The high from nicotine depends on whether you think it is there.

Fascinating observations from Gu et al.:

Significance

Nicotine is the primary addictive substance in tobacco, which stimulates neural pathways mediating reward processing. However, pure biochemical explanations are not sufficient to account for the difficulty in quitting and remaining smoke-free among smokers, and in fact cognitive factors are now considered to contribute critically to addiction. Using model-based functional neuroimaging, we show that smokers’ prior beliefs about nicotine specifically impact learning signals defined by principled computational models of mesolimbic dopamine systems. We further demonstrate that these specific changes in neural signaling are accompanied by measurable changes in smokers’ choice behavior. Our findings suggest that subjective beliefs can override the physical presence of a powerful drug like nicotine by modulating learning signals processed in the brain’s reward system.

Abstract

Little is known about how prior beliefs impact biophysically described processes in the presence of neuroactive drugs, which presents a profound challenge to the understanding of the mechanisms and treatments of addiction. We engineered smokers’ prior beliefs about the presence of nicotine in a cigarette smoked before a functional magnetic resonance imaging session where subjects carried out a sequential choice task. Using a model-based approach, we show that smokers’ beliefs about nicotine specifically modulated learning signals (value and reward prediction error) defined by a computational model of mesolimbic dopamine systems. Belief of “no nicotine in cigarette” (compared with “nicotine in cigarette”) strongly diminished neural responses in the striatum to value and reward prediction errors and reduced the impact of both on smokers’ choices. These effects of belief could not be explained by global changes in visual attention and were specific to value and reward prediction errors. Thus, by modulating the expression of computationally explicit signals important for valuation and choice, beliefs can override the physical presence of a potent neuroactive compound like nicotine. These selective effects of belief demonstrate that belief can modulate model-based parameters important for learning. The implications of these findings may be far ranging because belief-dependent effects on learning signals could impact a host of other behaviors in addiction as well as in other mental health problems.

Immune cells drive resilience to stress.

Evidence has been accumulating recently for back and forth interactions between the brain and immune system. Brachman et al. have now made the observation that lymphocytes isolated from stressed out mice, when transferred to naive mice, reduce anxiety and depression like behaviors in the naive mice. It would be interesting to see if a similar sort of transfer in humans had the same effect.

We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2−/− mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice. The mice receiving lymphocytes from defeated donors showed less anxiety, more social behavior, and increased hippocampal cell proliferation compared with those receiving no cells or cells from unstressed donors. Mice receiving stressed immune cells had reduced pro-inflammatory cytokine levels in the blood relative to the other groups, an effect opposite to the elevated donor pro-inflammatory cytokine profile. Furthermore, mice receiving stressed immune cells had microglia skewed toward an anti-inflammatory, neuroprotective M2-like phenotype, an effect opposite the stressed donors' M1-like pro-inflammatory profile. However, stress had no effect on lymphocyte surface marker profiles in both donor and recipient mice. The data suggest that chronic stress-induced changes in the adaptive immune system, contrary to conferring anxiety and depressive behavior, protect against the deleterious effects of stress. Improvement in affective behavior is potentially mediated by reduced peripheral pro-inflammatory cytokine load, protective microglial activity, and increased hippocampal cell proliferation. The data identify the peripheral adaptive immune system as putatively involved in the mechanisms underlying stress resilience and a potential basis for developing novel rapid-acting antidepressant therapies.

MindStuff: A Guide for the Curious User

When I am trying to collect together some ideas to form a lecture or longer piece of work, I frequently think “Haven’t I seen that before?” …. and sure enough I find the ideas better put together in a previous essay I’ve done than in my current effort. I’ve just gone back and read through my 2005 web essay: MindStuff: A guide for the curious user. My reaction is the same as when last summer’s Chaos seminar group discussed the last chapter of my Biology of Mind Book. I think to myself, “Did I really write this? This is good stuff…” While there are a number of places I would tweak and update the text, the MindStuff essay still provides fundamental and useful information, particularly the “The Guide” section that starts halfway through the essay. The purpose of this post is just to point to the text.

The neurochemistry of music.

I want to point to an interesting review article by Chanda and Levitin, that summaries studies showing how music engages four of our bodies' fundamental neurochemical systems. I pass on the abstract and the start of the introduction to the article to give you an idea of its scope:

Music is used to regulate mood and arousal in everyday life and to promote physical and psychological health and well-being in clinical settings. However, scientific inquiry into the neurochemical effects of music is still in its infancy. In this review, we evaluate the evidence that music improves health and well-being through the engagement of neurochemical systems for (i) reward, motivation, and pleasure; (ii) stress and arousal; (iii) immunity; and (iv) social affiliation. We discuss the limitations of these studies and outline novel approaches for integration of conceptual and technological advances from the fields of music cognition and social neuroscience into studies of the neurochemistry of music. 

Introduction 

Music is one of a small set of human cultural universals, evoking a wide range of emotions, from exhilaration to relaxation, joy to sadness, fear to comfort, and even combinations of these. Many people use music to regulate mood and arousal, much as they use caffeine or alcohol. Neurosurgeons use it to enhance concentration, armies to coordinate movements and increase cooperation, workers to improve attention and vigilance, and athletes to increase stamina and motivation.

The notion that ‘music is medicine’ has roots that extend deep into human history through healing rituals practiced in pre-industrial, tribal-based societies. In contemporary society, music continues to be used to promote health and well-being in clinical settings, such as for pain management, relaxation, psychotherapy, and personal growth. Although much of this clinical use of music is based on ad hoc or unproven methods, an emerging body of literature addresses evidence-based music interventions through peer-reviewed scientific experiments. In this review, we examine the scientific evidence supporting claims that music influences health through neurochemical changes in the following four domains:

(i) reward, motivation and pleasure 

(ii) stress and arousal 

(iii) immunity 

(iv) social affiliation.

These domains parallel, respectively, the known neurochemical systems of

(i) dopamine and opioids 

(ii) cortisol, corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) 

(iii) serotonin and the peptide derivatives of proopiomelanocortin (POMC), including alpha-melanocyte stimulating hormone and beta-endorphin 

(iv) oxytocin.

Although the evidence is often weak or indirect and all studies suffer from important limitations, the reviewed evidence does provide preliminary support for the claim that neurochemical changes mediate the influence of music on health.

Twitter predicts mortality from heart disease!

Here is an interesting item from Eichstaedt, Seligman, and collaborators:

Hostility and chronic stress are known risk factors for heart disease, but they are costly to assess on a large scale. We used language expressed on Twitter to characterize community-level psychological correlates of age-adjusted mortality from atherosclerotic heart disease (AHD). Language patterns reflecting negative social relationships, disengagement, and negative emotions—especially anger—emerged as risk factors; positive emotions and psychological engagement emerged as protective factors. Most correlations remained significant after controlling for income and education. A cross-sectional regression model based only on Twitter language predicted AHD mortality significantly better than did a model that combined 10 common demographic, socioeconomic, and health risk factors, including smoking, diabetes, hypertension, and obesity. Capturing community psychological characteristics through social media is feasible, and these characteristics are strong markers of cardiovascular mortality at the community level.

Metacognitive mechanisms underlying lucid dreaming.

Metacognition is the ability to observe, reflect on, and report one's own mental states during wakefulness. Dreaming is not typically accessible to this kind of monitoring, except in people who are lucid dreamers, aware that they are dreaming while in the sleep state (I can do this). Filevich et al. have looked for relationships between the neural correlates of lucid dreaming and thought monitoring:

Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring.

Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group.

Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams.

The neuroscience of motivated cognition.

I want to point to this interesting open source article by Hughes and Zaki, who review research from social psychology and cognitive neuroscience that provides insight into the structure of motivated cognition (that can bias or distort reality), suggesting that it pervades information processing and is often effortless. Here are the opening paragraphs:

People often believe that their thinking aims squarely at gaining an accurate impression of reality. Upon closer inspection, this assumption collapses. Instead, like the inhabitants of Garrison Keillor's Lake Woebegon, individuals often see themselves and close others as possessing unrealistically high levels of positive attributes such as likeability, morality, and attractiveness. This bias persists among individuals who should know better: over 90% college professors believe their work is better than that of their peers, CIA analysts overestimate the accuracy of their predictions for future events, and doctors overconfidently estimate their medical knowledge.

These cases exemplify the phenomenon of motivated cognition, by which the goals and needs of individuals steer their thinking towards desired conclusions. A variety of motivations pervasively shapes cognition. For example, people wish to live in a coherent and consistent world. This leads people to recognize patterns where there are none, perceive control over random events, and shift their attitudes to be consistent with their past behaviors. People also need to feel good about themselves and about others with whom they identify. As such, people often self-enhance, evaluating themselves as having more desirable personalities and rosier future prospects than their peers, and taking personal credit for successes, but not failures. People likewise elevate their relationship partners and in-group members (e.g., people who share their political affiliation) in demonstrably unrealistic ways. Motivations can also have the opposite effect, leading people to derogate out-group members, even when the lines that divide ‘us’ from ‘them’ are defined de novo by researchers.

The authors follow this by noting studies demonstrating motivated cognition in perception, attention, decision making, etc.

MindBlog's 9th anniversary

I realize that I have let MindBlog's 9th birthday slip past without note. The Feb. 6, 2006 post that started the blog, Dangerous Ideas, is no less relevant today than then. I don't pay attention to statistics, but the Blogger platform automatically reports that 200-500 actively engage a given post, with that number rising to to 500-1000 over the next several weeks. Feedburner reports ~ 1.6 million views of ~3,000 posts since MindBlog started. I don't have a sense of how many people make checking MindBlog posts a daily ritual. (A brief comment to this post on your use, as well as any critique, would be welcome!) As Andrew Sullivan (who is signing off from his well-known blog) notes, a daily routine seriously detracts from longer term projects with more depth. I'm finding myself spending more time trying to work up some unifying ideas about metacognition, and also taking more time with the activity I care most about, classical piano practice and performance (which dates back to ~1948, rather than 2006). I'm not going to worry if the daily posting frequency takes a hit.

What is different about the brains of "SuperAgers"

We all probably know some people well into their 80's and 90's who seem to maintain crystal clear intelligence, presence, and memory. A group of collaborators at Northwestern University has studied a group of such individuals, and was able to do postmortem anatomy of the brains of five them. Compared with average elderly individuals, they found fewer Alzheimer-type neurofibrillary tangles and an increased packing density of von Economo neurons, especially in the anterior cingulate. Von Economo neurons, large spindle shaped cells distinctive to humans and great apes, are located in only two parts of the brain: the anterior cingulate cortex, deep in the center of the brain, and the frontoinsular cortex, located inside the frontal lobes. In humans, both of these structures appear to be involved in aspects of social cognition such as trust, empathy, and feelings of guilt and embarrassment.

This human study is based on an established cohort of “SuperAgers,” 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20–30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds (n = 21) than in the healthy middle-aged group (n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50–60 year olds (p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles (p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons (p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age.

Training the mind not to wander with brain feedback.

deBettencourt and collaborators at Princeton University have placed student subjects in an MRI machine while they were performing a sustained attention task. When the machine detected indicators of an attentional lapse, it provided feedback when attention waned by making the task more difficult. Students used this to learn that their attention was lagging and performance improved. The abstract:

Lapses of attention can have negative consequences, including accidents and lost productivity. Here we used closed-loop neurofeedback to improve sustained attention abilities and reduce the frequency of lapses. During a sustained attention task, the focus of attention was monitored in real time with multivariate pattern analysis of whole-brain neuroimaging data. When indicators of an attentional lapse were detected in the brain, we gave human participants feedback by making the task more difficult. Behavioral performance improved after one training session, relative to control participants who received feedback from other participants' brains. This improvement was largest when feedback carried information from a frontoparietal attention network. A neural consequence of training was that the basal ganglia and ventral temporal cortex came to represent attentional states more distinctively. These findings suggest that attentional failures do not reflect an upper limit on cognitive potential and that attention can be trained with appropriate feedback about neural signals.

An informative genetic grammatical impairment - the biological basis of language

A fascinating article from van der Lely and Pinker:

•Specific language impairment is a heterogeneous family of genetic developmental disorders that affects the acquisition of language in 7% of children. 

•We have identified a subtype, Grammatical-SLI, which affects the children's syntax, morphology, and phonology in similar ways. 

•Grammatical abilities are not impaired across the board: the children handle forms that are local, linear, semantic, and holistic, while stumbling on those that are nonlocal, hierarchical, abstract, and composed. 

•The mosaic of impaired and spared abilities is consistent with new models of the neural bases of syntax, morphology, and phonology which distinguish several dorsal and ventral language pathways in the brain. 

•We foresee substantial progress in the biology of language – evolution, genetics, neurobiology, computation, behavior – if language and language impairments are differentiated into underlying pathways and components.

Specific language impairment (SLI), a genetic developmental disorder, offers insights into the neurobiological and computational organization of language. A subtype, Grammatical-SLI (G-SLI), involves greater impairments in ‘extended’ grammatical representations, which are nonlocal, hierarchical, abstract, and composed, than in ‘basic’ ones, which are local, linear, semantic, and holistic. This distinction is seen in syntax, morphology, and phonology, and may be tied to abnormalities in the left hemisphere and basal ganglia, consistent with new models of the neurobiology of language which distinguish dorsal and ventral processing streams. Delineating neurolinguistic phenotypes promises a better understanding of the effects of genes on the brain circuitry underlying normal and impaired language abilities.

The article contains some very useful summary graphics describing language areas and their interactions (click to enlarge):

Legend - Neural correlates of Extended and Basic syntax. Syntactic processing in the brain is implemented in distinct dorsal and ventral circuits which may correspond to Extended and Basic syntax. The dorsal route (unbroken red arrow) links Brodmann Area 44 (BA44, a part of Broca's area) via the arcuate fasciculus to the posterior superior temporal gyrus (STG, a part of Wernicke's area); this pathway has been implicated in complex syntactic processing, including hierarchical phrase structure and movement, that is, Extended syntax. The caudate nucleus of the basal ganglia (not shown), a subcortical structure, is interconnected with frontal cortex, and it has also been found to affect Extended syntax. The first of the two ventral circuits (blue arrow) links the frontal operculum (FO, the cortex inferior and medial to BA 44 and 45, mostly hidden) via the uncinate fasciculus to the anterior STG; it supports local phrase structure. The second (purple arrow) links Brodmann Areas 45 (BA45, another part of Broca's Area) and 47 via the extreme capsule fiber system to the middle portion of the superior and middle temporal lobe; it supports retrieval of stored words and associated semantic processing. The two ventral pathways, therefore, may correspond to Basic syntactic processing. Abbreviations: MTG, middle temporal gyrus; ITG, inferior temporal gyrus.

Legend - Neural correlates of Extended and Basic morphology. Regular inflectional forms (walked, played) are computed by Extended processes that closely overlap with those underlying Extended syntax, namely BA 45 extending into BA 44 and BA47, the arcuate fasciculus, and the superior and middle temporal cortex. The frontal regions are part of a circuit that also includes the caudate nucleus (not shown). In contrast, the storage and retrieval of irregular forms (‘brought’, ‘went’) appears to be mediated bilaterally (blue outline) in a more diffuse set of posterior and middle temporal lobe structures. Derived morphological forms, both regular (‘bravely’) and irregular (‘archer’), activate a third, bilateral network, which we tentatively associate with the ventral pathway, specifically, BA47 extending into BA45, and the anterior superior temporal gyrus (STG) and middle temporal gyrus (MTG) (purple lines). This network may support a network of related but whole word forms. Individuals with G-SLI are impaired in productive regular inflection, an Extended process that engages the dorsal route, but their performance is less impaired with the retrieval of irregular and derived forms, a Basic process which is more tried to lexical memory, and which engages bilateral ventral and posterior routes.

Legend - Neural correlates of Extended and Basic phonology. Phonological processing begins with spectrotemporal and segmental processing in bilateral auditory cortex (superior temporal gyrus, STG, and superior temporal sulcus, STS; right hemisphere not shown). From there it splits into two streams. A left-hemisphere dorsal stream runs to a sensorimotor integration area in the Sylvian portion of the parietal–temporal junction (SPT), and from there further bifurcates into a pathway along the superior longitudinal fasciculus to premotor areas (PM; pink arrow) and a pathway along the arcuate fasciculus to Broca's area (BA44; red arrow). These pathways connect acoustic speech representations to articulatory ones, the former perhaps to basic articulatory phonetic skills, the latter to complex syllables and words, self-monitoring speech, and verbal working memory. A bilateral ventral stream (right hemisphere portion not shown) runs from auditory cortex to the middle and inferior temporal gyri (MTG and ITG), and from there to the anterior temporal lobe, and also to a conceptual network widely distributed through the temporal and other lobes. This pathway connects the sounds of words to their meanings. We suggest that the Extended phonology which challenges G-SLI is associated with the part of the dorsal pathway that runs to Broca's area (red), but perhaps not the part that runs to premotor areas (pink), as articulation in the syndrome is relatively unimpaired. Basic phonology is associated with acoustic and phonological analysis in auditory cortex and with the ventral pathway.

Psilocybin as a key to consciousness.

Michael Pollan offers an engaging article "The Trip Treatment" in the Feb. 9 issue of The New Yorker magazine that describes the resurgence of interest and research on psychotropics like psilocybin, particularly their use in ameliorating end of life anxiety and stress. He points to interesting work by Carhart-Harris and collaborators that I wish I had been paying more attention to. Their article on the effects of psilocybin and MDMA on the resting state functional connectivity (RSFC) between different resting state networks (RSNs) describes experiments showing that psilocybin increases RSFC, making brain networks less differentiated from each other in the psychedelic state, decreasing the natural distinction between externally-focused attention (task positive networks) and introspection (default mode network). The idea is that this de-differentiation of brain networks, this transient disorganizing of brain activity, underlies mystical experiences such as feelings of unity, ineffability, sacredness, peace and joy, transcending space and time, sacredness, or finding some objective truth about reality.

What I would particularly point MindBlog readers to in this open source article is the excellent graphics depictions of Resting State Networks and their functional associations (visual, auditory, sensorimotor, default mode, executive control, dorsal attentional, etc.), and the illustration of marked increases in between-network RSFC under psilocybin.

I should point also to their more general theory of conscious states informed by neuroimaging research with psychedelics, which they term "The entropic brain hypothesis." Here is their summary graphic:

Spectrum of cognitive states. This schematic shows an “inverted u” relationship between entropy and cognition such that too high a value implies high flexibility but high disorder, whereas too low a value implies ordered but inflexible cognition. It is proposed that normal waking consciousness inhabits a position that is close to criticality but slightly sub-critical and primary states move brain activity and associated cognition toward a state of increased system entropy i.e., brain activity becomes more random and cognition becomes more flexible. It is proposed that primary states may actually be closer to criticality proper than secondary consciousness/normal waking consciousness.

A sense of the unfolding digital age.

I've just spent an hour following web links in the New York Times article on a recent course offered by recently deceased media columnist David Carr. The syllabus for Press Play, published on the blogging platform Medium, is a rich trove of pointers to articles describing the rise of more media rich chunks in the "Stream of Now" on mobile platforms and the decline of traditional web pages and blogging platforms such as Blogger, the one generating this post. This fuddy-duddy retired professor is feeling a bit left behind in the dust, but still not inclined to leap into the stream at the full velocity that 20-40 somethings seem to be managing!

Music training offsets decline in speech recognition on aging.

From Bidelman and Alain:

Musicianship in early life is associated with pervasive changes in brain function and enhanced speech-language skills. Whether these neuroplastic benefits extend to older individuals more susceptible to cognitive decline, and for whom plasticity is weaker, has yet to be established. Here, we show that musical training offsets declines in auditory brain processing that accompanying normal aging in humans, preserving robust speech recognition late into life. We recorded both brainstem and cortical neuroelectric responses in older adults with and without modest musical training as they classified speech sounds along an acoustic–phonetic continuum. Results reveal higher temporal precision in speech-evoked responses at multiple levels of the auditory system in older musicians who were also better at differentiating phonetic categories. Older musicians also showed a closer correspondence between neural activity and perceptual performance. This suggests that musicianship strengthens brain-behavior coupling in the aging auditory system. Last, “neurometric” functions derived from unsupervised classification of neural activity established that early cortical responses could accurately predict listeners' psychometric speech identification and, more critically, that neurometric profiles were organized more categorically in older musicians. We propose that musicianship offsets age-related declines in speech listening by refining the hierarchical interplay between subcortical/cortical auditory brain representations, allowing more behaviorally relevant information carried within the neural code, and supplying more faithful templates to the brain mechanisms subserving phonetic computations. Our findings imply that robust neuroplasticity conferred by musical training is not restricted by age and may serve as an effective means to bolster speech listening skills that decline across the lifespan.

MindBlog experiments with a brain enhancer.

I have done two previous posts on my personal experiments with compounds meant to promote longevity or vitality. The first dealt with resveratrol, a potential anti-aging compound. The second involved enhancers of energy production in the mitochondria of our body cells studied by the noted biochemist Bruce Ames (Acetyl L-carnitine, alpha-lipoic acid, biotin). In both cases I initially experienced some positive positive changes in energy and temperament, but after a few days unpleasant side effects led me to terminate the experiment. (Resveratrol caused arthritic symptoms, and the energy generated by N-acetyl l-carnitine and other components was more than I could handle, and expressed as agitation and nervousness.)

In this post I report my experience with one commercially available Nootropic (brain enhancing) mixture marketed by TruBrain,  whose main component is a daily dosage of 4 grams of piracetam (see below). The product is meant to promote cognitive focus in a more benign and effective way than caffeine energy drinks. The bottom line (see details below) is that after taking the mixture the first time I felt more calm and focused, with decreased mind noise and wandering (I think I'm being objective, but it is hard to rule out a placebo effect). After two days, I had to halve the dosage supplied to avoid several side effects noted in web accounts, brain fog, mild headaches, and body nervousness (hyperkinesia).  After the 10 day regime indicated by the instructions, I stopped the supplement for several days and did not note any obvious changes in ability to focus versus distractibility and mind wandering. (Which makes me wonder if the drug might have training my awareness so that it rendered itself unnecessary?) On resuming half dosage as before, I didn't notice the same dramatic effect as when first starting to take it, and the brain fog side effect briefly returned.  Got the same result on waiting a few more days and trying again. I suspect different people will react differently to the TruBrain supplement I was testing.   More details:

As background, I will mention that I get a steady stream of email from companies wanting me to promote or link to their products. I have a cut and paste standard reply that declines such invitations. One particularly persistent suitor has been an outfit called TruBrain . They sell a product meant to promote mental focus, and have a very slick website on which I was unable to find any links to basic science supporting their claims. After my query about this, they did send me an "evidence table" that lists some research references on the components of their brew (PDF here). I decided to relent on my usual refusal to deal with reviewing a commercial product, offered to try the stuff, and they sent a trial box.

The product came in a designer box almost up to Apple Product standards, with tidy little packets of pills to be consumed at breakfast and lunch, and most useful, a clear listing of the ingredients and amounts of the daily dosage. (I guess the cost of packaging and marketing is one reason the price of this supplement mix seems a bit steep to me.) Various combinations of the following ingredients and others are offered by vendors of Nootropics that you can quickly find on the web in a google search for nootropics or piracetam.

The ingredients:  

Piracetam 4g This is the heavy lifter in the mix, a cyclic derivative of the inhibitory neurotransmitter GABA (gamma amino butyric acid). It has extremely low toxicity, and several studies claim that it enhances attentional focus and decreases distractibility. The best guess is that it alters the function of acetylcholine synapses.  The majority of users report no side effects, but reported side effects do include nervousness, weight gain, increased body movements (hyperkinesia), headaches, irritability, depression, brain fog, G.I. distress.

Omega-3 Fatty Acids as DHA 200 mg
Acetyl-L Carnitine 200 mg (the energy producing ingredient in my second experiment noted above)
L-Tyrosine (an amino acid) 450 mg
CDP-Choline 345 mg
L-Theanine 300 mg (a compound in green tea).
Magnesium (as chelated lysinate/arginate) 80mg.

Diary:
Days 1 and 2 - notable calm and focus, decreased mind noise and mind wandering
Day 3 appearance of mild nervousness/agitation, hyperkinesia, brain fog or woozy feeling (not vestibular, balance and movement OK)
Day 4 side effects diminished, but still an unacceptable level of mind fog and body nervousness, alongside calm and focus, low mind noise and wandering.
Day 5 Dosage cut by half (3 instead of 5 pills taken with breakfast, 1 instead of 3 pills taken with lunch). Brain fog only remaining side effect, noticeable but marginally acceptable given enhancement of focus and inhibition of distractibility.
Day 10 By day 10, still taking half the recommended dosage, enhanced focus and reduced distractibility were continuing,  side effects were minimal.

I decided to see the effect of discontinuing the supplement. Would the enhanced focus and decreased distractibility wane over the next few days, returning me to my more normal multitasking distractible state? Or, alternatively, might I have undergone some brain training or conditioning, learning what greater calm, focus, decreased mind noise and wandering feels like, so that it continued after the supplement was withdrawn?  (There is speculation and debate over whether A.D.H.D. drugs might be neuroprotective, rewiring and normalizing a child's neural connections over time, so that more focused behavior continues after medication is withdrawn.)

Alas, I felt very little effect of discontinuing the supplement, focus versus distractibility and mind wandering seemed just fine.   After three days I resumed half the recommended, didn't note any change in focus, but the mind fog side effect returned for about half a day.  I waited another week and tried again...same result.  I may continue to putter with the product, but at this point am a bit underwhelmed.

How musical sound becomes rewarding - predictions and the brain

I would like to point out this review in Trends in Cognitive Sciences. Seeing more than the summary below does require a subscription or other access.

•Dopamine release in mesolimbic reward circuits leads to reinforcement tied to predictions and outcomes. 

•Musical pleasure involves complex interactions between dopamine systems and cortical areas. 

•Individual variability in superior temporal cortex may explain varied musical preferences. 

•Cognitive, auditory, affective, and reward circuits interact to make music pleasurable. 

Music has always played a central role in human culture. The question of how musical sounds can have such profound emotional and rewarding effects has been a topic of interest throughout generations. At a fundamental level, listening to music involves tracking a series of sound events over time. Because humans are experts in pattern recognition, temporal predictions are constantly generated, creating a sense of anticipation. We summarize how complex cognitive abilities and cortical processes integrate with fundamental subcortical reward and motivation systems in the brain to give rise to musical pleasure. This work builds on previous theoretical models that emphasize the role of prediction in music appreciation by integrating these ideas with recent neuroscientific evidence.

I will pass on some clips that summarize brain areas involved in auditory and music perception:

The superior temporal cortex (STC), which houses both primary and secondary auditory areas, is involved in a wide range of auditory processing relevant to music, including processing pitch and extraction of pitch and tonal relationships. It is also thought to store templates of sound events that we have accumulated over the years. Electrical stimulation of the STC elicits musical hallucinations, and increased activity in this region is associated with imagery and familiarity of music, suggesting that it stores previously heard auditory information. Acquired auditory information stored in this region may provide the basis for expectancy generation during music listening.

To appreciate music is to recognize patterns by sequencing structural information, recognizing the underlying structure, and forming predictions. These processes are continuously updated, refined, and revised with incoming information. These operations typically involve the frontal cortices of the brain, particularly the Inferior frontal gyrus (IFG)...The IFG and STG are often co-activated, and may possibly work together to process various aspects of music. Furthermore, there is evidence that white matter connectivity in this pathway is associated with the ability to learn new syntactic structures in the auditory domain. Finally, disruption of STG–IFG pathways has been observed in people with congenital amusia who show music perception deficits.

...dopaminergic coding of cues predicting upcoming rewards, and dopaminergic signaling of positive prediction errors, are essential to the high incentive reward value of musical experience. [One study] combined [¹¹C]-raclopride positron emission tomography and fMRI to show dopamine release in two regions of the striatum (caudate and nucleus accumbens, NAcc) while participants listened to self-selected highly pleasurable music. This study also found differential hemodynamic responses in these regions during anticipation versus experience of peak pleasure moments in the music

Changing bodies changes minds.

A fascinating review by Maister et al. notes studies showing that inducing illusory ownership over the body of a different race, age, or gender person changes implicit social biases, indicating that multisensory experience of our bodies underpins higher-level social attitudes.  I pass on their summaries:

•Multisensory correlations can induce illusory ownership of another person's body.
•Ownership can thus be induced over a body of a different race, age, or gender.
•Incorporating a body belonging to a social outgroup changes implicit social biases.
•The multisensory experience of the body underpins higher-level social attitudes. 

Research on stereotypes demonstrates how existing prejudice affects the way we process outgroups. Recent studies have considered whether it is possible to change our implicit social bias by experimentally changing the relationship between the self and outgroups. In a number of experimental studies, participants have been exposed to bodily illusions that induced ownership over a body different to their own with respect to gender, age, or race. Ownership of an outgroup body has been found to be associated with a significant reduction in implicit biases against that outgroup. We propose that these changes occur via a process of self association that first takes place in the physical, bodily domain as an increase in perceived physical similarity between self and outgroup member. This self association then extends to the conceptual domain, leading to a generalization of positive self-like associations to the outgroup.

And here is their description of manipulations of body ownership:

Rubber Hand Illusion (RHI)

Watching a rubber hand being stroked synchronously with one's own unseen hand causes the rubber hand to be attributed to one's own body, to ‘feel like it's my hand’. This synchronous stimulation not only elicits a subjective experience of ownership over the hand, but also causes the perceived location of one's own hand to drift towards the rubber hand  and a stress-evoked skin conductance response to be elicited when the rubber hand is threatened. The illusion of ownership over the rubber hand does not occur when the rubber hand is stroked asynchronously with respect to the subject's own hand, and thus experiments investigating body ownership commonly use asynchronous stimulation as a control condition. An illusion of the same intensity can be also developed over a virtual hand by either synchronous visuotactile or visuomotor correlations. This illusion persists through radical transformations such as extensive elongation of the arm  or change in the virtual hand position with respect to the real one.

Enfacement Illusion

The enfacement illusion is a facial analogue of the rubber hand illusion. Participants watch a video showing the face of an unfamiliar other being stroked with a cotton bud on the cheek, while the participant receives identical stroking on their own, congruent cheek in synchrony with the touch they see. As in the RHI, synchronous, but not asynchronous, visuotactile stimulation elicits illusory feelings of ownership over the other's face. Enfacement also influences social cognition and produces a measurable bias in self-face recognition, whereby participants perceive the other's face as looking more like their own.

Full Body Illusions

Illusory ownership over a physical manikin body that substituted the participant's real body was demonstrated in. Live video, from cameras attached to the manikin, was streamed to head-mounted displays on the participants, so that when looking down they would see the manikin body visually substituting their own. Synchronous tapping on the manikin body and the real body led to illusory body ownership, in a similar way to the more traditional rubber hand and enfacement illusions. More advanced systems have now been developed, using Immersive Virtual Reality (IVR). Participants wear a head-tracked stereo head-mounted display which provides computer generated images immersing the participant in a virtual world. The participant's own body is substituted by a virtual body, viewed from a first-person perspective, with a motion capture system so that their virtual body moves with their real body movements. This set up results in sensorimotor correlations (visual, proprioceptive, tactile, and motor) that elicit illusions of ownership and agency over the virtual body.

MindBlog's other lives - a piano concert

I thought I would share with MindBlog readers this video made at my piano recital last Sunday in Fort Lauderdale by Rex Coston, an amazing 90+ year old guy, who is totally on top of the web photo and video scene.
 

A further video clip Rex did is here.

Watching large scale brain network interactions in cognitive control.

We frequently face situations in which we must override our ongoing behavior to react to a situational demand, a process that is impaired in many patients with traumatic brain injury (TBI). Two large scale networks important in this cognitive control are the salience network and the default mode network (DMN). From the review by Kumfor et al:

The salience network is recruited in response to attention-grabbing changes in the environment, and it is anchored by the dorsal anterior cingulate cortex and orbital frontoinsular cortices, with robust connections with subcortical and limbic structures. Conversely, the DMN is activated when current situational demands are insufficient to capture our attention (e.g., during monotonous tasks); it encompasses a distributed set of regions including the medial and lateral temporal cortices and inferior lateral parietal cortices, centered on midline “hubs,” including the dorsomedial prefrontal and posterior cingulate cortices.

Jilka et al. have monitored the activity of these networks in control and TBI subjects while they carried out two cognitive control tasks: a stop signal task in which participants were shown either left or right arrows and asked to press the corresponding left or right keys - except when a red dot was shown; and a motor switching task in which participants learned to respond to blue targets with their left hand and red targets with their right hand - except when they were instructed to switch their response. Successful performance on both tasks correlated with increased functional connectivity between the right anterior insula node of the salience network and the DMN. Deficits in inhibition seen in TBI patients correlated with decreased functional connectivity. Here is their abstract:

Interactions between the Salience Network (SN) and the Default Mode Network (DMN) are thought to be important for cognitive control. However, evidence for a causal relationship between the networks is limited. Previously, we have reported that traumatic damage to white matter tracts within the SN predicts abnormal DMN function. Here we investigate the effect of this damage on network interactions that accompany changing motor control. We initially used fMRI of the Stop Signal Task to study response inhibition in humans. In healthy subjects, functional connectivity (FC) between the right anterior insula (rAI), a key node of the SN, and the DMN transiently increased during stopping. This change in FC was not seen in a group of traumatic brain injury (TBI) patients with impaired cognitive control. Furthermore, the amount of SN tract damage negatively correlated with FC between the networks. We confirmed these findings in a second group of TBI patients. Here, switching rather than inhibiting a motor response: (1) was accompanied by a similar increase in network FC in healthy controls; (2) was not seen in TBI patients; and (3) tract damage after TBI again correlated with FC breakdown. This shows that coupling between the rAI and DMN increases with cognitive control and that damage within the SN impairs this dynamic network interaction. This work provides compelling evidence for a model of cognitive control where the SN is involved in the attentional capture of salient external stimuli and signals the DMN to reduce its activity when attention is externally focused.

Causal emergence in our brains

I recently came across an important paper that I didn't spot when it first appeared in 2013. Tononi and collaborators question the common assumption that knowing everything about the micro level of neurons and their interactions can completely specify the behavior of macro levels of systems of neurons. They use simple simulated systems, including neural-like ones, to show quantitatively that the macro level can causally supersede the micro level, i.e., causal emergence can occur. In practical terms this means, for example, that interactions between nodes in the salience (attentional) or default brain networks that generate our behaviors might be better understood at their level than by knowing everything about the zillions of synapses that compose them. (This perspective is an antidote to the purists who maintain that macro level studies are putting the cart before the horse...not getting us there if we haven't painstakingly worked out the steps of what goes on between ion channels, nerve cells, simple systems of nerve cells, and increasingly higher levels of integration.) My primitive mathematical abilities preclude me from really understanding their computations except in the most general way, I want to pass on their abstract, which is a dense but clear read:

Causal interactions within complex systems can be analyzed at multiple spatial and temporal scales. For example, the brain can be analyzed at the level of neurons, neuronal groups, and areas, over tens, hundreds, or thousands of milliseconds. It is widely assumed that, once a micro level is fixed, macro levels are fixed too, a relation called supervenience. It is also assumed that, although macro descriptions may be convenient, only the micro level is causally complete, because it includes every detail, thus leaving no room for causation at the macro level. However, this assumption can only be evaluated under a proper measure of causation. Here, we use a measure [effective information (EI)] that depends on both the effectiveness of a system’s mechanisms and the size of its state space: EI is higher the more the mechanisms constrain the system’s possible past and future states. By measuring EI at micro and macro levels in simple systems whose micro mechanisms are fixed, we show that for certain causal architectures EI can peak at a macro level in space and/or time. This happens when coarse-grained macro mechanisms are more effective (more deterministic and/or less degenerate) than the underlying micro mechanisms, to an extent that overcomes the smaller state space. Thus, although the macro level supervenes upon the micro, it can supersede it causally, leading to genuine causal emergence—the gain in EI when moving from a micro to a macro level of analysis.