Temporal Processing in the Olfactory System: Can We See a Smell?

Sensory processing circuits in the visual and olfactory systems receive input from complex, rapidly changing environments. Although patterns of light and plumes of odor create different distributions of activity in the retina and olfactory bulb, both structures use what appears on the surface similar temporal coding strategies to convey information to higher areas in the brain. We compare temporal coding in the early stages of the olfactory and visual systems, highlighting recent progress in understanding the role of time in olfactory coding during active sensing by behaving animals. We also examine studies that address the divergent circuit mechanisms that generate temporal codes in the two systems, and find that they provide physiological information directly related to functional questions raised by neuroanatomical studies of Ramon y Cajal over a century ago. Consideration of differences in neural activity in sensory systems contributes to generating new approaches to understand signal processing.

For combat veterans suffering from post-traumatic stress disorder, ‘fear circuitry’ in the brain never rests

Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or under-react in response to stressful tasks, such as recalling a traumatic event or reacting to a photo of a threatening face. Now, researchers at NYU School of Medicine have explored for the first time what happens in the brains of combat veterans with PTSD in the absence of external triggers.

Their results, published in Neuroscience Letters, and presented today at the annual meeting of the American Psychiatry Association in San Francisco, show that the effects of trauma persist in certain brain regions even when combat veterans are not engaged in cognitive or emotional tasks, and face no immediate external threats. The findings shed light on which areas of the brain provoke traumatic symptoms and represent a critical step toward better diagnostics and treatments for PTSD.

A chronic condition that develops after trauma, PTSD can plague victims with disturbing memories, flashbacks, nightmares and emotional instability. Among the 1.7 million men and women who have served in the wars in Iraq and Afghanistan, an estimated 20% have PTSD. Research shows that suicide risk is higher in veterans with PTSD. Tragically, more soldiers committed suicide in 2012 than the number of soldiers who were killed in combat in Afghanistan that year.

"It is critical to have an objective test to confirm PTSD diagnosis as self reports can be unreliable," says co-author Charles Marmar, MD, the Lucius N. Littauer Professor of Psychiatry and chair of NYU Langone’s Department of Psychiatry. Dr. Marmar, a nationally recognized expert on trauma and stress among veterans, heads The Steven and Alexandra Cohen Veterans Center for the Study of Post-Traumatic Stress and Traumatic Brain Injury at NYU Langone Medical Center.

The study, led by Xiaodan Yan, a research fellow at NYU School of Medicine, examined “spontaneous” or “resting” brain activity in 104 veterans of combat from the Iraq and Afghanistan wars using functional MRI, which measures blood-oxygen levels in the brain. The researchers found that spontaneous brain activity in the amygdala, a key structure in the brain’s “fear circuitry” that processes fearful and anxious emotions, was significantly higher in the 52 combat veterans with PTSD than in the 52 combat veterans without PTSD. The PTSD group also showed elevated brain activity in the anterior insula, a brain region that regulates sensitivity to pain and negative emotions.

Moreover, the PTSD group had lower activity in the precuneus, a structure tucked between the brain’s two hemispheres that helps integrate information from the past and future, especially when the mind is wandering or disengaged from active thought. Decreased activity in the precuneus correlates with more severe “re-experiencing” symptoms—that is, when victims re-experience trauma over and over again through flashbacks, nightmares and frightening thoughts.

Individuals who drink heavily and smoke may show ‘early aging’ of the brain

• Alcohol treatment interventions work best when patients understand and are actively involved in the process.
• A first-of-its-kind study looks at the interactive effects of smoking status and age on neurocognition in one-month-abstinent alcohol dependent (AD) individuals in treatment.
• Results show that AD individuals who currently smoke have more problems with memory, ability to think quickly and efficiently, and problem-solving skills than those who do not smoke, effects which seem to become greater with increasing age.

Treatment for alcohol use disorders works best if the patient actively understands and incorporates the interventions provided in the clinic. Multiple factors can influence both the type and degree of neurocognitive abnormalities found during early abstinence, including chronic cigarette smoking and increasing age. A new study is the first to look at the interactive effects of smoking status and age on neurocognition in treatment-seeking alcohol dependent (AD) individuals. Findings show that AD individuals who currently smoke show more problems with memory, ability to think quickly and efficiently, and problem-solving skills than those who don’t smoke, effects which seem to become exacerbated with age.

Results will be published in the October 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Several factors – nutrition, exercise, comorbid medical conditions such as hypertension and diabetes, psychiatric conditions such as depressive disorders and post-traumatic stress disorder, and genetic predispositions – may also influence cognitive functioning during early abstinence," explained Timothy C. Durazzo, assistant professor in the department of radiology and biomedical imaging at the University of California San Francisco, and corresponding author for the study. "We focused on the effects of chronic cigarette smoking and increasing age on cognition because previous research suggested that each has independent, adverse affects on multiple aspects of cognition and brain biology in people with and without alcohol use disorders. This previous research also indicated that the adverse effects of smoking on the brain accumulate over time. Therefore, we predicted that AD, active chronic smokers would show the greatest decline in cognitive abilities with increasing age."

"The independent and interactive effects of smoking and other drug use on cognitive functioning among individuals with AD are largely unknown," added Alecia Dager, associate research scientist in the department of psychiatry at Yale University. "This is problematic because many heavy drinkers also smoke. Furthermore, in treatment programs for alcoholism, the issue of smoking may be largely ignored. This study provides evidence of greater cognitive difficulties in alcoholics who also smoke, which could offer important insights for treatment programs. First, individuals with AD who also smoke may have more difficulty remembering, integrating, and implementing treatment strategies. Second, there are clear benefits for thinking skills as a result of quitting both substances."

Durazzo and his colleagues compared the neurocognitive functioning of four groups of participants, all between the ages of 26 and 71 years of age: never-smoking healthy individuals or “controls” (n=39); and one-month abstinent, treatment-seeking AD individuals, who were never-smokers (n = 30), former-smokers (n = 21) and active-smokers (n = 68). Evaluated cognitive abilities included cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions, and working memory.

"We found that, at one month of abstinence, actively smoking AD [individuals] had greater-than-normal age effects on measures of learning, memory, processing speed, reasoning and problem-solving, and fine motor skills," said Durazzo. "AD never-smokers and former-smokers showed equivalent changes on all measures with increasing age as the never-smoking controls. These results indicate the combination of alcohol dependence and active chronic smoking was related to an abnormal decline in multiple cognitive functions with increasing age."

"These results indicate the combined effects of these drugs are especially harmful and become even more apparent in older age," said Dager. "In general, people show cognitive decline in older age. However, it seems that years of combined alcohol and cigarette use exacerbate this process, contributing to an even greater decline in thinking skills in later years."

Durazzo agreed. “Chronic cigarette smoking, excessive alcohol consumption, and increasing age are all associated with increased oxidative damage to brain tissue,” he said. “Oxidative damage results from increased levels of free radicals and other compounds that directly injure neurons and other cells that make up the brain. Cigarette smoking and excessive alcohol consumption expose the brain to a tremendous amount of free radicals. We hypothesize that chronic, long-term exposure to cigarette smoke and excessive alcohol consumption interacts with the normal aging process to produce greater neurocognitive decline in the active-smoking AD group.”

Cigarette smoking is a “modifiable health risk” that is directly associated with at least 440,000 deaths every year in the United States, Durazzo noted. “Chronic smoking, and to a lesser extent, alcohol use disorders are also associated with an increased risk for Alzheimer’s disease,” he said. “So, the combination of these modifiable health risks may place an individual at even greater risk for development of Alzheimer’s disease. Given the above, in conjunction with the findings from our cognitive and neuroimaging research, we completely support programs that routinely offer smoking cessation programs to all individuals seeking treatment for alcohol/substance abuse disorders.”

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

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

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.

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?

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.

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.

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

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

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

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

Turning off tremors

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

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

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

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.

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.

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

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.

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

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.

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.

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

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

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.

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

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.

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.

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.

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

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.

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

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.

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.

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.

Bach to the blues, our emotions match music to colors

Whether we’re listening to Bach or the blues, our brains are wired to make music-color connections depending on how the melodies make us feel, according to new research from the University of California, Berkeley. For instance, Mozart’s jaunty Flute Concerto No. 1 in G major is most often associated with bright yellow and orange, whereas his dour Requiem in D minor is more likely to be linked to dark, bluish gray.

Moreover, people in both the United States and Mexico linked the same pieces of classical orchestral music with the same colors. This suggests that humans share a common emotional palette – when it comes to music and color – that appears to be intuitive and can cross cultural barriers, UC Berkeley researchers said.

“The results were remarkably strong and consistent across individuals and cultures and clearly pointed to the powerful role that emotions play in how the human brain maps from hearing music to seeing colors,” said UC Berkeley vision scientist Stephen Palmer, lead author of a paper published this week in the journal Proceedings of the National Academy of Sciences.

Using a 37-color palette, the UC Berkeley study found that people tend to pair faster-paced music in a major key with lighter, more vivid, yellow colors, whereas slower-paced music in a minor key is more likely to be teamed up with darker, grayer, bluer colors.

“Surprisingly, we can predict with 95 percent accuracy how happy or sad the colors people pick will be based on how happy or sad the music is that they are listening to,” said Palmer, who will present these and related findings at the International Association of Colour conference at the University of Newcastle in the U.K. on July 8.  At the conference, a color light show will accompany a performance by the Northern Sinfonia orchestra to demonstrate “the patterns aroused by music and color converging on the neural circuits that register emotion,” he said.

The findings may have implications for creative therapies, advertising and even music player gadgetry. For example, they could be used to create more emotionally engaging electronic music visualizers, computer software that generates animated imagery synchronized to the music being played. Right now, the colors and patterns appear to be randomly generated and do not take emotion into account, researchers said.

They may also provide insight into synesthesia, a neurological condition in which the stimulation of one perceptual pathway, such as hearing music, leads to automatic, involuntary experiences in a different perceptual pathway, such as seeing colors.  An example of sound-to-color synesthesia was portrayed in the 2009 movie The Soloist when cellist Nathaniel Ayers experiences a mesmerizing interplay of swirling colors while listening to the Los Angeles symphony. Artists such as Wassily Kandinksky and Paul Klee may have used music-to-color synesthesia in their creative endeavors.

Nearly 100 men and women participated in the UC Berkeley music-color study, of which half resided in the San Francisco Bay Area and the other half in Guadalajara, Mexico. In three experiments, they listened to 18 classical music pieces by composers Johann Sebastian Bach, Wolfgang Amadeus Mozart and Johannes Brahms that varied in tempo (slow, medium, fast) and in major versus minor keys.

In the first experiment, participants were asked to pick five of the 37 colors that best matched the music to which they were listening. The palette consisted of vivid, light, medium, and dark shades of red, orange, yellow, green, yellow-green, green, blue-green, blue, and purple.

Participants consistently picked bright, vivid, warm colors to go with upbeat music and dark, dull, cool colors to match the more tearful or somber pieces. Separately, they rated each piece of music on a scale of happy to sad, strong to weak, lively to dreary and angry to calm.  

Two subsequent experiments studying music-to-face and face-to-color associations supported the researchers’ hypothesis that “common emotions are responsible for music-to-color associations,” said Karen Schloss, a postdoctoral researchers at UC Berkeley and co-author of the paper. 

For example, the same pattern occurred when participants chose the facial expressions that “went best” with the music selections, Schloss said. Upbeat music in major keys was consistently paired with happy-looking faces while subdued music in minor keys was paired with sad-looking faces. Similarly, happy faces were paired with yellow and other bright colors and angry faces with dark red hues.

Next, Palmer and his research team plan to study participants in Turkey where traditional music employs a wider range of scales than just major and minor. “We know that in Mexico and the U.S. the responses are very similar,” he said. “But we don’t yet know about China or Turkey.”