rise to the perception of touch, pain, and temperature. Free nerve endings are known to provide information of pain and temperature to the brain. There are several properties worth reporting, i.e. receptor size, myelination, location, conduction speed, and response adaptation. More information can be found in Table 3.1 and 3.2 below and also Fig-1.

1. Mechanoreceptors with small fields can distinguish two closely spaced objects better (higher spatial resolution) than receptors that have a large field size (low spatial resolution).
2. Some receptors are located superficially near the epidermis and are called Type-I receptors. Conversely, receptors located in deep skin are of Type-II receptors. 
3. Fast conduction is important to provide afferent signals that build the withdrawal response or reflex arc, e.g. to detect adverse event. 
4. Response adaptation, in this case, refers to how the fibers respond to continuous touch stimulation: slow-adapting fibers (SA) and fast-adapting (FA) fibers. FA-fibers are only sensitive to the onset and offset of the stimulus. As such, their response property is called phasic, dependent on on/off time. SA-fibers, however, respond continuously but gradually to a stimulus, that is, with a tonic response. See below!

Fig-1: Properties of mechanoreceptors and free nerve endings in the peripheral system. Take note the bottom left figure. Rapidly adapting receptors exhibit phasic response, while slow-adapting receptors show a more tonic response.

All somatosensory information is sent to the central nervous system through spinal nerves. In the case of the head, neck, and face region, information is sent through a set of cranial nerves out of the brain stem. The entire body surface can therefore be divided into discrete areas that are represented by a dermatome, and the map representing the skin surface devoted to all spinal nerves is called the dermatomal map. Although it appears that the boundaries are exact in this representation, there is actually some overlap in innervation between adjacent spinal nerves. Dermatomal maps are valuable as a clinical tool in the event of injury or infection to a particular dorsal root.

Fig-2: Graphical illustration of a dermatomal map in relation to the spinal cord.

As mentioned on top, an incoming stimulus makes contact with receptor organ on the skin. An action potential is generated in the immediate vicinity of the receptor organ itself, unlike conventional multipolar neurons where the depolarizing signal must first reach the cell body to produce an action potential. With the mechanoreceptor, action potentials then flow along the peripheral to reach the spinal cord. The cell body of a mechanoreceptor neuron is located in the dorsal root ganglion next to the spinal cord. There, the neuron carries synapse with interneurons and cortical neurons, some of which send information to the cerebral cortex. 

The topic on ascending pathways and somatosensory cortices have been discussed in the earlier blog post. To add on, the primary somatosensory cortex or S1 in the postcentral gyrus is arranged in a colunnar organization (Mountcastle, 1997). Somatosensory inputs from different parts of the body are arranged as columns of neurons that run from the surface to the white matter and encompass all six layers of the cortex. An example is shown here for a part of Area 3b that represents the digits. The expanded view at the bottom shows that each digit is represented by a different column, which in turn is subdivided into inputs from FA- and SA-type afferents.

2. Perceptual aspects of tactile sensation

Among the different somatosenses, the perception of touch was the first to be studied and remains the most widely studied topic. The perception of touch became the main interest of Fechner and Weber in their pioneering work in psychophysics, and was later developed further by Weinstein in 1960s. Tactile sensation can be examined based on the intensity, spatial, and temporal aspects. 

• Tactile intensity. To measure the absolute detection threshold of touch on the various parts of the body, a device called aesthesiometer was invented using nylon filaments. In practice, the filaments will produce skin deformity that in turn gives rise to a perception of touch. See the figure below. The facial regions have the lowest absolute threshold (most sensitive), whereas the foot area has the highest (least sensitive). Another measure of psychophysical properties of touch is the difference threshold but it warrants careful and systematic experiments as it can be influenced by two main factors: intensity of the stimulus and the location of the contact.
• Place of contact. According to Weber, the two-point limen is the smallest separation of two points applied simultaneously to the skin that can still be discriminated, i.e. they evoke the sensation of two separate points. Traditionally, the two-point limen was seen to improve steadily from the shoulder to the fingertip, resulting in a near twice reduction of the threshold. What is the physiological basis for this? The size and density of the mechanoreceptors. The smaller the size of the receptive field, the greater the ability to discriminate two different contact points. Such property is apparent for FA-I and SA-I type afferents that are more superficial on the skin. Differences in packing density also play an important role in determining tactile acuity (Vallbo & Johansson). The superiority in acuity (discriminative ability) of the fingertips allow visually-impaired people to read Braille alphabets.

Fig-3: Although the facial regions are most sensitive to touch (*), it is the fingers that show the highest spatial discrimination ability. Similarly, much of the upper torso is quite sensitive to touch but shows poor spatial resolution. The feet display just the opposite pattern: relatively good acuity or discrimination ability (#) but poor sensitivity.

• Temporal aspect. Much of the research done with the temporal aspects made use of either a prolonged stimulation or a short but repetitive vibrotactile stimulation. Prolonged application of vibrotactile stimulation is shown to cause adaptation by reducing the sensitivity of vibration at the skin stimulation site (Gescheider and Wright, 1969). In contrast, vibratory stimuli produce a different threshold value than static/prolonged stimuli do. Temporal changes in touch can best be detected by fast-adapting mechanoreceptors. The relation between vibration frequency and skin displacement is therefore a U-shaped recruitment curve. Our perception is determined by the property of the mechanoreceptors active: 
• Very small vibrations between 200–300 Hz are captured by the FA-II receptors (Pacinian) that respond to vibrations > 50 Hz, 
• Whereas FA-I receptors (Meissner) respond to vibrations between 20–40 Hz. 
• For stronger vibrations well above these threshold levels, more than one type of mechanoreceptor typically responds to movements of the skin. 

Lastly, vibrotactile stimulation has been widely used to examine sensory processing and memory in primates (e.g. Romo et al.). Touch is ... an intermediary sensory system in that its spatial resolving power is poorer than that of vision but superior to that of audition, and its temporal resolving capacity is better than vision but inferior to audition (Lynette Jones, MIT).

3. Perceptual aspects of limb position

Proprioception and kinesthesia are critically important to the motor system in guiding our movement through the environment. Unlike tactile sensation, proprioceptive stimuli are primarily internal that are generated by the position or movement of a body part. Static forces on the joints, muscles, and tendons, which maintain limb position against the force of gravity, indicate the position of a limb. The movement of a limb is indicated by dynamic changes in the forces applied to muscles, tendons, and joints. More recent studies have looked into how proprioception and kinesthesia are also responsible for sensing effort and force exertion through tension placed on the muscles. 

Receptors associated with the limb position sense generally can be divided into 4 groups depending on the discharge properties, type of stimulus, and the neurons innervating the organ. Interestingly, some mechanoreceptors are found to give rise to the sensation of limb position and movement, e.g. presumably due to skin stretch, vibration. For historical reason, the naming convention is different from the receptors innervating the skin. Compare the table above and below. Both Group I and II afferents are analogous to the Aα and Aβ fibers respectively, that have large diameters and heavily myelinated. Muscle spindles are arranged in parallel with the extrafusal fibers that make up the main body of the muscle. This parallel arrangement is the best for detecting a change in fiber length, and the speed of that change. Consequently, these fibers are among the fastest in terms of signal transmission to the spinal cord.

From a clinical and sports science perspective, it is common to associate proprioception to primarily balance and postural control; and kinesthesia to the sensation of movement. In one of the clinical tests, for example, we look into how the proprioceptive components are working properly when the visual cues are missing and proprioceptive cues are the major sources of information.

The roles of proprioception and kinesthesia in motor control and learning cannot be denied. Every time we consciously move one limb, a command is issued from the motor centers of our brain to the appropriate muscles. If the perceptual centers in our brain could somehow get a copy of that command, then it would have the means to know what movement is taking place. This information would be independent of that being generated by the proprioceptors in the muscles and joints. Such is the principle of corollary discharge. Not only that these receptors sense movement and position, but they also allow us to perceive the sensation of effort and force. A comprehensive review of this system has been written by Proske & Gandevia, 2012. 

The sensitivity of the limb position and movement in space is quite remarkable. Among the joints, the hip joint appears to be the most sensitive to detecting a movement as little as 0.2°. Among the major limb joints, the following order has been reported in terms of decreasing sensitivity: shoulder, knee, ankle, elbow, wrist, and finger base. Unfortunately, the data from kinesthetic experiments is complicated by several factors such as the direction of the joint movement, the degree to which the limb is stretched, and the precise way in which the measurements are performed. From psychophysics, the Weber fraction for weight discrimination is about 0.02. On the other hand, the perceived effort (force generation) can be fitted to a power function with an exponent value of 1.7.

One popular paradigm to test proprioception is the joint position matching test. Experimental factors that affect matching errors (Goble, 2010): (1) Ipsilateral matching, (2) Left arm advantage - right hemisphere damage people are more prone to proprioceptive deficits, (3) Tau effect - longer time to complete reference movement by experimenter leading to targets being perceived as further from the starting point, (4) Age of participants (matching errors increase in older population) (5) Left workspace bias in joint position matching task. To elaborate on the second factor: a study by Naito and colleagues (2005, 2007) used a tendon vibration paradigm in combination with neuroimaging to map regions of the brain responsible for processing input from key proprioceptors—the muscle spindles. Hence, they concluded proprioceptive performance lies more within the right hemisphere.

Stroke Rehabilitation (III): Impairments in Somatosensation

(1) Prevalence of somatosensory loss post-stroke

Evidence-based practice and research have established that impairments resulting from a stroke happen not only in motor domains (e.g. inability to perform reaching, loss of balance, and slurred speech) but also in somatosensory domains (loss of tactile sensation, limb position sense, and perceiving force). Carey LM (1995) stated that the loss of somatosensation occurs in about 60% of stroke survivors and has detrimental impacts on the quality of life, e.g. in spontaneous use of the hand and object manipulation. 

Intact somatosensation is essential for motor control since it is reliant on both intact feedforward and intact feedback from afferent inputs. It has been suggested that a learned non-use phenomenon with sensory loss leads to further deterioration of motor abilities. Despite this fact, the association between sensory impairment and outcomes following stroke has received limited focus in rehabilitation research. One reason is that most clinicians assume that spontaneous motor recovery occurs in the first 4 weeks post-stroke in the acute phase (Jia-Ching et al, 2005; Wing et al, 1990; Heller A et al, 1991; Lincoln NB et al, 1991), and that somatosensory recovery will arguably follow suit and therefore receives less attention. Another reason is the complexity in measuring the sensing ability of different modalities.

More recently, Connell et al (2008) conducted a newer prospective study with 70 patients with a first stroke assessed on admission day, and 2, 4, and 6 months post-stroke. Their findings did not contradict the earlier findings by Carey LM (1995). Of the sample collected, the authors found that 7–53% had impaired tactile sensations, 31–89% impaired stereognosis, and 34–64% impaired proprioception. Specifically, proprioception and stereognosis (the ability to perceive 3D shape and depth) were more frequently impaired than tactile sensations. This is in contrast to a study by Kim et al. [16] on acute stroke patients, who found that proprioception was less impaired when compared with localization and two-point discrimination regardless of the lesion.

Connell et al further said that the different somatosensory modalities showed only slight agreement between impairment within the same body areas, suggesting that the modalities are independent of each other. This suggests that it is necessary to include all somatosensory modalities while assessing one body part. In contrast, the high agreement between sensory modalities in adjacent body areas means that it is probably not necessary to assess all related body parts, e.g. there was redundancy between the wrist and hand, or between the ankle and foot.

(2) NSA and RASP scales

One challenge of sensory assessment post-stroke is the variety of sensing modalities of somatosensation, ranging from tactile or touch, pressure, position sense, movement direction, pain, to temperature. Another important barrier is the lack of standardization and low reliability of the clinical assessment scale (Winward, et al 1999). At the moment, there are three common clinical assessment scales for sensory impairment: the sensation parts of the Fugl-Meyer Assessment for UE/LE, Nottingham Sensory Assessment (NSA), and Rivermead Assessment of Somatosensory Performance (RASP). All sensory tests are conducted in the absence of vision.

NSA was developed as a standardized clinical sensory assessment, assessing both sides of the body and all areas. The original version uses a 5-scale rating system, has good intra-rater reliability (the same clinicians did multiple times), but poor inter-rater reliability (different clinicians did the same assessment) and was time-consuming (Lincoln NB, et al, 1991). The NSA measures tactile sensations (light touch, temperature, pinprick, pressure, tactile localization, and bilateral simultaneous touch), on the face, trunk, shoulder, elbow, wrist, hand, hip, knee, ankle, and foot, on both the paretic and normal side. The poor reliability has prompted a revision of NSA according to the Erasmus MC version (Em-NSA) (Stolk-Hornsveld, 2006) with lesser items to test but uses 3-scale rating system. Although NSA was shown to have concurrent validity with the more established and gold standard Fugl-Meyer Assessment for sensorimotor impairments (Scalha et al, 2011), this scale is still less attractive, with some clinicians view this to be a mere screening tool at best.

The RASP is a multi-modal sensory tool that tests six sensations (sharp/dull discrimination, surface pressure, tactile localization, temperature discrimination, joint movement, and joint movement direction discrimination), and two secondary sensations (sensory extinction and two-point discrimination) (Winward et al, 2002). The scale for proprioception was shown to have excellent test-retest reliability among sub-acute survivors and good concurrent validity with Motricity Index and Barthel Index, an ordinal scale used to measure performance in activities of daily living (ADL).

(3) Sensory impairments over time

One focus area in stroke rehab is the ability of a clinical assessment to predict recovery. The power of predictability helps clinicians to assess the stroke severity and to provide the most accurate intervention given a particular condition. Connell et al (2008) found the initial somatosensory impairment was significantly related to sensing ability at 6 months, accounting for 46–71% of the variance. The authors argued that the remaining factors were attributed e.g. to more cognitive factors, perceptual ability, and motivation. The spontaneous recovery over time was more obvious in the upper limb compared to the lower limb. 

In a study by Meyer and colleagues in Belgium (Meyer S. et al, 2016), the authors recruited acute stroke patients (< 1 week) and conducted sensory tests. Confirming earlier studies, they found that 41–63% of stroke survivors in the acute phase had a sensory loss in one of the modalities within the first week, but the deficits improved to 3–50% when assessed 6-month post-stroke. Proprioception score of Em-NSA moderately predicts motor ability at 6-month post-stroke as measured by the Fugl-Meyer UE and Action Research Arm Test. As a comparison, stereognosis moderately predicted motor ability at six months post-stroke as measured by Fugl-Meyer UE, the Motricity Index, and Action Research Arm Test. 

Using RASP, the somatosensory subtest of proprioception demonstrated the greatest level of recovery, but no patient achieved full recovery on all somatosensory subtests (Winward et al, 2007). In another study using the original NSA, Connell et al (2008) reported that most recovery of the upper limb tactile sensations and stereognosis occurred in the first 4 months, whereas recovery in proprioception continued over 6 months. Although the motor and functional recovery demonstrated continual improvement over time, somatosensory recovery showed marked variation in subtests both within and between patients. Both Connell's and Winward's studies reported that individual somatosensory modality recovery may be independent of other somatosensory modalities, despite the existence of parallel processing in the central nervous system.

Functional MRI has been beneficial to elucidate plastic changes in the brain following a stroke. Recently Carey et al. (2002) demonstrated in a single case study of severe sensory loss that there was little evidence of neural plastic changes in the early stages after stroke (2 weeks). However, a return of activation in ipsilesional primary and bilateral secondary somatosensory cortices was observed at 3 months and this was maintained at 6 months.

(4) Somatosensory recovery

Kessner et al (2016): Most cortical reorganization within the motor system occurs within 2–3 months post-stroke and stabilizes after 6 months. However, much less is known about the time course of recovery from somatosensory deficits, and about the mutual interaction of somatosensory and motor recovery. The deficits recovered at least partially, mostly within 3 months. Interestingly, some modalities (graphesthesia impairment and movement detection) even appeared to deteriorate during the time course after initial recovery (Julkunen, et al 2005). After about 6 months of recovery, the prevalence of somatosensory deficits seems to be lower. The initial somatosensory deficit was the strongest predictor for long-term somatosensory ability. Taken together, most patients recover at least partially from their somatosensory deficits, mainly during the first three to six months after stroke (Fig. 1). However, not all modalities necessarily recover with positive results. 

The probability and duration to reach a good rehabilitative plateau phase (Barthel index > 60, ambulation > 150 ft) are significantly worse, if stroke patients had combined motor and somatosensory deficits compared to motor deficits only. The authors summarized that somatosensory deficits after stroke have an important negative effect on motor and functional performance, especially proprioceptive impairments!

(5) Somatosensory-specific interventions

Retraining focusing on somatosensory-specific interventions is lacking. Stroke survivors with sensory impairments share that they often feel this is often a neglected aspect in their rehab program (Doyle, Bennet, Fasoli, & McKenna, 2010). 

A randomized controlled trial of sensory retraining has shown improvement in stroke patients’ sensory discrimination functions following a series of tactile and proprioceptive training (Carey et al., 2011). Such improvement was maintained and slightly increased at 6 weeks and 6 months follow-up. Evidently, the impact of somatosensory interventions on the recovery of sensation post-stroke is thought to be positive and significant. The authors have also argued that such a form of intervention is clinically beneficial, where reduction in deficit was targeted to improve lost abilities. 

On the other hand, Gopaul et al. (2018) proposed that the combination of somatosensory training with motor training may result in greater improvements in both motor and somatosensory functions, as compared to interventions that focus on individual function recovery. Most studies of such combined interventions have comprised active training components as it has the potential to drive neural plasticity (produce greater cortical activation extending to multiple areas), particularly when delivered insufficient dose. For example, Byl and colleagues (2008) demonstrated that patients who received higher-dose (72 hours) of integrated active-somatosensory and passive-motor training performed sensory discrimination tasks more accurately as compared to those receiving lower-dose (12-13.3 hours) of training. Despite the improvements observed, motor improvements were considered smaller than somatosensory improvements due to the reinforcement of passive movement training (mental practice and mirror therapy) in their study.

Stroke Rehabilitation (II): Robotic Assessment of Proprioception

Previous studies have found the importance of somatosensory signals in motor control. Deaffarented patients are shown to have unique and distinct movement patterns compared to healthy control. Within the scope of motor behavior, movement-related somatosenses here means bodily senses that cover proprioception (sense of joint position), kinesthesia (sense of limb movement), and other senses originating from the mechanoreceptors, but does not include pain and thermal receptors. A large literature also shows that the somatosensory system is important for motor learning.

Neurological injuries (e.g. stroke, Parkinson's Disease, and multiple sclerosis) are often accompanied by somatosensory deficits. There has been a growing interest to assess and train the somatosensory system in a clinical setting. In the case of stroke, the somatosensory test is part of a standard clinical assessment. However, a recent systematic review (Connell & Tyson, 2012) has shown that such evaluation is known to be unreliable. The authors commented that the sensory section of the Fugl-Meyer Assessment and Erasmus version of Nottingham Sensory Assessment has the best balance between usability and robustness. In a stroke study, it was found that proprioception and stereognosis were more frequently impaired than tactile sensations and that there is little agreement in impairment among different somatosensory modalities (Connell et al, 2008). More research on assessments and interventions for somatosensory impairment post-stroke is warranted.

Broadly speaking, there are two classes in the assessment of proprioception: joint-position matching (JPM) tasks and psychophysical threshold method (PTM).

JPM tasks evaluate the ability to replicate the position or velocity of a joint angle or a limb position in the absence of vision. Participants respond by replicating the reference movement or position using the same limb (unilateral protocol) or the contralateral limb (bilateral). 

On the other hand, PTM tasks assess the ability to detect the intensity of proprioceptive stimuli, or discriminate two stimuli equal in nature but differ in amplitude/intensity. For example, the stimuli can be tactile, position, angle, or vibration. Participants respond typically with a verbal response.

Although some traditional tools such as goniometers can be used, the reliability of such measurements is unproven. For this reason, the use of robotic devices in the assessment of somatosensory integrity becomes popular. Robotics promise increased precision and accuracy, in addition to better reliability compared with standardized observer-based ordinal scales. Examples of such devices include KINARM (bimanual upper limb), MIT Manus (upper limb), Lokomat (lower limb), Wristbot (wrist), AMADEO (fingers). Other devices include an isokinetic dynamometer for the lower limb (Biodex).

Joint Position Matching Task
Joint position matching (JPM) tasks can be exercised on both lower and upper limbs, and either using unilateral or bilateral matching limbs. A thorough review of this test is described by Goble (2010). Instead of a pure sensory test, JPM is seen to involve some working memory component. Let's begin with the lower limb assessment. A few studies used Biodex lower limb devices to study lower limb proprioception. In a study by Willem et al (2002), subjects lied down in a supine position with the ankle in position 15° plantar-flexion. Active and passive joint-position sense using JPM method was assessed at the ankle, and muscle strength (isokinetic peak torque) was determined. This is also an example of a unilateral protocol, i.e. the same limb is used to replicate the movement.

Fig-1: An example of the joint position matching task using the same limb of lower extremities.

Another study investigates the hip and knee joint proprioception in healthy subjects and incomplete SCI subjects (Domingo and Lam, 2014) using a Lokomat exoskeleton. During the task, the subject's knee (or hip) was first moved passively by the robot into a position (joint angle θ). After a short break, the robot then moves it to a so-called distractor position. The subject was then asked to bring the joint back to the original position by using a joystick control (θ_S). The nominal value |θ ─ θ_S| is the matching error, reflecting the subject's performance. Refer to the figure above.

For the upper limb, studies mostly involved the more proximal limb, i.e. shoulder and elbow joints. A study with a bimanual protocol or two-arm matching task used two groups of subjects. In the first group, subjects moved both middle fingers to the same spatial location (extrinsic). The second group, however, was asked to move the right finger to a mirror-symmetric location of the left middle finger with respect to the body midline (intrinsic). The authors showed that bimanual accuracy is higher for tasks involving extrinsic coordinate (Iandolo, et al, 2015).

KINARM has proven to be a popular robotic tool for bimanual tasks studying sensorimotor behavior in the healthy and clinical population. Dukelow et al did a series of studies using KINARM in patients with stroke and see whether proprioception can be assessed objectively. In one study, 74 healthy subjects and 113 subjects with acute stroke (62 left-affected, 51 right-affected) performed a JPM task with vision occluded. The robot moved the most affected arm at a preset speed of 28 cm/sec, direction, and magnitude. Stroke patients were then asked to mirror-match the movement with their opposite, active arm (Semrau et al, 2013). For control subjects, both arms were tested. All subjects performed 36 total movements, for a total of 6 movements in each of 6 movement directions. See the figure below. The authors found that most stroke patients (69% of left-affected; median, 28.0°; 49% of right-affected subjects; median, 22.1°) made significantly larger directional errors than 95% of the controls (95% of range, <22.4°; median, 14.8°).

Fig-2: An example of the joint position matching task using bilateral limbs of upper extremities.

Recently, Konczak, Masia, and colleagues (2016) used a wrist robotic device and found the anisotropic nature of sensory acuity using JPM method on the dominant arm. Active matching acuity for flexion/extension was found to be 4.64 ± 0.24°; abduction/adduction: 3.68 ± 0.32°; supination/pronation: 5.15 ± 0.37°. A similar study was also performed with young children (Marini F, et al., 2017) and it was found that the anisotropic nature of sensory acuity does not change significantly across age. See the figure below for more illustration.

Fig-3: An example of the joint position matching task of the wrist (distal upper limb).

Psychophysical Threshold Method

Assessment using PTM yields a certain psychometric function with nominal value or threshold of detection in movement speed or position/angle. The method utilizes principles of Psychophysics, which is discussed in a separate blog entry on the "Human Sensory Perception". The shape of this function reflects the variability of responses about this threshold. The most common paradigm used in PTM tasks is a method of constant stimuli but one drawback of such method is the length procedure (Simo et al, 2014); and the same trial usually repeats until 3 to 5 correct judgments of the same stimulus are achieved. More recently, a revised and faster version of PTM paradigm was proposed by Mrotek et al (2017) using the "method of adjustment" during ten iterative trials. Here, subjects repeatedly adjust the magnitude of the stimulus until it is just perceptible, with an equal number of trials approaching that estimated threshold from below (i.e., starting from smaller stimulus magnitudes) and above (starting from larger magnitudes). Typical force magnitude and the threshold of detection can be found below for a hemiparetic patient (left) and normal control (right).

Fig-4: An illustration of a psychophysical method in assessing the threshold of detection.

Studies involving the lower limb have investigated the use of robotic devices in assessing knee joint proprioception. Using a custom-made device similar to the one by Biodex, Hurkmans et al. (2007) assessed the smallest detectable angular change in the knee joint. A similar method was used to find the smallest detectable passive knee movement in both sagittal as well as the frontal plane (Cammarata, et al., 2011). This method lets the subjects respond when they are just able to detect a change in joint position. In another study by Lam at UBC (Chrishold et al, 2016) in patients with spinal cord injury, Lokomat was used to test hip and joint again. Here, the joint was moved passively in 4 different movement speeds (0.5, 1.0, 2.0, and 4.0 deg/s) in both flexion and extension directions. The subject had to respond when the movement was first felt.

Assessment of proprioception in conjunction with motor adaptation has been studied by Ostry et al (2010). This study involves MIT-Manus robotic arm that produces a velocity-dependent curl field which perturbs the movement of the upper limb. Sensory acuity was assessed using an adaptive staircase method or PEST. The authors found that motor adaptation causes a shift in sensory acuity, a term called sensory recalibration (by another group, Henriques et al.). In another study, threshold detection of a wrist movement was assessed using a Wristbot by Konczak and colleagues. The authors found that the mean threshold for wrist flexion was 2.15°± 0.43° and 1.52°± 0.36° for abduction.

Conclusion
The robotic-based somatosensory assessment has gained popularity. It has great potential clinical applications in areas that involve human movements and movement disorders. Until now, there is no clinical biomarkers to predict somatosensory impairment in stroke (see: Boyd et al, 2018 for a review).


Reference: Based on a nice book chapter, "Robotic techniques for the assessment of proprioceptive deficits and for proprioceptive training" by Casadio et al., 2018. Figures are taken from the relevant individual citation therein.

The Somatosensory System - a brief overview

Principles of Sensory Coding

The sensory system is a part of our nervous system that processes sensory information. Through the five sense-doors, it is responsible for giving direct representations of the outside world. Some key principles govern the way our sensory system works. First, the sensory system extracts sensory information arriving based on the type of stimulus (modality), location, intensity, and duration. Second, the arriving stimulus creates certain perceptual experiences within us. The conversion of stimulus information into neural signals by the sensory system is called sensory coding. Arriving external stimuli will be captured as energy by specialized peripheral "sensors" called receptors. These sensitive organs can be found in all five senses: eyes, ears, nose, tongue, and bodily receptors. The basic sensory modalities include light, sound, smell, taste, temperature, and pressure. Law of receptor specificity says that different nerve fibers are dedicated to different sensory modalities. 

• Location coding: we are aware of a specific site of touching or pressure (location of the stimulus) as it impinges a specific receptor on the skin. Such receptor is broadly called the receptor field. This receptor field in turn makes a specific connection in the brain such that different areas in the brain are stimulated. Location coding is not preserved in the chemosensory modality. 
• Intensity coding: the greater the stimulus intensity beyond a certain threshold of detection (see: Psychophysics), the greater the output of the receptor. More importantly, the intensity of a stimulus is coded in frequency terms -- the greater the stimulus intensity, the greater the discharge rate of action potential. However, other non-sensory factors are able to influence this frequency: fatigue, motivation, etc. 
• Duration coding: our awareness stay as long as the stimulus exists. To some senses, the awareness of a stimulus may decline over time, a process called adaptation, and it is caused by the way ion channels work. E.g. we perceive the cushion-like feeling when we first sit on the chair, but that awareness gradually disappears. 
• From the receptors, signals are transmitted through several anatomically distinct pathways following a concept of parallel pathways. Parallel processing is an important feature of hierarchical sensory processing. Brain compartments that process sensory information have an orderly, topographic, structured representation. The sensory systems do not enjoy equal representation in the brain (e.g. the somatotopic map of touch perception). 

The visual system, centered on the Occipital Cortex, is arguably the most dominant percept. Among the senses, however, the somatosenses or the perception of 'body' is intimately related to the motor cortex to plan and guide goal-directed movement. This post attempts to summarize their neural substrates and behavior.

There are three types of somatosenses based on the modality, the type of stimuli our brain perceives. First, the mechanoreceptors detect touch, pain, and temperature stimuli, and are embedded inside the dermal layer of the skin. A wide variety of receptors are able to detect vibration, stretch, pressure, shape, and texture. The proprioception & kinesthesia, embedded mainly in the joints and muscles, detect the position and movement of the trunk and limbs. And lastly, the senses of the internal organs in the body detect pain sensation or discomfort.

Proprioception is one of the core themes in my lab. Originally thought only to be sensed by certain sensory neurons in the muscle, proprioceptive information is also received by other mechanoreceptors in the skin and muscles. There is a set of specialized sensory neurons coming from the muscles. Embedded deep inside the extrafusal fibers is a set of muscle spindles that carry Type Ia and II sensory neurons. They encode muscle length or stretch. When the muscles contract, however, they lose sensitivity and fire less. It is the gamma motor neurons that increase or offset the loss of sensitivity by introducing tension to the muscle spindle. Type Ia neurons, in particular, are sensitive to the change in the stretch over time or velocity. Type Ib sensory neurons originate in the tendon organ that encodes muscle tension, but not stretch or length. Microelectrode recording is able to distinguish their discharge pattern in response to a certain behavior manipulation.

Fig-1:  Major ascending pathways; taken from [3].        

The Ascending Pathways
The spinal cord plays a critical role as it contains massive highways from and to the brain. Cross-sectionally, the spinal cord is divided into the core grey matter (H-shaped butterfly) surrounded by white matter. The ventral portion of the grey matter contains cell bodies of alpha motor neurons. The dorsal portion contains sensory axons and cell bodies of interneurons. The spinal cord is important for short-latency reflex.

The spinal cord serves as the base in the motor hierarchy but it is the first station of the sensory inflow to the brain. 

Sensory information from the trunk and limbs enters the spinal cord and travels up to the cerebral cortex through the thalamus, the ventral-posterior-lateral nucleus. 

The pathways called the ascending sensory pathways, work in parallel to ensure timely information delivery. The cell bodies of the sensory receptors are collectively called the dorsal root ganglion.

Two sensory pathways are present depending on the type of modality. The more precise receptors (touch, kinesthesia) ascend to the medulla and the thalamus through dorsal columns. The axons cross at the medulla forming the medial lemniscus to the opposite side of the brain, just like the descending motor pathways and hence contralateral in nature. The second pathway is dedicated to more poorly localized percepts such as pain and temperature. Upon entering the gray matter, the axons immediately cross and form the spinothalamic tract up to the thalamus. This tract is part of the bigger anterolateral pathways.

Thalamus as a Relay System
Thalamus is an important structure near the middle of the cerebral hemisphere, medial and caudal to the basal ganglia. It has two lobes in both left/right hemispheres and receives information from one part of the central nervous system (e.g. basal ganglia, cerebellum, motor cortex) and sends it to the other region through projection fibers. It is an essential link between sensory receptors and the cortex for all modalities except olfaction. This oval-shaped structure is situated bilaterally and consists of several distinct nuclei.

There are two types of thalamic nuclei in the thalamus: specific and non-specific. The name arises due to the way the nucleus is related to different brain regions. The non-specific nuclei, mainly in the internal medullary lamina, possess complicated input-output connections and does not bear selectivity or specificity to a certain cortical region or cortical function. The specific thalamic nuclei, whose outputs are excitatory (glutamatergic system), consist of four main divisions:

1. Anterior division: consists only of one nuclei and is linked to the mammillary bodies (part of the hypothalamus) and hippocampal formation, the cingulate and frontal lobe.
2. Medial division: it is connected to the basal ganglia, amygdala, and the midbrain, been implicated in memory.
3. Ventral division: the division that is very important for sensorimotor-related behavior. The ventro-anterior and ventro-lateral nuclei send information from the basal ganglia and cerebellum to motor cortex. We just mention the area that's involved in sending somatosensory information to S1. 
4. Posterior division: this area is mainly for the auditory (medial geniculate nucleus) and visual system (lateral geniculate nucleus); there is also the pulvinar nuclei that carry various functions and are interconnected to the parietal and occipital lobe.

The thin outer layer of the thalamus, called the reticular nucleus, is thought to provide inhibitory feedback. This means that the thalamus is not merely a congregation of relays but able to perform some information processing in the nuclei.

The Somatosensory Cortex
Axons in the ventral-posterior-lateral nucleus terminate primarily in the postcentral gyrus, or more popularly now as the primary somatosensory cortex or S1. It is situated between the central sulcus and postcentral sulcus, caudal to the primary motor cortex. We gain insights into this area by using the same electrical stimulation technique similar to the ones used in cortical motor experiments. Penfield found that these neurons are sensitive to tactile stimulation of the skin surface. Other scientists e.g. Woolsey, Kaas, etc. performed similar experiments on monkeys.

Like the primary motor cortex, the bodily representation in S1 is arranged in an orderly fashion or somatotopic. It turns out that the topography is not simple and the postcentral gyrus is further subdivided into Area 3a, 3b, 1, and 2 (correspondingly BA-3a/b, BA-1, and BA-2). Area 3 processes the basic somatosensory information and is arguably the only S1-proper as it receives the most projections from the thalamus. Neurons in BA-3a/b are found to have the smallest receptive fields. So what are the functional divisions of the somatosensory cortex?

• Proprioceptive sensory information from the muscles and joints is represented in Area 3a.
• Cutaneous and tactile information is represented in Area 3b.
• Area 3a/3b sends projections to Area 1 where higher-order processing takes place.
• Lastly, Area 2 is where information from Area 1 is fused with information from muscles and joints to facilitate richer tactile recognition related to grasping such as size and shape, and joint information while moving. The cells have the largest receptive fields.

Fig-2:  The primary somatosensory cortex; adapted from [2]. Note how the coronal section reveals BA-4 as well.

The cortical-body mapping is represented by the homunculus map. Just like M1, the larger the area in S1 of a certain body map, the greater the number of 'computational efficiency' power involved. For example: our highly discriminative sense of touch in the index finger is due to the large area in S1 dedicated to processing somatosensory stimuli from this part of the body. By virtue of synaptic plasticity, it is important to note that the mapping can be modified by experience. Experiments in monkeys (e.g. Jenkins and Merzenich, et al., 1990) focusing on tactile sensation have shown that the cortical representation of the digits expands after repeated training or usage of that digits.

What's next? S1 and beyond

From the primary area, somatosensory information is transmitted to secondary areas such as the second somatosensory area (SII), insula, and parietal association areas. Okie, honestly their functionalities are rather vague and mixed. The second somatosensory cortex (SII, or S2) is located on the upper ceiling of the lateral fissure, an area called the parietal operculum. It receives inputs from all four divisions of the primary somatosensory cortex. These inputs appear to be crucial for if they are removed, SII will not elicit any response to tactile stimulation. Removal of SII neurons, on the other hand, do not influence neural response in S1. SII has projections to the insular cortex and temporal areas associated with tactile memory. One function of the insular cortex in body awareness is in understanding and judging pain.

The somatosensory cortex is also tightly linked to other, more posterior areas in the parietal lobe. Areas such as BA-5 and BA-7 receive inputs from S1 and are important in guiding movements, i.e. reaching and grasping. However, to make movements, we need visual inputs and proper decision-making. The integration of visual and somatosensory codes occurs in the posterior parietal cortex and it is often called the somatosensory association areas. The areas send projections to the frontal lobe, parahippocampal region, cingulate gyrus, etc. for higher-order cognition and learning. These areas integrate sensory information of multiple modalities and hence they are multimodal.

Fig-3:  Relationship between S1 and the association sensory cortex of the brain; taken from [1]. It can be seen that neurons in S1 project to M1, and the so-called secondary motor and somatosensory cortices.

Final remark: the homunculus

Homunculus describes the somatotopic mapping of afferent and efferent projections that are responsible for our movement and bodily senses. Typically, a large area of the body in the brain corresponds to higher processing resources in the brain (and vice versa). Humans are well-known to possess good fine motor skills as shown by the large hand representation in the motor and somatosensory cortices. See below.

Fig-4: Homunculus of the somatosensory (afferent) and motor (efferent) projections.

As mentioned, the primary motor cortex (M1) receives a large projection from S1. Both areas are also organized in an orderly somatotopic fashion. One advantage of having the motor and somatotopic maps in close proximity (i.e., on either side of the central sulcus) is that it permits a more precise registration in the connectivity. The specificity in terms of bodily representation between M1 and S1 is reflected by the homotopic connection.

This connection is understandable given how closely the two systems must cooperate when we physically interact with an object. Indeed, the projections of S1 to M1 are organized in a homotopic fashion—that is, a given part of the motor cortex receives projections from the same part on the body map of the somatosensory cortex. Such interaction requires processes that rely on feedback signals from tactile receptors in the skin and proprioceptive receptors in the muscles.

References

[1]  Chapter 18 - The Functional Organization of Perception and Movement. In Kandel E.R. et. al. (2000). Principles of Neural Science 4e, McGraw-Hill.

[2]  Figure 20-1 (p.384) and Figure 23-1 (p.453). In Kandel E.R. et. al. (2000). Principles of Neural Science 4e, McGraw-Hill.
[3]  Chapter 7 - Audition, Chemical, Body Senses. In Carlson, Neil R. (2013). Physiology of Behavior 11e. Pearson Education.