When we typically think of how decision-making works in the brain, we think of new input coming in, perhaps through the eyes or ears, being processed in the relevant sensory areas, and then sent to the ‘decision-making’ areas (the basal ganglia, prefrontal cortex, or anterior cingulate cortex) where this information is used to make a decision. [...]... Read more »
Chubykin, A., Roach, E., Bear, M., & Shuler, M. (2013) A Cholinergic Mechanism for Reward Timing within Primary Visual Cortex. Neuron, 77(4), 723-735. DOI: 10.1016/j.neuron.2012.12.039
Brain white matter plays a key role in connecting functional brain areas. These connections are required for complex brain processing required for memory and executive functions, i.e planning and problem solving.Diffusion tensor imaging (DTI) is a relatively recent brain imaging tool that provides a method of analyzing regional human white matter function. Additionally, when DTI is paired with cognitive testing it allows for study of the brain regions and circuits responsible for specfic cognitive domains.Efrat Sasson and colleagues from Tel Aviv University in Israel and the United States recently published a study of DTI paired with neuropsychological testing in 52 subjects ranging in age from 25 to 82 years of age. They focused on the effects of aging on changes in neuropsychological performance and white matter imaging.The key elements of the design of their study included:Subjects: 52 right-handed adults (20 males and 32 females) without a history of any neurological or psychological disorderNeuropsychological testing: Each subject completed a computerized cognitive test battery known as Mindstreams testing "memory, executive function, visual spatial processing, verbal function, attention, information processing speed and motor skills".Cognitive domain identification: 20 cognitive function areas were analyzed using factor analysis to identify relevant common factors. Three cogntive domains were identified in the factor analysis including: executive function, memory and information processing speedImaging: 3T MRI brain images were obtained white matter bundle regions of interest were identified including the cingulum, the fornix, the inferior longitudinal fasciculus, the superior longitudinal fasciculus and the uncinate fasciculusStatistical analysis: Regression analysis of regional DTI indices, age and neuropsychological test performance. The findings of this study are really quite impressive and highlight the specific white matter bundles associated with cognition and the effects of age on white matter changes. The findings demonstrate the key role white matter temporal lobe projections play:Cingulum bundle: memoryFornix bundle: memorySuperior longitudinal fasciculus bundle: executive function and information processing speedInferior longitudinal fasciculus bundle: memory and information processing speedUncinate fasciculus: memoryThe image on the right shows areas of the right and left temporal lobes identified in green. White matter bundle projections to the temporal lobe have been shown in this study to play a key role in cognitive function.Measures of white matter integrity (fractional anisotropy) from DTI show deterioration with age in these key regional bundles. This implies white matter deterioration may contribute the decline in executive function, memory and information processing found with aging.Understanding this effect may point the way to interventions that might slow the rate of white matter aging in the brain. These types of interventions may reduce the level of age-related cognitive decline in humans.Readers with more interest in this important study can access the free full-text manuscript by clicking on the reference below.Photo of great blue heron from the authors file.Image of temporal lobes is an iPad screen shot from the app Brain Tutor.Sasson E, Doniger GM, Pasternak O, Tarrasch R, & Assaf Y (2013). White matter correlates of cognitive domains in normal aging with diffusion tensor imaging. Frontiers in neuroscience, 7 PMID: 23493587... Read more »
Sasson E, Doniger GM, Pasternak O, Tarrasch R, & Assaf Y. (2013) White matter correlates of cognitive domains in normal aging with diffusion tensor imaging. Frontiers in neuroscience, 32. PMID: 23493587
Research has demonstrated that experiencing head or neck trauma or minor acute infections such as influenza can increase risk for stroke among adults. Inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia. Fullerton (University of California, San Francisco, USA) and colleagues hypothesized that trauma and acute infections are independently associated with childhood arterial ischemic stroke (AIS). Researchers carried out a case-control study of 126 children who were admitted to hospital with AIS and 378 age- and primary care facility-matched controls. All the children were selected from a cohort of 2.5 million children and adolescents aged 19 years or younger who were enrolled in the Kaiser Permanente Medical Care Program.As reported in the Annals of Neurology, the team found that children who had medical treatment for head or neck trauma within the previous 12 weeks had a 7.5-fold increased risk for AIS compared with those who had not.The median time to stroke following head or neck trauma was short, at a median of 0.5 days, and when trauma exposure was redefined as being within the past week, the increased risk for AIS was much greater, at 39 times the risk among children who had not experienced trauma during this period.Similarly, seeking treatment for a minor infection such as upper respiratory tract infection, acute otitis media, or acute gastroenteritis within the previous 4 weeks also increased the risk for AIS 4.6-fold compared with having no infection over this time. Overall, 33% of children who had AIS had a history of infection over the previous month compared with 13% of controls.Atherosclerosis, the pathologic process underlying most coronary artery disease and the majority of ischemic stroke in humans, is an inflammatory process. Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory. Previous studies also demonstrated that HIV infection is associated with an increased risk of stroke, particularly cerebral infarction in young patients. This risk is probably mediated by increased susceptibility of HIV-infected patients to meningitis and protein S deficiency. Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems.Such studies suggest that trauma and acute infection could be used as "targets for primary stroke prevention strategies and considerable opportunities therefore exist for the development of novel therapies.Hills, N., Johnston, S., Sidney, S., Zielinski, B., & Fullerton, H. (2012). Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke Annals of Neurology, 72 (6), 850-858 DOI: 10.1002/ana.23688 Emsley, H., & Tyrrell, P. (2002). Inflammation and Infection in Clinical Stroke Journal of Cerebral Blood Flow & Metabolism, 1399-1419 DOI: 10.1097/00004647-200212000-00001Qureshi, A., Janssen, R., Karon, J., Weissman, J., Akbar, M., Safdar, K., & Frankel, M. (1997). Human Immunodeficiency Virus Infection and Stroke in Young Patients ... Read more »
Hills, N., Johnston, S., Sidney, S., Zielinski, B., & Fullerton, H. (2012) Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke. Annals of Neurology, 72(6), 850-858. DOI: 10.1002/ana.23688
Qureshi, A., Janssen, R., Karon, J., Weissman, J., Akbar, M., Safdar, K., & Frankel, M. (1997) Human Immunodeficiency Virus Infection and Stroke in Young Patients. Archives of Neurology, 54(9), 1150-1153. DOI: 10.1001/archneur.1997.00550210078016
Cluster headaches are a relatively rare but serious pain disorder. Unlike the female-predominant migraine headache, cluster headaches occur predominantly in men. These headaches tend to be acute in onset and affect only one side of the head.The term cluster describes the typical chronological pattern of these headaches. The tend to occur regularly for days or weeks and are then separated by periods of remission lasting months or years.Attacks typically last between 15 minutes and 3 hours. This type of pattern makes cluster headache a good candidate for imaging studies conducted during and between attacks.Qui and colleagues from the People's Republic of China conducted a brain conductivity study in a series of male subjects. The key elements of the design of the study included:Subjects: 12 male right-handed men between the ages of 19 and 46 off medication with a control group of 12 right-handed men without a history of cluster headachesImaging sequence: Case subjects completed two fMRI scans. One was done during an acute attack and a second scan was completed at least four hours after an attack but during the cluster period. Imaging protocol: Resting-state functional connectivity with focus on the hypothalamus, a brain region linked to cluster headache in previous studies.The key findings from this study were:Statistically significant increased right hypothalamus connectivity occurred during the cluster attack phase compared to between attacks in the cluster subjectsThis increased hypothalamic connectivity could be linked to three regions/circuitsFirst region: Anterior cingulate cortex (ACC), several frontal cortex regions, the parahippocampal region and the amygdalaSecond region: precuneus, supramarginal gyrus and the supratemporal gyrusThird region: precuneus, parietal lobe, posterior cingulate cortex (PCC)Case subjects between cluster attacks continued to show connectivity patterns distinct from controls in the right hypothalamus and circuits connected to regions of the temporal lobe, the insular cortex, the occipital lobe and the uncusThe authors note their findings confirm that the ipsilateral hypothalamus (hemi-hypothalamus on the same side as the headache) appears to be a key area of involvement in cluster headache. The brain image on the left highlights the right hypothalamus in the green color.The authors also note (acronym clarifications in parentheses added by me): "Our findings in the acute spontaneous CH (cluster headache) attack showed that the altered rs-FC (resting state functional connectivity) of the hypothalamus is involved in the processing and modulation of pain referred to as the pain matrix, and/or is involved in cognitive and emotional modulation of pain". The findings of a connection between the hypothalamus and the occipital (or vision lobe) is interesting as this occipital lobe is typically not involved in brain pain circuitry. However, the authors note that many cluster headache sufferers have light sensitivity (photophobia) and symptom may reflect some changes in the occipital lobe connectivity.The typical pattern of cluster headaches makes it a promising model to study not only headaches but pain processing in general. This is an informative and important study and interested readers can access the free full-text article by clicking on the reference below. Photo of sandhill crane taken at Venice, Florida rookery is from the author's files. Brain hypothalamus figure is an iPad screenshot from the 3D Brain app.Qiu E, Wang Y, Ma L, Tian L, Liu R, Dong Z, Xu X, Zou Z, & Yu S (2013). Abnormal brain functional connectivity of the hypothalamus in cluster headaches. PloS one, 8 (2) PMID: 23460913... Read more »
Qiu E, Wang Y, Ma L, Tian L, Liu R, Dong Z, Xu X, Zou Z, & Yu S. (2013) Abnormal brain functional connectivity of the hypothalamus in cluster headaches. PloS one, 8(2). PMID: 23460913
The retina is a beautiful and wondrous structure, and it has some really weird cells. Retina by Cajal (source)Retinal Ganglion Cells (RGC) have all sorts of differentiating characteristics. Some are directly sensitive to brightness (like rods and cones), while some are sensitive to the specific direction that a bar is traveling. I am discussing really amazing new techniques to see inside cells this month, and have already posted about the magic that is Array Tomography. Today we'll look at another amazing new technique that (like array tomography) combines nano-scale detail with a scale large enough to see many neurons at once. This technique is called Serial Block-face Electron Microscopy (SBEM), and was recently used to investigate how starburst amacrine cells control the direction-sensitivity of retinal ganglion cells.Serial Block-face EM (source)SBEM images are acquired by embedding a piece of tissue (like a retina) in some firm substance and slicing it superthin (like 10s of nanometers thick) with a diamond blade. The whole slicing apparatus is set up directly under a scanning electron microscope, so as soon as the blade cuts, an image is taken of the surface remaining. Then another thin slice is shaved off and the next image is taken, and so on.Using this technique, Briggman et al. (2011) are able to trace individual neurons and their connections for a (relatively) large section of retina. What is so great about this paper is that before they sliced up the retina, they moved bars around in front of it and measured the directional selectivity of a bunch of neurons. Then, using blood vessels and landmarks to orient themselves, they were able to find the exact same cells in the SBEM data and trace them.Briggman et al. (2011) Fig1C: Landmark blood vesselsThe colored circles above represent the cell bodies and the black 'tree' shape are the blood vessel landmarks. Once they found the cell bodies, the could trace the cells through the stacks of SBEM data. What is really neat is that you can try your hand at this yourself. This exact data set has been turned into a game called EYEWIRE by the Seung lab at MIT. Reconstructing the cells, they could not only tell which cells connected to which other cells, but they could also see exactly where on the dendrites the cells connected. This is the really amazing part. They found that specific dendritic areas made synapses with specific cells.Briggman et al. (2011) Fig4: dendrites as the computational unitThis starburst amacrine cell overlaps with many retinal ganglion cells (dotted lines represent the dendritic spread of individual RGCs)...BUT its specific dendrites (left, right, up down etc) synapse selectively onto RGCs sensitive to a particular direction. Each color represents synapses onto a specific direction-sensitivity. e.g. yellow dots are synapses from the amacrine cell onto RGCs which are sensitive to downward motion.This suggests that each individual dendritic area of these starburst amacrine cells inhibits (probably) a specific type of RGC, and that these dendrites act relatively independently of one another. "The specificity of each SAC dendritic branch for selecting a postsynaptic target goes well beyond the notion that neuron A selectively wires to neuron B, which is all that electrophysiological measurements can test. Instead the dendrite angle has an additional, perhaps dominant, role, which is consistent with SAC dendrites acting as independent computational units." -Briggman et al (2011)(discussion)These cells are weird for so many reasons, but the ability of the dendrites to act so independently of one another is a new and exciting development that I hope to see more research on soon. © TheCellularScaleBriggman KL, Helmstaedter M, & Denk W (2011). Wiring specificity in the direction-selectivity circuit of the retina. Nature, 471 (7337), 183-8 PMID: 21390125... Read more »
Briggman KL, Helmstaedter M, & Denk W. (2011) Wiring specificity in the direction-selectivity circuit of the retina. Nature, 471(7337), 183-8. PMID: 21390125
This is the unexpected story of working to find a path to restore some shredded soul, not through power lifting masses of weights, or sprinting all out till wiped out, but through Sharpening knives, grinding coffee beans - both by hand - making espresso on the stove, latte art - all manual, all small tasks, small skill focus, all about practice of motor learning or just small motor actions as a quest to reduce stress right now.
Often, working out sits in this place, but i feel a little too drained right now for that, except for light runs. Seems there may be a reason - or at least a good thing happening - neurologically - in finding practices that focus, soothe and restore.... Read more »
Draganski, B., Gaser, C., Busch, V., Schuierer, G., Bogdahn, U., & May, A. (2004) Neuroplasticity: Changes in grey matter induced by training. Nature, 427(6972), 311-312. DOI: 10.1038/427311a
Draganski, B. (2006) Temporal and Spatial Dynamics of Brain Structure Changes during Extensive Learning. Journal of Neuroscience, 26(23), 6314-6317. DOI: 10.1523/JNEUROSCI.4628-05.2006
Holzel, B., Carmody, J., Evans, K., Hoge, E., Dusek, J., Morgan, L., Pitman, R., & Lazar, S. (2009) Stress reduction correlates with structural changes in the amygdala. Social Cognitive and Affective Neuroscience, 5(1), 11-17. DOI: 10.1093/scan/nsp034
Pursuing rewards is a crucial part of survival for any species. The circuitry that tells us to seek out pleasure is what ensures that we find food, drink, and mates. In order to engage in this behavior, we must learn associations between rewards and the stimuli that predict them. That way we can know that [...]... Read more »
Bromberg-Martin, E., & Hikosaka, O. (2009) Midbrain Dopamine Neurons Signal Preference for Advance Information about Upcoming Rewards. Neuron, 63(1), 119-126. DOI: 10.1016/j.neuron.2009.06.009
Study says laser light can turn cocaine addiction on and off in rats.
Francis Collins, the director of the National Institutes of Health (NIH), had one word for it: “Wow.”
Writing in the director’s blog at the online NIH site, Collins said that a team of researchers from NIH and UC San Francisco had succeeded in delivering “harmless pulses of laser light to the brains of cocaine-addicted rats, blocking their desire for the narcotic.”
Wow, indeed. It didn’t take long for the science fiction technology of optogenetics to make itself felt in addiction studies. The idea of using targeted laser light to strengthen or weaken signals along neural pathways has proven surprisingly robust. The study by the NIH and the University of California at San Francisco, published in Nature, showed that lab rats engineered to carry light-activated neurons in the prefrontal cortex could be deterred from seeking cocaine. Conversely, laser light used in a way that reduced signaling in this part of the brain led previously sober rats to develop a taste for the drug. As Collins described the work:
The researchers studied rats that were chronically addicted to cocaine. Their need for the drug was so strong that they would ignore electric shocks in order to get a hit. But when those same rats received the laser light pulses, the light activated the prelimbic cortex, causing electrical activity in that brain region to surge. Remarkably, the rat’s fear of the foot shock reappeared, and assisted in deterring cocaine seeking.
All this light zapping took place in a brain region known as the prelimbic cortex. In their paper, Billy T. Chen and coworkers said that they “targeted deep-layer pyramidal prelimbic cortex neurons because they project to brain structures implicated in drug-seeking behavior, including the nucleus accumbens, dorsal striatum and amygdala.” These three subcortical regions are rich in dopamine receptors. In rats that had been challenged with foot shocks before being offered cocaine, “optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking.”
What this demonstrates is that similar regions in the human prefrontal cortex, known to regulate such actions as decision-making and inhibitory response control, may be “compromised” in addicted people. This abnormally diminished excitability in turn “impairs inhibitory control over compulsive drug seeking…. We speculate that crossing a critical threshold of prelimbic cortex hypoactivity promotes compulsive behaviors”
This all sounds vaguely unsettling; sort of a cross between phrenology and lobotomy. But it is no such thing, and the study authors believe that stimulation of the prelimbic cortex “might be clinically efficacious against compulsive seeking, with few side effects on non-compulsive reward-related behaviors in addicts.” For now, the researchers confess that they don’t know whether the reduction in cocaine seeking is caused by altered emotional conditioning, or pure cognitive processing.
Actually, nobody expects optogenetics to be used in this way with humans. The thinking is that transcranial magnetic stimulation, the controversial technique that employs noninvasive electromagnetic stimulation at various points on the scalp to alter brain behavior, would be used in place of invasive zaps with lasers. Expect to hear about clinical trials to test this theory in the near future. David Shurtleff, acting deputy director at the National Institute on Drug Abuse (NIDA), said in a prepared statement that the research “advances our understanding of how the recruitment, activation and the interaction among brain circuits can either restrain or increase motivation to take drugs.”
Chen B.T., Yau H.J., Hatch C., Kusumoto-Yoshida I., Cho S.L., Hopf F.W. & Bonci A. (2013). Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking, Nature, 496 (7445) 359-362. DOI: 10.1038/nature12024
Photo credit: Billy Chen and Antonello Bonci
... Read more »
Chen Billy T., Yau Hau-Jie, Hatch Christina, Kusumoto-Yoshida Ikue, Cho Saemi L., Hopf F. Woodward, & Bonci Antonello. (2013) Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature, 496(7445), 359-362. DOI: 10.1038/nature12024
Regular aerobic exercise has been associated with enhanced cognition in both children and adults. Most of these types of studies have been cross-sectional in design. Cross-sectional studies do a good job of examining association but do not prove causality. Prospective randomized control trials are better at examining the cause-effect relationship.So an important research question in the exercise-cognition domain is: Can an exercise intervention improve cognition in a prospective randomized control trial?Chaddock-Heyman at the University of Illinois published such a study in the journal Frontiers in Human Neuroscience. Their study is strengthened by the addition of fMRI measures of regional brain activation. The key elements in their study included:Subjects: 23 eight and nine year old children selected from the Urbana, Illinois school systemIntervention: Nine month intense after-school program incorporating an average of 77 minutes of moderate to vigorous physical activity daily. Control children were placed on a wait list and did not participate in the after-school programPrimary outcome measures: Pre- and post-testing performance on a task of attention and interference control along with pre- and post-testing fMRI with regional analysis of change over timeThe results of the study pointed to improved cognitive performance in the intervention group compared to the control children. Improvement in cognitive tasks was also associated with a significant reduction in activation of the right prefrontal cortex. Reduction in right prefrontal cortex under task performance (without an increase in errors) is generally seen as evidence of more efficient brain processing.The authors note that in the U.S. physical education activities in school are being cut back or dropped for budgetary reasons. They propose this trend may have adverse effects on childhood brain and cognitive development. Adding a nationwide structured program to increase childhood physical activity is probably not going to happen in the near future. However, parents can use the results of the current study to plan regular physical activities for their children. Exercise targets guidelines for children are 60 minutes of moderate to vigorous activity daily.Readers with more interest in this topic can access the free full-text version of the study by clicking on the link below.Photo of osprey at Fort Myers Beach, Florida is from the author's files.Chaddock-Heyman, L., Erickson, K., Voss, M., Knecht, A., Pontifex, M., Castelli, D., Hillman, C., & Kramer, A. (2013). The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention Frontiers in Human Neuroscience, 7 DOI: 10.3389/fnhum.2013.00072... Read more »
Chaddock-Heyman, L., Erickson, K., Voss, M., Knecht, A., Pontifex, M., Castelli, D., Hillman, C., & Kramer, A. (2013) The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention. Frontiers in Human Neuroscience. DOI: 10.3389/fnhum.2013.00072
Many bloggers like to write about studies that advance our understanding on how the brain FUNCTIONS, including myself. Function, however, depends on the smooth running of processes both between neurons (circuits) and within neurons. Unfortunately things don’t always go smoothly, and sometimes broken, misshapen and aggregated proteins can build up in cells, disrupting their normal [...]... Read more »
Wong E, & Cuervo AM. (2010) Autophagy gone awry in neurodegenerative diseases. Nature neuroscience, 13(7), 805-11. PMID: 20581817
Shoji-Kawata, S., Sumpter, R., Leveno, M., Campbell, G., Zou, Z., Kinch, L., Wilkins, A., Sun, Q., Pallauf, K., MacDuff, D.... (2013) Identification of a candidate therapeutic autophagy-inducing peptide. Nature, 494(7436), 201-206. DOI: 10.1038/nature11866
Last week Science published a study (a follow-up of Salimpoor et al., 2011) in which Canadian researchers showed that music can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal dopaminergic system. ... Read more »
Salimpoor, V., van den Bosch, I., Kovacevic, N., McIntosh, A., Dagher, A., & Zatorre, R. (2013) Interactions Between the Nucleus Accumbens and Auditory Cortices Predict Music Reward Value. Science, 340(6129), 216-219. DOI: 10.1126/science.1231059
Salimpoor, V., Benovoy, M., Larcher, K., Dagher, A., & Zatorre, R. (2011) Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience. DOI: 10.1038/nn.2726
What do we (not) know about how paracetamol (acetaminophen) works? (Toussaint et al., 2010). . .From the beginning, the focus of the search for paracetamol’s analgesic mechanism has concentrated on the central nervous system. When administered intraventricularly [i.e., directly into the ventricular system of the brain], acetaminophen produces no significant analgesia (115, 132). This finding lead to attempts to inject acetaminophen into the spinal cord (i.t.), which produced marked dose-related antinociception (132).Yesterday’s post about Tylenol as a cure for mortality salience and existential dread got me a little worked up. The first author’s public endorsement of acetaminophen as a possible treatment for chronic anxiety disorders was too much to handle (along with the less than stellar experimental rigor). Is watching a 4 min clip of a David Lynch film really the same thing as a clinically diagnosed psychiatric disorder (Randles et al., 2013)? Why Tylenol and not other pain relievers? What is the hypothesized mechanism of action? Wouldn’t we already know by now, from epidemiological studies at the very least, if Tylenol was an effective anti-anxiety medication?So I started wondering about acetaminophen's actual mechanism of action. I was quite surprised that it's somewhat mysterious. Randles et al. cited one paper on this:Second, acetaminophen affects a number of brain regions, some of which are not directly related to physical or social distress (Toussaint et al., 2010).This led me to believe there was evidence from human neuroimaging studies. Turns out there isn't, beyond the Dewall et al. (2010) paper, which states:Although the precise mechanisms by which acetaminophen exerts an analgesic effect are still unclear, it is widely accepted that acetaminophen reduces pain through central, rather than peripheral, nervous system mechanisms (Anderson, 2008; H.S. Smith, 2009).I would like to point out that the spinal cord is part of the central nervous system. So if it's really true that acetaminophen exerts its pain-relieving effects through synapses in the spinal cord, then what does this say about providing relief from the angst of social exclusion, mortality salience, and existential dread? That it's based on nociceptive spinal cord neurons in laminae I, II, and V? For a visual illustration of this pathway, I highly recommend viewing the animation, Dissection of DLF blocks analgesia, at Neuroscience Online. One hypothesis is that Tylenol (acetaminophen) may act on descending serotonergic pathways (purple projection) at the level of the spinal cord (red synapses). Figure modified from Neuroscience Online.However, it's not that simple. The review paper by Toussaint et al. (2010) concluded, "No one mechanism has been definitively shown to account for its analgesic activity." For its proposed mechanisms of action, they presented evidence both for and against Cyclooxygenase (EC 126.96.36.199, COX) inhibition, COX-1, COX-2, 'COX-3', peroxidase, nitric oxide synthase, cannabinoid receptors, and of course serotonin:There is substantial evidence that paracetamol’s mechanism of analgesia in some manner involves the descending serotonergical pathway. 5-HT neurons, largely originating in raphe nuclei located in the brain stem (117, 118) send projections down to the spinal cord that synapse on afferent neurons entering the spinal cord. These descending projections exert an inhibitory (analgesic) effect on the incoming pain signal before it is transmited to higher CNS centres.Note that these are not the same serotonergic pathways often implicated in depression. The terminal synapses for the latter are indeed located in the brain and not the spinal cord.Last night, in real life, I followed the Watertown news live via @sethmnookin and @taylordobbs (like many others).This morning I dreamt that my workplace had transformed into an institutional fortress taken over by a gang of murderous criminals. The actual law enforcement authorities were too busy watching television talk shows to do anything about it. The thugs were threatening and torturing and killing people in the building. I managed to escape down a balcony exit and hid out for a while, avoiding detection but fearful that the thugs would find me and kill me. They were unstoppable, and there seemed to be no way out. I informed an old West-style sheriff, who managed to detain a carload of the evildoers. While continuing to hide, I wondered whether I would be able to shoot them all dead with a fully automatic weapon before they shot and killed me.Then an early morning doorbell rang and woke me up. It was an unexpected FedEx delivery. In my barely awake state, I thought it might be a bomb.Why am I telling you all this?? Because I find it very hard to believe that Tylenol, a drug that's relatively ineffective for my own headache pain, could possibly alleviate the anxiety caused by this nightmare. Or by the real life nightmare that's affected so many people in Boston.ReferencesDewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, Eisenberger NI. (2010). Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 21:931-7. Randles, D., Heine, S., & Santos, N. (2013). The Common Pain of Surrealism and Death: Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats. Psychological Science DOI: 10.1177/0956797612464786... Read more »
Toussaint, K., Yang, X., Zielinski, M., Reigle, K., Sacavage, S., Nagar, S., & Raffa, R. (2010) What do we (not) know about how paracetamol (acetaminophen) works?. Journal of Clinical Pharmacy and Therapeutics, 35(6), 617-638. DOI: 10.1111/j.1365-2710.2009.01143.x
I have had “Thrift Shop” stuck in my head for what seems like days.Yes, it is always on the radio, and yes, I usually listen to it when it is playing. Don't judge me. But why (*Stella scream* wwhhhhyyyyy!) has it established a permanent residence in my brain? I’m going to use a few studies to make the case that it isn’t my fault; I’m led around by my biochemistry. Basically, I’m blaming it on my neurons.Hmmm…where to start. Let’s try to figure out why we like a song (or music in general) in the first place. A study by Valorie Salimpoor et al. in 2011 suggests that it comes down to the biochemistry of pleasure. We, as humans, as animals, find many things in our lives to be pleasurable. Why is this? Well, our brain tells us so. Pleasure is, in essence, a reward for a good stimulus. In the brain, it is largely mediated by dopamine, which also works to reinforce and motivate these behaviors. Now, most people will agree that music is a pleasurable stimulus, but as an abstract stimulus (one not directly related to survival) is it regulated by the same dopamine pathways? In this 2011 study, subjects were asked to select their own “highly pleasurable music” to play for these tests (since musical preferences are so individualized). Then the researchers used PET scanning to estimate dopamine release. Since there are physiological changes that occur during moments of extreme pleasure, they also used the “chills” or “musical frission” response, an objective phychophysiological measurement of clear and discrete patterns of autonomic nervous system arousal. To tease out the response to the music versus the anticipation of the music, they combined the temporal specificity of functional MRI (through the temporal profile of blood oxygenation level - BOLD) with the neurochemical specificity of the PET scan.Salimpoor's group found that the pleasure experienced when listening to music is associated with dopamine activity, that there was a positive correlation between the intensity of “chills” and dopamine release, and an increased BOLD response. In fact, dopamine levels surge during key passages of favorite music and just in anticipation of it. This release is pivotal for establishing and maintaining the behavior, making listening to music a valued experience.Ok, biochemistry…check. Let’s go bigger: What parts of your brain light up when you hear music you like? Salimpoor et al. has published a new study in the April 2013 edition of Science that looks at neural processes active when this pleasurable musical event is happening. Specifically, they look at the reward value the first time a song is heard. We now know that dopamine is involved in familiar music, so what about previously unheard music? To test this, the researchers recruited people, asked them to share their musical tastes (“indie” and “electronic” were the most popular), and used music excerpts selected from a music-recommendation software to pick a unheard song within that preference. To assess reward value, to see if participants liked a song enough that they wanted to hear it again, they were given the option purchase the music with their own money (I know if I have to use my own money then I make sure I love it). Then the participants underwent fMRI scans while listening to musical excerpts and were asked to provide bids of how much they were willing to spend for each song.The researchers found that the reward value (amount of the bid) was directly related to the region of the brain associated with positive prediction error (the NAcc for you brain folks), or pleasant surprises. Increased functional connectivity with this region was made with the auditory cortices, the region known to play a role in the retrieval of previously stored sound information (STG), and the areas implicated in beat processing (caudate and premotor areas). Additionally, increased connectivity was found in regions associated with emotional processing and value-guided decision-making (VMPFC, OFC, and amygdala), but only when sounds gain reward values. When added to the dopamine findings, the activity in these brain regions suggests that when you hear new music your brain looks at its stored information about sound relationships and makes a decision on whether or not to like it based on previous listening experiences and the expectations of tonal events associated with that type of music. If you like it, then your brain gives you a pleasure reward and you end up using your money to buy the song (or otherwise find ways to hear it again). If you like it better than you expected, you get even more delight.Now we know why we like the song and want to hear it again (and again and again…).In the next post we will go further and explore what turns this likeable song into an earworm. Or is it its likeablity at all? (insert cliffhanger music here…dun dun duuuunnnn…)Salimpoor, V., Benovoy, M., Larcher, K., Dagher, A., & Zatorre, R. (2011). Anatomically distinct dopamine release during anticipation and experience of peak emotion to music Nature Neuroscience, 14 (2), 257-262 DOI: 10.1038/nn.2726Salimpoor, V., van den Bosch, I., Kovacevic, N., McIntosh, A., Dagher, A., & Zatorre, R. (2013). Interactions Between the Nucleus Accumbens and Auditory Cortices Predict Music Reward Value Science, 340 (6129), 216-219 DOI: 10.1126/science.1231059...and an article in ScienceNOW "Why Your Brain Loves That New Song"(image via rockandtheology) ... Read more »
Salimpoor, V., Benovoy, M., Larcher, K., Dagher, A., & Zatorre, R. (2011) Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience, 14(2), 257-262. DOI: 10.1038/nn.2726
Salimpoor, V., van den Bosch, I., Kovacevic, N., McIntosh, A., Dagher, A., & Zatorre, R. (2013) Interactions Between the Nucleus Accumbens and Auditory Cortices Predict Music Reward Value. Science, 340(6129), 216-219. DOI: 10.1126/science.1231059
Lazarus sign, also known as Lazarus reflex, is a complex form of reflex movement of the arms in brain dead patients.
In this phenomenon, the arms of the brain dead patients or the patients with brainstem failure raises to the chest and often fall crossed on to the body (in a place that you may have seen in some of the Egyptian mummies). “The arms flex quickly to the chest from the patient's side, the shoulders adduct, and in some patients, the hands cross or oppose just below the chin. The limbs then return to the patient's side, sometimes asymmetrically,” Researchers reported.
Even weirder is the presence of minor shaky movements of the arms of the patients or the presence of goose bumps on the arms and torso in some cases. Researchers have also reported "respiratory-like movement in a patient with brain death" along with Lazarus sign.
This reflex is a kind of reflex arc generated by the spine that is why it can occur even after brain death, while the other organs are still working. Researchers have found that this phenomenon occurs after several minutes of the removal of the medical ventilators that helped to pump air in and out of brain-dead patients, so that the bodies of the patients would stay alive.
Researchers have also found the presence of Lazarus sign during the testing for apnea - brief pause in breathing - that is one of the criteria for the determination of brain death used by the neurologists.
You can see a video of this reflex here.
Calixto Machado (2007). Brain death: a reappraisal. Springer. p. 79. ISBN 978-0-387-38975-2.
"Practice Parameters: Determining Brain Death in Adults". American Academy of Neurology. 1994. Retrieved 12 July 2009.
Urasaki E, Fukumura A, Itho Y, Itoyama Y, Yamada M, Ushio Y, Wada S, Yokota A, (1988). [Lazarus' sign and respiratory-like movement in a patient with brain death]. [Article in Japanese]. No To Shinkei, 40(12):1111-1116.
Ropper, A. (1984). Unusual spontaneous movements in brain-dead patients Neurology, 34 (8), 1089-1089 DOI: 10.1212/WNL.34.8.1089... Read more »
Ropper, A. (1984) Unusual spontaneous movements in brain-dead patients. Neurology, 34(8), 1089-1089. DOI: 10.1212/WNL.34.8.1089
T’is the season of finals again, and with it, a surging interest in prescription “smart drugs” (see Fig 1). High school and college students are increasingly turning to ADHD medicine (Ritalin, Adderall) in hopes of enhancing school and test performance. Intuitively this makes sense: drugs that increase energy, attention and concentration should inevitably lead to [...]... Read more »
Lakhan SE, & Kirchgessner A. (2012) Prescription stimulants in individuals with and without attention deficit hyperactivity disorder: misuse, cognitive impact, and adverse effects. Brain and behavior, 2(5), 661-77. PMID: 23139911
Smith ME, & Farah MJ. (2011) Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals. Psychological bulletin, 137(5), 717-41. PMID: 21859174
A new paper could prompt a rethink of a technique that’s become very hot in neuroscience lately: Confounds in multivariate pattern analysis The authors are Princetonians Michael T. Todd and colleagues, and the method in question is multivariate pattern analysis (MVPA). I’ve written about this before and there’s a blog dedicated to it. MVPA searches [...]... Read more »
Todd, M., Nystrom, L., & Cohen, J. (2013) Confounds in multivariate pattern analysis: Theory and rule representation case study. NeuroImage. DOI: 10.1016/j.neuroimage.2013.03.039
Sure, a company can do its job to create an attractive, pleasurable product for us consumers. But—you guessed it—the store does its own part in tricking us, ensuring that the phrase "you touch it, you buy it" often holds true.... Read more »
James R. Wolf, Hal R. Arkes, & Waleed A. Muhanna. (2008) The power of touch: An examination of the effect of duration of physical contact on the valuation of objects. Judgment and Decision Making, 3(6), 476-482. info:/
I remember the first time I realized just how easily false information gets spread about.A terrifying starry nightI was in French class in high school. Our homework had been to find out 1 interesting fact about Van Gogh and tell it to the class. When it was my turn, I said some boring small fact that I no longer remember. My friend sitting behind me, however, had a fascinating fact: When Van Gogh was a young child, he was actually afraid of the moon.The teacher and the class were all quite impressed and thought about how interesting that was and how that fact might be reflected in the way that he paints the Starry Night. Though this fact was new to everyone, including the teacher, no one even thought to question its truth. In fact, the teacher was so enthralled by this idea that she passed the information on to all the other French classes that day.When talking to my friend later that day, he admitted that he had not done the assignment, and just made the 'fact' up. I was completely surprised, not only that someone had not done their homework *gasp*, but that I hadn't even thought to question whether this was true or not. The best lies have an element of truth (source) Misinformation like this spreads like wildfire and is exceptionally difficult to undo. The more things you can link this piece of information to in your brain, the more true you might think it and even after your learn that it's not true, you still might inadvertently believe it or fit new ideas into the context it creates. Myths like the corpus callosum is bigger in women than in men is just one of those things that is easy to believe.An interesting paper by Lewandowsky et al. (2012) explains how this kind of persistent misinformation is detrimental to individuals and to society with the example of vaccines causing autism. This particular piece of misinformation is widely believed to be true despite numerous attempts to publicize the correct information and the most recent scientific findings showing no evidence for a link between the two. The authors of this paper give some recommendations for making the truth more vivid and effectively replacing the misinformation with new, true information. For example:"Providing an alternative causal explanation of the event can fill the gap left behind by retracting misinformation. Studies have shown that the continued influence of misinformation can be eliminated through the provision of an alternative account that explains why the information was incorrect." Lewandowsky et al. (2012)Misinformation can be replaced with information, but it takes more work to replace a 'false fact' than to just have the truth out there in the first place. It is much better when misinformation is not spread around in the first place, than when it is retroactively corrected. This paper is also covered over at The Jury Room. © TheCellularScaleLewandowsky, S., Ecker, U., Seifert, C., Schwarz, N., & Cook, J. (2012). Misinformation and Its Correction: Continued Influence and Successful Debiasing Psychological Science in the Public Interest, 13 (3), 106-131 DOI: 10.1177/1529100612451018... Read more »
Lewandowsky, S., Ecker, U., Seifert, C., Schwarz, N., & Cook, J. (2012) Misinformation and Its Correction: Continued Influence and Successful Debiasing. Psychological Science in the Public Interest, 13(3), 106-131. DOI: 10.1177/1529100612451018
A key element in discovering valid mental disorder categories is to differentiate a mental disorder from other valid mental disorder categories.Biological markers for mental disorders have been slow to develop. Functional brain imaging techniques and other research tools are evolving to help in the important task of improving the validity of clinical neuroscience disorders.Adjustment disorder is a relatively common condition that has lagged in research attention. Adjustment disorder is defined as an abnormal and excessive response to a stressor that produce significant distress and impairment. The response may include elements of anxiety, depression or abnormal behavior.Adjustment disorder with depressive symptoms may be difficult to distinguish from major depression and other types of mood disorder. However, a recent study of the technique of quantitative electroencephalogram (qEEG) supports adjustment disorder as a distinct condition different from major depressive disorder.The key elements of the design of this study included the following:Subjects: 31 subjects with adjustment disorder with depressed mood and 51 subjects with major depressive disorder using DSM-IV criteriaqEEG: Standard qEEG techniques were employed including calculation of absolute power and coherence for delta, theta, alpha and beta band widthsStatistical analysis: Independent t-test comparison of absolute power and coherence using Neurostat softwareThe key findings from the study included:Absolute power means were lower for the adjustment disorder group in the frontal regionsInterhemispheric coherence values for the delta and beta bands involving the right posterior region were lower in the adjustment disorder groupIntrahemispheric coherence was lower in the alpha bandwidth in the frontal and temporal areas in the adjustment disorder groupThe authors note the findings support adjustment disorder being a relatively less severe mood disorder. However, they noted that the differences may be explained by different patterns of anxiety disorder comorbidity between the two groups.Weaknesses in this study included not including a no mental disorder control group. Additionally, the adjustment disorder group had a statistically higher percentage of male subjects so the two groups were not gender matched.It would be interesting to see if this difference between adjustment disorder and major depression could be replicated in default network connectivity analysis using functional MRI.However, this study is important as it presents a novel biological marker candidate for adjustment disorder with depressed mood. It may stimulate additional biological marker studies is patients suffering significant stress-related anxiety and mood responses.Individuals with more interest in this study can access the free full-text article in the link below.Photo of great white heron from the Venice, FL rookery is from the author's files.Jeong HG, Ko YH, Han C, Kim YK, & Joe SH (2013). Distinguishing Quantitative Electroencephalogram Findings between Adjustment Disorder and Major Depressive Disorder. Psychiatry investigation, 10 (1), 62-8 PMID: 23482820... Read more »
Jeong HG, Ko YH, Han C, Kim YK, & Joe SH. (2013) Distinguishing Quantitative Electroencephalogram Findings between Adjustment Disorder and Major Depressive Disorder. Psychiatry investigation, 10(1), 62-8. PMID: 23482820
The annual meetings of the American Association of Physical Anthropologists were going on all last week, and I gave my first talk before the Association. The talk focused on using resampling methods and the abysmal human fossil record to assess whether human-like brain size growth rates were present in our >1 mya ancestor Homo erectus. This is something I've actually been sitting on for a while, but wanted to wait til the talk to post for all to see. Here's a brief version:Background: Humans' large brains are critical for giving us our unique capabilities such as language and culture. We achieve these large (both absolutely, and relative to our body size) brains by having really high brain growth rates across several years; most notable are exceptionally high, "fetal-like" rates during the first 1-2 years of life. Thus, rapid brain growth shortly after birth is a key aspect of human uniqueness - but how ancient is this strategy?Materials: We can plot brain size at birth in humans and chimpanzees (our closest living relatives) to visualize what makes humans stand out (Figure 1).Figure 1. Brain size (volume) at given ages. Humans=black, chimpanzees=red. Ranges of brain size at birth, and the chronological age of the Mojokerto fossil, in blue.Human data come from Cogueugniot and Hublin (2012), and chimpanzees from Herndon et al. (1999) and Neubauer et al. 2012. The earliest fossil evidence able to address this question comes from Homo erectus. Because of the tight relationship between newborn and adult brain size (DeSilva and Lesnik 2008), we can use adult Homo erectus brain volumes (n=10, mean = 916.5 cm^3) to predict that of the species' newborns: mean = 288.9 cm^3, sd = 17.1). An almost-recent analysis of the Mojokerto Homo erectus infant calvaria suggests a size of 663 cm^3 and an age of 0.5-1.25 years (Coqueugniot et al. 2004; this study actually suggests an oldest age of 1.5 years, but the chimpanzee sample here requires us to limit the study to no more than 1.25 years).Methods: Resampling statistics allow inferences about brain growth rates in this extinct species, incorporating the uncertainty in both brain size at birth, and in the chronological age of the Mojokerto fossil. We thus ask of each species, what growth rates are necessary to grow one of the newborn brain sizes to any infant between 0.5-1.25 years? And from there, we compare these resampled growth rates (or rather, 'pseudo-velocities') between species - is H. erectus more similar to modern humans or chimpanzees? There are 294 unique newborn-infant comparisons for humans and 240 for the chimpanzee sample. We therefore compare these empirical pairs of extant species to 7500 resampled H. erectus newborn-infant pairs, randomly selecting a newborn H. erectus size based on the parameters above, and randomly selecting an age from 0.5-1.25 years for the Mojokerto specimen. This procedure is used to compare both absolute size change (the difference between an infant and a newborn size, in cm^3/year), and and proportional size change (infant/newborn size).Results: Humans' high early brain growth rates after birth are reflected in the 'pseudovelocity curve' (Figure 2). Chimps have a similar pattern of faster rates earlier on, but these are ultimately lower than humans'. Using the Mojokerto infant's brain size (and it's probable ages) and the likely range of H. erectus neonatal brain sizes (mean = 288, sd = 17), it is fairly clear that H. erectus achieved its infant brain size with high, human-like rates in brain volume increase.Figure 2. Brain size growth rates ('pseudo-velocity') at given ages. Humans=black, chimpanzees=red. Ranges of brain size at birth, and Homo erectus, in blue.However, if we look at proportional size change, the factor by which brain size increases from birth to a given age, we see a great deal of overlap, both between age groups within a species, band between different species. Cross-sectional data creates a great deal of overlap in implied proportional size change between ages within a species; it is easier to consider proportional size change between taxa, conflating ages, then (Figure 3). Humans show a massive amount of variation in potential growth rates from birth to 0.5-1.25 years, and chimpanzees also show a great deal of variation, albeit generally lower than in the human sample. Relative growth rates in Homo erectus are intermediate between the two extant species.Figure 3. Proportional brain size increase (infant/newborn size). Significance: Brain size growth shortly after birth is critical for humans' adaptative strategy: growing a large brain requires a lot of energy and parental (especially maternal) investment (Leigh 2004). Plus, in humans this rapid increase may correspond with the creation of innumerable white-matter connections between regions of the brain (Sakai et al. 2012), important for cognition or intelligence. The H. erectus fossil record (1 infant and 10 adults) provides a limited view into this developmental period. However, comparative data on extant animals (e.g. brain sizes from birth to adulthood), coupled with resampling statistics, allow inferences to be made about brain growth rates in H. erectus over 1 million years ago.Assuming the Mojokerto H. erectus infant is accurately aged (Coqueugniot et al. 2004), and that Homo erectus followed the same neonatal-adult scaling relationship as other apes and monkeys (DeSilva and Lesnik 2008), it is likely that H. erectus had human-like rates of absolute brain size growth. Thus, the energetic and parental requirements to raise such brainy babies, seen in modern humans, may have been present in Homo erectus some 1.5 million years ago or so. This may also imply rapid white-matter proliferation (i.e. neural connections) in this species, suggesting an intellectually (i.e. socially or linguistically) stimulating childhood in this species. At the same time, relative brain size growth appears to scale with overall brain size: larger brains require proportionally higher growth rates. This is in line with studies suggesting that in many ways, the human brain is a scaled-up version of other primates (e.g. Herculano-Houzel 2012).This study was made possible with published data, and the free statistical programming language R. Contact me if you want the R code used for this analysis, I'm glad to share it!!!ReferencesCoqueugniot H, Hublin JJ, Veillon F, Houët F, & Jacob T (2004). Early brain growth in Homo erectus and implications for cognitive ability. Nature, 431 (7006), 299-302 PMID: 15372030... Read more »
Coqueugniot H, Hublin JJ, Veillon F, Houët F, & Jacob T. (2004) Early brain growth in Homo erectus and implications for cognitive ability. Nature, 431(7006), 299-302. PMID: 15372030
Coqueugniot H, & Hublin JJ. (2012) Age-related changes of digital endocranial volume during human ontogeny: results from an osteological reference collection. American journal of physical anthropology, 147(2), 312-8. PMID: 22190338
DeSilva JM, & Lesnik JJ. (2008) Brain size at birth throughout human evolution: a new method for estimating neonatal brain size in hominins. Journal of human evolution, 55(6), 1064-74. PMID: 18789811
Herculano-Houzel S. (2012) The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost. Proceedings of the National Academy of Sciences of the United States of America, 10661-8. PMID: 22723358
Herndon JG, Tigges J, Anderson DC, Klumpp SA, & McClure HM. (1999) Brain weight throughout the life span of the chimpanzee. The Journal of comparative neurology, 409(4), 567-72. PMID: 10376740
Leigh SR. (2004) Brain growth, life history, and cognition in primate and human evolution. American journal of primatology, 62(3), 139-64. PMID: 15027089
Neubauer, S., Gunz, P., Schwarz, U., Hublin, J., & Boesch, C. (2012) Brief communication: Endocranial volumes in an ontogenetic sample of chimpanzees from the taï forest national park, ivory coast. American Journal of Physical Anthropology, 147(2), 319-325. DOI: 10.1002/ajpa.21641
Sakai T, Matsui M, Mikami A, Malkova L, Hamada Y, Tomonaga M, Suzuki J, Tanaka M, Miyabe-Nishiwaki T, Makishima H.... (2013) Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain. Proceedings. Biological sciences / The Royal Society, 280(1753), 20122398. PMID: 23256194
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