Mild stress during pregnancy increases risk of subsequent brain lesions

I'm passing on this work from Rangon et al. Not exactly a friendly abstract, but it gets the message across:

Cerebral palsy remains a public health priority. Recognition of factors of susceptibility to perinatal brain lesions is key for the prevention of cerebral palsy. In most cases, the pathophysiology of these lesions is thought to involve prior exposure to predisposing factors that make the developing brain more vulnerable to perinatal events. The present study tested the hypothesis that exposure to chronic minimal stress throughout gestation would sensitize the offspring to neonatal excitotoxic brain lesions, which mimic lesions observed in cerebral palsy. Pregnant mice were exposed to chronic, ultramild stress, applied throughout gestation. Neonatal brain lesions were induced by intracerebral injection of glutamate analogs. Excitotoxic lesions were significantly worsened in pups exposed to gestational stress. Stress induced a significant rise of circulating corticosterone levels both in pregnant mothers and in newborn pups. The deleterious effects of stress on excitotoxicity were totally suppressed in mice with reduced levels of glucocorticoid receptors. Stress induced a significant increase of neopallial NMDA binding sites in the offspring. At adulthood, animals exposed to stress and neonatal excitotoxic challenge showed a significant impairment in the Morris water maze test when compared with animals exposed to the excitotoxic challenge but not the gestational stress. These findings suggest that stress during gestation, which may mimic low-level stress in human pregnancy, could be a novel risk factor for cerebral palsy.

dericbownds.net - new website design

My website apart from this blog has been an evolutionary accretion of my amateur code done over many years, kind of a mess. Also a confusion of professional and personal stuff. Having received comments on how much more coherent the blog design was (a professional template, provided by blogger), I've enlisted the assistance of a friend and internet consultant, Kelly Doering, to clean up the act. You might have a look at the new product.

Novel environments stimulate memory molecules

Remembering something requires changes in how our nerve cells talk to each other, and a process called long termed potentiation, or LTP, is regarded as a good model for one such underlying change. LTP refers to an enhancement of the synapse between two nerve cells such that an action potential arriving in a presynaptic terminal causes a larger voltage change in the postsynaptic terminal. This process is thought to require the synthesis of new proteins in the synapse and is essential in establishing long term memories(LTM). Moncada and Viola have made the interesting observation that weak inhibitory avoidance training, which induces short- but not long-term memory (LTM), can be consolidated into LTM by an exploration to a novel, but not a familiar, environment occurring close in time to the training session. "This memory-promoting effect caused by novelty depends on activation of dopamine D1/D5 receptors and requires newly synthesized proteins in the dorsal hippocampus. The results indicate the existence of a behavioral tagging process in which the exploration to a novel environment provides the plasticity-related proteins to stabilize the inhibitory avoidance memory trace."

Imperceptible cross modal stimuli produce percepts.

A brief review by Chapman notes that Ramos-Estebanez et al. have done an intriguing experiment involving visuotactile interactions, asking whether subthreshold sensory stimulation can sum across modalities to produce a reportable percept. Some clips from the review and the original article:

The study combined transcranial magnetic stimulation (TMS) to V1 with peripheral electrical stimulation (PES) to the left and right index fingers. For many subjects, TMS at sufficient magnitude directly over V1 evokes phosphenes, spots or "sparks" of light in the visual field that do not correlate with any external stimulus.

Figure. Test conditions used in the experiment in conjunction to TMS delivered to the occipital cortex. PES was delivered in conjunction with occipital TMS at varying ISIs (40, 60, 80, and 100 ms) to either the right or left hand and with the hands in the uncrossed or crossed position.


TMS and PES levels were set at 80% of the threshold stimulation intensity. Subthreshold TMS to left V1 produced phosphene perceptions in ~10% of trials. When subthreshold PES to the left hand was added to TMS, there was no significant change in phosphene perception. However, when PES to the right hand was combined with TMS, a dramatic effect emerged: subjects suddenly reported phosphene perceptions up to 50% of trials. This result suggests that the two imperceptible stimuli combine across modalities to produce a salient percept. At no point did the subjects experience reportable sensations in either hand. The striking effect of stimulation to the right hand persisted whether the hands were crossed or uncrossed. This is what one might expect from "hardwired" connections between the right side of the body and unimodal areas representing the right visual hemifield.

These experiments supplement previous work by showing that even subthreshold sensory stimuli can combine across modalities and that the time course of this interaction occurs within an early, specific temporal range. Many questions remain, because the physiological and anatomical underpinnings of early crossmodal interactions are still being uncovered. However, as our understanding of crossmodal interactions evolves, studies such as these may gradually reshape our current concept of brain organization.

Irritating Images

A 'random sample' from a recent Science Magazine, on Art that Jars:

Some images are literally eyesores. Scientists have long known that the wrong mix of shapes and colors can cause discomfort, headaches, or even seizures. Now, they're starting to figure out why.

Psychologist Arnold Wilkins of the University of Essex, U.K., and artist Debbie Ayles--who creates paintings inspired by her migraines (such as the one shown here)--used a Sciart grant from the Wellcome Trust to tease out the keys to annoying art. Focus groups at an exhibition of Ayles's work last year helped identify narrow stripes and juxtaposed complementary colors as inducers of discomfort. Wilkins then compared the subjective ratings of a variety of paintings with each picture's energy intensity, measured by Fourier analysis of stripes' spatial frequency.

At a talk in Cambridge, U.K., last week, Wilkins said the pictures the focus groups found unpleasant featured vertical stripes at the width that we're visually most sensitive to--about 3 stripes per degree of the visual field (a finger held at arm's length corresponds to about 1 degree). The stripe factor applies to type fonts, too--letter length and thickness make Times New Roman a slower read than Verdana, says Wilkins. He says his results can be applied to design, from picking an optimal type size and font for children's books to choosing public murals.

Suppression of emotional memories.

Here is the abstract from Depre et al.'s article (PDF here):

Whether memories can be suppressed has been a controversial issue in psychology and cognitive neuroscience for decades. We found evidence that emotional memories are suppressed via two time-differentiated neural mechanisms: (i) an initial suppression by the right inferior frontal gyrus over regions supporting sensory components of the memory representation (visual cortex, thalamus), followed by (ii) right medial frontal gyrus control over regions supporting multimodal and emotional components of the memory representation (hippocampus, amygdala), both of which are influenced by fronto-polar regions. These results indicate that memory suppression does occur and, at least in nonpsychiatric populations, is under the control of prefrontal regions.

They used used a Think/No-Think paradigm (T/NT) in which individuals attempt to elaborate a memory by repetitively thinking of it (T condition) or to suppress a memory by repetitively not letting it enter consciousness (NT condition).

Fig. 1. (A) Experimental procedure. Individuals were first trained during structural scanning to associate 40 cue-target pairs. During the experimental phase, brain activity was recorded using fMRI while individuals viewed only the face (16 faces per condition, 12 repetitions per face; 3.5 s per face). On some trials they were instructed to think of the previously learned picture; on other trials they were instructed not to let the previously associated picture enter consciousness. The presentation of only the cue (i.e., the face) ensures that individuals manipulate the memory of the target picture. The additional faces (8 items) not shown during this phase acted as a behavioral baseline. During the test phase, the individuals were shown the 40 faces and asked to describe the previously associated picture. (B) Behavioral results: percentage recall for each participant for T trials (green) and NT trials (red), with the dotted line indicating baseline recall for items not viewed in the experimental phase.

Fig. 2. Functional activation of brain areas involved in (A) cognitive control, (B) sensory representations of memory, and (C) memory processes and emotional components of memory (rSFG, right superior frontal gyrus; rMFG, right middle frontal gyrus; rIFG, right inferior frontal gyrus; Pul, pulvinar; FG, fusiform gyrus; Hip, hippocampus; Amy, amygdala). Red indicates greater activity for NT trials than for T trials; blue indicates the reverse. Conjunction analyses revealed that areas seen in blue are the culmination of increased activity for T trials above baseline as well as decreased activity of NT trials below baseline.

Here is the last portion of their discussion:

At a broader level, our findings extend research suggesting that prefrontal brain areas associated with inhibitory mechanisms (BA 10 and superior, inferior, and middle FG) are lateralized predominantly to the right hemisphere. We have shown the involvement of these areas in the suppression of emotional memories, which replicates current literature suggesting that these areas are active in the suppression of emotional reactivity. Activity in these brain areas, along with inhibition over Hip and Amy, suggests that suppression of emotional memories may use mechanisms similar to those used in emotion regulation. Thus, various right-lateralized PFC areas may be involved in coordinating suppression processes across many behavioral domains, including memory retrieval, motor processes, feelings of social rejection, self motives, and state emotional reactivity.

Our findings may have implications for therapeutic approaches to disorders involving the inability to suppress emotionally distressing memories and thoughts, including PTSD, phobias, ruminative depression/anxiety, and OCD. They provide the possibility for approaches to controlling memories by suppressing sensory aspects of memory and/or by strengthening cognitive control over memory and emotional processes through repeated practice. Refinement of therapeutic procedures based on these distinct means of manipulating emotional memory might be an exciting and fruitful development in future clinical research.

Our results suggest that effective voluntary suppression of emotional memory only develops with repeated attempts to cognitively control posterior brain areas underlying instantiated memories. In this sense, memory suppression may best be conceived as a dynamic process in which the brain acquires multiple modulatory influences to reduce the likelihood of retrieving unwanted memories.

Remembering small pattern differences.

Bannerman and Sprengel discuss (PDF here) and offer perspective on work of McHugh et al. from Tonegawa's laboratory showing synaptic details of how the mouse hippocampus carries out pattern separation. The findings explain how we detect small changes in our environment, perhaps allowing us to update and guide our choices. They offer a nice graphic of the hippocampus, which is central in this processes.

Knowing what, when, and where. In the mouse brain, the dentate gyrus region of the hippocampus can detect small changes in the animal's spatial environment and differentiate between recent experiences that occur in the same place. The white arrows trace a path of signaling between different regions of the hippocampus. Sensory information can enter the hippocampus from the entorhinal cortex and is sent back to the entorhinal cortex after processing.

Can Systems Biology integrate Chinese and Western Meidicine?

Here is the PDF of an interesting article by Jane Qui that I pass on in part because I have been struck by the number of emails I have received from readers of this blog asking questions about alternative medicine and cures (a subject on which I an NOT an expert). The article addresses the question of whether a formidable gap can be addressed:

Modern Western medicine generally prescribes treatments for specific diseases, often on the basis of their physiological cause. Traditional Chinese medicine, however, focuses on symptoms, and uses plant and animal products, minerals, acupuncture and moxibustion — the burning of the mugwort herb (Artemisia vulgaris) on or near the skin. But whether these methods are effective and, if they are, how they work remain a source of some derision. The greatest divide is in the testing. In the West, researchers test a drug's safety and efficacy in randomized, controlled trials. Traditional Chinese treatments are mixtures of ingredients, concocted on the spot on the basis of a patient's symptoms and characteristics and using theories passed down through generations.

The article discusses how researchers in China and elsewhere, meanwhile, are advocating systems biology — the study of the interactions between proteins, genes, metabolites and components of cells or organisms — as a way to assess the usefulness of traditional medicines.

Attentional expertise in long-term meditators: neural correlates

More from Richie Davidson's laboratory here at Wisconsin. The article is open-access, you can go there for the graphics:

Meditation refers to a family of mental training practices that are designed to familiarize the practitioner with specific types of mental processes. One of the most basic forms of meditation is concentration meditation, in which sustained attention is focused on an object such as a small visual stimulus or the breath. In age-matched participants, using functional MRI, we found that activation in a network of brain regions typically involved in sustained attention showed an inverted u-shaped curve in which expert meditators (EMs) with an average of 19,000 h of practice had more activation than novices, but EMs with an average of 44,000 h had less activation. In response to distracter sounds used to probe the meditation, EMs vs. novices had less brain activation in regions related to discursive thoughts and emotions and more activation in regions related to response inhibition and attention. Correlation with hours of practice suggests possible plasticity in these mechanisms.

Internet connectivity model

Don't ask me what k-shell decomposition is, but Carmi et al. (PDF here) perform an analysis of the internet using it to yield an interesting model of internet connectivity and a summary graphic. Analysis of this sort is also applied to brain networks. Their abstract, followed by the graphic:

We study a map of the Internet (at the autonomous systems level), by introducing and using the method of k-shell decomposition and the methods of percolation theory and fractal geometry, to find a model for the structure of the Internet. In particular, our analysis uses information on the connectivity of the network shells to separate, in a unique (no parameters) way, the Internet into three subcomponents: (i) a nucleus that is a small ({approx}100 nodes), very well connected globally distributed subgraph; (ii) a fractal subcomponent that is able to connect the bulk of the Internet without congesting the nucleus, with self-similar properties and critical exponents predicted from percolation theory; and (iii) dendrite-like structures, usually isolated nodes that are connected to the rest of the network through the nucleus only. We show that our method of decomposition is robust and provides insight into the underlying structure of the Internet and its functional consequences. Our approach of decomposing the network is general and also useful when studying other complex networks.

Visualization of our data of the Internet at the AS level. (Upper) A plot of all nodes, ordered by their k-shell indices, using the program of ref. 13. The legend to the left denotes degree, and the legend to the right denotes k-shell index. (Lower) A schematic plot of the suggested Medusa model decomposition of the AS level Internet into three components.

Thoughts on, reservations about, science blogging...

I've just had a brief exchange with David Dobbs, who wrote the piece on Williams Syndrome mentioned a few posts back. He has decided to cut back on blogging, and I found his comments on this, and a reaction to comments by Andrew Sullivan, worth passing on. The mindsets of blogging and book writing are very different. (And...the reason I haven't gone beyond very preliminary efforts to do a second version of my "Biology of Mind" book.)

Whole brain structural networks - some neat movies

Hagmann et al propose that diffusion MRI provides an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables study of the basic and potentially complex network properties of the entire brain. For two human subjects they find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world. The link to their article takes you to three fascinating movies: one showing whole brain tractography, a second showing partition of the white-gray matter interface into approximately 1000 regions of interest, and the third, included here via YouTube so you don't have to download the quicktime movie, showing connections between different visual areas.

A musical interlude...

I put my playing of a Debussy Reverie on YouTube about 10 months ago, and am completely amazed that it has by now had ~18,000 viewings, and over 50 largely constructive comments, many of which suggested to "slow down." So, I did a second version and posted it two months ago, which I pass on here. Response has been more favorable.

Genetics and tonal languages

It is likely that there are heritable differences of brain structure and function that affect language acquisition and usage...cognitive biases in a population of acquirers could influence the direction of language change across generations. These biasing effects could result in linguistic differences between populations, producing nonspurious (causal) correlations between genetic and linguistic diversities. Dediu and Ladd:

... propose that the linguistic typology of tone is affected by such a bias. Human languages differ typologically in the way they use voice fundamental frequency (pitch). All languages use consonants and vowels to distinguish one word or grammatical category from another, but, in addition, so-called "tone languages" (e.g., Chinese) use pitch for this purpose as well, whereas "non-tone languages" (e.g., English) use pitch only at sentence level (to convey emphasis, emotion, etc.). In tone languages, that is, pitch is organized into tone phonemes that are functionally comparable with consonant and vowel phonemes. Tone languages are the norm in sub-Saharan Africa and are very common in continental and insular southeast Asia. They are rare in the rest of Eurasia, North Africa, and Australia. They are relatively common in Central America, the Caribbean, and the Amazon basin, and occur sporadically elsewhere among the aboriginal languages of the Americas..

Here is their Abstract:

The correlations between interpopulation genetic and linguistic diversities are mostly noncausal (spurious), being due to historical processes and geographical factors that shape them in similar ways. Studies of such correlations usually consider allele frequencies and linguistic groupings (dialects, languages, linguistic families or phyla), sometimes controlling for geographic, topographic, or ecological factors. Here, we consider the relation between allele frequencies and linguistic typological features. Specifically, we focus on the derived haplogroups (note: these are sets of nucleotide polymorphisms) of the brain growth and development-related genes ASPM and Microcephalin, which show signs of natural selection and a marked geographic structure, and on linguistic tone, the use of voice pitch to convey lexical or grammatical distinctions. We hypothesize that there is a relationship between the population frequency of these two alleles and the presence of linguistic tone and test this hypothesis relative to a large database (983 alleles and 26 linguistic features in 49 populations), showing that it is not due to the usual explanatory factors represented by geography and history. The relationship between genetic and linguistic diversity in this case may be causal: certain alleles can bias language acquisition or processing and thereby influence the trajectory of language change through iterated cultural transmission.

Most popular consciousness papers for June 2007

That is, the five most downloaded from the eprint archive maintained by the Association for the Scientific Study of Consciousness.

1. Rosen, Alan and Rosen, David B. (2006) The Design of a
Sensation-generating Mechanism in the Brain: A first step towards a
quantitative definition of consciousness. In: Consciousness and
Cognition (1223 downloads from 9 countries).
http://eprints.assc.caltech.edu/195/

2. Sagiv, Noam and Ward, Jamie (2006) Crossmodal interactions: lessons
from synesthesia. In: Visual Perception, Part 2 (1171 downloads from
20 countries). http://eprints.assc.caltech.edu/224/

3. Ruby, Perrine and Legrand, Dorothée (2007) Neuroimaging the self?
In: Sensorimotor foundations of higher cognition. OUP (882 downloads
from 14 countries). http://eprints.assc.caltech.edu/275/

4. Koriat, A. (2006) Metacognition and Consciousness. In: Cambridge
handbook of consciousness. CUP (804 downloads from 15 countries).
http://eprints.assc.caltech.edu/175/

5. Windt, Jennifer Michelle and Metzinger, Thomas (2006) The
philosophy of dreaming and self-consciousness: What happens to the
experiential subject during the dream state? In: The new science of
dreaming (780 downloads from 22 countries).
http://eprints.assc.caltech.edu/200/

Modulating emotional appraisal by false physiological feedback.

Grey et al. examine how emotional appraisal is influenced by physiological feedback. Their observations make me wonder whether trying the opposite trick, giving false feedback that suggests less autonomic arousal, could chill out reactions to an emotional stimulus... Their main points:

James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined.

We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. Twelve participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level.

Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order “cognitive” representations of bodily arousal state.

Williams Syndrome - evidence for a discrete social brain

David Dobbs offers a very well written essay (PDF here) on Williams Syndrome in the Sunday New York Times Magazine (7/8/07). The syndrome is caused by a well-defined deletion in chromosome 7 that occasionally occurs during the synthesis of egg or sperm cells. Patients have a low IQ (~60) and compromised spatial skill and analytical thought, but are hyper-sociable and friendly, very talkative. An pathway from the orbitofrontal (OFC) cortex to the amygdala that usually signals dangerous or angry faces is inactive; but curiously the OFC-amygdala connection still works normally for nonsocial threats such as pictures of snakes, sharks or car crashes. The existence of this syndrome provides perhaps the strongest evidence for genetically and developmentally distinct class of 'social brain' mechanisms distinct from other higher sensory, motor, and analytical skills.

A Sunday Walk....

Around my house on Twin Valley Road in Town of Middleton, Wisconsin. (It is a stone schoolhouse built in 1860, converted to a residence).

How pain preempts cognition - and about itching

I found these two articles on pain and itching interesting, particularly since I've been going through an orgy of both after exposing myself to poison oak or ivy while working in the yard. Bingel et al. show some brain correlates of why I found it difficult to focus on normal cognitive activities during this period:

It is well known that pain attracts attention and interferes with cognition. Given that the mechanisms behind this phenomenon are largely unknown, we used functional magnetic resonance imaging and presented visual objects with or without concomitant pain stimuli. To test for the specificity of pain, we compared this modulatory effect with a previously established modulatory effect of working memory on visual object processing. Our data showed a comparable behavioral effect of both types of modulation and identified the lateral occipital complex (LOC) as the site of modulation in the ventral visual stream, for both pain and working memory. However, the sources of these modulatory effects differed for the two processes. Whereas the source of modulation for working memory could be attributed to the parietal cortex, the modulatory effect of pain was observed in the rostral anterior cingulate cortex (rACC), an area ideally suited to link pain perception and attentional control.
A) fMRI effects of the interaction of background visibility with working memory load were observed in bilateral LOC, reflecting a phasic modulation of LOC activity.
(B) Corresponding activation and parameter estimates related to the interaction of Pain × Visibility.

Now, on to itching (also central to my poison oak story, still going on....). Johanek et al. note a curious distinction between histamine induced itching and itching caused by cutaneous application of spicules from the cowhage plant. They show a different class of afferent C-fiber afferents signaling non-histamine induced itching:

The neuronal pathways for itch have been characterized mainly based on responses to histamine. Intracutaneous application of histamine produces intense itch and a large area of axon-reflexive vasodilation ("flare") around the application site. Both phenomena are thought to be mediated through neuronal activity in itch-specific, mechanoinsensitive C-fiber afferents (CMi). However, mechanical and electrical stimuli that do not activate CMi fibers can cause the sensation of itch, and itch may occur without flare, suggesting that other neuronal itch pathways exist. Because cutaneous application of spicules from the plant Mucuna pruriens (cowhage) has been anecdotally reported to produce itch without flare, we performed psychophysical experiments to investigate whether the mechanisms underlying cowhage- and histamine-induced itch differ. Although histamine and cowhage produced itch of similar magnitude, the itch to cowhage was not correlated with the itch to histamine; some subjects had intense itch to cowhage and little itch to histamine and visa versa. Laser Doppler measurements of blood flow revealed that histamine led to a large area of vasodilation, whereas cowhage produced vasodilation restricted to the application site. Pretreatment of the skin with an antihistamine blocked the itch produced by histamine but did not prevent cowhage-induced itch. Desensitization of the skin with topical capsaicin abolished cowhage-induced itch but did not significantly alter histamine-induced itch. These findings indicate that cowhage itch is signaled through a population of capsaicin-sensitive afferent nerve fibers that is distinct from CMi fibers mediating histamine-induced itch. Cowhage may be useful to investigate the neural pathway mediating nonhistaminergic itch.

Negative suggestions enhancing pain -an antidote?

Benedetti et al. provide an interesting review of the nocebo effect (the anticipation of pain enhancing its magnitude). This is the opposite of the placebo effect, where a more positive expectation can lower perceived pain. Their article (PDF here) provides some interesting graphics of brain imagining showing this effect, and discusses relevant brain receptors.
Recent experimental evidence indicates that negative verbal suggestions induce anticipatory anxiety about the impending pain increase, and this verbally-induced anxiety triggers the activation of cholecystokinin (CCK) which, in turn, facilitates pain transmission. CCK-antagonists have been found to block this anxiety-induced hyperalgesia, thus opening up the possibility of new therapeutic strategies whenever pain has an important anxiety component.