Now, however, a brain imaging study — published online by the journal Nature Neuroscience on Mar. 2 — challenges this basic assumption. Using high-resolution functional magnetic resonance imaging (fMRI), a team of researchers from Vanderbilt and Boston universities, have discovered that more complex processing occurs in the initial stages of the visual system than previously thought. Specifically, they have found evidence of processing in the human lateral geniculate nucleus (LGN), a small node in the thalamus in the middle of the brain that relays nerve impulses from the retina to the primary visual cortex.
An important function of the visual cortex is the processing of rudiments of shape, the angles of lines and edges, which are important for defining the outlines of objects. The researchers found that the human LGN is also sensitive to the orientation of lines and that this effect is enhanced when a person simply pays attention to the orientations in an image.
“Our results demonstrate that even the simplest brain structures may play a fundamental role in complex neural processes of perception and attention,” said Frank Tong, professor of psychology at Vanderbilt, who conducted the study with postdoctoral fellow Michael Pratte and Sam Ling at Boston University. “They also highlight how higher cortical areas can influence and modulate how we see by modifying the responses of neurons at the earliest stages in the visual pathway through feedback connections.”
“The findings challenge the conventional wisdom about how and where in the brain the processing of visual orientation information first occurs,” commented Michael A. Steinmetz, acting director of the Division of Extramural Research at the National Eye Institute, which provided funding for the study. “The research also underscores the concept that the perception of visual stimuli evolves from dynamic processes in widely distributed networks in the brain.”
The research was supported by National Institutes of Health grants R01 EY01782 and R01 EB000461 and NIH Fellowship F32-EY022569.
- Sam Ling, Michael S Pratte, Frank Tong. Attention alters orientation processing in the human lateral geniculate nucleus. Nature Neuroscience, 2015; DOI:10.1038/nn.3967
Vanderbilt University. “Results challenge conventional wisdom about where the brain begins processing visual information.” ScienceDaily. ScienceDaily, 2 March 2015. <www.sciencedaily.com/releases/2015/03/150302121615.htm>.
Target Health Presenting a Case Study at CBINET Meeting in San Francisco on Risk-based Monitoring
Target Health is pleased to announce that Dr. Jules T. Mitchel, President of Target Health, will present a Case Study, entitled Impact of Risk-Based Monitoring and eSource Methodologies on Clinical Sites, Patients, Regulators and Sponsors. The Risk-Based Monitoring for Small to Mid-Sized Organizations conference will be held in San Francisco, March 26- 27. Let us know if you plan to attend.
CBI’s Risk-Based Monitoring conference addresses the unique challenges of small to mid-sized organizations by delving into strategies for change management, streamlining processes and utilizing technology with fewer resources and limited budgets. With practical case studies and insights on enabling RBM, the forum provides actionable takeaways for building your own approach including ensuring buy-in from senior leadership to study teams and monitors; developing processes for risk identification, categorization, documentation and follow-through; as well as building off of current technologies/framework to enable streamlined execution
Views From Boston and Hawaii – You Choose
Our very good friend and colleague, Dr. Phil Lavin, former CEO of Averion, just left a sunny Hawaiian vacation for Boston’s snowiest year. Here’s a photo in his own backyard.
ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Do You Know About Charles Bonnet Syndrome?
Charles Bonnet (1720-1793), erudite naturalist
Visual release hallucinations, also known as Charles Bonnet syndrome (CBS), is the experience of complex visual hallucinations in a person with partial or severe 1) ___. First described by Charles Bonnet in 1760, it was first introduced into English-speaking psychiatry in 1982. Sufferers, who are mentally healthy people with often significant vision 2) ___, have vivid, complex recurrent visual hallucinations (fictive visual percepts). One characteristic of these hallucinations is that they usually are Lilliputian (hallucinations in which the characters or objects are smaller than normal). The most common hallucination is of faces or cartoons. Sufferers understand that the hallucinations are not 3) ___, and the hallucinations are only visual, that is, they do not occur in any other senses, e.g. hearing, smell or taste. Among older adults (>65 years) with significant vision loss, the prevalence of Charles Bonnet syndrome has been reported to be between 10% and 40%; a recent Australian study has found the prevalence to be 17.5%. Two Asian studies, however, report a much lower prevalence. The high incidence of non-reporting of this disorder is the greatest hindrance to determining the exact prevalence; non-reporting is thought to be a result of sufferers being afraid to discuss the symptoms out of fear that they will be labeled 4) ___. People suffering from CBS may experience a wide variety of hallucinations. Images of complex colored patterns and images of people are most common, followed by animals, plants or trees and inanimate objects. The 5) ___ also often fit into the person’s surroundings.
CBS predominantly affects people with visual impairments due to old age, diabetes or other damage to the eyes or optic pathways. In particular, central vision loss due to a condition such as macular 6) ___ combined with peripheral vision loss from glaucoma may predispose to CBS, although most people with such deficits do not develop the syndrome. The syndrome can also develop after bilateral optic nerve damage due to methyl alcohol poisoning.
There is no treatment of proven effectiveness for CBS. Some people experience CBS for anywhere from a few days, to up to many years, and these hallucinations can last only a few seconds or continue for most of the day. For those experiencing CBS, knowing that they are suffering from this syndrome and not a mental illness seems to be the best treatment so far, as it improves their ability to cope with the hallucinations. Most people with CBS meet their hallucinations with indifference, but they can still be disturbing because they may interfere with daily life. It seems that there are a few activities that can make the hallucinations stop although many people are not aware of these. Interrupting vision for a short time by closing the eyes or blinking is sometimes helpful. Because there is no prescribed treatment, the first starting place is to reassure the CBS sufferer of their 7) ___, and some charities provide specialist hallucination counseling buddies (people who have or have had CBS and are no longer fazed by it) to talk to on the telephone. Sometimes it is care-givers and/or physicians that need advice and guidance. The treating physician will consider on a case by case basis, whether to treat any depression or other problems that may be related to CBS. A recent case report suggests selective serotonin reuptake inhibitors may be helpful.
The disease is named after the Swiss naturalist Charles Bonnet, who initially described the condition in 1760. He first documented it in his 89-year-old grandfather who was nearly blind from cataracts in both 8) ___ but perceived men, women, birds, carriages, buildings, tapestries, physically impossible circumstances and scaffolding patterns. The syndrome is discussed in Vilayanur S. Ramachandran’s book Phantoms in the Brain. Ramachandran suggests that James Thurber, who was blinded in one eye as a child, may have derived his extraordinary imagination from the syndrome.
ANSWERS: 1) blindness; 2) loss; 3) real; 4) insane; 5) hallucinations; 6) degeneration; 7) sanity; 8) eyes
Oliver Sacks MD (1933 to Present)
Oliver Wolf Sacks MD – The poet laureate of contemporary medicine.
Oliver Sacks National Best Seller
Oliver Wolf Sacks, CBE (born 9 July 1933) is an American-British neurologist, writer, and amateur chemist who is Professor of Neurology at New York University School of Medicine. Between 2007 and 2012, he was professor of neurology and psychiatry at Columbia University, where he also held the position of Columbia Artist. Before that, he spent many years on the clinical faculty of Yeshiva University’s Albert Einstein College of Medicine. He also holds the position of visiting professor at the United Kingdom’s University of Warwick. Sacks is the author of numerous best-selling books, including several collections of case studies of people with neurological disorders. His 1973 book Awakenings, an autobiographical account of his efforts to help victims of encephalitis lethargica regain proper neurological function, was adapted into the Academy Award-nominated film of the same name in 1990 starring Robin Williams and Robert De Niro. He and his book Musicophilia: Tales of Music and the Brain were the subject of Musical Minds, an episode of the PBS series Nova.
Sacks was the youngest of four children born to a North London Jewish couple: Samuel Sacks, a physician (died June 1990), and Muriel Elsie Landau, one of the first female surgeons in England. Sacks has a large extended family, and his first cousins include Israeli statesman Abba Eban, writer and director Jonathan Lynn, and economist Robert Aumann. When Sacks was six years old, he and his brother Michael were evacuated from London to escape the Blitz, retreating to a boarding school in the Midlands where he remained until 1943. Unknown to his family, at the school, he and his brother Michael subsisted on meagre rations of turnips and beetroot and suffered cruel punishments at the hands of a sadistic headmaster. He attended St Paul’s School in London. During his youth he was a keen amateur chemist, as recalled in his memoir Uncle Tungsten. He also learned to share his parents’ enthusiasm for medicine and entered The Queen’s College, Oxford, in 1951, from which he received a Bachelor of Arts degree in physiology and biology in 1954. At the same institution, in 1958 he went on to undertake a Master of Arts and earn a BM BCh, thereby qualifying to practice medicine.
Sacks left England for Canada then made his way from there to the United States for a different career path. He undertook residencies and fellowship work at Mt. Zion Hospital in San Francisco and at UCLA. After converting his British qualifications to American recognition (i.e., an MD as opposed to BM BCh), Sacks moved to New York, where he has lived and practiced neurology since 1965. In 1966, Sacks began consulting at chronic care facility Beth Abraham Hospital (now Beth Abraham Health Services, a member of Center Light Health System) in the Bronx. At Beth Abraham, Sacks worked with a group of survivors of the 1920s sleeping sickness, encephalitis lethargica, who had been unable to move on their own for decades. These patients and his treatment of them were the basis of Sacks’ book Awakenings.
Sacks served as an instructor and later clinical professor of neurology at the Albert Einstein College of Medicine from 1966 to 2007, and also held an appointment at the New York University School of Medicine from 1992 to 2007. In July 2007 he joined the faculty of Columbia University Medical Center as a professor of neurology and psychiatry. At the same time, he was appointed Columbia University’s first Columbia University Artist at the University’s Morningside Heights campus, recognizing the role of his work in bridging the arts and sciences. Since 1966 Sacks has served as a neurological consultant to various New York City nursing homes that are run by the Little Sisters of the Poor, and from 1966 to 1991 was a consulting neurologist at Bronx Psychiatric Center. Sacks returned to New York University School of Medicine in 2012, serving as both a professor of neurology and consulting neurologist in the center’s epilepsy center. Sacks’ work at Beth Abraham helped provide the foundation on which the Institute for Music and Neurologic Function (IMNF) is built; Sacks is currently an honorary medical advisor. The Institute honored Sacks in 2000 with its first Music Has Power Award. The IMNF again bestowed a Music Has Power Award on Sacks in 2006 to commemorate his 40 years at Beth Abraham and honor his outstanding contributions in support of music therapy and the effect of music on the human brain and mind. Sacks remains a consultant neurologist to the Little Sisters of the Poor, and maintains a practice in New York City. He serves on the boards of the The Neurosciences Institute and the New York Botanical Garden.
Beginning in 1970, Sacks wrote of his experience with neurological patients. His books have been translated into over 25 languages. In addition to his books, Sacks is a regular contributor to The New Yorker and The New York Review of Books, as well as other medical, scientific, and general publications. He was awarded the Lewis Thomas Prize for Writing about Science in 2001. Sacks’ work has been featured in a broader range of media than those of any other contemporary medical author and in 1990, The New York Times said he has become a kind of poet laureate of contemporary medicine. His descriptions of people coping with and adapting to neurological conditions or injuries often illuminate the ways in which the normal brain deals with perception, memory and individuality. Sacks considers that his literary style grows out of the tradition of 19th-century clinical anecdotes, a literary style that included detailed narrative case histories. He also counts among his inspirations the case histories of the Russian neuropsychologist A. R. Luria. Sacks describes his cases with a wealth of narrative detail, concentrating on the experiences of the patient (in the case of his A Leg to Stand On, the patient was himself). The patients he describes are often able to adapt to their situation in different ways despite the fact that their neurological conditions are usually considered incurable. His most famous book, Awakenings, upon which the 1990 feature film of the same name is based, describes his experiences using the new drug L-Dopa on Beth Abraham post-encephalitic patients. Awakenings was also the subject of the first documentary made (in 1974) for the British television series Discovery. In his other books, he describes cases of Tourette syndrome and various effects of Parkinson’s disease. The title article of The Man Who Mistook His Wife for a Hat is about a man with visual agnosia and was the subject of a 1986 opera by Michael Nyman. The title article of An Anthropologist on Mars, which won a Polk Award for magazine reporting, is about Temple Grandin, an autistic professor. Seeing Voices, Sacks’ 1989 book, covers a variety of topics in deaf studies.
In November 2012 Oliver Sacks released his latest book, Hallucinations. In this work Sacks takes a look into why ordinary people can sometimes experience hallucinations and removes the stigma placed behind the word. He explains, Hallucinations don’t belong wholly to the insane. Much more commonly, they are linked to sensory deprivation, intoxication, illness or injury. Sacks writes about the not so well known phenomenon called Charles Bonnet Syndrome, which has been found to occur in elderly people who have lost their eyesight. The book has been described by Entertainment Weekly as, Elegant – An absorbing plunge into a mystery of the mind, Sacks has sometimes faced criticism in the medical and disability studies communities. During the 1970s and 1980s, his book and articles on the Awakenings patients were criticized or ignored by much of the medical establishment, on the grounds that his work was not based on the quantitative, double-blind study model. His account of abilities of autistic savants has been questioned by researcher Makoto Yamaguchi. According to Yamaguchi, Sacks’ mathematical explanations are also irrelevant.
Arthur K. Shapiro, described as the father of modern tic disorder research,referring to Sacks’ celebrity status and that his literary publications received greater publicity than Shapiro’s medical publications, said he is a much better writer than he is a clinician Howard Kushner’s A Cursing Brain?: The Histories of Tourette Syndrome, says Shapiro contrasted his own careful clinical work with Sacks’ idiosyncratic and anecdotal approach to a clinical investigation. More sustained has been the critique of his political and ethical positions. Although many characterize Sacks as a compassionate writer and doctor, others feel that he exploits his subjects. Sacks was called the man who mistook his patients for a literary career by British academic and disability-rights activist Tom Shakespeare, and one critic called his work a high-brow freak show. Such criticism was echoed by a Sacks-like caricature played by Bill Murray in the film The Royal Tenenbaums. Sacks has stated I would hope that a reading of what I write shows respect and appreciation, not any wish to expose or exhibit for the thrill but it’s a delicate business.
Since 1996 Sacks has been a member of the American Academy of Arts and Letters(Literature). In 1999 he became a Fellow of the New York Academy of Sciences. Also in 1999, he became an Honorary Fellow at The Queen’s College, Oxford. In 2002 he became Fellow of the American Academy of Arts and Sciences(Class IV – Humanities and Arts, Section 4 – Literature) and he was awarded the 2001 Lewis Thomas Prize by Rockefeller University. Sacks has been awarded honorary doctorates from the Georgetown University(1990), College of Staten Island (1991), Tufts University (1991), New York Medical College (1991), Medical College of Pennsylvania (1992), Bard College(1992), Queen’s University (Ontario) (2001), Gallaudet University (2005), University of Oxford (2005), Pontificia Universidad Cat?lica del Peru (2006), and Cold Spring Harbor Laboratory (2008). Oxford University awarded him an honorary Doctor of Civil Law degree in June 2005.
Sacks received the position Columbia Artist from Columbia University in 2007, a post that was created specifically for him. In this capacity he gains unconstrained access to the University, regardless of department or discipline. He was appointed Commander of the Order of the British Empire (CBE) in the 2008 Queen’s Birthday Honors. 84928 Oliversacks, a 2 miles (3.2 km)-diameter main-belt minor planet discovered in 2003, was named in his honor. In February 2010 Sacks was named as one of the Freedom From Religion Foundation’s Honorary Board of distinguished achievers. He has described himself as an old Jewish atheist.
Throughout his life, Sacks has suffered from a condition known as prosopagnosia or face blindness. In a December 2010 interview Sacks discussed how he had also lost his stereoscopic vision the previous year due to a malignant tumor in his right eye. He now has no vision in his right eye. His loss of stereo vision was recounted in his book The Mind’s Eye, published in October 2010. Sacks discussed his struggles with prosopagnosia in an interview with Lesley Stahl on 18 March 2012 episode of 60 Minutes. Sacks has never married or lived with anyone and says that he is celibate. In a December 2001 interview, he stated that he had not had a relationship in many years and has described his shyness as a disease. Sacks swims almost every day and has done so for decades, especially when he lived in the City Island section of the Bronx. He discussed his work and his personal health problems in 28 June 2011 BBC documentary Imagine. Sacks has also written about a near-fatal accident he had at age 41, a year after the publication of Awakenings, when he fell and broke his leg while mountaineering alone.
During his time at UCLA, Sacks lived in Topanga Canyon and experimented heavily with various drugs. He described his experiences in an article published in 2012 by The New Yorker and his 2012 book Hallucinations. Sacks describes a transformative incident he had after taking a massive dose of amphetamine, then reading a book by the 19th century migraine physician Edward Liveing (father of George Downing Liveing). Sacks claimed this experience convinced him to chronicle and publish his observations of neurological diseases and oddities, becoming the Liveing of our Time. In February 2015, writing in The New York Times, Sacks announced that he had been diagnosed with terminal cancer – multiple metastases in the liver from the ocular melanoma to which he had previously lost his vision in one eye. Measuring his remaining time in months, Sacks announced his intent to live in the richest, deepest, most productive way I can, and wrote that I want and hope in the time that remains to deepen my friendships, to say farewell to those I love, to write more, to travel if I have the strength, to achieve new levels of understanding and insight.
Photo of the younger Oliver Sacks, pulling into Greenwich Village in NYC
My Own Life: Oliver Sacks on Learning He Has Terminal Cancer
By OLIVER SACKS
19 February 2015: A MONTH ago, I felt that I was in good health, even robust health. At 81, I still swim a mile a day. But my luck has run out – a few weeks ago I learned that I have multiple metastases in the liver. Nine years ago it was discovered that I had a rare tumor of the eye, an ocular melanoma. The radiation and lasering to remove the tumor ultimately left me blind in that eye. But though ocular melanomas metastasize in perhaps 50% of cases, given the particulars of my own case, the likelihood was much smaller. I am among the unlucky ones. I feel grateful that I have been granted nine years of good health and productivity since the original diagnosis, but now I am face to face with dying. The cancer occupies a third of my liver, and though its advance may be slowed, this particular sort of cancer cannot be halted. It is up to me now to choose how to live out the months that remain to me. I have to live in the richest, deepest, most productive way I can. In this I am encouraged by the words of one of my favorite philosophers, David Hume, who, upon learning that he was mortally ill at age 65, wrote a short autobiography in a single day in April of 1776. He titled it My Own Life. I now reckon upon a speedy dissolution, he wrote. I have suffered very little pain from my disorder; and what is more strange, have, notwithstanding the great decline of my person, never suffered a moment’s abatement of my spirits. I possess the same ardor as ever in study, and the same gaiety in company.
I have been lucky enough to live past 80, and the 15 years allotted to me beyond Hume’s three score and five have been equally rich in work and love. In that time, I have published five books and completed an autobiography (rather longer than Hume’s few pages) to be published this spring; I have several other books nearly finished. Hume continued, I am a man of mild dispositions, of command of temper, of an open, social, and cheerful humor, capable of attachment, but little susceptible of enmity, and of great moderation in all my passions. Here I depart from Hume. While I have enjoyed loving relationships and friendships and have no real enmities, I cannot say (nor would anyone who knows me say) that I am a man of mild dispositions. On the contrary, I am a man of vehement disposition, with violent enthusiasms, and extreme immoderation in all my passions. And yet, one line from Hume’s essay strikes me as especially true: It is difficult, he wrote, to be more detached from life than I am at present.
Over the last few days, I have been able to see my life as from a great altitude, as a sort of landscape, and with a deepening sense of the connection of all its parts. This does not mean I am finished with life. On the contrary, I feel intensely alive, and I want and hope in the time that remains to deepen my friendships, to say farewell to those I love, to write more, to travel if I have the strength, to achieve new levels of understanding and insight. This will involve audacity, clarity and plain speaking; trying to straighten my accounts with the world. But there will be time, too, for some fun (and even some silliness, as well). I feel a sudden clear focus and perspective. There is no time for anything inessential. I must focus on myself, my work and my friends. I shall no longer look at News Hour every night. I shall no longer pay any attention to politics or arguments about global warming. This is not indifference but detachment – I still care deeply about the Middle East, about global warming, about growing inequality, but these are no longer my business; they belong to the future. I rejoice when I meet gifted young people ? even the one who biopsied and diagnosed my metastases. I feel the future is in good hands.
I have been increasingly conscious, for the last 10 years or so, of deaths among my contemporaries. My generation is on the way out, and each death I have felt as an abruption, a tearing away of part of myself. There will be no one like us when we are gone, but then there is no one like anyone else, ever. When people die, they cannot be replaced. They leave holes that cannot be filled, for it is the fate – the genetic and neural fate – of every human being to be a unique individual, to find his own path, to live his own life, to die his own death. I cannot pretend I am without fear. But my predominant feeling is one of gratitude. I have loved and been loved; I have been given much and I have given something in return; I have read and traveled and thought and written. I have had an intercourse with the world, the special intercourse of writers and readers. Above all, I have been a sentient being, a thinking animal, on this beautiful planet, and that in itself has been an enormous privilege and adventure.
Correction: February 26, 2015: Because of an editing error, Oliver Sacks’s Op-Ed essay misstated the proportion of cases in which the rare eye cancer he has – ocular melanoma – metastasizes. It is around 50%, not 2%, or only in very rare cases. When Dr. Sacks wrote, I am among the unlucky 2%, he was referring to the particulars of his case. (The likelihood of the cancer’s metastasizing is based on factors like the size and molecular features of the tumor, the patient’s age and the amount of time since the original diagnosis.)
Oliver Sacks, a professor of neurology at the New York University School of Medicine, is the author of many books, including Awakenings and The Man Who Mistook His Wife for a Hat.
A version of this op-ed appears in print on February 19, 2015, on page A25 of the New York edition with the headline: My Own Life.Sources: The New York Times; Oliver Sacks’ Website; Wikipedia
Intensive Therapy Induces Contralateral White Matter Changes In Chronic Stroke Patients With Broca’s Aphasia
Expressive aphasia is also known as Broca’s aphasia (non-fluent aphasia) is characterized by the loss of the ability to produce language (spoken or written). It is one subset of a larger family of disorders known collectively as aphasia. Expressive aphasia differs from dysarthria, which is typified by a patient’s inability to properly move the muscles of the tongue and mouth to produce speech. Expressive aphasia also differs from apraxia of speech which is a motor disorder characterized by an inability to create and sequence motor plans for speech. Comprehension is typically only mildly to moderately impaired in expressive aphasia. This contrasts with receptive aphasia, which is distinguished by a patient’s inability to comprehend language or speak with appropriately meaningful words. Expressive aphasia is caused by acquired damage to the anterior regions of the brain, including (but not limited to) the left posterior inferior frontal gyrus or inferior frontal operculum, also described as Broca’s area (Brodmann area 44 and Brodmann area 45). Expressive aphasia is also a symptom of some migraine attacks.[
Aphasia is a common and devastating consequence of stroke that results in severe communication deficits. Although the long-term prognosis for patients with aphasia who have large left hemisphere lesions is generally poor, emerging evidence suggests that verbal communication in these patients can be improved by therapy. However, deciding which treatment to administer can be difficult, and the neural processes underlying successful treatment remain poorly understood. As a result, a clinical trial, published in Brain & Language 136 (2014) 1-7, enrolled 20 patients presenting with only one ischemic stroke in the territory of the left middle cerebral artery and with moderate to severe nonfluent aphasia. All had had received several courses of traditional speech therapy prior to the study. During the study, the patients were exposed to two treatment conditions: Melodic Intonation Therapy (for the treated group) or no treatment (for the untreated group). No subject received any additional speech interventions. The treated group underwent speech and language assessments as well as diffusion tensor imaging (DTI) before and after an intensive course of Melodic Intonation Therapy. Diffusion MRI (or dMRI) is a magnetic resonance imaging (MRI) method which came into existence in the mid-1980s, which allows the mapping of the diffusion process of molecules, mainly water, in biological tissues, in vivo and non-invasively. Melodic Intonation Therapy consisted of 1.5 hours of therapy per day, 5 days per week over approximately 15 weeks, for a total of 75 sessions and at least 110 hours of therapy. The patients in the untreated group underwent the same speech and language assessments and DTI twice with a similar time-period in between scans as the treated group.
Results showed that the treated group, but not the untreated group, had reductions in fractional anisotropy in the white matter underlying the right inferior frontal gyrus (IFG, pars opercularis and pars triangularis), the right posterior superior temporal gyrus, and the right posterior cingulum. Furthermore, greater improvements were found in speech production which were associated with greater reductions in fractional anisotropy (FA) in the right IFG (pars opercularis). Thus, the study showed that an intensive rehabilitation program for patients with nonfluent aphasia led to structural changes in the right hemisphere, which correlated with improvements in speech production.
Frightening Visual Hallucinations: Atypical Presentation of Charles Bonnet Syndrome Triggered by the Black Saturday Bushfires
Charles Bonnet syndrome (CBS) is a disorder in which psychologically normal people, often with vision impairment, experience complex visual hallucinations. The hallucinations are purely visual and do not occur in any other sensory modality, and people with CBS have full insight into the unreal nature of the hallucinations. This report in the Medical Journal of Australia (2010;193:181-182), describes the case of a CBS sufferer who experienced a distressing change in the nature of her visual hallucinations following a stressful event – the Black Saturday bushfires of February 2009 in Australia.
A healthy and alert 80-year-old woman presented for an orthoptic consultation in September 2009. The patient was legally blind (i.e., her best corrected visual acuity was less than 6/60), with diagnosed age-related macular degeneration and closed-angle glaucoma. She had a known 4-year history of CBS, a condition that caused her to have complex visual hallucinations, usually triggered when she was in unfamiliar surroundings. She reported that the nature of her hallucinations had changed significantly.
Previously, the patient had experienced images such as an elephant walking down the street with a child on its back and intricate blue designs when looking at white plates or colored carpets. While the patient was aware that the images were not real, occasionally her insight was delayed if the hallucination fit into the surrounding environment. For example, she would see a truck while travelling as a passenger in a car and, upon alerting the driver that they were about to collide with the truck, would be informed that it was a letterbox by the side of the road. When the hallucinations had first appeared, the patient had thought there is something going on in my head and reported her symptoms to her husband and then to her ophthalmologist, who explained the benign nature of the disorder. Since that time, she had not been troubled by the hallucinations, explaining usually I can laugh at it. Initially, the patient’s experience with CBS followed the typical pattern – she experienced hallucinations weekly that usually lasted only for several seconds.
The patient’s hallucinations became atypical on Black Saturday, 7 February 2009, a day of intense heat and bushfires in the southern Australian state of Victoria. Bushfires raged in 14 regions across the state, resulting in 173 deaths. The patient lives in an area affected by the fires and was evacuated from her home on Black Saturday. That day and subsequently, she experienced hallucinations that were horrific in nature to her, such as seeing a prickly coat on her short-haired dog, spiral wire-like hair protruding from the heads of bald family members, and their faces beginning to melt, like wax dripping. She saw people’s legs covered with curly, black, wiry hair. Despite her visual impairment, the patient is a talented artist and has drawn her disturbing hallucinations.
The hallucinations that commenced on Black Saturday persisted for days, rather than seconds, and the images frightened the patient for the several days during which she experienced them. She reported experiencing great stress during the bushfires and also recalled earlier distressing episodes with significant fires as a child, while living in London: a chimney caught fire in her home; she witnessed the burning of the Crystal Palace in 1936; and she was present during the Blitz between September 1940 and May 1941, when London was subjected to intense aerial firebombing. She reported that these stressful episodes relating to fire increased her fear on Black Saturday and explained that fire has a particularly bad effect on me. Following discussion about CBS and her experiences, a review was not considered necessary from an orthoptic point of view, but she was encouraged to make contact as necessary if symptoms changed. She was also instructed to continue seeing her ophthalmologist and her psychologist.
This case demonstrates that a stressful life event can change the nature of hallucinations experienced in CBS, with an accompanying change in emotional experience (from non-distressing to distressing). In general, hallucinations can result from false sensory input to the brain and occur in the absence of external stimuli. When a person presents with visual hallucinations, an underlying psychiatric disorder, neurological abnormality or drug intake can be suspected. Visual hallucinations can also occur as a result of lesions in the visual system, from the cornea to the cortex. The occurrence of complex visual hallucinations, as reported in this case, was first described by Swiss philosopher, naturalist and lawyer Charles Bonnet in 1760, after whom the disorder was later named. CBS is characterized by vivid, elaborate and recurrent visual hallucinations in psychologically normal people, who have full insight into the unreal nature of the hallucinations. The hallucinations are purely visual and do not occur in any other sensory modality. Images of complex patterns and people are most common, and the hallucinations often fit into the surrounding situation. They can appear for several minutes every week, and can continue to occur for 12 months or more. Often CBS occurs upon waking, but not exclusively so.
Two theories have been proposed to explain CBS: the release and sensory deprivation theories. The release theory postulates that a lesion at any level of the visual pathway leads to the release of defective electrochemical impulses, thereby causing visual hallucinations. The sensory deprivation theory proposes a similar mechanism, except that it is reduced sensory input to the brain as a result of an ocular lesion that causes spontaneous discharge of neurons at the level of the retina or cortex. Triggers for the onset of CBS have not been clearly identified, and the circumstances the person finds themselves in at the onset of an episode can vary. It is possible that this patient suffered with acute stress disorder, as she had a past history of exposure to fire-related trauma and reported distressing recollection of the bushfires, but she did not report other symptoms of acute stress disorder. The change in nature of her hallucinations may represent interplay between CBS and an acute or post-traumatic stress disorder.
The number of cases of CBS in Australia is not known. Reticence to discuss symptoms of CBS out of fear of being labelled insane is common. Most people only tell a family member about their symptoms and very few discuss the problem with a medical professional. Further, the symptoms of CBS are probably not always recognized and therefore correctly identified. As in this patient, CBS is usually associated with vision impairment, and it is important for clinicians to be aware that these types of hallucinations may occur in patients with advancing age and early vision impairment. The prevalence of CBS in people with impaired vision has been reported to be between 10% and 40%, with a much lower prevalence in Asian populations (<1%). It is estimated that almost half a million Australians have vision impairment, and the prevalence of CBS hallucinations among these patients has been found to be 17.5%, suggesting that about 85,000 people in Australia may have CBS. However, while there is an association between CBS and loss of vision, it can also occur in individuals with no obvious ocular abnormality.
There is no treatment of proven effectiveness for CBS, but the use of selective serotonin reuptake inhibitors has been associated with a reduction in hallucinations. Sporadic reports of effective medications can be found in the literature, but no controlled clinical trials have been published. Some sufferers indicate that closing their eyes or blinking may make the hallucinations stop.
Moving Toward a National Medical Device Postmarket Surveillance System
Despite rigorous premarket evaluation, what really counts is how well a medical device works when it’s used day-to-day by patients, caregivers and clinicians. Beyond clinical trials, real-life patient experience may reveal unanticipated device risks and confirm long-term benefits. Similar to other medical products such as drugs or vaccines, medical devices offer vital, sometimes life-saving, benefits, but they must be balanced against certain risks. A strong postmarket surveillance system can provide more robust and timely benefit-risk profiles for devices so that providers and patients can make better informed health care decisions.
In 2012, CDRH laid out a strategy to strengthen the nation’s postmarket surveillance system for devices. As described in that strategy, FDA’s vision for medical device postmarket surveillance consisted of a national system that quickly identifies poorly performing devices, accurately characterizes and disseminates risk and benefit information about real-world device performance, and efficiently generates data to help support premarket clearance or approval of new devices and new uses of currently marketed devices.
Achieving this vision for a national system requires thoughtful input and active participation from many key national and international stakeholders. In 2013, after receiving public input on the 2012 strategy, FDA published an update that described the five major steps the FDA would take to create a National Medical Device Postmarket Surveillance System (MDS) including:
(1) Establish a multi-stakeholder Medical Device Postmarket Surveillance System Planning Board to identify the governance structure, practices, policies, procedures, methods and business model(s) necessary to facilitate the creation of a sustainable, integrated medical device postmarket surveillance system.
(2) Establish a unique device identification (UDI) system and promote its incorporation into electronic health information.
(3) Promote the development of national and international device registries for selected products.
(4) Modernize adverse event reporting and analysis.
(5) Develop and use new methods for evidence generation, synthesis, and appraisal.
FDA has begun implementing the UDI rule, including development of a Global UDI Database (GUDID) as the repository for information that unambiguously identifies devices through their distribution and use. FDA has continued to build registry capabilities both domestically (such as the National Breast Implant Registry) and internationally (such as the International Consortium of Vascular Registries). FDA has also established a Medical Device Registry Task Force consisting of key registry stakeholders under CDRH’s Medical Device Epidemiology Network (MDEpiNet) Program. Importantly, we also commissioned the Engelberg Center for Health Care Reform at the Brookings Institution to convene and oversee deliberations of the Medical Device Postmarket Surveillance System Planning Board.
FDA has announcd the release of the Planning Board’s report Strengthening Patient Care: Building an Effective National Medical Device Surveillance System, which outlines recommended steps toward achieving the MDS and strategies for implementation. The report provides a pathway to realizing a national system that harnesses novel data sources, modern analytical techniques and the participation of all stakeholders to optimize patient care. Interested stakeholders will be able to share their feedback on the report through a public docket. In the coming months, FDA will also get reports from the Medical Device Registry Task Force. As noted in the 2013 Update, these reports will address significant issues such as defining effective registry governance and data quality practices, which will enrich the national dialogue on development of registries as a crucial source of data on device performance.
FDA’s vision of a National Medical Device Postmarket Surveillance System is a 21st Century solution to an age-old problem. The system relies on the experience gained by health care providers in their daily use of medical devices leveraged by modern technology. This experience, made possible by new tools and systems unimaginable a generation ago, provides real-time data about what happens to patients in clinical practice. FDA will be able to leverage these capabilities not only to quickly identify poorly performing devices, but also to facilitate device approval/clearance and patient access, to reduce postmarket data collection for manufacturers, and to better inform healthcare decisions by providers and patients alike. FDA is looking forward to overcome the challenges and embracing the opportunities that lie ahead, and is optimistic that with the engagement of the public and private sectors, FDA can collectively build a medical device postmarket surveillance system that will achieve all of the goals.
Baked Halibut, with Ginger/Carrot/Squash/Potato Sauce, Topped with Maple Cashews
1.5 pound (approx) of butternut squash
2 fresh halibut fillets (for 2 people, approx 8 oz each)
2 or 3 carrots, peeled and cut into 1 inch pieces
1 sweet potato, cleaned, peeled and cut into large pieces
3 cups chicken stock or 2 cans broth
1 Tablespoon Splenda
1 Tablespoon Agave
Pinch kosher salt, plus more to taste
1/4 cup olive oil or coconut oil
1/2 to 1 container Tofutti
1 Tablespoon fresh ginger, finely grated
2 small garlic cloves, minced
1 teaspoon (Mega Foods) turmeric with black pepper
1 Pinch chili flakes (optional)
1/2 teaspoon ground cinnamon
Zest of 1 orange (do this before juicing)
1/3 cup fresh orange juice (might take 2 whole oranges)
Pinch black pepper (optional-grind to taste)
2 cups unsalted cashews (use garnish recipe below)
Get all the ingredients together – ©Joyce Hays, Target Health Inc.
Clean the halibut and put in an oiled baking dish – ©Joyce Hays, Target Health Inc.
Make the cashew recipe first and set aside (see below)
Preheat oven to 350 degrees
Clean the veggies. Cut into large pieces
Combine the carrots, parsnips, butternut squash, sweet potato, broth, Splenda, and salt in a 4-qt. saucepan over medium heat; bring to a simmer, cover, and cook until the veggies are tender, 20 minutes. Drain the veggies, reserving the 1/4 cup of cooking liquid.
After cooking, drain the veggies, reserving 1/4 cup of the liquid. ©Joyce Hays, Target Health Inc.
1. Heat oil in a 2-qt. saucepan over medium-low heat. Add the ginger and garlic and cook, stirring frequently, until softened and fragrant, about 2-3 minutes.
2. Remove from heat and place in a food processor along with veggies, Agave, pinch chili flakes and orange juice; pur?e until smooth, scraping down the sides of the bowl as necessary.
3. Add 1-2 tbsp. reserved cooking liquid to make a smooth puree.
Put drained veggies, garlic and ginger in food processer and pulse. Add the saved veggie liquid a little at a time and pulse again until you get a smooth pureed sauce for the halibut. ©Joyce Hays, Target Health Inc.
4. Oil your baking dish and put the cleaned fish in
Pour the sauce over the halibut and bake, covered, for about 20 minutes. Use a covered baking dish or cover with foil. – ©Joyce Hays, Target Health Inc.
5. Cover the halibut with the sauce and bake in covered baking dish, in (350 degree) oven for 15 to 20 minutes.
6. Just before serving the fish, garnish with the roasted maple cashews
7. Serve topped with the maple roasted cashews if desired.
Recipe for Maple Cashews Roasted (Garnish)
2 cups cashews
2-3 Tablespoons pure maple syrup
2 Tablespoons coconut oil
1/2 teaspoon kosher sea salt (optional)
Preheat oven to 350F. Line a shallow, rimmed baking dish with parchment paper.
In a medium-size mixing bowl, stir together the nuts, syrup, sugar and salt until the nuts are well-coated.
Spread the nuts on the baking sheet and roast for 15 minutes, stirring twice during the process to avoid burning.
Allow the nuts to cool if you want to chop them up a bit; otherwise, sprinkle over fish and serve
Baked halibut with the ginger/carrot sauce and baked mini potatoes ©Joyce Hays, Target Health Inc.
We started this meal with chilled Te Koko sauvignon and a tomato avocado salad with lemon/oil dressing. This was followed with the baked halibut with orange/carrot/ginger sauce and crispy baked maple cashews. Also some left-over cauliflower with soy topping and garlic broccoli. Dessert was a combination of various fresh citrus fruit, grapes and blueberries.
This weekend we saw at the MetOpera a first production for the Met and for us, La Donna del Largo. This quickly became for me (not sure if Jules would agree) my favorite Rossini opera. I know everyone loves Gioachino Rossini’s Marriage of Figaro and we do too, but I like La Donna del Largo much better because there is one glorious aria after another. This particular production, had four magnificent voices: the well known tenor, Juan Diego Flores, was in his usual fine form with many high notes; the soprano who often sings with Flores, Joyce DiDonato did not disappoint with her beautiful trills. But the big surprises were a new tenor, winner of a MetOpera competition, John Osborn with a gorgeous full voice and many high notes and last but not least, mezzo-soprano from Trieste, Daniela Barcellona, who sang the role of a man, with such a magnificent voice of velvet, we definitely want to hear her again. This was the kind of Saturday we love the best. We walked out of the Met, on a cloud. When we entered one of our favorite restaurants, the Maitre D’ (who happens to be from Italy) asked why I was shining. He understood when I told him that beautiful music does that to me. Of course when he heard Rossini he nodded his head.
Life was good for us this weekend
New Zealand, Te Koko is one of the best sauvignon blancs around. – ©Joyce Hays, Target Health Inc.
From Our Table to Yours!
The work by Dr. Michael Kesden, assistant professor of physics at UT Dallas, and his colleagues provides for the first time solutions to decades-old equations that describe conditions as two black holes in a binary system orbit each other and spiral in toward a collision.
The research is available online and in the Feb. 27 issue of the journal Physical Review Letters.
Kesden said the solutions should significantly impact not only the study of black holes, but also the search for gravitational waves in the cosmos. Albert Einstein’s general theory of relativity predicts that two massive objects orbiting in a binary system should move closer together as the system emits a type of radiation called gravitational waves.
“An accelerating charge, like an electron, produces electromagnetic radiation, including visible light waves. Similarly, any time you have an accelerating mass, you can produce gravitational waves,” Kesden said.
“The energy lost to gravitational waves causes the black holes to spiral closer and closer together until they merge, which is the most energetic event in the universe,” he said. “That energy, rather than going out as visible light, which is easy to see, goes out as gravitational waves, which are very weak and much more difficult to detect.”
While Einstein’s theories predict the existence of gravitational waves, they have not been directly detected. But the ability to “see” gravitational waves would open up a new window to view and study the universe.
Optical telescopes can capture photos of visible objects, such as stars and planets, and radio and infrared telescopes can reveal additional information about invisible energetic events. Gravitational waves would provide yet another medium through which to examine astrophysical phenomena, Kesden said.
“Using gravitational waves as an observational tool, you could learn about the characteristics of the black holes that were emitting those waves billions of years ago, information such as their masses and mass ratios,” he said. “That’s important data for more fully understanding the evolution and nature of the universe.”
This year, a large-scale physics experiment called the Laser Interferometer Gravitational-Wave Observatory (LIGO) aims to be the first to directly detect gravitational waves. LIGO is the largest project funded by the National Science Foundation.
“The equations that we solved will help predict the characteristics of the gravitational waves that LIGO would expect to see from binary black hole mergers,” Kesden said. “We’re looking forward to comparing our solutions to the data that LIGO collects.”
The equations Kesden solved deal specifically with the spin angular momentum of binary black holes and a phenomenon called precession.
Angular momentum is a measure of the amount of rotation a spinning object has. Spin angular momentum includes the rotation’s speed and the direction in which that spin points. For a simple object like a spinning figure skater, the direction of angular momentum would point up.
Another type of angular momentum, called orbital angular momentum, applies to a system in which objects are in orbit about one another. Orbital angular momentum also has a magnitude and a direction.
In an astrophysical setting like a binary black hole system, the directions of the individual types of angular momenta change, or precess, over time.
“In these systems, you have three angular momenta, all changing direction with respect to the plane of the orbit — the two spin angular momenta and the one orbital angular momentum,” Kesden said. “The solutions that we now have describe the orientations of the precessing black hole spins.”
In addition to solving existing equations, Kesden also derived equations that will allow scientists to statistically track spin precession from black hole formation to merger far more efficiently and quickly.
“We can do it millions of times faster than was previously possible,” he said. “With these solutions, we can create computer simulations that follow black hole evolution over billions of years. A simulation that previously would have taken years can now be done in seconds. But it’s not just faster. There are things that we can learn from these simulations that we just couldn’t learn any other way.”
Researchers from the University of Cambridge, the Rochester Institute of Technology and the University of Mississippi also contributed to the Physical Review Letterspaper. The researchers were supported in part by the National Science Foundation and UT Dallas.
- Michael Kesden, Davide Gerosa, Richard O’Shaughnessy, Emanuele Berti, Ulrich Sperhake. Effective Potentials and Morphological Transitions for Binary Black Hole Spin Precession. Physical Review Letters, 2015; 114 (8) DOI:10.1103/PhysRevLett.114.081103
University of Texas at Dallas. “New insight found in black hole collisions.” ScienceDaily. ScienceDaily, 26 February 2015. <www.sciencedaily.com/releases/2015/02/150226110448.htm>.
Unlike other chemicals, agricultural pesticides are intentionally applied to the environment to help farmers control insects, weeds and other potentially harmful pests threatening agricultural production. They can therefore affect land ecosystems but also surface waters from runoff. According to estimates, ca. 4 million tons of agricultural pesticides are applied annually, equating to an average of 0.27 kilograms per hectare of the global land surface. “We know from earlier investigations for example that pesticides can reduce the biodiversity of invertebrates in freshwater ecosystems by up to 42 percent and that we can expect an increased application of pesticides as a result of climate change,” explains Prof. Dr. Matthias Liess from the UFZ, who was recently appointed to a term of five years on the scientific advisory board “National Action Plan on Sustainable Use of Plant Protection Products” where he advises the Federal Ministry of Food and Agriculture. Liess warns of an increase in the application of pesticides in many developing countries as farmers increasingly switch from traditionally extensive agricultural practices to more intensive ones. Until now the global extent of the potential water pollution from the application of insecticides has remained largely unknown.
The international team of scientists therefore came up with a global model with a raster of ca. ten kilometres, into which agricultural data from FAO and land use data from NASA among other data were entered. Annual average temperatures and monthly maximum precipitation measurements from around 77,000 weather stations were also taken into account. Following that, the researchers then estimated the so-called runoff potential (RP), in other words the amount of insecticides that enters streams and rivers through the rainwater from agricultural land. “In this respect, daily rainfall intensity, terrain slope, and insecticide application rate play an equally important role as well as the crops cultivated,” explains junior professor Dr. Ralf B. Schäfer from the University of Koblenz-Landau. “In order to test such complex models, we therefore carried out control measurements of insecticide contamination in freshwater ecosystems from four different regions.”
Several world maps were produced: the vulnerability map only takes into account the geographic and climatic background. The risk map on the other hand shows the risks from this natural vulnerability through anthropogenic land use. In Central Europe, scientists largely assessed the risk for water bodies as medium to high. In the northern hemisphere, insecticide runoff presented an overall more significant latitudinal gradient. “The risks of insecticide exposure to water bodies increased significantly the further South one travelled on a North-South gradient in Europe, North America and Asia, mainly driven by a higher insecticide application rate as a result of higher average temperatures,” Dr. Mira Kattwinkel reports, who is now conducting research at the Swiss Federal Institute of Aquatic Science and Technology (Eawag). Because the economy and the population are growing rapidly in many countries of the southern hemisphere, scientists expect a higher insecticide application rate in those countries in the future to cover an increase in agricultural production. The map could therefore still change colour considerably in other parts of the world. At the moment it is water bodies in the Mediterranean, the USA, Central America and Southeast Asia that are particularly vulnerable.
In Southeast Asia, countries such as the Philippines or Vietnam are greatly affected for example. UFZ researchers are looking into solutions for such regions within the framework of the LEGATO-project together with the International Rice Research Institute (IRRI), in an attempt to reduce pesticide application rates. One approach for example could be to revitalise the functioning of ecosystems so that the natural competitors of rice pests can help to avoid their mass reproduction and subsequent harvest yield losses.
“Our analysis provides a global map of hotspots for insecticide contamination that are a major risk for biodiversity in water bodies. To our knowledge this is the first study that assesses insecticide contamination of water bodies on a global scale,” Prof. Dr. Matthias Liess summarizes the significance of the new investigation. The researchers intend to use the global map to sensitize citizens and authorities about this issue in vulnerable regions and to incite local investigations. Buffer zones along the edge of water bodies can significantly reduce negative impacts for example. Efficient environmental management and conservation efforts in the future should focus on informing authorities and farmers about the costs, impacts and alternatives. Ultimately, mitigation and management takes place at the local level, determining the extent to which a water body will be affected under the application of such chemicals.
- Alessio Ippolito, Mira Kattwinkel, Jes J. Rasmussen, Ralf B. Schäfer, Riccardo Fornaroli, Matthias Liess. Modeling global distribution of agricultural insecticides in surface waters. Environmental Pollution, 2015; 198: 54 DOI:10.1016/j.envpol.2014.12.016
- J.H. Spangenberg, J.-M. Douguet, J. Settele, K.L. Heong. Escaping the lock-in of continuous insecticide spraying in rice: Developing an integrated ecological and socio-political DPSIR analysis. Ecological Modelling, 2015; 295: 188 DOI:10.1016/j.ecolmodel.2014.05.010
Helmholtz Centre For Environmental Research – UFZ. “Agricultural insecticides pose a global risk to surface water bodies, researchers find.” ScienceDaily. ScienceDaily, 25 February 2015. <www.sciencedaily.com/releases/2015/02/150225082836.htm>.