Dietary polyamine supplement prevents aging-related memory impairments in Drosophila

It is well known that aging results in cognitive decline, including memory impairments, even in the absence of any dementing neurodegenerative disorders per se such as Alzheimer’s disease. Given the rapidly aging populations in many countries, the causes of the aging-related memory impairments have been a focus of intensive research. One central challenge for research on aging-related memory impairments has been posed by the relatively long lifespan of most animal models. Conditioning paradigms that can be used in Drosophila (aka "fruit flies") provide a model where aging-related memory impairments are seen over the course of days and weeks instead of years, thus offering a model that can be effectively used to study the underlying molecular mechanisms.

In their recent study, Dr. Varun K Gupta et al. (2013) conducted a series of experiments where they first observed that polyamine spermidine and putrescine levels decreased in the heads of aging Drosophila. In the following experiment they observed that dietary sperminide supplement reduced aging-related memory impairment in the Drosophila, as assessed with a maze-learning task involving olfactory cues and electric shocks. Investigating the possible underlying molecular mechanisms, the authors observed that dietary spermidine, in addition to reducing aging-related memory impairment, prevented aging-related decrease of autophagy. Furthermore, when the autophagic mechanisms were genetically impaired, the spermidine-induced reduction of aging-related memory impairment was blocked.

This impressive set of findings demonstrates how the Drosophila model can be highly effectively used to study molecular mechanisms that underlie aging-related memory impairments. The authors point out that prior to their observations, few substances (and all of them exogenous) have been observed to protect against aging-related memory impairments. Spermidine, being an endogenous substance, thus holds a lot of potential for further studies and might ultimately provide a candidate substance for prevention of aging-related memory deficits in humans.

Reference: Gupta VK, Scheunemann L, Eisenberg T, Mertel S, Bhukel A, Koemans TS, Kramer JM, Liu KSY, Schroeder S, Stunnenberg HG, Sinner F, Magnes C, Pieber TR, Dipt S, Fiala A, Schenck A, Schwaerzel M, Madeo F, Sigrist SJ. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner. Nature Neuroscience (2013) e-publication ahead of print. http://dx.doi.org/10.1038/nn.3512


Economic conditions at the time of birth predict cognitive ability late in life

Severe economic recessions are known to adversely affect population health, and it is also well known that exposure to adverse stimuli during early stages of life can hinder development. The question of whether economic-societal conditions at the time of birth, such as poverty brought about by economic downturns and wellbeing by economic booms, can impact cognitive functions later in life is a highly interesting one that has been addressed relatively little. Due to large in-depth surveys carried out in the 2000s across multiple European countries among the aging population, it has become possible to address this important question.

In their recent study, Doblhammer et al. (2013) examined whether economic cycle at the time of birth could predict poor cognitive functioning at older age. They specifically inspected whether cycles in economic indicators during the first half of the 20th Century (excluding war years) would predict cognitive ability as assessed with five interview measures, on orientation to time, recall, delayed recall, verbal fluency, and numerical ability. Multiple potentially intervening factors were carefully controlled for in the analyses. The results showed that economic downturns at the time of birth significantly predicted poorer cognitive function in the elderly. While it is naturally difficult to pinpoint causal factors in this type of study design (the authors mention malnutrition and psychological stress/insecurity within families as possible explanations) these results nonetheless bear high societal significance by demonstrating that economical factors can have lasting consequences on cognitive function.  

Reference: Doblhammer G, van den Berg GJ, Fritze T. Economic conditions at the time of birth and cognitive abilities late in life: evidence from ten European countries. PLoS ONE (2013) 8: e74915. http://dx.doi.org/10.1371/journal.pone.0074915


Watching short emotional movie clips robustly activates the human dorsal visual stream areas

Rapid advances in neuroimaging method development are currently making it possible to answer one of the most intriguing questions in cognitive neuroscience, specifically, how does seeing emotion-arousing events in one’s environment modulate the various systems (e.g., emotional, attentional, somatomotor) of the brain. Up until relatively recently, neuroimaging studies on the neural basis of emotions utilized stimuli such as emotional pictures and sounds to delineate brain structures responding to emotional events. More naturalistic stimuli such as movies that elicit more robust and genuine emotions have been used recently and in such early studies, more extensive set of brain areas have been shown to be modulated by emotional valence and arousal than in studies using more artificial stimuli, thus warranting further research into the neural basis of emotions with naturalistic stimuli.

In their recent study, Goldberg et al. (2014) presented healthy volunteers with short ~14 s clips taken from commercial movies during functional magnetic resonance imaging of brain hemodynamic activity. The subjects had prior to the scanning session watched longer clips of ~a few minutes that contained the short experimental clips to familiarize the subjects with the emotional events and content of the clips. The clips ranged from neutral to strongly emotional, which was used in modeling hemodynamic activity. In separate control experiments the clips were played upside down, and the soundtrack and video inputs were mixed, to control for the possibility of low-level sensory differences between emotional and neutral clips. The authors observed responses to emotional clips in a number of brain areas, however, the most robust responses to emotionally arousing clips were noted in the dorsal visual stream.

These highly interesting findings of dorsal stream activity enhancement by emotionally arousing movie clips are interpreted by the authors to indicate initial step in the chain of events ultimately leading to action towards emotionally meaningful objects. Methodologically, the study also presents an interesting and a potentially very useful advance: by familiarizing the subjects with the movie material in advance, the authors could effectively utilize very short movie clips to trigger the recollection of the previously seen emotional events during the scanning. Given that there are limitations to how long a given subject can be scanned, and that the signal-to-noise ratio limitations of even modern neuroimaging methods require one to obtain multiple repetitions of similar events (e.g., emotional responses) over the duration of the experiment, this setup of the authors offers an attractive alternative paradigm for further neuroimaging studies of emotions.

Reference: Goldberg H, Preminger S, Malach R. The emotion–action link? Naturalistic emotional stimuli preferentially activate the human dorsal visual stream. Neuroimage (2014) 84: 254–264. http://dx.doi.org/10.1016/j.neuroimage.2013.08.032


Human electrocorticography shows phase resetting of visual cortical oscillatory activity by auditory stimuli

Perception is inherently multisensory, as evidenced by multisensory integration effects such as increased comprehensibility of speech when lip movements of a speaker are clearly visible in a noisy environment, as well as by audio-visual illusions such as the ventriloquism and McGurk effects. At the neural level, it has been increasingly recognized that there are cross-modal inputs even to primary sensory cortical areas that take place already at very short latencies from stimulus onset, however, understanding of the neural mechanisms by which auditory stimuli influence visual processing has been relatively limited. Given recent findings in other sense modalities, phase resetting of oscillatory visual cortex activity by auditory stimuli has emerged as a potential mechanism by which auditory stimuli might facilitate processing of visual stimuli in visual cortical areas.

In their recent study, Mercier et al. (2013) recorded brain electrical activity intracranially in patients undergoing presurgical mapping procedures. Oscillatory and evoked activity was recorded with electrodes placed in a number of occipital-visual cortical areas during presentation of auditory-only, visual-only, and audiovisual stimuli. While the authors observed also some responses in visual cortical areas evoked by auditory stimuli, the most robust effects that auditory stimuli caused in visual cortical areas was modulation / phase resetting of the ongoing oscillatory activity by auditory stimuli. Such phase resetting might be the neurophysiological-level mechanism that supports behaviorally measurable multisensory interaction effects.

Reference: Mercier MR, Foxe JJ, Fiebelkorn IC, Butler JS, Schwartz TH, Molholm S. Auditory-driven phase reset in visual cortex: human electrocorticography reveals mechanisms of early multisensory integration. Neuroimage (2013) 79:19-29. http://dx.doi.org/10.1016/j.neuroimage.2013.04.060


Self-initiated task selection is predicted by multi-voxel pattern activity in medial prefrontal and parietal cortices

Based on clinical observations in brain-damaged individuals, it has been known for a long time that the brain mechanisms underlying externally triggered and internally initiated goal-directed behavior must be different, as there are patients who do very well when the clinician asks them to carry out various cognitive and behavioral tasks, including ones that measure so-called executive functions, however, the very same patients might be unable to take initiative and make their own internally driven choices to pursue meaningful goals on their own. In neuroimaging studies, the neural basis of switching from one task to another has been mostly studied using cue-stimulus triggered paradigms. What has remained less well known, due in large part to obvious methodological challenges in measuring the timing of “internal triggers”, is which brain mechanisms underlie genuine internally driven task selection.

In their recent study, Soon et al. (2013) used functional magnetic resonance imaging in a group of 34 healthy volunteers to study brain mechanisms that precede internally initiated task selection. The authors set up a paradigm where subjects voluntarily engaged into mental tasks of adding or subtracting. Brain hemodynamic activity patterns preceding task initiation / selection were then examined using multivoxel pattern analysis algorithms. It was observed that intention to switch task could be decoded from patterns of hemodynamic activity within medial prefrontal cortex and parietal cortex, areas partly overlapping with the so-called default-mode network, as early as four seconds before the subjects self-estimated having become consciously aware of their choices.

These highly important findings not only disclose brain areas that underlie internally driven task selection, but also provide important methodological advances that can be utilized in further studies on this important research question. Notably, it was shown that specifically the distributed pattern of brain activity held the information that predicted the initiation of task switch, the overall amplitudes of hemodynamic activity within the medial prefrontal and parietal cortices failed to do so. The task paradigm devised by the authors is also one that can be readily modified for further studies of the neural basis of voluntary task selection.

Reference: Soon CS, He AH, Bode S, Haynes JD. Predicting free choices for abstract intentions. Proc Natl Acad Sci USA (2013) 110: 6217-6222. http://dx.doi.org/10.1073/pnas.1212218110