Temporoparietal junction

The temporoparietal junction (TPJ) is an area of the brain where the temporal and parietal lobes meet, at the posterior end of the lateral sulcus (Sylvian fissure). The TPJ incorporates information from the thalamus and the limbic system as well as from the visual, auditory and somatosensory systems. The TPJ also integrates information from both the external environment as well as from within the body. The TPJ is responsible for collecting all of this information and then processing it.
This area is also known to play a crucial role in self–other distinctions processes and theory of mind (ToM). Furthermore, damage to the TPJ has been implicated in having adverse effects on an individual's ability to make moral decisions and has been known to produce out-of-body experiences (OBEs). Electromagnetic stimulation of the TPJ can also cause these effects. Apart from these diverse roles that the TPJ plays, it is also known for its involvement in a variety of widespread disorders including anxiety disorders, amnesia, Alzheimer's disease, autism spectrum disorder and schizophrenia.
Anatomy and function.
The brain contains four main lobes: temporal lobe, parietal lobe, frontal lobe and the occipital lobe. The temporoparietal junction lies in the region between the temporal and parietal lobes, near the lateral sulcus (Sylvian fissure). Specifically, it is composed of the inferior parietal lobule and the caudal parts of the superior temporal sulcus. There are two halves to the temporoparietal junction, with each component in their respective hemispheres of the brain. Each half of the TPJ pertains to various aspects of cognitive function. Often, however, the separate halves of the TPJ will work in coordination. The TPJ is mainly involved in information processing and perception.
Right temporoparietal junction.
The right temporoparietal junction (rTPJ) is involved in the processing of information in terms of the ability of an individual to pay attention. Evidence from neuroimaging studies as well as lesion studies revealed that the rTPJ plays a pivotal role in analyzing signals from self-produced actions as well as with signals from the external environment. For example, an individual with lesions in their rTPJ would more than likely exhibit a sense of hemi-neglect, wherein they would no longer be able to pay attention to anything they observe on the left. So, if someone were to have a lesion in their rTPJ, then over time the awareness of the left limbs may fade without treatment. Visual signals provide the sensory information necessary for the brain to process spatial recognition of the world. When vision is limited, knowledge of existence begins to fade away since as far as the brain is concerned the object does not exist. Furthermore, the rTPJ plays a role in the way individuals observe and process information, thus impacting social interaction. Empathy and sympathy require an individual to simultaneously distinguish between different possible perspectives on the same situation. Imaging studies show that this ability depends upon the coordinated interaction of the rTPJ to identify and process the social cues presented to it. This rapid process allows for an individual to quickly react to situations.
Left temporoparietal junction.
The left temporoparietal junction (lTPJ) contains both Wernicke's area and the angular gyrus, both prominent anatomical structures of the brain that are involved in language cognition, processing, and comprehension of both written and spoken language. Steven Pinker discusses this brain region, theorising that it underlies an amodal 'language of thought' or Mentalese. The lTPJ, in this account, takes in observations from external environments, such as conversations, makes connections in the brain regarding past memories or incidents and then converts those thoughts and connections to written and spoken language. Pinker's full account of this is explained in The Language Instinct: How the Mind Creates Language. The lTPJ also plays an important role in reasoning of other's beliefs, intentions, and desires. Activation of the lTPJ was observed in patients processing mental states such as beliefs when an fMRI was used on patients as they were asked to make inferences regarding the mental states of others such as lying. This study was further supplemented by a study which identified that lesions to the left TPJ can impair cognitive processes specifically involved in the inference of someone else's belief, intention, or desire. Individuals with lesions in the lTPJ were no longer able to correctly identify when someone was lying or insinuating a false sense of belief or desire. The lTPJ is also involved in the processing of associating and remembering the names of individuals and objects.
Disorders.
The dopaminergic-serotonergic system mediates our ability to distinguish and understand others’ beliefs as well as predict their behavior in light of that understanding. In certain disorders involving the dopaminergic-serotonergic system, this mentalizing process is disrupted and part or all of the process is impaired; this includes amnesia, Alzheimer's disease, and schizophrenia.
Amnesia.
Amnesia is a deficit in memory caused by brain damage, disease, or physiological trauma. Amnesia is best understood via Henry Molaison, or patient H.M., who suffered from severe epilepsy and eventually had a temporal lobectomy. After surgery, his epilepsy improved but then he had anterograde amnesia, wherein long-term memory formation is inhibited. Short-term memory remained normal except that he could never remember anything that had happened after his surgery for very long. Based on general known roles of the TPJ, it is known that the TPJ is involved in the memory processing system of the body. Studies have also revealed that certain types of epileptic amnesia could be attributed to TPJ. fMRI studies indicated that there was lower activation of the rTPJ in patients with epileptic amnesia. Furthermore, it was noticed the autobiographical memories were affected in these patients. As such, the rTPJ along with the right cerebellum were identified as core components of autobiographical memory.
In terms of treatment, most forms of amnesia fix themselves without actually undergoing treatment. However, options such as cognitive therapy or occupational therapy have proved to help. Therapy will focus on various methods to improve a patient's memory and with repetition over time, a patient's memory as a whole will improve and eventually become close to normal.
Alzheimer's disease.
Alzheimer's disease is the most common form of dementia and is also the sixth leading cause of death in the United States. This disease has no known cure and is a disease that worsens as it progresses and eventually leads to death. Reduced metabolism in the TPJ, along with the superior frontal sulcus, correlates with Alzheimer's patients’ inability to perceive themselves as others do (with a third-person point of view); the discrepancy between a patient's understanding of their own cognitive impairment and the actual extent of their cognitive impairment increases as metabolism in the TPJ decreases. Additionally, the TPJ contains the praxicon, a dictionary of representations of different human actions, which is necessary to distinguishing between actions of the self and other people. Because dementia (including Alzheimer's) patients with anosognosia are unable to distinguish between the normal actions of other people and their own diminished abilities, it is expected that damage to the TPJ is arresting this cognitive function.
In terms of treatment options for managing the symptoms of Alzheimer's, current options include pharmaceuticals, psychosocial intervention, caregiving, and feeding tubes. Current pharmaceuticals are either acetylcholinesterase inhibitors or an NMDA receptor antagonist. Psychosocial interventions are used to supplement pharmaceutical usage as it can take some time to get used to. Since Alzheimer's disease does eventually lead to death with the condition worsening over time, all family members can really do is provide care for those afflicted and try to make their lives as easy as possible as the situation worsens.
Autism spectrum disorder.
There may be a connection between the temporoparietal junction and how individuals with autism spectrum disorder's recognition of socially awkward situations may differ from neurotypicals’. Research reported in 2015 from an experiment in which participants, high-functioning adults with autism spectrum disorder (ASD) and neurotypical (NT) controls, were asked to watch socially awkward situations (a complete episode of the sitcom "The Office") under an fMRI, which measured their brain activity. Several brain regions implicated in social perceptual and cognitive processes were of interest: "the dorsal, middle and ventral parts of medial prefrontal cortex (DMPFC, MMPFC and VMPFC), right and left temporo-parietal junctions (RTPJ and LTPJ), right superior temporal sulcus (RSTS) and temporal pole, and posterior medial cortices [posterior cingulate, precuneus (PC)]." In general, participants’ activity in several of those brain regions tracked the episode's socially awkward moments to similar extents—the results were evidence of a of group difference : their activity near the RTPJ, spanning into the posterior end of the RSTS, showed notable quantitative differences between the ASD and NT groups (with ASD group showing lower activity).
Research reported in 2016 on ASD-related structural or physiological differences found using neuroimaging noted that results are often inconsistent across the literature, which could be caused by a variety of variance sources. (Re-)analysis using a technique they developed to reduce one common external source of variance showed group differences in TPJ. However, although statistically significant, results did not display the discriminative power sufficient to classify diagnostic groups, instead yielding accuracy results close to random. They concluded that ASD is a highly heterogeneous syndrome/diagnostic category whose differences from NT controls are difficult to characterize globally using neuroimaging.
Schizophrenia.
The decreased ability for schizophrenia patients to function in social situations has been related to a deficit within the theory of mind process. There have been relatively few studies that have examined the role of theory of mind in schizophrenia patients; the findings of these studies as they relate to the activation of the TPJ are varied. Some studies have found decreased activation of the TPJ in schizophrenia patients who were asked to make inferences about other peoples' social intentions based on cartoons; other studies, however, performed similar assessments of schizophrenia patients and found that the TPJ actually became hyperactive, compared to control individuals without schizophrenia, in the TPJ. This indicates that there is abnormal activation of the TPJ in these patients while performing tasks that involving understanding social intention of others, but the directionality of this abnormal activity is not clear, or possibly not universal throughout schizophrenia patients. It was found that the changes in activation in the TPJ were lateralized; they found that there was reduced activity in only the right TPJ and proposed that based on previous research about the different roles of the right and left TPJ the findings indicated that there was a more general deficit in the overall mentalizing process for these patients, but their ability to understand other individuals' basic social intentions through observing interaction is not impaired.
A study found that there was a connection between the auditory hallucinations in schizophrenia and the TPJ; the TPJ has been determined as a critical node in the auditory-verbal hallucination system. This study found that there was a significant decrease in the connectivity between the left TPJ and the right hemispheric homotope of the Broca's area, which is related to the production of language that is also characteristic of AVH events. This aspect of impairment seen in schizophrenia patients may also be related to the involvement of the TPJ with producing out of body experiences.
Anxiety disorders.
A recent study showed reduced activity in the TPJ of adolescents compared to adults during an extinction task, suggesting a role for the TPJ in anxiety disorders.
Future of possible treatments.
Vasopressin is a neuropeptide that is involved in regulating social behaviors, including social memory and recognition. One study examined the connection between vasopressin and cortical areas that are involved in processing social interactions including the TPJ. This study looked specifically at the brain regions that were active in men who were given vasopressin and tested based on familiarity related tasks. They found that the introduction of vasopressin caused a localized specific change in social recognition-related activity in the left TPJ/Brodmann area 39; the presence of vasopressin diminishes the heightened activity in the left TPJ that is present upon exposure to an unfamiliar social stimulus indicating that the presence of vasopressin leads individuals to associate an unfamiliar face with a familiar category more readily. While recognizing that this is the first study that has looked into this connection, the authors propose that it has potential to lead into further research about regulating the TPJ with vasopressin or a similar compound, which could allow pharmacologists to target this area of the brain and help with certain disorders including autism, social anxiety disorder. Perhaps such an approach could also be used to treat certain symptoms of schizophrenia or other disorders with know social cognitive impairments.
Current research.
Current research involving the TPJ is extensive, ranging from issues of physiology to issues of mental state. A wide range of cognitive processes rely on the TPJ and as such gaining information about it is crucial. Research is conducted by studying the role TPJ plays both with and without lesions when stimulated, and with task-based fMRI. Research concerns various issues such as theory of mind, out-of-body experiences, temporal order judgments, morality, etc. This is a growing field due to the prevalence of ailments that involve TPJ as well as because of the importance of perception in everyday life.
Theory of mind.
Theory of mind requires the collaboration of functionally related regions of the brain to form the distinction between self and other mental states and to create a comprehensive understanding of those mental states so that we may recognize, understand, and predict behavior. In general the theory of mind process is mediated by the dopaminergic-serotonergic system, which involves the TPJ as well as other associative regions necessary for mentalizing. Recent studies suggest that both the left TPJ, working in conjunction with the frontal cortex, and the right TPJ are involved in the representation of mental states; furthermore they suggest that the TPJ is particularly active in making the distinction between the mental states of self and others. A study in "Nature Neuroscience" from 2004 describes how the TPJ is involved in processing socially relevant cues including gaze direction and goal-directed action and also explains that results from the study show that lesions to this area of the brain result in an impaired ability to detect another persons belief. Moreover, studies have reported an increase in activity in the TPJ when patients are absorbing information through reading or images regarding other peoples' beliefs but not while observing information about physical control stimuli. Some studies, however, have shown that the TPJ, along with the cingulate cortex, is more specifically involved with attributing beliefs, but the process of mentalizing more generally is associated more with the medial prefrontal cortex. Another study in "Current Biology" from 2012 identifies the importance of the TPJ in both low-level, such as simple discrimination, and high-level, such as the ability to empathize, sociocognitive operations. In July 2011, a review from "Neuropsychologia" presented a model of the mentalizing network that established that mental states are first detected in the TPJ. The TPJ is composed of two discrete anatomical regions, the inferior parietal lobule (IPL) and the caudal parts of the superior temporal sulcus (pSTS), and both are active in the process of distinction between mental states of different individuals; thus, it is probable that this detection is the outcome of the combination and coordination of these two parts. Additionally, the right TPJ is involved in the ventral attention stream and contributes to the ability to focus attention on a particular stimuli or objective. It has also been observed that the interaction and communication between the dorsal and ventral streams involves the TPJ.
Out-of-body experiences.
The TPJ is also a crucial structure for self-processing. Several neuro-imaging studies have shown an activation of the TPJ during different aspects of self-processing such as visuo-spatial perspective, self-other distinction, mental own body imagery, and vestibular and multi sensory integration. Damage in the TPJ has been linked to out-of-body experiences (OBEs), the feeling that one's self is located outside one's physical body.
An OBE is defined by the presence of three characteristics: disembodiment, the impression of seeing the world from a distant and elevated visuo-spatial perspective, and the impression of seeing one's own body from this elevated perspective. OBEs mostly occur to people with epilepsy or migraines, but approximately 10% of the healthy population also experience OBEs once or twice in a lifetime. They usually occur spontaneously and are of short duration, making OBEs hard to study. Here is an example of a patient describing what he or she experienced during an OBE:
"“I was in bed and about to fall asleep when I had the distinct impression that “I” was at the ceiling level looking down at my body in the bed. I was very startled and frightened; immediately [afterward] I felt that, I was consciously back in the bed again.”"
It is suggested that OBEs are caused by multi-sensory disintegration in the TPJ disrupting different aspects of self-processing such as illusory reduplication, illusory self-location, and illusory perspective. The brain integrates different sensory inputs to create a representation of one’s body and its location in its surrounding. Some inhibition of discrepant inputs is required to have coherency, but in some cases, those discrepant inputs are so strong and come from more than one sensory source that it leads to two different representations of one’s own body. This multi-sensory disintegration at the TPJ leads to OBEs. An electromagnetic stimulation to the right TPJ of an patient with epilepsy induced an OBE. The author also states that these experiences are closely related to schizophrenia and phantom limb.
Temporal order judgement.
Temporal order is the arrangement of events in time. By judging this, one can understand how we process things. Temporal order judgments require an individual to determine the relative timing between two spatially separate events. One study revealed that subjects had to determine the order of appearance of two objects as well as which object fit a certain property better. What was learned from this study was that when identifying the order or appearance, fMRI studies showed that there was bilateral activation of the TPJ. Meanwhile, when it comes to object characterization based on a property, it was noticed that there was only activation of the lTPJ. As such, it is evident that TPJ is involved in the “when” pathway of the brain.
Morality.
Part of judging how virtuous an action was, whether someone is a "good person" or what one ought to do, morality usually (among other considerations) differentiates by actor intention. This applies to self-assessment as well as of others.
Connections made at the TPJ help an individual understand their emotions: the TPJ allows association of emotions with events or individuals, aiding in any related decision making process. Studies also show a relation between theory of mind and moral judgment, which further implicates the rTPJ in morality cognition.
However, errors in this emotional processing can arise when patients have lesions in the TPJ or when the brain is electrically stimulated. Transcranial magnetic stimulation (TMS) to the rTPJ seems to affect the ability of an individual, when they make moral decisions, to consider actors’ mental states. Patients’ general ability to judge moral scenarios was not obviously impaired, but it did seem to specifically affect how much they integrated a protagonist's into the judgement—only affecting the judgement of a scenario in which the protagonist explicitly intends and so deliberately acts to cause significant harm but completely fails solely due to an incorrect belief (about tool/weapon used). TMS can be used to disrupt neural activity in the rTPJ just a patient was to make a moral decision or that decision making process—constituting two different testing environments, but experimental results were unaffected.


Visual crowding

Visual crowding is the inability to view a target stimulus distinctly when presented in a clutter. Crowding impairs the ability to discriminate object features and contours among flankers, which in turn impairs people's ability to respond appropriately to the target stimulus.
An operational definition of crowding explains what crowding is and how it is different from similar effects such as masking, lateral interaction and surround suppression; effects that make the target more challenging to see as well. There are different criteria that are used to differentiate crowding from these other effects. Firstly, crowding makes it difficult to identify an object but not detecting it among the clutter. Crowded objects are collectively perceived to have high contrast, but they remain indistinct. The eccentricity of the target and the distance between the target and flankers influence crowding. As the distance between the target and the flankers' increases at a given eccentricity the ability to detect the target also improves as the eccentricity of a target is increased the more it pops out from the flankers and the more easily it is identified.
Crowding is anisotropic, which means it has different values when measured in different directions. Radially positioned flankers make it harder to identify the target than tangentially positioned ones. Crowding is stronger in the upper field of the four quadrants than the lower ones. A recent study tells us that crowding is intense where the distractor and the target are in the same visual field than when they are in separate visual fields despite equal retinal distance. Crowding is also asymmetrical meaning that a single flanker at an eccentric locus higher than the target makes it harder to identify the target than the single flanker at an eccentric locus closer to the fovea. Crowding is not just a spatial phenomenon it happens over time as well, when a target is moving it is found to be more crowded when the flankers are leading than when they follow the target.
Information that survives crowding.
There is much information that gets through to peoples conscious even under the circumstances of crowding these include the appearance of a feature, people can easily perceive the appearance of a feature but cannot identify or discriminate the changes in this feature. Secondly, After effects from adaptation survive crowding, adapting to a target in a crowded stimulus can help people form an orientation[8] and track the motion of the target. Next is combined orientation, even though people are not able to tell the individual orientation of a target stimulus in a crowded setting, they can reliably report an average combined orientation of the stimulus, which means that the orientation signals from the target stimulus are combined than lost.
Some target identity information survives crowding, people can identify more correct targets from a crowded setting when they are asked to report information on both the target and the flanker. Sometimes certain information such as the target information is lost, but the people are able to make better "target “ responses in this condition. Some information on the target is preserved, but most of the times the location information is lost.
Reduction.
Crowding is broken when the target and stimulus are different than when they are similar. The difference of target group from the flanker group of stimulus in shape, size, orientation, polarity, spatial frequency, depth, color, motion and order, breaks crowding.  Crowding happens among faces(holistic crowding) having an inverted face flanker when searching for an upright face breaks crowding. Which makes upright faces more effective flankers. Providing cue about the target location tends to reduce crowding. Crowding is broken when the flankers are collectively masked, but this happens only when the flankers are masked with noise or using metacontrast masks but not with substitution masks. When people are adapted to look for a target stimulus in a certain spatial position, it renders the flankers perceptually invisible (adaptation induced blindness), thus releasing the effect of crowding.
Mechanism.
Neurophysiological studies have not made much progress in narrowing down the locus of the brain at which crowding occurs. Previous researches have demonstrated that crowding is “dichoptical” meaning that the target is perceived by one eye and the distractor by the other. Which should mean that the effect of crowding occurs in the cortex. Different researchers have claimed different sites to be the processing center for crowding e.g. (V1, V2, V3, V4 some researchers claim crowding happens at a later stage of visual processing). So, the locus of the brain at which crowding occurs is still not clearly defined.
Models.
From the many models that try and explain the process of crowding, there is still a lack of an actual model that helps predict the entirety of how crowding works. All models have three major division that remains as its essence: masking, pooling and substitution. The pooling can be of the low-level features or the pooling of attention. One of the model that nicely predicts is the model by Wilkinson where he boils down the process of crowding to the interaction between complex cells and simple cells, where the simple cells suppress weak complex cell responses and the complex cells respond actively resulted from spatial pooling and then they suppress simple cell activity in their receptive cell area[41].
Another model that best predicts crowding process proposes a quantitative model for a spatial integration of orientation signals, As per the principles of population coding, this model satisfactorily predicts properties like critical spacing, compulsory averaging and the inner and outer asymmetry.
Levels.
Different studies implicitly assume that crowding is a unitary effect due to a single stage of processing. The other notion states that crowding happens independently at several stages of visual processing. This notion supports the view that crowding is influenced by the similarity and configuration of flankers and the target. By this notion, the effect is selectively observed between whole objects, object parts, and features. This view is also consistent with Bouma's law. This view has gained much support. Crowding in a natural setting may also occur in layers depending on the location, content and attention dependence.
Bouma’s Law.
Herman Bouma, a Dutch vision researcher and gerontologist stated, “For complete visual isolation of a letter presented at an eccentricity of φ deg, … no other letters should be present within (roughly) 0.5 φ distance." At a later stage, he reduced the proportionality constant from 0.5 to 0.4. This gave rise to the notion of “critical spacing” which is proportional to the eccentricity. Critical spacing is the sufficient distance needed for the identification of an object among its flankers in the retinotopically organized cortex. Bouma explains how the effect of crowding is dependent on the eccentricity of a subject and the distance between the flankers and the object. Many studies support the claim that critical space needed for crowding depends on the eccentricity of the subject. The proportionality constant named b, after Bouma, is dependent on how similar the flankers are to the target, the number of possible targets, and the arbitrary threshold criterion. The value of Boumas proportionality constant ‘b’ is different among studies, but most of the times it is reported to be ≈0.4 - 0.5. This rule is sometimes raised to the status of a 'law' but this remains controversial.


Rhinal sulcus

In the human brain, the entorhinal cortex appears as a longitudinal elevation anterior to the parahippocampal gyrus, with a corresponding internal furrow, the external rhinal sulcus (or rhinal fissure), separating it from the inferiolateral surface of the hemisphere close to the lamina terminalis. It is analogous to the collateral fissure found further caudally in the inferior part of the temporal lobe.


Adequate stimulus

The adequate stimulus is a property of a sensory receptor that determines the type of energy to which a sensory receptor responds with the initiation of sensory transduction. Sensory receptor are specialized to respond to certain types of stimuli. The adequate stimulus is the amount and type of energy required to stimulate a specific sensory organ.
Many of the sensory stimuli are categorized by the mechanics by which they are able to function and their purpose. Sensory receptors that are present within the body typically are made to respond to a single stimulus. Sensory receptors are present all throughout the body, and they take a certain amount of a stimulus to trigger these receptors. The use of these sensory receptors allows the brain to interpret the signals to the body which allow a person to respond to the stimulus if the stimulus reaches a minimum threshold to signal the brain. The sensory receptors will activate the sensory transduction system which will in turn send an electrical or chemical stimulus to a cell, and the cell will then respond with electrical signals to the brain which were produced from action potentials. The minuscule signals, which result from the stimuli, enter the cells must be amplified and turned into an sufficient signal that will be sent to the brain.
A sensory receptor's adequate stimulus is determined by the signal transduction mechanisms and ion channels incorporated in the sensory receptor's plasma membrane. Adequate stimulus are often used in relation with sensory thresholds and absolute thresholds to describe the smallest amount of a stimulus needed to activate a feeling within the sensory organ.
Categorizations of receptors.
They are categorized through the stimuli to which they respond. Adequate stimulus are also often categorized based on their purpose and locations within the body. The following are the categorizations of receptors within the body:
Classes.
There are several different types of stimuli to which adequate stimuli respond. The following are examples of stimuli to which receptors may:
Sensory receptors.
Sensory receptors are the ends of nerves within the body that respond to stimuli. There are many different types of sensory receptors that each respond to stimuli that they are uniquely fitted to res Types of sensory receptors include the following:
Classic examples of absolute threshold.
In 1962, Eugene Galanter, a psychologist, tested stimuli till people were able to feel them approximately 50% of the time, then used the following as examples of absolute threshold:
Through these conditions, Galanter was able to show that human's sensory organs are often more sensitive than originally thought.


Neural pathway

A neural pathway is the connection formed by axons that project from neurons to make synapses onto neurons in another location, to enable a signal to be sent from one region of the nervous system to another. Neurons are connected by a single axon, or by a bundle of axons known as a nerve tract, or fasciculus. Shorter neural pathways are found within grey matter in the brain, whereas longer projections, made up of myelinated axons, constitute white matter.
In the hippocampus there are neural pathways involved in its circuitry including the perforant pathway, that provides a connectional route from the entorhinal cortex to all fields of the hippocampal formation, including the dentate gyrus, all CA fields (including CA1), and the subiculum.
Descending motor pathways of the pyramidal tracts travel from the cerebral cortex to the brainstem or lower spinal cord. Ascending sensory tracts in the dorsal column–medial lemniscus pathway (DCML) carry information from the periphery to the cortex of the brain.
Naming.
The first named pathways are evident to the naked eye even in a poorly preserved brain, and were named by the great anatomists of the Renaissance using cadaver material. Examples of these include the great "commissures" of the brain such as the corpus callosum (Latin, "hard body"; not to be confused with the Latin word "colossus" the "huge" statue), "anterior commissure", and "posterior commissure". Further examples include the pyramidal tract, crus cerebri (Latin, "leg of the brain"), and "cerebellar peduncles" (Latin, "little foot of the cerebellum"). Note that these names describe the "appearance" of a structure but give no information on its function, location, etc.
Later, as neuroanatomical knowledge became more sophisticated, the trend was toward naming pathways by their origin and termination. For example, the nigrostriatal pathway runs from the substantia nigra (Latin, "black substance") to the corpus striatum (Latin, "striped body"). This naming can extend to include any number of structures in a pathway, such that the cerebellorubrothalamocortical pathway originates in the cerebellum, synapses in the red nucleus ("ruber" in Latin), on to the thalamus, and finally terminating in the cerebral cortex.
Sometimes, these two naming conventions coexist. For example, the name "pyramidal tract" has been mainly supplanted by lateral corticospinal tract in most texts. Note that the "old" name was primarily descriptive, evoking the pyramids of antiquity, from the appearance of this neural pathway in the medulla oblongata. The "new" name is based primarily on its origin (in the primary motor cortex, Brodmann area 4) and termination (onto the alpha motor neurons of the spinal cord).
In the cerebellum one of the two major pathways is that of the mossy fibers. Mossy fibers project directly to the deep nuclei, but also give rise to the following pathway: mossy fibers → granule cells → parallel fibers → Purkinje cells → deep nuclei. The other main pathway is from the climbing fibers and these project to Purkinje cells and also send collaterals directly to the deep nuclei.
Functional aspects.
In general, neurons receive information either at their dendrites or cell bodies. The axon of a nerve cell is, in general, responsible for transmitting information over a relatively long distance. Therefore, most neural pathways are made up of axons. If the axons have myelin sheaths, then the pathway appears bright white because myelin is primarily lipid. If most or all of the axons lack myelin sheaths (i.e., are "unmyelinated"), then the pathway will appear a darker beige color, which is generally called "grey".
Some neurons are responsible for conveying information over long distances. For example, motor neurons, which travel from the spinal cord to the muscle, can have axons up to a meter in length in humans. The longest axon in the human body belongs to the Sciatic Nerve and runs from the great toe to the base of the spinal cord. These are archetypal examples of neural pathways.
Basal ganglia pathways and dopamine.
Neural pathways in the basal ganglia in the cortico-basal ganglia-thalamo-cortical loop, are seen as controlling different aspects of behaviour. This regulation is enabled by the dopamine pathways. It has been proposed that the dopamine system of pathways is the overall organiser of the neural pathways that are seen to be parallels of the dopamine pathways. Dopamine is provided both tonically and phasically in response to the needs of the neural pathways.


Sensorimotor network

In neuroscience, the sensorimotor network (SMN) is a large-scale brain network . The SMN includes somatosensory (post-central gyrus) and motor (pre-central gyrus) regions and extends to the supplementary motor areas. Studies have shown that this network is activated during motor tasks such as finger tapping indicating that these regions may involve a pre-mediated state that ready the brain when performing and coordinating a motor task. Dysfunction in the SMN has been implicated in various neuropsychiatric disorders.


Visual extinction

Visual extinction is a neurological disorder which occurs following damage to the parietal lobe of the brain. It is similar to, but distinct from, hemispatial neglect. Visual extinction has the characteristic symptom of difficulty to perceive contralesional stimuli when presented simultaneously with an ipsilesional stimulus, but the ability to correctly identify them when not presented simultaneously. Under simultaneous presentation, the contralesional stimulus is apparently ignored by the patient, or extinguished. This deficiency may lead to difficulty on behalf of the patient with processing the stimuli’s 3D position.
History.
Visual Extinction is the result of unilateral cerebral damage and has always been poorly understood. Researchers have been studying visual extinction in great depth since the 1990s. It has since been commonly associated with damage to the right hemisphere of the brain. Studies have suggested that visual extinction may be a result of sensory imbalance. This imbalance is due to weak or delayed afferent inputs in the hemisphere affected by the extinction.
Research done by Pavlovskaya, Sagi, Soroker and Ring show that visual extinction is dependent on simple stimuli properties. These properties are thought to reflect connectivity constraints during the early steps of visual processing.
Physiological basis.
Visual extinction arises from damage to the parietal lobe of the brain. This damage most frequently arises following a stroke or other infarction in that area – however, any traumatic event sufficient to cause widespread tissue damage in the area may cause sufficient harm. Although both sides of the brain are vulnerable to such damage, it is more unusual for extinction to occur when the left hemisphere is damaged than the right.
When presented with simultaneous stimuli, the patient will ignore the contralesional stimuli, and only report the ipsilesional. Their ability to report the stimuli correctly when presented singly indicates that this is not a problem with vision per se. This bias against contralesional stimuli is evident even when patients are presented with two signals within the ipsilesional visual field, whose processing remains intact following the damage, since it is done in the opposite brain hemisphere. This implies that extinction can be somewhat controlled by biasing the point of visual fixation contralesionally, such that all relevant stimuli are contained within the functioning side of the visual field, findings supported in experiment
Fatigue and habituation effects have previously been connected to visual extinction; experiments such as those done by Vuilleumier and Rafal eliminate the connection of these effects with visual extinction.
Historically, it was believed that the parietal damage weakened afferent neuron input to the visual cortex, and so the extinction event was caused by the signals originating in the contralesional field being lost during transmission. However, this does not account for the ability of extinction patients being able to correctly identify contralesional stimuli in isolation. A more current theory is called the "race theory."
Race theory holds that stimuli are competing for processing power within the brain. Following parietal damage, all contralesional messages are lowered in priority for the brain’s processing in some way – potentially by signal transmission delay – such that when presented with alternative stimuli, the contralesional stimulus doesn’t arrive at the decision center simultaneously with the ipsilesional stimulus, and thus is denied conscious processing.
The race theory sees some support in findings by Marzi et al., where patients who show extinction also display aggravated delays in their reaction time to stimuli, both when compared to patients who have other forms of right-brain damage and undamaged patients. In the study, patients were shown to be able to focus their attention and improve reaction time, but still have subnormal performance. This theory is given further support by Gorea and Sagi’s inducing of extinction-like events in undamaged patients when presented with simultaneous stimuli of different intensities, with the lower intensity stimulus being extinguished by the mere presence of the high intensity stimulus.
Extinction frequency may also be affected by reporting method, due to how visual processing interacts with the rest of the brain. Reported extinctions drop when the patient is told to relay the extinction news by a method other than speaking – particularly, the use of the eyes in a feedback loop (looking to the side if there is a single stimuli, and up if there are two). This may work by eliminating the need for hemispheric transfer of information – routing the response to the motor cortex instead of the visual cortex – and so shortening the path and response time, a conclusion supported by increased detection of isolated contralesional stimuli under such circumstances.
Although extinction is compared with hemispatial neglect, the two are different disorders. It is possible to exhibit one without the other, and the neural basis for each appears to be different, hemispatial neglect arising from tempo-parietal junction damage. Although patients may exhibit these disorders simultaneously, this occurs in less than half of the afflicted population.
Diagnosis.
Diagnosis is achieved through several related methods. One approach involves having patients sit in front of a computer screen, on which either stars or triangles are projected simultaneously in different areas of the screen. Patients are then asked to identify the locations and identities of the shapes. Another similar approach is to project colored letters on the screen, again asking patients to identify the letter and color in different parts of the screen. From this information, a diagnosis of visual extinction can be attained. A positive diagnosis results from a patient's inability to correctly identify shapes or letters projected simultaneously in different areas of the screen. However, the most common test for visual extinction is the finger confrontation model. In this test, the doctor asks the patient to note which of his hands have moving fingers. This can be used immediately following a stroke, for the doctor’s quick diagnosis.
Treatment.
Without any sort of treatment, visual extinction usually worsens in severity of symptoms or remains completely stagnant. Simple exercises, such as reading and copying tasks, can be useful in treating the symptoms and increasing brain activity, though the damaged area can never be completely healed since the dead brain cells do not regenerate. An individual should keep up with exercises designed to maintain or improve function in order to create the best chance of improvement and/or maintenance at his or her current state.
Treatment methods for patients who suffer from visual extinction generally involve use and training of an individual's vision. A doctor may instruct a patient to scan rows of lights in different ways in an attempt to regenerate function. Some light boards do exist that are used specifically to aid this task. Other methods exist that are designed to force the patient to focus on multiple stimuli at the same time. These cueing and scanning methods do yield results, but they are not consistent across all patients. In successful cases, generally forty hours of retraining the patients' vision were necessary as well as some additional work done at home with similar exercises.
Other computer scanning methods of treatment were shown to be effective with specialized equipment designed specifically for scanning and cueing exercises to force patients to focus on multiple stimuli simultaneously. Again, the results of these methods were not consistent, but in laboratory settings rehabilitation was successful. Of the individuals who recovered some function, not all maintained the function they recovered, losing it after about five months.
In another, single-stimulus rehabilitatory approach, the patient is shown a computer screen with a box in each corner and a fixation cross at the center. When a stimulus appears in any of the boxes, the patient is instructed to indicate seeing it as quickly as possible. This task is eased somewhat by an indicating icon before the stimulus – either an arrow that points to the box the stimulus is most likely (but not guaranteed) to be in, or a cross to indicate that the stimulus could appear in any box. Following thirty hour-long sessions, patients demonstrated a significant decrease in both extinction and hemispatial neglect.
In patients whose brain damage was in the right hemisphere, left limb activation (LLA) was another treatment that proved effective. The theory behind this method of treatment is that any use of the damaged side of the brain will enhance all functions related to the damaged hemisphere and that use of the opposite (healthy) side will only cause further impairment. LLA therefore is merely the concentrated use of the left side of the body in patients whose damage is in the right hemisphere (since the right hemisphere controls the left side of the body). This forces the patient to exercise spatial awareness using the damaged side of the brain, increasing activity around the lesion. While generally a treatment used for visual neglect (a different but related neurological disorder), LLA still increases brain activity around damaged area in patients with visual extinction and generates improvement in some patients. The reason this treatment does not work in some cases of visual extinction is that damage can be on either side of the brain as opposed to in visual neglect where the damage is always on the right.
Society & Culture.
This condition does not inhibit patients from social interaction. In fact, most people would not be able to distinguish a visual extinction patient from a non-visual extinction patient in passing. Patients have selective spatial interactions, typically within the range of six degrees of the angle of vision. When two visual stimuli are presented to a patient, they can be processed as a single object due to the corresponding neuronal functions which are linked through long-range lateral interactions. Visual Extinction is often mistaken for attentional deficit. Some researchers believe visual extinction may be connected to a restriction in attention capacity. Attention allows a person to identify and react to pertinent objects in space, while ignoring other irrelevant objects. Patients with visual extinction, especially those with unilateral damage to the right parietal lobe, may be unable to attend and orient to objects in collateral space, therefore presenting neglect to visual stimuli.
A delay in reaction time is observed in many patients, but it is unknown whether this is a primary result of the stroke or resulting from the visual extinction. Detrimental social aspects may be repercussions of the stroke, which caused the visual extinction, but not from the visual extinction condition alone.
Visual Extinction and Image Preprocessing.
Visual extinction has been involved in several studies regarding preprocessing of images in the brain. A study performed by Dr Vuilleumier examined the effect of using faces as the stimulus in studying an extinction event. Subjects were presented with two simultaneous stimuli – some combination of a schematic face, a shape, a word, and a scrambled face. Faces in the contralesional field were less likely to be extinguished than other stimuli, but faces in the ipsilesional field appeared to induce more extinction events. The appearance of a face was prioritized in attention, despite the handicap presented of extinction damage.
Visual extinction has also been used to demonstrate brain bias towards gestalt processing. When presented with a figure containing illusory contours, patients were able to correctly report the presence of stimuli in both contralesional and ipsilesional hemispheres, due to their unconscious processing of the whole field to produce the illusion. This experiment implied that the attention center prioritizes the visualization of surfaces over other stimuli – therefore, although under race model the ipsilesional stimuli should extinguish the contralesional, the creation of the gestalt takes priority over detection of both. Further, a study using Gabor signals (alternating blurred and noisy black and white bars, commonly used by opticians in diagnostic tests) investigated how the orientation of these signals affected their extinction rate. Bilateral stimuli were least extinguished when both stimuli were oriented horizontally, although both stimuli being oriented vertically also showed a reduction in extinguishing rate when compared to one stimulus vertical and one horizontal – in what could be assumed by the brain to represent two different surfaces.
Combining the brain bias towards facial processing and surface discovery, a follow-up study by Dr. Vuilleumier exposed subjects to paired visual stimuli in three phases. In the initial phase, stimuli were simply bilateral pairs, and extinction frequency was measured. In the next stage, the stimuli were surrounded with an oval, so that they appeared to represent eyes in a face. The extinction rate for this appearance was greatly reduced. Finally, the patients were shown the stimuli minus the contextual oval – however, the reduced extinction rate persisted, as though the patients had learned to group these stimuli. The effect did not occur when the stimuli were surrounded by a nonoval shape, pointing towards facial processing as being the key to this phenomenon.
Visual feedback has also been studied in relation to visual extinction. Patients were asked to touch a known target in a darkened room. A light attached to the patient’s hand was sometimes briefly illuminated, to provide information about where the hand was in relation to the target. In some of these trials, a distracting light was also lit, which induced an extinction event in the patient. Although the patient reported in such cases that he had not seen the indicator light on his hand, their performance was correspondingly better, similar to the results when visual feedback had been available. Although the patient was not cognizant of having received the information, they were able to correctly act upon it, in a manner similar to blindsight.
Visual extinction has also been researched with regard to the effect of repetition on visual detection rate. Patients were shown a colored (red or green) letter (O or E), one to each visual field, and then asked variably to report the color or shape of one letter or the other. Extinction was found to be increased in the contralesional field when the patient was asked to report on a repeated characteristic – if both stimuli had been the same shape, or same color – regardless of whether the other characteristic had also been changed. This is another example of repetition blindness.
Future & Research.
Researchers conduct studies involving first-episode stroke patients. These patients typically have unilateral cerebral damage and/or contralateral extinction. Current research is focusing on the more detailed role of the parietal lobe in visual extinction.
The ability to understand which factors in visual processing determine whether a contralesional event, occurring on the half of the patient's brain or body opposing the site of a lesion, is observed or eliminated can provide crucial insights connecting to the mechanisms of attention and operation.
Routine eye examinations have begun to incorporate the knowledge of visual extinction. Such examinations screen for simple, unsuspected visual field defects or abnormalities, while screening for the more severe extinction, by testing all quadrants of the visual field.


RU-59063

RU-59063 is a nonsteroidal androgen or selective androgen receptor modulator (SARM) which was first described in 1994 and was never marketed. It was originally thought to be a potent antiandrogen, but subsequent research found that it actually possesses dose-dependent androgenic activity, albeit with lower efficacy than dihydrotestosterone (DHT). The drug is an "N"-substituted arylthiohydantoin and was derived from the first-generation nonsteroidal antiandrogen (NSAA) nilutamide. The second-generation NSAAs enzalutamide, RD-162, and apalutamide were derived from RU-59063.
RU-59063 has high affinity for the human androgen receptor (AR) (Ki = 2.2 nM; Ka = 5.4 nM) and 1,000-fold selectivity for the AR over other nuclear steroid hormone receptors, including the , , , and . It shows 3- and 8-fold higher affinity than testosterone for the rat and human AR, respectively, and up to 100-fold higher affinity for the rat AR than the first-generation NSAAs flutamide, nilutamide, and bicalutamide. It also has slightly higher affinity for the AR than DHT and nearly equal affinity to that of the very-high-affinity AR ligand metribolone (R-1881). In addition, RU-59063, unlike testosterone and DHT, shows no specific binding to human plasma.


Leukoencephalopathy

Leukoencephalopathy (leukodystrophy-like diseases) is all of the brain white matter diseases, whether their molecular cause is known or not. It can refer specifically to any of these diseases:
The classification of leukoencephalopathies is a matter of debate. Some authors divide leukoencephalopathies into hereditary disorders and acquired disorders. The hereditary demyelinating disorders are then classified according to the localization of the underlying metabolic defect, and they include the leukodystrophies when myelin growth is the underlying problem.
The acquired demyelinating disorders are classified according to their underlying causes into five groups: noninfectious–inflammatory, infectious–inflammatory, toxic–metabolic, hypoxic–ischemic (vascular problems like Binswanger's disease), and traumatic.
This classification is diffuse sometimes. For example CADASIL is at the same time hereditary and hypoxic.


Tradipitant

Tradipitant (VLY-686 or LY686017) is an experimental drug that is a neurokinin 1 antagonist. It works by blocking substance P, a small signaling molecule. Originally, this compound was owned by Eli Lilly and named LY686017. VLY-686 was purchased by Vanda Pharmaceuticals from Eli Lilly and Company in 2012. Vanda Pharmaceuticals is a U.S. pharmaceutical company that as of November 2015 only has three drugs in their product pipeline: tasimelteon, VLY-686, and iloperidone.
Indications.
Pruritus.
It is being investigated by Vanda Pharmaceuticals for chronic pruritus (itchiness) in atopic dermatitis. In March 2015, Vanda announced positive results from a Phase II proof of concept study. A proof of concept study is done in early stage clinical trials after there have been promising preclinical results. It provides preliminary evidence that the drug is active in humans and has some efficacy.
Alcoholism.
VLY-686 reduced alcohol craving in recently detoxified alcoholic patients as measured by the Alcohol Urge Questionnaire. In a placebo controlled clinical trial of recently detoxified alcoholic patients, VLY-686 significantly reduced alcohol craving as measured by the Alcohol Urge Questionnaire. It also reduced the cortisol increase seen after a stress test compared to placebo. The dose given was 50 mg per day.
Social anxiety disorder.
In a 12-week randomized trial of LY68017 in 189 patients with social anxiety disorder, 50 mg of LY68017 did not provide any statistically significant improvement over placebo.
Gastroparesis.
Tradipitant underwent phase II clinical trials assessing its utility in the treatment of gastroparesis the results of which were announced on December 3rd, 2018. In a study performed over 4 weeks with a patient population of 141 patients, Tradipitant met its primary endpoint of decreased nausea scores as recorded in daily patient diaries. It also showed a statistically significant improvement in nausea-free days, and key gastroparesis scales.


Special visceral efferent fibers

Special visceral efferent fibers (SVE) are the efferent nerve fibers that provide motor innervation to the muscles of the pharyngeal arches in humans, and the branchial arches in fish.
Some sources prefer the term "branchiomotor" or "branchial efferent".
The only nerves containing SVE fibers are cranial nerves: the trigeminal nerve (V), the facial nerve (VII), the glossopharyngeal nerve (IX), the vagus nerve (X) and the accessory nerve (XI).


Infralimbic cortex

The infralimbic cortex (IL) is a cortical region in the ventromedial prefrontal cortex which is important in tonic inhibition of subcortical structures and emotional responses, such as fear.
Connectivity.
Primates.
GABAergic neurons within the amygdala, known as intercalated (ITC) cells, receive a strong projection from the IL medial prefrontal cortex (mPFC) in primates. ITC cells are thought to play a role as the 'off switch' for the amygdala, inhibiting the amygdala's central nucleus output neurons and its basolateral nucleus neurons. Further, it has been shown that electrical stimulation of IL reduces conditioned fear and strengthens extinction memory, explaining cortical control over extinction processes, one of the simplest forms of emotional regulation.
Rodents.
Amygdala ITC cells receive strong projection from the IL mPFC in rodents as well.


Tectopulvinar pathway

The tectopulvinar pathway and the geniculostriate pathway are the two visual pathways that travel from the retina to the early visual cortical areas. From the optic tract, the tectopulvinar pathway sends neuronal radiations to the superior colliculus in the tectum, then to the lateral posterior-pulvinar thalamic complex. Approximately 10% of retinal ganglion cells (mostly magnocellular) project onto the tectopulvinar pathway.
The tectopulvinar pathway is a phylogenetically older pathway than the geniculostriate pathway, and is the only visual pathway present in fish, amphibians, and reptiles. The tectopulvinar pathway terminates at the prestriate cortex (also known as the extrastriate cortex or visual area V2), which receives large feedforward input from the striate cortex; the geniculostriate pathway also converges to the same location. . At the thalamic pulvinar nucleus, visual information is routed either to the medial pulvinar, which sends connections to cingulate, posterior parietal, premotor and prefrontal cortical areas; or to the lateral pulvinar, which sends connections to the temporal lobe dorsal stream cortical areas (and in particular, to region MT – a critical region for motion perception).
Damage to the tectopulvinar pathway is most commonly characterized by visual ataxia, a deficit characterized by an inability to perform visually guided hand movements in reaching and grasping objects, as well as by spatial attentional deficits.
Function.
The tectopulvinar pathway is a fast-acting pathway that provides the viewer with information on the absolute spatial information of objects. The pathway plays a large role in directing visual spatial attention and is particularly responsive to novel stimuli that appear or move in peripheral vision; however, because it receives mostly magnocellular visual input, the tectopulvinar pathway is not sensitive to fine detail. It directs visual spatial attention most notably through guided eye movements, via cranial nerves III ( the oculomotor nerve), IV ( the trochlear nerve), and VI (the abducens nerve). Directing visual spatial attention and eye movements to salient peripheral stimuli is necessary to bring likely important visual information to center vision. Furthermore, the tectopulvinar pathway has been suggested to support residual visual perceptual abilities in blindsight patients.
Superior Colliculus.
Within the pathway, the superior colliculus functions to orient the viewer’s gaze and attention via eye and head movements towards objects of interest in egocentric space. The superior colliculus’s role in directing eye movements is especially well-studied: multiple lines of evidence show that artificially blocking and increasing superior colliculus activity modulates (inhibits and biases, respectively) eye saccades to the affected side. Recent evidence has argued that superior colliculus function is not limited to basic motor and low-level visual control, but more generally in target selection and in both covert and overt attentional control. Further studies contend that superior colliculus function encompasses a wide range of behavioral responses such as in arm-reaching, and not just in eye and head movements.
The superior colliculus is also a center for multisensory auditory and visual integration. Recent studies have shown that the superior colliculus responds especially strongly when auditory input arrives temporally and synchronously with visual input. Superior colliculus activity was measured to be greater in these multisensory events than in single modality events
Pulvinar Nucleus.
Further along the pathway, the pulvinar nucleus performs similar tasks to the superior colliculus in directing visual spatial attention. Pulvinar lesions often create visuomotor deficits and neglect-like attentional deficits. Lastly, the pulvinar nucleus has been implicated in guiding attention for behavioral responses: greater neuronal activity was recorded for stimuli that serve as targets or cues for active behavior than for stimuli that are not associated with active behavior.


Archives Italiennes de Biologie

The Archives Italiennes de Biologie: A Journal of Neuroscience is a quarterly peer-reviewed open access scientific journal. The journal was established in 1882; publication was suspended between 1936 and 1957. It originally covered all aspects of biology, especially physiology, but now focusses on neuroscience.
Editors-in-chief.
The following persons have been editors-in-chief of the journal:
Abstracting and indexing.
The journal is abstracted and indexed in the Science Citation Index, Current Contents/Life Sciences, BIOSIS Previews, Chemical Abstracts Service, and Index Medicus/MEDLINE/PubMed. According to the "Journal Citation Reports", the journal has a 2013 impact factor of 1.422.


Calcium-activated potassium channel

Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that Calcium levels inside of a cell could affect the permeability of potassium through that cell membrane. Then in 1970, Meech was the first to observe that intracellular calcium could trigger potassium currents. In humans they are divided into three subtypes: large conductance or BK channels, which have very high conductance which range from 100 to 300 pS, intermediate conductance or IK channels, with intermediate conductance ranging from 25 to 100 pS, and small conductance or SK channels with small conductances from 2-25 pS.
This family of ion channels is, for the most part, activated by intracellular Ca2+ and contains 8 members in the human genome. However, some of these channels (the KCa4 and KCa5 channels) are responsive instead to other intracellular ligands, such as Na+, Cl−, and pH. Furthermore, multiple members of family are both ligand and voltage activated, further complicating the description of this family. The KCa channel α subunits have six or seven transmembrane segments, similar to the KV channels but occasionally with an additional N-terminal transmembrane helix. The α subunits make homo- and hetero-tetrameric complexes. The calcium binding domain may be contained in the α subunit sequence, as in KCa1, or may be through an additional calcium binding protein such as calmodulin.
Structure.
Knowing the structure of these channels can provide insight into their function and mechanism of gating. They are made up of two different subunits, alpha and beta. The alpha subunit is a tetramer which forms the pore, the voltage sensor, and the calcium sensing region. This subunit of the channel is made up of seven trans-membrane units, and a large intracellular region. The voltage sensor is made by the S4 transmembrane region, which has several Arginine residues which act to ‘sense’ the changes in charge and move in a very similar way to other voltage gated potassium channels. As they move in response to the voltage changes they open and close the gate. The linker between the S5 and S6 region serves to form the pore of the channel. Inside of the cell, the main portion to note is the calcium bowl. This bowl is thought to be the site of calcium binding.
The beta subunit of the channel is thought to be a regulatory subunit of the channel. There are four different kinds of the beta subunit, 1, 2, 3, and, 4. Beta 2 and 3 are inhibitory, while beta 1 and 4 are excitatory, or they cause the channel to be more open than not open. The excitatory beta subunits affect the alpha subunits in such a way that the channel seldom inactivates.
Homology Classification and Descriptions.
Human KCa Channels.
Below is a list of the 8 known human calcium-activated potassium channel grouped according to sequence homology of transmembrane hydrophobic cores:
BK channel.
Though not implied in the name, but implied by the structure these channels can also be activated by voltage. The different modes of activation in these channels are thought to be independent of one another. This feature of the channel allows them to participate in many different physiologic functions. The physiological effects of BK channels have been studied extensively using knockout mice. In doing so it was observed that there were changes in the blood vessels of the mice. The animals without the BK channels showed increased mean arterial pressure and vascular tone. These findings indicate that BK channels are involved in the relaxation of smooth muscle cells. In any muscle cell, increased intracellular calcium causes contraction. In smooth muscle cells the elevated levels of intracellular calcium cause the opening of BK channels which in turn allow potassium ions to flow out of the cell. This causes further hyperpolarization and closing of voltage gated calcium channels, relaxation can then occur. The knockout mice also experienced intention tremors, shorter stride length, and slower swim speed. All of these are symptoms of ataxia, indicating that BK channels are highly important in the cerebellum.
Subtypes of BK Channels
IK channel.
Intermediate conductance channels seem to be the least studied of all of the channels. Structurally they are thought to be very similar to BK channels with the main differences being conductance, and the methods of modulation. It is known that IK channels are modulated by calmodulin, whereas BK channels are not.
IK channels have shown a strong connection to calcification in vasculature, as inhibition of the channel causes a decrease in vascular calcification. Over-expression of these channels has quite a different effect on the body. Studies have shown that this treatment causes proliferation of vascular smooth muscle cells. This finding has sparked further exploration surrounding these channels and researchers have found that IK channels regulate the cell cycle in cancer cells, B and T lymphocytes, and stem cells. These discoveries show promise for future treatments surrounding IK Channels.
Subtypes of IK Channels
SK channel.
Small conductance calcium activate potassium channels are quite different from their relatives with larger conductance. The main and most intriguing difference in SK Channels is that they are voltage insensitive. These channels can only be opened by increased levels of intracellular calcium. This trait of SK channels suggests that they have a slightly different structure than the BK and IK channels.
Like other potassium channels they are involved in hyperpolarization of cells after an action potential. The calcium activated property of these channels allows them to participate in vaso-regulation, auditory tuning of hair cells, and also the circadian rhythm. Researchers were trying to figure out which channels were responsible for the re-polarization and after-hyperpolarization of action potentials. They did this by voltage clamping cells, treating them with different BK, and SK channel blockers and then stimulating the cell to create a current. The researchers found that the re-polarization of cells happens because of BK channels and that a part of the after-hyperpolarization occurs because of current through SK channels. They also found that with blocking SK channels, current during after-hyperpolarization still occurred. It was concluded that there was a different unknown type of potassium channel allowing these currents.
It is clear that SK channels are involved in AHP. It is not clear exactly how this happens. There are three different ideas on how this is done. 1) Simple diffusion of Calcium accounts for the slow kinetics of these currents, 2) The slow kinetics is due to other channels with slow activations, or 3) The Calcium simply activates a second messenger system to activate the SK channels. Simple diffusion has been shown to be an unlikely mechanism because the current is temperature sensitive, and a diffusive mechanism would not be temperature sensitive. This is also unlikely because only the amplitude of the current is changed with concentration of Calcium, not the kinetics of the channel activation.
Subtypes of SK Channels
Prokaryotic KCa Channels.
A number of prokaryotic KCa channels have been described, both structurally and functionally. All are either gated by calcium or other ligands and are homologus to the human KCa channels, in particular the KCa1.1 gating ring. These structures have served as templates for ligand gating.


Epineurium

The epineurium is the outermost layer of dense irregular connective tissue surrounding a peripheral nerve. It usually surrounds multiple nerve fascicles as well as blood vessels which supply the nerve. Smaller branches of these blood vessels penetrate into the perineurium. In addition to blood vessels which supply the nerve, lymphocytes and fibroblasts are also present and contribute to the production of collagen fibers that form the backbone of the epineurium. In addition to providing structural support, lymphocytes and fibroblasts also play a vital role in maintenance and repair of the surrounding tissues.
When the spinal nerve leaves the vertebral canal via an intervertebral foramen, two layers of the spinal meninges, the arachnoid and the dura invaginate the nerve to form a dural sleeve of connective tissue, which is the epineurium. The outer portion of this sleeve comprises the external epineurium which permits longitudinal nerve excursion and absorption of longitudinal stress. The layer of the epineurium that extends within the nerve to define the fascicles is termed the internal epineurium. Together, these two layers form the epineurium, which varies in thickness along the course of a nerve. The epineurium is usually most abundant around joints, as its function is to protect the nerves from stretching and subsequent injury. Epineurium is primarily made from collagen.
Clinical significance.
A common surgical procedure to repair a torn nerve via the epineurium is termed an epineurial repair.
Schwannomas often remain completely encapsulated by the epineurium as they grow.
Epineurial barriers can be used to limit the formation of neuromas after neurotmesis. The epineurium is an effective barrier against axon growth.


John J. Bullington

John Jefferson Bullington (July 12, 1879 – August 31, 1929) was an American lawyer, soldier, and politician.
Bullington was born in Vandalia, Illinois and went to the public schools in Fayette County, Illinois. He went to Austin College in Effingham, Illinois. He taught school and was admitted to the Illinois bar in 1909. He practiced law in Taylorville, Illinois. Bullington served in the United States Army during the Mexican Border Campaign and World War I. He was commissioned a colonel. Bullington served in the Illinois House of Representatives in 1917-1918 and was a Democrat. Bullington died in a hospital in St. Louis, Missouri after surgery to remove a brain tumor.


Kamianske

Kamianske (, , formerly Dniprodzerzhynsk is an industrial city in Dnipropetrovsk Oblast of Ukraine and a port on the Dnieper. Administratively, it serves as the administrative center of Kamianske Raion. Kamianske hosts the administration of Kamianske urban hromada, one of the hromadas of Ukraine. Population:
The city was known as Dniprodzerzhynsk from 1936 to 2016. On 19 May 2016, it was renamed back to its historical name of Kamianske. Along with the city's name change, the city's hydroelectric station was renamed to Middle Dnieper Hydroelectric Power Plant.
Besides the hydroelectric station, the city houses a few other industrial enterprises: Prydniprovsky Chemical Plant (closed down), Bahley Coke Factory and Dnieper Metallurgical Combine.
History.
The first written evidence of settlement in the territory of Kamianske appeared in 1750. At that time the villages of Romankovo and Kamianske, which make up the modern city, formed a part of the Nova (New) Sich of the Zaporizhian cossacks. The city was known as Kamianske, lit. "Stony Place" (, "Kamenskoye") until 1936 when it was renamed to Dniprodzerzhynsk - the name honored the Dnieper River () and the communist Felix Dzerzhynsky (1877-1926), the founder of the Bolshevik secret police, the Cheka.
Soviet leader Leonid Brezhnev was born and raised in Kamianske.
On 15 May 2015 the President of Ukraine Petro Poroshenko signed a bill into law that started a six-month period for the removal of communist monuments and the mandatory renaming of settlements with names related to Communism.
On 19 May 2016, the Ukrainian Verkhovna Rada voted to rename a number of populated places in Ukraine including the city of Dniprodzerzhynsk, which reverted to using the name Kamianske.
Until 18 July 2020, Kamianske was incorporated as a city of oblast significance and the center of Kamianske Municipality. The municipality was abolished in July 2020 as part of the administrative reform of Ukraine, which reduced the number of raions of Dnipropetrovsk Oblast to seven. The area of Kamianske Municipality was merged into the newly established Kamianske Raion.
1979 mid-air collision.
On 11 August 1979 two Aeroflot planes collided over the Central Ukraine, killing all 178 people on both planes.
1996 tram accident.
On 2 July 1996 a traffic accident happened in Dniprodzerzhynsk. An overcrowded tram that was moving along a steep hill on Chapaeva Street began to slide rapidly downhill (because of a brake failure), causing it to derail and hit a concrete wall before coming to a stop very close to a school. A total of 34 people died and more than 100 received injuries as a result of the accident. Following a government inquiry into the causes of the accident, the then mayor, Serhiy Shershnev, and his deputy, Ihor Laktionov, resigned.
Geography.
While mostly located on right bank of Dnieper, Kamianske stretches over the hydroelectric station onto the left bank where the portion of city is known as "Livyi bereh" neighborhood (literally "Left bank"). The neighborhood arches to the west of the Kamianske's suburb of Kurylivka.
To the east Kamianske municipality borders Dnipro city creating an urban sprawl.
Climate.
The climate is moderately continental, dry. The amount of precipitation per year is about 400 mm. The average daily temperature is -6 ° C in January, + 21 ° C in July.
Economy.
The economic base of Kamianske is almost exclusively centered on heavy industry, with ferrous metallurgy being the backbone of the local economy. Around 57% of the total industrial production is metallurgy and metal working. The chemical industry comes second with ca. 17% share of the total industrial output. While the exceedingly industrialized nature of the local economy ensures a rather high employment rate (as of 01.11.2007, official unemployment stood at 1.40%), it also contributes to excessive pollution and radiation levels in the city.
Culture.
Several Eastern Orthodox churches, the largest being the Orthodox Cathedral of Saint Nicholas, which dates from 1894, serve the faithful of the city. By 2018, there were 22 parishes of Ukrainian Orthodox Church in Kamianske.
The Roman Catholic Church of Saint Nicholas built by the city's Polish community at the end of the nineteenth century, has become one of the centers of Roman Catholicism in Eastern Ukraine. The Catholic Parish of Saint Nicholas also includes a monastery run by the Order of Friars Minor Capuchin.
The town has an active Jewish community with a new synagogue and community center.
Ecology.
Kamianske is a city with a very difficult environmental conditions. The city is on the top 10 of the most air-polluted cities of Ukraine. There have been suggestions to assign the status of the ecological disaster city. Right-bank part of the city is mostly polluted, where the metallurgical, chemical industrial enterprises are located.
In 2008, an interdepartmental commission for solving environmental problems was created.
International relations.
Twin towns — Sister cities.
Kamianske is twinned with:


Foveal avascular zone

Within the fovea is a region devoid of retinal blood vessels known as the foveal avascular zone (FAZ). The geometric centre of the FAZ is often taken to be the centre of the macula and thus the point of fixation. It is an important landmark in Fluorescein angiography. Its diameter is 0.5mm, the central 1.5 degrees of an individual's Visual field.


Lateral sulcus

The lateral sulcus (also called Sylvian fissure or lateral fissure) is one of the most prominent features of the human brain. The lateral sulcus is a deep fissure in each hemisphere that separates the frontal and parietal lobes from the temporal lobe. The insular cortex lies deep within the lateral sulcus.
Anatomy.
The lateral sulcus divides both the frontal lobe and parietal lobe above from the temporal lobe below. It is in both hemispheres of the brain. The lateral sulcus is one of the earliest-developing sulci of the human brain. It first appears around the fourteenth gestational week.
The insular cortex lies deep within the lateral sulcus.
The lateral sulcus has a number of side branches. Two of the most prominent and most regularly found are the ascending (also called vertical) ramus and the horizontal ramus of the lateral fissure, which subdivide the inferior frontal gyrus. The lateral sulcus also contains the transverse temporal gyri, which are part of the primary and below the surface auditory cortex.
Due to a phenomenon called the Yakovlevian torque, the lateral sulcus is often longer and less curved on the left hemisphere than on the right.
It is also located near the Sylvian point.
The area lying around the Sylvian fissure is often referred to as the perisylvian cortex.
The human secondary somatosensory cortex (S2, SII) is a functionally-defined region of cortex in the parietal operculum on the ceiling of the lateral sulcus.
Discovery.
The cerebral cortex was not depicted in a realistic manner until the 17th century with the Sylvian fissure being first accurately painted by Girolamo Fabrici d'Acquapendente in 1600 to provide plates for his "Tabulae Pictae".
Its first description is traditionally taken to be in 1641, possibly by Caspar Bartholin, where its discovery was attributed to Franciscus Sylvius (1614–1672), professor of medicine at Leiden University in the book "Casp. Bartolini Institutiones Anatomicae" where it is noted that "F.S. [F.S. probably refers to Franciscus Sylvius] If you examine the indentations which are represented in Figure 5 quite attentively, you will notice that they are very deep and that the brain is divided from one side to the other by the 'anfractuosa fissura,' which starts in the front part near the ocular roots, and from there moves backwards above the base of the spinal cord, following the temporal bones, and it divides the upper part of the brain from the lower."
It seems likely, however, that, since Caspar Bartholin died in 1629 and Franciscus Sylvius only started medicine in 1632, these words are by either Caspar's son Thomas Bartholin or Franciscus Sylvius himself. In 1663 in his "Disputationem Medicarum", Sylvius described the lateral fissure: "Particularly noticeable is the deep fissure or hiatus which begins at the roots of the eyes (oculorum radices) . . . it runs posteriorly above the temples as far as the roots of the brain stem (medulla radices). . . . It divides the cerebrum into an upper, larger part and a lower, smaller part".
In popular culture.
Pop musician David Bowie referred to depth psychologist Carl Jung as "...crashing out with Sylvian" in his lyrics to "Drive In Saturday" released on his 1973 album "Aladdin Sane". In 2015, artist Tanja Stark suggested Bowie had drawn a cryptic link between Jung’s waking hallucinatory visions (see "The Red Book") and the Sylvian fissure, a region discovered by that time to produce hallucinogenic visions and ‘paranormal’ perceptions when electrically stimulated and, presciently in 2006, to generate what neurologists called an ‘illusory shadow person’ or doppelgänger phenomenon; themselves highly charged and recurring Bowie archetypes (Penfield 1955; Arzy et al., 2006). Stark notes another song on that album "Oh You Pretty Things" sings of the hallucinatory spectre of .."a crack in the sky and a hand reaching down to me", evoking the iconic imagery of Michelangelo's painting The Creation of Adam.
Stark observes that the American Medical Journal reported that Michelangelo's "The Creation of Adam" appears to conform deliberately to the neuroanatomical shape of the brain, its Sylvian fissure clearly evident, suggesting Michelangelo may have intentionally conflated theology with neurology ( Meshberger 1990: 1837). Others though, have likened the cloak to the uterus and umbilical cord.


Yale Center for Emotional Intelligence

The Yale Center for Emotional Intelligence is a research center at Yale University in New Haven, Connecticut. It was established in 2013 by research psychologist Dr. Mark Brackett.
YCEI has been referred to as "home to the original scientific theory of emotional intelligence". It offers free trainings in social-emotional learning to grade school teachers and students, with the goal of designing "effective approaches for supporting school communities in understanding the value of emotions, teaching the skills of emotional intelligence, and building and sustaining positive emotional climates in homes, schools, and workplaces."
Its research focuses on four research categories: assessment; school and the workplace; creativity; and RULER, the center's defining approach to social emotional learning.
The YCEI is funded by foundation and federal grants, corporate support, training revenue, and philanthropists. Facebook and the Dalio Foundation are among them.
On October 24, 2015, the YCEI collaborated with singer-songwriter Lady Gaga and the Born This Way Foundation to host the Emotion Revolution summit at the Yale School of Management, where they presented a landmark study of 22,000 high school students. This study revealed that the most common words students used to describe their emotions at school were “tired,” “stressed,” and “bored.” The summit brought together 200 high school students, policy makers, and academic officials, to discuss ways to recognize and channel emotions for positive outcomes.
The center founded InspirEd, an open-source toolkit for educators to learn and teach emotional intelligence in their classrooms.
On January 19, 2021, Dena Simmons resigned from her founding position as Assistant Director after seven years, citing tokenism and discrimination in the workplace.


Guren

Guren (紅蓮) is a Japanese word meaning "crimson-colored lotus" commonly encountered in the West when used in an artistic connotation. In Japan, Guren (紅蓮) is "crimson-colored (紅) lotus flower (蓮の花)". It is compared to the color of a flame of a burning fire. In Buddhist terminology, Guren is also an abbreviation for Guren Jigoku (紅蓮地獄), which is the seventh of The Eight Cold Hells. Those who fell here after death, it is said that the skin is torn due to severe cold, and the blood looks like a crimson-colored lotus flower. The 10th century may have had a water jar of Guren in its right hand.


Loop optimization

In compiler theory, loop optimization is the process of increasing execution speed and reducing the overheads associated with loops. It plays an important role in improving cache performance and making effective use of parallel processing capabilities. Most execution time of a scientific program is spent on loops; as such, many compiler optimization techniques have been developed to make them faster.
Representation of computation and transformations.
Since instructions inside loops can be executed repeatedly, it is frequently not possible to give a bound on the number of instruction executions that will be impacted by a loop optimization. This presents challenges when reasoning about the correctness and benefits of a loop optimization, specifically the representations of the computation being optimized and the optimization(s) being performed.
Optimization via a sequence of loop transformations.
Loop optimization can be viewed as the application of a sequence of specific loop transformations (listed below or in "Compiler transformations for high-performance computing") to the source code or intermediate representation, with each transformation having an associated test for legality. A transformation (or sequence of transformations) generally must preserve the temporal sequence of all dependencies if it is to preserve the result of the program (i.e., be a legal transformation). Evaluating the benefit of a transformation or sequence of transformations can be quite difficult within this approach, as the application of one beneficial transformation may require the prior use of one or more other transformations that, by themselves, would result in reduced performance.
Common loop transformations include:
The unimodular transformation framework.
The unimodular transformation approach uses a single unimodular matrix to describe the combined result of a sequence of many of the above transformations. Central to this approach is the view of the set of all executions of a statement within "n" loops as a set of integer points in an "n"-dimensional space, with the points being executed in lexicographical order. For example, the executions of a statement nested inside an outer loop with index "i" and an inner loop with index "j" can be associated with the pairs of integers . The application of a unimodular transformation corresponds to the multiplication of the points within this space by the matrix. For example, the interchange of two loops corresponds to the matrix formula_1.
A unimodular transformation is legal if it preserves the temporal sequence of all dependencies; measuring the performance impact of a unimodular transformation is more difficult. Imperfectly nested loops and some transformations (such as tiling) do not fit easily into this framework.
The polyhedral or constraint-based framework.
The polyhedral model handles a wider class of programs and transformations than the unimodular framework. The set of executions of a set of statements within a possibly imperfectly nested set of loops is seen as the union of a set of polytopes representing the executions of the statements. Affine transformations are applied to these polytopes, producing a description of a new execution order. The boundaries of the polytopes, the data dependencies, and the transformations are often described using systems of constraints, and this approach is often referred to as a constraint-based approach to loop optimization. For example, a single statement within an outer loop " and an inner loop " is executed once for each pair such that .
Once again, a transformation is legal if it preserves the temporal sequence of all dependencies. Estimating the benefits of a transformation, or finding the best transformation for a given code on a given computer, remain the subject of ongoing research as of the time of this writing (2010).


The Myelin Project

The Myelin Project is 501(c)(3) nonprofit organization established in 1989 by Augusto Odone and his wife, Michaela. Their son, Lorenzo, suffered from adrenoleukodystrophy (ALD), the most common of the leukodystrophies. The story of the Odones' struggle was dramatized in the 1992 film "Lorenzo's Oil".
The Myelin Project has three branches in the United States, Germany, and the United Kingdom. The Myelin Project's scientific advisory committee includes researchers from Yale University and the University of Wisconsin–Madison in the United States, the Istituto Superiore di Sanità and San Raffaele Hospital in Italy, the Hôpital de la Salpêtrière and the Institute Pasteur in France, Queen's University at Kingston in Canada, the University of Cambridge and University of Edinburgh in the United Kingdom, and the Max-Planck-Institut in Germany.
The project's aims.
The Myelin Project aims to advance research, advocacy, and family support for ALD and adrenomyeloneuropathy (AMN).
The nonprofit is currently run by a president and board of directors. Patricia Louisell Chapman, current president of the organization, had two brothers die of AMN, and currently has a son, Michael, born in 1979, who began developing symptoms of AMN in 2005 at the age of 26. She was a personal friend of the Odones and was a founding board member of the organization.


American Autonomic Society

The American Autonomic Society is a scientific society with a particular focus on clinical aspects of the autonomic nervous system. Its official journal, "Clinical Autonomic Research", is published by Springer Science+Business Media.