Animal study highlights potential new target for treating anxiety disorders
Increasing acidity in the brain’s emotional control center reduces anxiety, according to an animal study published February 26 in The Journal of Neuroscience. The findings suggest a new mechanism for the body’s control of fear and anxiety, and point to a new target for the treatment of anxiety disorders.
Anxiety disorders, which are characterized by an inability to control feelings of fear and uncertainty, are the most prevalent group of psychiatric diseases. At the cellular level, these disorders are associated with heightened activity in the basolateral amygdala (BLA), which is known to play a central role in emotional behavior.
Many cells in the BLA possess acid-sensing ion channels called ASIC1a, which respond to pH changes in the environment outside of the cell. Maria Braga, DDS, PhD, and colleagues at the Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, found that activating ASIC1a decreased the activity of nearby cells and reduced anxiety-like behavior in animals. These findings add to previous evidence implicating the role of ASIC1a in anxiety.
“These findings suggest that activating these channels, specifically in fear-related areas such as the amygdala, may be a key to regulating anxiety,” explained Anantha Shekhar, MD, PhD, who studies panic disorders at Indiana University and was not involved in this study. “Developing specific drugs that can stimulate these channels could provide a new way to treat anxiety and fear disorders such a post-traumatic stress and panic disorders.”
To determine the effect ASIC1a activation has on neighboring cells, Braga’s group bathed BLA cells in an acidic solution in the laboratory and measured the signals sent to nearby cells. Lowering the pH of the solution decreased the activity of cells in the BLA.
Activating ASIC1a also affected animal behavior. When the researchers administered a drug that blocks ASIC1a directly into the BLA of rats, the rats displayed more anxiety-like behavior than animals that did not receive the drug. In contrast, when rats received a drug designed to increase the activity of ASIC1a channels in the BLA, the animals displayed less anxiety-like behavior.
“Our study emphasizes the importance of identifying and elucidating mechanisms involved in the regulation of brain function for the development of more efficacious therapies for treating psychiatric and neurological illnesses,” Braga said. While the findings suggest that drugs targeting ASICs may one day lead to novel therapies for anxiety disorders, Braga noted that “more research is needed to understand the roles that ASIC1a channels play in the brain.”
Link to the article:
I figured it is about time to write something about the blog’s title, bell’s palsy, since I’ve seen there are a lot of people searching for this topic about facial paralysis.
Bell’s palsy is a common condition that presents with an acute onset of lower motor neuron (LMN – could say like peripheral nerves) facial weakness affecting the muscles on one side of the face.
People of all ages may be affected, including children, although it is most common in patients aged 30-50 years. The exact cause in not known, but there are certain conditions known to be responsible.
If we take a look in pathogenesis, how the condition evolves, we see that there is segmental demyelination in a local conduction block proximally. And what this actually means? Every nerve has its sheath around that is made of substance called myelin. This myelin sheath does not cover the whole nerve, but in segments, leaving tiny gaps, called Nodes of Ranvier (take a look at the picture below). And these gaps are like capacitors that stores electrical charge and allows bursts of electric impulses (know as action potentials) to move along the neuron in a saltatory fashion. Think of it as the action potential would jump from one of these gaps to the next one. This actually prevents loosing the charge. Now imagine that you widen this gap. This slows the nerve conduction, spread it even more and you get a block, conduction block. Now you cannot get the full use of that nerve leaving you weakness.
Since this conduction block happens proximally (closer to its origin), it allows a relatively rapid and complete recovery in about 85% of cases. This is because myelin rapidly regenerates. In others, axonal degeneration occurs, which will produce a severe paralysis. Again, think of it as the whole neuron is cut, and that is why it is so severe. Often this is then followed by incomplete recovery associated with aberrant re-innervation, that is, fibers from the periocular muscles my regenerate and supply the mouth, and vice versa. Such faulty re-innervation may lead to “jaw-winking”, and even hemifacial spasm. Where axonal degeneration has occurred, electromyography of the facial muscles will show fibrillation and features of denervation, although these changes may not appear until some 10 days after the onset. In some instances the pathogenesis is a mixture of axonal degeneration and demyelination.
Ok, let’s leave this aside and let’s carry on and look how this condition actually presents clinically. Normally patients may present with pain in or behind the ear preceding or appearing with the development of facial weakness. There is inability to close the eye or move the lower face and mouth on one side of the face.
The lack of blinking leads to tears spilling out of the eye, which waters to cause complaints of blurred vision. The cheek is flaccid and saliva and fluids may escape from the corner of the mouth. The weakness commonly progresses over 24-72 hours to reach a maximum. In many patients there are complaints of numbness in the affected side of the face, although trigeminal sensation is spared and there should be no weakness of jaw movement, since it is supplied by the motor root of the trigeminal nerve. Trigeminal sensation is sensation on the skin of the face, because sensory innervation of it comes from fifth cranial nerve – trigeminal nerve. Hence the name.
About 40-50% of patients are aware of disturbed taste on the ipsilateral anterior part of the tongue (ipsilateral means it is on the same side as the lesion). This points to a lesion in the distal part of the facial nerve below the geniculate ganglion, but above the origin of the chorda tympani (branch of facial nerve that is responsible for taste). Many patients also notice hyperacusis (over-sensitivity to certain frequency ranges of sound and difficulty tolerating everyday sounds, some of which may seem unpleasantly loud) because the stapedius muscle (very small muscle that moves the smallest bone in the human body and makes us hear) is supplied by a branch of the facial nerve, which leaves the nerve in the facial canal proximal to the chorda tympani.
If a zoster infection is responsible, there will be herpetic vesicles on the pinna (the visible part of the ear that resides outside of the head, also called auricle or auricula) or in the external auditory canal on the affected side. Ramsay Hunt described a herpetic infection of the geniculate ganglion with the development of an acute facial palsy – Hunt’s syndrome. In some of these patients the 8th cranial nerve (auditory nerve, responsible for hearing) may also be infected, producing acute vertigo, deafness and tinnitus (ringing of the ears). A few patients may show a bilateral (on both sides) facial palsy of lower motor neuron (LMN) pattern; this may appear as part of a Guillain-Barre syndrome, from Lyme disease, from sarcoidosis or even carcinomatous meningitis.
About 85% of patients show signs of improvement within some 3 weeks of the onset. About 70% of patients recover normal function in the face but some 16% are left with asymmetry, signs of aberrant re-innervation and some weakness. An incomplete palsy at the onset or signs of recovery starting within 3-4 weeks usually are good prognostic features for recovery. This is mirrored in the electrophysiological findings. In the more severely affected, where axonal degeneration has taken place, recovery is slower and often incomplete. Recurrent facial palsies require more intensive investigation to exclude any compressive lesion on the middle ear or skull base, and to look for any systemic upset such as sarcoidosis, hypertension, diabetes.
Normally when there is suspicion of Bell’s palsy several investigations are made. Such as blood tests. Full blood count, erythrocyte sedimentation rate (ESR), fasting glucose levels, tests for Borrelia. Of course there is imaging; in selected patients MRI and/or CT scanning, chest X-ray. Electromyography (EMG) studies as these may assess the severity of damage and help in prognosis; they may also indicate a more widespread neuropathy. ENT examination…
Once all the tests are conclusive and the Bell’s palsy diagnosis is made, patients can undergo treatment. There appears to be little difference in outcome between patients treated with steroids and those who are not. Many doctors believe that a short intensive course of steroids given within 5-7 days of the onset of palsy may reduce the swelling of the facial nerve and so prevent axonal degeneration. Prednisolon 40 mg daily for 5 days and then tapered off over the next week is a typical regimen. It has been suggested that such a course should be given to all patients seen acutely with a complete palsy at the time of consultation or with impaired taste.
Because of the possible infective causation by herpes virus, acyclovir has also been used in treatment of an cute facial palsy. This certainly should be given if a zoster infection (Hunt’s syndrome) is suspected. The combination of acyclovir with steroids in those patients with complete facial palsies has also been used. Surgical decompression of the facial nerve has had its supporters over the years, although there has been no rigorous controlled trial to indicate benefit and as over 70% of patients will make a full recovery with no treatment it is hard to justify the surgical risks.
Care of the eye is always important if there is incomplete lid closure but as the cornea is not anesthetic, the patient will be aware of any intruding foreign body. Occasionally it may be necessary to suture the lids partially together, a tarsorrhaphy, to protect the eye.
In those patients left with marked residual weakness or asymmetry, a number of surgical measures may be used to try to improve their appearance. These include plastic surgery with implants of soft tissues to restore the contours. Such measures will improve the symmetry of the face at rest but are by no means a ‘cure’.
The Reticular Formation
It’s a ‘diffuse net’ which is formed by nerve cells and fibers. It extends from the neuroaxis spinal cord through medulla, pons, midbrain, subthalamus, hypothalamus and thalamus (spinal cord is relayed superiorly to the cerebral cortex).
Many afferent and efferent pathways project in and out of the RF from most parts of the CNS. The main pathways through the RF is poorly defined and difficult to trace using silver stains. Reticular formation can be divided into three columns : median, medial and lateral columns.
Functions of the Reticular formation
1. Control of skeletal muscles:
- RF modulates muscle tone and reflex activities (via reticulospinal and reticulo bulbar tracts). It is important in controlling muscles of facial expression when associated with emotions.
2. Control somatic and visceral sensation (influence can be excitatory or inhibitory)
3. Control of autonomic nervous system
4. Control of endocrine nervous system (hypothalamus and the pituitary)
5. Influence on the biological clock (rhythm)
6. The reticular activating system (arousal and level of consciousness are controlled by the RF)
When a person smiles for a joke, the motor control is provided by the RF on both side of the brain. The fibers from RF is separated from corticobulbar pathway (supply for facial muscles). If a patient suffers a stroke that involves corticobulbar fibers, he or she has facial paralysis on the lower part of the face, but is still able to smile symmetrically.
The Limbic System
|Limbic structures||Functions of the limbic system|
||1. Influence the emotional behavior:a. Reaction to fear and angerb. Emotions associated with sexual behavior
2. Hippocampus is involved in converting short term memory to long term memory (If the hippocampus is damaged, patient is unable to store long term memory – Anterograde amnesia)
The Basal Ganglia and their connections
Connections of the Basal Ganglia
Yellow arrow : Pallidofugal fibers
Caudate nucleus and the Putamen: main sites of receiving inputs
Globus pallidus: main site from which output leaves
Afferent and Efferent fibers
|Connections of the caudate nucleus and Putamen||Connections of the Globus pallidus|
|CS: CorticostriateTS: Thalamostriate
BS: Brainstem striatal fibers
SN: Striatonigral fibers
Functions of the Basal Nuclei
Basal Nuclei controls muscular movements by influencing the cerebral cortex (it doesn’t have direct control through descending pathways to the brainstem and spinal cord). It helps to prepare for the movements (enables the trunk and limbs to be placed in appropriate positions before discrete movements of the hands and feet).
Functional connections of the Basal Nuclei and how they influence muscle activities
1. Ben Greenstein, Ph.D, Adam Greenstein, BSc (Hons) Mb, ChB Color Atlas of Neuroscience
2. Allan Siegel Ph.D, Hreday N. Sapru Ph.D Essential Neuroscience, 1st Edition
3. Stanley Jacobson, Elliot M. Marcus Neuroanatomy for the Neuroscientist
4. Patrick f. Chinnery Neuroscience for Neurologists
5. Dale Purves Neuroscience, 3rd Edition
6. Suzan Standring Gray’s Anatomy
7. Keith L. Moore, Arthur F. Dalley, Anne M. R. Agur Clinically Oriented Anatomy
8. Frank H. Netter Atlas of Human Anatomy
9. Walter J. Hendelman, M.D., C.M. Atlas of Functional Neuroanatomy
10. Mark F. Bear, Barry W. Connors, Michael A. Paradiso Neuroscience Exploring the Brain
11. Dale Purves et al. Principles of Cognitive Neuroscience
12. Eric R. Kandel et al. Principles of Neural Science
Descending tracts have three neurons:
1. 1st order neurons (UMN): cell bodies are in the cerebral cortex and other supra spinal areas
2. 2nd order neurons: short and situated in the anterior grey column of the spinal cord
3. 3rd order neuron (LMN): situated in the anterior grey column and innervate the skeletal muscles through anterior roots of the spinal nerves
Corticospinal tract: rapid, skilled and voluntary movements
1st order neuron
Axons arise from the pyramidal cells of the cerebral cortex (situated in the 5th layer), 2/3 from the pre central gyrus and 1/3 from the post central gyrus:
1. 1/3 of fibers arise from the 1stry motor cortex (Area 4)
2. 1/3 of fibers arise from the 2ndry motor cortex (Area 6)
3. 1/3 of fibers arise from the parietal lobe
(Area 1, 2 and 3).
Descending fibers converge in the corona radiata and pass though the posterior limb of the internal capsule; organization of fibers within the internal capsule:
1. close to genu (medial): concerned with the cervical parts of the body
2. away from the genu (lateral): concerned with the lower extremity.
The tract then passes through the middle 3/5 of the basis pedunculi of the midbrain; organization of fibers in the midbrain:
- medially: cervical parts of the body
- laterally: lower limbs.
When the tract enters the pons, it’s broken into many bundles by the transverse pontocerebellar fibers. In the medulla oblongata, the bundles group together to form the pyramids. At the junction of the MO and the spinal cord, most fibers cross the midline at the decussation of the pyramids and enter the lateral white column of the spinal cord to form the lateral corticospinal tract (LCST). LCST descends length of the spinal cord and terminates in the anterior grey column of all the spinal segments.
The fibers which didn’t cross, descend in the anterior white column of the spinal cord as the anterior corticospinal tract (ACST). Fibers of the ACST eventually cross and terminate in the anterior grey column of the spinal cord segments in the cervical and upper thoracic regions.
2nd order neuron:
It’s an internuncial neuron.
3rd order neuron:
It’s a alpha or gamma motor neuron.
To read more click on this link to the full article: Descending Tracts
They are located in the white matter and conduct afferent information (may or may not reach consciousness). There are two types of information:
- Exteroceptive : originates from outside the body (pain, temperature and touch
- Proprioceptive : originates from inside the body (from muscles and joints)
Normally there are three neurons in an ascending pathway:
- 1st order neuron: cell body is in the posterior root ganglion
- 2nd order neuron: decussates (crosses to the opposite side) and ascends to a higher level of the CNS
- 3rd neuron: located in the thalamus and passes to a sensory region of the cortex
Pain and temperature pathway: lateral spinothalmic tract
1st order neuron
Peripheral process extends to skin or other tissues and ends as free nerve endings (receptors). Cell body is situated in the posterior root ganglion. Central process extends into the posterior grey column and synapses with the 2nd order neuron.
2nd order neuron
The axon crosses obliquely to the opposite side in the anterior grey and white commissures within one spinal segment of the cord. It ascends in the contralateral white column as the lateral spinothalamic tract (LSTT).
As the LSTT ascends through the spinal cord new fibers are added to the anteromedial aspect of the tract (sacral fibers are lateral and cervical fibers are medial). The fibers carrying pain are situated anterior to those conducting temperature.
As the LSTT ascends through the medulla oblongata, it’s joined by the anterior spinothalamic tract and the spinotectal tract and forms the spinal lemniscus. Spinal lemniscus ascends through the pons and the mid brain.
Fibers of the LSTT end by synapsing with the 3rd order neurons in the ventral posterolateral nucleus of the thalamus (here crude pain and temperature sensations are appreciated).
3rd order neuron
Axons pass through the posterior limb of the internal capsule and corona radiata to reach the somatosensory area in the post central gyrus of the cerebral cortex. From here information is transmitted to other regions of the cerebral cortex to be used by motor areas. The role of the cerebral cortex is interpreting the quality of the sensory information at the level of the consciousness.
Light (crude) touch and pressure pathway: anterior spinothalamic tract (ASTT)
1st order neuron
It is similar to the pain and temperature pathway.
2nd order neuron
The axon crosses obliquely to the opposite side in the anterior grey and white commissures within several spinal segments. It ascends in the contralateral white column as the anterior spinothalamic tract (ASTT). As the ASTT ascends through the spinal cord new fibers are added to the anteromedial aspect of the tract (sacral fibers are lateral and cervical fibers are medial).
As the ASTT ascends through the medulla oblongata, it’s joined by the lateral spinothalamic tract and the spinotectal tract and forms the spinal lemniscus. Spinal lemniscus ascends through the pons and the midbrain. Fibers of the ASTT end by synapsing with the 3rd order neurons in the ventral posterolateral nucleus of the thalamus (here crude awareness of touch and pressure sensations are appreciated).
3rd order neuron
Axons pass through the posterior limb of the internal capsule and corona radiata to reach the somatosensory area in the post central gyrus of the cerebral cortex. The sensations can be crudely localized. Very little discrimination is possible.
To read more click on this link to the full article: Ascending Tracts (pdf).
Introduction Brain waves
The brain generates tiny electrical pulses as The brain produces four main waves with thoughts traverse the labyrinth of the mind. The specific frequencies:
physical conduits of these thoughts are the millions of nerve cells or neurons in the brain. Just as radio signals, in order to make a comprehensible message, are beamed out on radio waves, a band of signals within a defined frequency, so the brain’s activity also occurs in waves. Brain waves can be measured on an electro-encephalograph machine (which is normally abbreviated to EEG Machine). By attaching sensitive electrodes to the scalp, it is possible to measure accurately the type of brain wave that a subject is producing. These waves are usually expressed in the number of cycles per second (CPS) or with their frequency (Hz).
1. Beta level brain waves – range 12-16 Hz (also 13-25 Hz)
2. Alpha level brain waves – range 8-12 Hz 3. Theta level brain waves – range 4-7 Hz
4. Delta level brain waves – range 0.5-3 Hz
The following chart relates each type of brain wave to its principal function. We must remember however, that when we speak of someone being ‘in alpha’ we mean that this is their characteristic and predominant brain wave. Other brain waves will also be present, but in smaller quantities than usual.
The linking of left and right brain activities is important in producing a shift from learning to accelerated learning. Yet our society is very ‘beta orientated’. We are busy thinking about the problem in hand, but don’t leave ourselves sufficiently open to other influences, which would help us memorize faster and make the sort of less expected connections that we call creative thinking.
In beta you don’t see the wood for concentrating on the trees. But learn to relax, increase the proportion of the alpha and ideally theta brain waves, and you have created the conditions where you may begin to see the whole picture.
‘Alpha’ is a natural and receptive state of mind, that we can all attain through the techniques of relaxation. They principally involve simple and pleasant relaxation exercises and listening to certain types of music.
The theta brain wave pattern is especially interesting. It occurs spontaneously to most of us in the twilight state between being fully awake and falling asleep. Arthur Koestler called it ‘reverie’. This drowsy stage is associated with fleeting semi-hallucinatory images. Thousands of artistic and literary inspirations and scientific inventions have been credited to this state, a sort of freeform thinking that puts you in touch with your subconscious.
Brain waves interpretation
Many psychologists would agree it is a reasonable hypothesis that, when left/right brain symbiosis takes place, conscious and subconscious are also united. The proportion of theta brain waves becomes much higher than normal. This is the moment when logical left brain activity declines. The left brain, which normally acts as a filter or censor to the subconscious, drops its guard, and allows the more intuitive, emotional and creative depths of the right brain to become increasingly influential.
If the hypothesis is true, then do women, popularly characterised as more intuitive, reach a walking theta state more often than men; and can this be associated with the fact that their left/right brain link, the Corpus callosum, is larger and richer in connective capabilities than men’s? We do not yet know, but it is a fascinating area for future research.
At the University of Colorado Medical Centre and at the Biofeedback Centre in Denver, Dr. Thomas Budzyski has found that, when people were trained to achieve and maintain theta brain waves using biofeedback techniques, they did indeed learn much faster. Moreover, many emotional and attitudinal problems were solved at the same time.
To read more click on this link to the full article: Brain Waves (pdf).