'Good Vibrations:' Brain Ultrasound Improves Mood

May 15, 2013 — Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) stimulation (tDCS), shown to improve memory. Transcranial ultrasound stimulation (TUS) has also shown promise.

Ultrasound consists of mechanical vibrations, like sound, but with frequencies far greater than the upper limit of human hearing, around 20 thousand to 20 million cycles per second (20 kilohertz to 20 megahertz). Ultrasound vibrations penetrate bodily tissue including bone, and are widely used to image anatomical structures via echo effects, e.g. visualizing unborn babies in mothers' wombs, and organs, blood vessels, nerves and other structures in medical procedures. Virtually every part of the body, including the brain, has been safely imaged with low to moderate intensity ultrasound.

High intensity, focused ultrasound can damage tissue by heating and cavitation, and has been used to ablate tumors and other lesions. 'Sub-thermal' ultrasound can safely stimulate neural tissue. In 2002 a UCLA group led by Alexander Bystritsky noticed beneficial side effects in psychiatric patients whose brains were imaged by TUS. A team led by Virginia Tech's W. Jamie Tyler has shown TUS-induced behavioral and electrophysiological changes in animals. A Harvard group led by S-S Yoo has used focused ultrasound aimed at mouse motor cortex to wag the mouse's tail. But clinical trials of TUS aimed at human mental states have been lacking.

Now, in an article in the journal Brain Stimulation, a group from the Departments of Anesthesiology and Radiology at the University of Arizona Medical Center in Tucson, Arizona has investigated TUS for modulating mental states in a pilot study in human volunteers suffering from chronic pain. A clinical ultrasound imaging device (General Electric LOGIQe) was used, with the ultrasound probe applied at the scalp overlying the brain's temporal and frontal cortex (visible on the imaging screen). In random order, each subject received two 15 second exposures: sham/placebo, and 8 megahertz ultrasound (undetectable to subjects). Following exposure, subjects reported (by visual analog scales) significant improvement in mood both 10 minutes and 40 minutes after TUS, but not after sham/placebo. In a followup study (led by University of Arizona psychologists Jay Sanguineti and John JB Allen) preliminary results suggest 2 megahertz TUS (which traverses skull more readily) may be more effective in mood enhancement than 8 megahertz TUS.

The mechanism by which TUS can affect mental states is unknown (as is the mechanism by which the brain produces mental states). Tyler proposed TUS acts by vibrational stretching of neuronal membranes and/or extracellular matrix, but two recent papers from the group of Anirban Bandyopadhyay at National Institute of Material Sciences (NIMS) in Tsukuba, Japan (Sahu et al. [2013] Appl. Phys. Letts. 102, 123701; Sahu et al [2013] Biosensors and Bioelectronics 47:141) have suggested another possibility. The NIMS group used nanotechnology to study conductive properties of individual microtubules, protein polymers of tubulin (the brain's most prevalent protein). Major components of the neuronal cytoskeleton, microtubules grow and extend neurons, form and regulate synapses, are disrupted in Alzheimer's disease, and theoretically linked to information processing, memory encoding and mental states. Bandyopadhyay's NIMS group found that microtubules have remarkable electronic conductive properties when excited at certain specific resonant frequencies, e.g. in the low megahertz, precisely the range of TUS.

Dr. Stuart Hameroff, lead author on the new TUS study, said: "This suggests TUS may stimulate natural megahertz resonances in brain microtubules, enhancing not only mood and conscious mental states, but perhaps also microtubule functions in synaptic plasticity, nerve growth and repair. We plan further studies of TUS on traumatic brain injury, Alzheimer's disease and post-traumatic stress disorders. 'Tuning the tubules' may help a variety of mental states and cognitive disorders."

http://www.sciencedaily.com/releases/2013/05/130515094825.htm

1.Deep brain stimulation: a fix when the drugs don’t work

14 May 2013, 6.09am EST

1. Deep brain stimulation: a fix when the drugs don’t work

   Author

   1. 

      Amy Reichelt

      Research Fellow in Neuroscience at University of New South Wales

   Disclosure Statement

   Amy Reichelt does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.

   University of New South Wales does not contribute to the cost of running The Conversation. Find out more.

   
   
2.  

   The Conversation is funded by CSIRO, Melbourne, Monash, RMIT, UTS, UWA, Canberra, CDU, Deakin, Flinders, Griffith, JCU, La Trobe, Massey, Murdoch, Newcastle. QUT, Swinburne, UniSA, USC, USQ, UTAS, UWS and VU.

   

   Implanted electrodes can alleviate symptoms of Parkinson’s and Alzheimer’s, and help treat addiction. Wikimedia Commons

   
   

   Neurological disorders can have a devastating impact on the lives of sufferers and their families.

   
   
3. 
   Symptoms of these disorders differ extensively – from motor dysfunction in Parkinson’s disease, memory loss in Alzheimer’s disease to inescapable cravings in drug addiction.

   
   
4. 
   Drug treatments are often ineffective in these disorders. But what if there was a way to simply switch off a devastating tremor, or boost a fading memory?

   
   
5. 
   Recent advances using Deep Brain Stimulation (DBS) in selective brain regions have provided therapeutic benefits and have allowed those affected by these neurological disorders freedom from their symptoms, in absence of an existing cure.
   

   A pacemaker for the brain

   Artificial cardiac pacemakers are typically associated with controlling and resynchronising heartbeats by electrical stimulation of the heart muscle.
   

   

   Schematic of deep brain stimulation. stutteringmedia

   Click to enlarge

   
   In a similar manner, DBS sends electrical impulses to specific parts of the brain that control discrete functions. This stimulation evokes control over the neural activity within these regions.
   Prior to switching on the electrical stimulation, electrodes are surgically implanted within precise brain regions to control a specific function.

   
   
6. 
   The neurosurgery is conducted under local anaesthetic to maintain consciousness in the patient. This ensures that the electrode does not damage critical brain regions.

   
   
7. 
   The brain itself has no pain receptors so does not require anaesthetic.

   
   
8. 
   Following recovery from surgery the electrodes are activated and the current calibrated by a neurologist to determine the optimal stimulation parameters.

   
   
9. 
   The patient can then control whether the electrodes are on or off by a remote battery-powered device.
   

   
   

   
   
10. Deep Brain Stimulation surgery.

    
    

    Turning off tremors

    Perhaps the most documented success of DBS is in the control of tremors and motor coordination in Parkinson’s disease.

    
    
11. 
    This is caused by the degeneration of neurons in an area of the brain called the substantia nigra. These neurons secrete the neurotransmitter dopamine.
    

    

    Basal ganglia circuits, including substantia nigra. Wikimedia Commons

    Click to enlarge

    
    Deterioration of these neurons reduces the amount of dopamine available to be released in a brain area involved in movement, the basal ganglia.

    
    
12. 
    Drug therapy for Parkinson’s disease involves the use of levodopa (L-DOPA), a form of dopamine that can cross the blood brain barrier and then be synthesised into dopamine.

    
    
13. 
    The administration of L-DOPA temporarily reduces the motor symptoms by increasing dopamine concentrations in the brain. However, side effects of this treatment include nausea and disordered movement.

    
    
14. 
    DBS has been shown to provide relief from the motoric symptoms of Parkinson’s disease and essential tremors.

    
    
15. 
    For the treatment of Parkinson’s disease electrodes are implanted into regions of the basal ganglia – the subthalamic nucleus or globus pallidus, to restore control of movement.

    
    
16. 
    These are regions innervated by the deteriorating substantia nigra, therefore the DBS boosts stimulation to these areas.

    
    
17. 
    Patients can then switch on the electrodes, stimulating these brain regions to enhance control of movement and diminish tremors.
    

    Restoring fading memories

    Recently, DBS has been used to diminish memory deficits associated with Alzheimer’s disease, a progressive and terminal form of dementia.
    

    

    British author Terry Pratchett has been diagnosed with Alzheimer’s Disease. Bolt of Blue

    
    The pathologies associated with Alzheimer’s disease involve the formation of amyloid plaques and neurofibrillary tangles within the brain leading to dysfunction and death of neurons.

    
    
18. 
    Brain regions primarily affected include the temporal lobes, containing important memory structures including the hippocampus.

    
    
19. 
    Recent clinical trials with DBS involve the implantation of electrodes within the fornix – a structure connecting the left and right hippocampi together.

    
    
20. 
    By stimulating neural activity within the hippocampi via the fornix, memory deficits associated with Alzheimer’s disease can be improved, enhancing the daily functioning of patients and slowing the progression of cognitive decline.
    

    Deactivating addiction

    Another use of DBS is in the treatment of substance abuse and drug addiction. Substance-related addictions constitute the most frequently occurring psychiatric disease category and patients are prone to relapse following rehabilitative treatment.

    
    
21. 
    Persistent drug use leads to long term changes in the brain’s reward system.

    
    
22. 
    Understanding of the reward systems affected in addiction has created a range of treatment options that directly target dysregulated brain circuits in order to normalise functionality.

    
    
23. 
    One of the key reward regions in the brain is the nucleus accumbens and this has been used as a DBS target to control addiction.

    
    
24. 
    Translational animal research has indicated that stimulation of the nucleus accumbens decreases drug seeking in models of addiction. Clinical studies have shown improved abstinence in both heroin addicts and alcoholics.
    

    

    Diagram of a rat self-administering morphine. Wikimedia Commons

    Click to enlarge

    
    Studies have extended the use of DBS to potentially restore control of maladaptive eating behaviours such as compulsive binge eating.

    
    
25. 
    In a recent study, binge eating of a high fat food in mice was decreased by DBS of the nucleus accumbens. This is the first study demonstrating that DBS can control maladaptive eating behaviours and may be a potential therapeutic tool in obesity.

    
    
26. 
    Despite its therapeutic use for more than a decade, the neural mechanism of DBS is still not yet fully understood.

    
    
27. 
    The remedial effect is proposed to involve modulation of the dopamine system – and this seems particularly relevant in the context of Parkinson’s disease and addiction.

    
    
28. 
    DBS potentially has effects on the functional activity of other interconnected brain systems. While it can provide therapeutic relief from symptoms of neurological diseases, it does not treat the underlying pathology.

    
    
29. 
    But it provides both effective and rapid intervention from the effects of debilitating illnesses, restoring activity in deteriorating brain regions and aids understanding of the brain circuits involved in these disorders.

    
    

Pre-operative transcranial magnetic stimulation useful for language mapping

Pre-operative transcranial magnetic stimulation useful for language mapping

2MM | On 11, May 2013
                              
1. When compared to gold standard direct intraoperative cortical stimulation (DCS), pre-operative navigational transcranial magnetic stimulation (nTMS) showed an overall sensitivity of 90.2% for detecting language areas. 
2. nTMS had a sensitivity of 100% for broca’s area when compared with DCS. 
Evidence Rating Level: 2 (Good) 

Study Rundown: nTMS is a cutting edge tool for pre-operative brain mapping that is gaining wider acceptance and utilization. It already has demonstrated efficacy in identification of the motor cortex when compared with the gold-standard DCS. This study demonstrates good overall correlation between repetitive nTMS and DCS for language areas. Given its high sensitivity for language areas, this technique is especially useful for generating negative response maps to help surgeons avoid language regions during craniotomies and resections. However, the technique also had low specificity for positively identifying language areas and further refinements are needed.
Click to read the study in Neurosurgery

Relevant Reading: Navigated transcranial magnetic stimulation for preoperative functional diagnostics in brain tumor surgery

In-Depth [prospective study]: This study was conducted on 20 consecutive patients with tumors in the vicinity of eloquent regions of the brain. Patients were examined with nTMS pre-operatively, then underwent intraoperative awake DCS. Results from both studies were compared to evaluate the accuracy of nTMS. Pre-operative nTMS maps demonstrated an overall sensitivity of 90.2% and overall specificity of 23.8% for language areas when compared to DCS. nTMS sensitivity for identifying the anatomy broca’s area was 100%. Ultimately, 7 out of the 20 patients still had some evidence of aphasia one week post-operatively.

By Allen Ho

http://www.2minutemedicine.com/pre-operative-transcranial-magnetic-stimulation-useful-for-language-mapping/

Treating depression without drugs

TMS treatment in Vero Beach

 

 

Posted: 10:53 PM
Last Updated: 5 hours and 20 minutes ago

• By: Jon Shainman

VERO BEACH, Fla. - For many people, the treatment of depression involves prescription drugs. But what happens if the pills don't do the trick?

For most of Jesse White's 33 years, he's been looking for some sense of stability.

"Four rehabs, I've been to some of the best in the country, White said.

Six months ago, his brother died in a motorcycle crash. White fell into a deep depression.

"You could sleep for a week, get up and go right back to sleep.  It's terrible you have no energy," he recalled.

With those failed rehab stints behind him, a friend told him about what was happening at the University of Florida's Center for Psychiatry and Addiction Medicine in Vero Beach.

In what looks like a dentist chair, White would begin TMS or Transcranial Magnetic Stimulation.
"This stuff works, it may seem like snake oil from the tabloids but it works ," said Dr. Wayne Creelman, head of the UF center.

Dr. Creelman says after 30 consecutive daily treatments of about half an hour each, his patients have an 85-percent success rate.

"Becoming more motivated.  They're sleeping less, they're appetites are improving," said Dr. Creelman.

When undergoing treatment for TMS, a magnetic coil is attached to the scalp. Using magnetic pulses, doctors first need to locate the patients' motor strip. Then, they have to find what's called the dorso lateral nucleus.

"It almost feels a little like a thump on the head," said Jesse White.

The electrical current activates the neurons in the region to help regulate the chemical imbalance and improve your mood.

"I feel great. I don't have any more anxiety like I did. I go to the beach, I do stuff by myself that you would have never caught me doing before unless I was drinking or something like that you know," said White.

So why isn't TMS more popular?  One reason, the FDA says it can't be a "first treatment option." Not only that, there's the cost of about 10-thousand dollars, and most insurance companies don't cover it.
Dr. Creelman, who's written many books on how drugs *do* work, says rather than give patients another antidepressant that may fail them, why not give them a different chance at success .

White finishes his treatments in another week. He hopes this is the one, that keeps his mind health y for good.

If you'd like to find out more about TMS, the UF facility in Vero Beach is hosting a new patient information session Wednesday night May 15th from 5-6pm at their office across from the Indian River Medical Center at 840 37th Place.

For more information, you can call them at 772-794-0179.

http://www.wptv.com/dpp/news/local_news/special_reports/treating-depression-without-drugs

J Formos Med Assoc. 2013 May 2. pii: S0929-6646(13)00093-4. doi: 10.1016/j.jfma.2013.02.008. [Epub ahead of print]

Neuroimaging and electroencephalographic changes after vagus nerve stimulation in a boy with medically intractable myoclonic astatic epilepsy.

Fan PC, Peng SS, Yen RF, Shieh JY, Kuo MF.

Source

Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

Myoclonic astatic epilepsy (MAE) is characterized by multiple seizure types, which are often refractory. Although vagus nerve stimulation (VNS) is an alternative treatment for medically intractable seizures, its exact mechanism of action remains unclear. Herein, we report the case of a 4-year-old boy with intractable MAE who has been in a seizure-free status for 2 years and 3 months since 6 months after the implantation of a vagus nerve stimulator (Model 103, Cyberonics, Inc., Houston, TX). Various test results 6 months after VNS were compared with those before VNS. Results of an electroencephalograph revealed disappearance of epileptiform discharges and an increased beta-gamma spectrum rhythm. The brain diffusion-tensor imaging showed an increased ratio of fraction anisotropy in the right fimbria-fornix, indicating improved diffusion of the white matter tract, and ¹⁸F-fluorodeoxyglucose positron emission tomography revealed globally improved cerebral glucose metabolism. His cognitive and social-emotional performances also improved at 2 years after VNS. To the best of our knowledge, this is the first report to describe the effects of VNS on fimbria-fornix and glucose metabolism in MAE.
Copyright © 2013. Published by Elsevier B.V.

PMID:

23643463

[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23643463

CONFERENCE NEWS  New Clinical TMS Society Established May 2, 2013 A new transcranial magnetic stimulation (TMS) society open to all TMS providers has been established. The Clinical TMS Society (Clinical TMS) coordinates TMS practices and connects physician and non-physician members from across the world. The focus of this professional association is to optimize clinical practice, awareness, and affordability of TMS. According to Dr Tarique Perera, President of Clinical TMS, “Our society will be a valuable-industry neutral resource for clinical TMS providers. We hope to optimize and standardize the delivery of TMS and make the treatment more affordable . . . Pooling resources and outcome data will allow us to better serve patients and increase public awareness of TMS." Because cost can be a major limiting factor, a task force will be formed to expand private and public insurance coverage of TMS. ‬ Formed in January 2013, the society already has a substantial membership that includes some of the largest clinical practices and several leaders in TMS research. Clinical TMS will be hosting an inaugural meeting in conjunction with the American Psychiatric Association Meeting in San Francisco, May 18 to May 19, at the InterContinental Hotel. The conference will start at 6:30 PM on May 18, with a poster session, followed by a dinner reception with a keynote address given by Alvaro Pascaul-Leone, MD. On the next day, leaders in the field will present a series of workshops covering topics such as research, education, clinical standards, and reimbursement. More information on becoming a member of Clinical TMS and the meeting can be found at www.clinicaltmssociety.org. http://www.psychiatrictimes.com/mdd/content/article/10168/2139862

J Nat Sci Biol Med. 2013 Jan;4(1):8-13. doi: 10.4103/0976-9668.107254.

Vagal nerve stimulator: Evolving trends.

Ogbonnaya S, Kaliaperumal C.

Source

Department of Neurosurgery, Cork University Hospital, Cork, Ireland.

Abstract

Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for 'VNS' and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future.

KEYWORDS:

Depression, neurogenesis, obesity, seizure, vagus nerve stimulator

PMID:

23633829

[PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/23633829