Category Archives: Behavior

A little smile may make you less depressed – Botox and depression treatment



Converging lines of evidence suggest a role for facial expressions in the pathophysiology and treatment of mood disorders. To determine the antidepressant effect of onabotulinumtoxinA (OBA) treatment of corrugator and procerus muscles in people with major depressive disorder, we conducted a double blind, randomized, placebo-controlled trial. In an outpatient clinical research center, eighty-five subjects with DSM-IV major depression were randomized to receive either OBA (29 units for females and 40 units for males) or saline injections into corrugator and procerus frown muscles (74 subjects were entered into the analysis). Subjects were rated at screening, and 3 and 6 weeks after OBA treatment. The primary outcome measure was the response rate, as defined by ! 50% decrease in score on the MontgomeryeAsberg Depression Rating Scale (MADRS). Response rates at 6 weeks from the date of injection were 52% and 15% in the OBA and placebo groups, respectively (Chi-Square (1) ¼ 11.2, p < 0.001, Fisher p < 0.001). The secondary outcome measure of remission rate (MADRS score of 10 or less) was 27% with OBA and 7% with placebo (Chi-square (1) ¼ 5.1, p < 0.02, Fisher p < 0.03). Six weeks after a single treatment, MADRS scores of subjects were reduced on average by 47% in those given OBA, and by 21% in those given placebo (ManneWhitney U, p < 0.0005). In conclusion, a single treatment with OBA to the corrugator and procerus muscles appears to induce a significant and sustained antidepressant effect in patients with major depression.


We develop the concept of emotional proprioception, whereby the muscles of facial expression play a central role in encoding and transmitting information to the brain’s emotional circuitry, and describe its underlying neuroanatomy. We explore the role of facial expression in both reflecting and influencing depressed mood. The circuitry involved in this latter effect is a logical target for treatment with botulinum toxin, and we review the evidence in support of this strategy. Clinical trial data suggest that botulinum toxin is effective in treating depression. We discuss the clinical and theoretical implications of these data. This novel treatment approach is just one example of the potential importance of the cranial nerves in the treatment of depression.



Chronic migraine affects 2% of the population. It results in substantial disability and reduced quality of life. Medications used for prophylaxis in episodic migraine may also work in chronic migraine. The efficacy and safety of OnabotulinumtoxinA (BOTOX) in adults with chronic migraine was confirmed in the PREEMPT programme. However, there are few real-life data of its use.

Method: 254 adults with chronic migraine were injected with OnabotulinumtoxinA BOTOX as per PREEMPT Protocol between July 2010 and May 2013, their headache data were collected using the Hull headache diary and analysed to look for headache, migraine days decrements, crystal clear days increment in the month post treatment, we looked at the 50% responder rate as well.

Results: Our prospective analysis shows that OnabotulinumtoxinA, significantly, reduced the number of headache and migraine days, and increased the number of headache free days. OnabotulinumtoxinA Botox also improved patients’ quality of life. We believe that these results represent the largest post-marketing cohort of patients treated with OnabotulinumtoxinA in the real-life clinical setting.

 Conclusion: OnabotulinumtoxinA is a valuable addition to current treatment options in patients with chronic migraine. Our results support findings of PREEMPT study in a large cohort of patients, we believe, is representative of the patients seen in an average tertiary headache centre. While it can be used as a first line prophylaxis its cost may restrict its use to more refractory patients who failed three oral preventive treatments < Website promoting botox use for depression


Cereve Sleep system for Insomnia – launches in 2017

Patients with insomnia, the frontal cortex stays active, preventing them from getting deeper, more restorative sleep. These patients often describe a “racing mind” that interferes with getting a sound sleep.

FDA Approves New Device for Insomnia

Gently cooling the forehead within a precise, clinically proven therapeutic range reduced this activity in the frontal cortex. The new software-controlled bedside device cools and pumps fluid to a forehead pad that is worn throughout the night. Three clinical studies that included more than 230 patients over 3800 research nights demonstrated the safety and efficacy of the device. In one of these — a randomized, placebo-controlled trial of people with primary insomnia at seven clinical sites across the United States — results from polysomnographic sleep measurements showed a statistically significant reduction in latency to stage 1 sleep, the time taken to get into the first stage of sleep, as well as latency to stage 2 sleep.

Cereve FDA product for sleep

This is the first and only insomnia device cleared to reduce sleep latency to stage 1, the first stage of sleep, as well as stage 2, a stage of sleep that typically represents over 50% of the sleep period.

Blue light and cognition

Exposure to blue wavelength light, which is similar to the kind of light that we get on a bright sunny day, can improve attention and alertness during the day as well as at night. A study at  SLEEP 2016: 30th Anniversary Meeting of the Associated Professional Sleep Societies (lead author Anna Alkozei, PhD, postdoctoral fellow in the Department of Psychiatry, University of Arizona)  found that thirty minutes of exposure to blue wavelength light during the day, in comparison to an amber light exposure led to subsequently faster reaction times on a cognitive task forty minutes after the light exposure had already ended. Participants who were exposed to blue light also showed more efficient responding, which means they answered more items correctly per second, than individuals who were exposed to amber placebo light. Finally, we also found that individuals who were exposed to blue light showed greater activation within the prefrontal cortex when performing the task, an area necessary for optimal cognitive performance, than individuals who were exposed to amber light. While previous studies have shown that blue light exposure can affect attention and alertness during the period of exposure, the findings add to this research by showing that the effects of blue light exposure can have a lasting effect on brain function and performance on cognitive tasks over half an hour after the light exposure had ended. In addition, it was found that while blue light exposure led to faster response times, individuals did not sacrifice accuracy for speed. This means, we might be able to use blue light in order to increase our alertness before having to engage in cognitive processes that require quick and accurate decision-making, such as testing or interview situations. Blue light has recently also been used in situations where natural sunlight does not exist, such as the International Space Station.

Exposure to Blue Wavelength Light is Associated with Increased Dorsolateral Prefrontal Cortex Responses, and Increases in Response times During a Working Memory Task.
SLEEP 2016
Abstract ID: 0072
Presentation Date: (Poster) Sunday, June 12 and (Oral) Wednesday, June 15

The study included 35 healthy adults (18 female; mean age, 21 years). They were randomly assigned to a 30-minute exposure of blue-wavelength light using the Philips goLITE BLU Energy Light device (λ = 469 nm) or amber (placebo) light, immediately followed by a working memory task (N-Back task) during functional MRI. All exposure was completed in the morning after a normal night of sleep. With increases in cognitive load, the blue-light group had faster reaction times (P = .04) and more efficient responding (ie, they answered more items correctly per second; P = .01). These findings are important as they link the acute behavioral effects of blue light to enhanced activation of key cortical systems involved in cognition and mental control. Considering a wide range of research has shown that exposure to blue light during the day and at night leads to increases in alertness during the period of exposure, it could be used as a nonpharmacological way to improve attention in situations where alertness and quick decision-making are important. The melanopsin receptors that are providing light information to the circadian system is most sensitive to blue light, so it’s never going to be surprising that blue light has a strong effect on biological rhythms.


Blue light and cognitive performance

Blue light and cognitive performance

Light and Time: The Discovery of a New Photoreceptor System within the Eye


One hundred and fifty years of research had explained how we see: Light is detected by the rods and cones and their graded potentials are assembled into an image by inner retinal neurones, which then trigger the retinal ganglion cells whose axons form the optic nerve, and after layers of neuronal processing, an image is created in the visual cortex. This representation of the eye left no room for an additional class of ocular photoreceptor. However, two parallel lines of investigation, one in fish and the other in rodents, overturned this conventional view of the eye. We now know that the rods and cones are not the only photosensory neurones of the vertebrate eye, and this discovery in humans is having a major impact on clinical ophthalmology.

Fish lead the way

The discovery of the VA-opsin gene family in fish led to the demonstration in 1998 that a sub-set of inner retinal horizontal and ganglion cells are directly light sensitive. These results provided the first unambiguous evidence for a non-rod, non-cone photoreceptor within the eye of any vertebrate and the vital “proof of principle” supporting a growing body of evidence that the mammalian eye might also contain such photoreceptors.

A curious finding in mammals?

A long-standing question had been how circadian rhythms (24h body clocks) of mammals are regulated by light. Puzzling results from a range of animal models with genetic defects of the eye showed that visual blindness and loss of most (but not all) of the rods and cones did not alter the ability of the 24h circadian clock to align (entrain) to the light and dark of dawn and dusk. Eye loss in these mice would completely block these responses to light. Although these results were consistent with the possibility that mammals might possess another light sensor within the eye, these initial studies could not preclude the alternative explanation that only a very small number of rods and/or cones mediate these effects of light. Indeed, as this author experienced, there was huge and hostile resistance initially to the very notion of non-rod, non-cone photoreceptors within the mammalian eye.

Mammals also possess novel photoreceptors

This ambiguity led to the development of a genetically-engineered mouse model entirely lacking rods and cones (rd/rd cl), and the demonstration around the turn of the century that a broad range of responses to light including the regulation of circadian rhythms, hormonal rhythms and pupil constriction all occur in the absence of the rods and cones. There had to be another photoreceptor – but what was it? Over the next five years researchers using the rd/rd cl mouse, rats, and the macaque monkey, showed that the eye contains a small number of directly light-sensitive retinal ganglion cells (pRGCs) that utilize the photopigment melanopsin (OPN4) which is maximally sensitive to blue light (λmax ~ 480nm). So, unlike fish, mammals don’t have VA opsin but another new photopigment molecule – melanopsin. However, now we know that fish have both VA opsin and melanopsin photopigments within the eye, and that most if not all the cells in the inner retina (horizontal, bipolar, amacrine and ganglion cells) can detect light!

Humans are like mice

Studies in two profoundly blind subjects with genetic diseases of the eye, and lacking functional rods and cones showed that we also have pRGC photoreceptors maximally sensitive in the blue part of the spectrum. Like mice these cells not only regulate the body clock but also sleep and pupil constriction. And remarkably, seem to provide us with a subconscious “awareness” of light. These basic findings in animal models and most recently humans are now informing clinical ophthalmology and the advice given to patients with eye diseases.

Ophthalmology has become more complicated

Until recently, body clocks and sleep timing were rarely addressed in ophthalmology and specific guidelines relating to sleep disturbance in ocular disease are lacking. It is important to stress that sleep disruption is much more than the frustration of feeling sleepy at an inappropriate time. The sustained disruption of sleep is closely linked to the added susceptibility of a range of health problems, including cognitive decline, depression and attentional failures. Thus, ocular disease not only causes visual loss but has the potential to inflict multiple additional health problems. For example, people with eye diseases of the inner retina, which result in retinal ganglion cell death (e.g. glaucoma), are at particular risk of circadian rhythm and sleep disruption. Furthermore, individuals lacking eyes entirely because of trauma will have no ability to regulate their biological rhythms. Such individuals should receive counselling regarding the problems of sleep disruption, and would be strong candidates for treatment with appropriately timed medications that help consolidate sleep timing. By contrast, eye diseases associated with rod and cone photoreceptor death need not result in the loss of pRGC photoreception. In these cases individuals should be encouraged where possible to expose their eyes to sufficient day-time light to maintain normal circadian regulation and sleep-wake timing.

Global Implications for Health

The World Health Organization suggests that at any one time worldwide 49 million people will have vision loss and over 270 million severe sight problems. There are also about 250 million people with visual impairment; it is very likely that many of these individuals could benefit from an understanding of how their visual blindness might be affecting their pRGC system, and by extension their biological rhythms of sleep and allied physiology. Unfortunately, few people worldwide are even aware of this new light sensing system and the important role it plays in regulating our physiology and behavior.

Blue light systems in eye

Philips goLITE BLU Rechargeable Energy Light HF3429/60

Philips goLITE BLU HF3429 Energy light