Hippocampal 5-HT4 serotonin receptor levels predict memory performance in human volunteers

The neurochemical basis of cognitive functions is one of the most fundamental of cognitive neuroscience research areas. Indeed, there is a vast body of literature documenting the effects of manipulating function of various neurotransmitter systems on different cognitive and perceptual functions. Given the increasing incidence of memory deficits with aging populations in western countries, neurotransmitter basis of memory functions is one of the most prominent research questions in this exciting area of research. In addition to findings linking acetylcholine function with memory consolidation, there is a body of literature suggesting a significant role for serotonin system in memory functions.

A recent study by Dr. Mette Haahr et al. (2012) combined mapping of levels of specific serotonin receptor called 5-HT4R in hippocampi of 30 healthy volunteers with neuropsychological measures of memory performance. Two memory tests were utilized; in a so-called Reys Auditory Verbal Learning Test, the participants were presented with 15 words on five separate accounts with free immediate recall of the list, as well as presentation of an interference list, on each trial. Delayed recall of the list occurred 30 minutes after the cessation of the task. This allowed deriving indices of both immediate recall and delayed recall. In another test called Rey-Osterrieth’s Complex Figure Test, the participants were to copy a complex geometric figure and then reproduce it from memory after delays of 3 and 30 minutes, with the number of aspects of the figure memorized after the 3-minute delay representing immediate recall, and memorization after the 30-min delay representing delayed recall.

When the memory performance of the participants was correlated with 5-HT4R receptor density in hippocampal areas, as quantified with positron emission tomography following injection of [11C]SB207145 tracer substance, negative correlations were observed between immediate recall scores in Reys Auditory Verbal Learning Test and 5-HT4R receptor densities in the hippocampus bilaterally, and with delayed recall scores in the right hippocampus. The authors note that theirs is the first study examining associations between hippocampal 5-HT4R density and memory functions in humans and, while the observed inverse relationship between receptor densities and memory function warrant further studies looking at the complex interactions between intrinsic serotonergic tonus and receptor levels, the authors suggest their findings predicting that stimulation of the human 5-HT4R could improve memory functions.

Reference: Haahr ME, Fisher P, Holst K, Madsen K, Jensen CG, Marner L, Lehel S, Baare W, Knudsen G, Hasselbalch S. The 5-HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans. Human Brain Mapping (2012) e-publication ahead of print. http://dx.doi.org/ 10.1002/hbm.22123

Superior-posterior temporal cortex decodes distances to sound sources

Quick and accurate localization of perceptual objects in our environment is a fundamentally important ability where the sense of hearing significantly complements that of vision. For instance, objects that are occluded or out of one’s field of vision (such as a rare bird chirping on branch behind a bird watcher) are efficiently and almost automatically segregated and localized by the auditory system in the three-dimensional space that surrounds oneself.  While a number of previous studies have suggested that there are neurons in superior-posterior temporal cortical areas specialized in localization of the directions that sounds emanate from, it has remained less well known wherein and how distance to sound sources are processed in the human brain. Importantly, the most salient sound distance cue, intensity of the sound, is not always a reliable one, as sound intensity can and does vary independently of source distance. Therefore it is feasible to assume that there are also other cues that the auditory system uses to decode distances to sound sources.  

A recent ingenious study by Dr. Norbert Kopčo et al. (2012) combined psychophysics, computational modeling, and functional magnetic resonance imaging to probe the neural basis of sound distance processing. The authors presented healthy volunteers with sounds at varying distances (15-100 cm) in a virtual reverberant environment. The behavioral results suggested that direct-to-reverberant ratio is, out of the intensity-independent distance cues, the most reliable one, but that discrimination performance is best explained by utilization of a combination direct-to-reverberant ratio and inter-aural level difference cues. Furthermore, inspection of the functional magnetic resonance data collected during presentation of the sounds at varying distances disclosed planum temporale and posterior superior temporal gyrus contralateral to the direction of stimulation as the auditory system structures underlying the decoding of distances to sound sources.

Reference: Kopčo N, Huang S, Belliveau JW, Raij T, Tengshe C, Ahveninen J. Neuronal representations of distance in human auditory cortex. Proc Natl Acad Sci USA (2012) 109: 11019-11024. http://dx.doi.org/10.1073/pnas.1119496109

Childhood maltreatment correlates with reactivity of amygdala to subliminally presented negative facial expressions

The human amygdala is known to respond to emotional stimuli that are presented subliminally, such as photographs of facial expressions presented so briefly (few tens of milliseconds) that conscious percept of the stimuli fails to take place. Interestingly, hyper-responsiveness of human amygdala to negative facial expressions has been observed in a number of psychiatric conditions including clinical depression, anxiety disorders, and borderline personality. One of the critical questions has been whether these deviations in pre-attentive amygdala responsiveness reflect a trait (caused by for example due to adverse childhood events) that predisposes to psychiatric conditions, or whether the psychiatric conditions (i.e., state) cause the negative processing bias.

In their recent study, Dannlowski et al. (2012) investigated in a sizeable group of healthy volunteers (N=150) whether childhood maltreatment predicts amygdala hyper-responsiveness to subliminally presented negative facial expressions. During functional magnetic resonance imaging, pictures depicting neutral, positive, and negative facial expressions were presented briefly (33 ms) followed immediately by presentation of a neutral facial expression that served as a masker stimulus. The authors assessed childhood maltreatment using childhood trauma questionnaire, which is a retrospective 25-item self-report questionnaire.

As hypothesized by the authors, there was a significant correlation between the childhood trauma questionnaire scores and amygdala hyper-responsiveness to subliminally presented sad facial expressions, which was not confounded by trait anxiety, current depression level, age, gender, intelligence, education level, or recent stressful life-events that the authors carefully controlled. While the authors quite correctly caution that only a prospective study could provide decisive evidence on a causal relationship between childhood maltreatment and pre-attentive amygdala hyper-responsiveness to negative facial expressions, these results nonetheless provide significant evidence for a link between maltreatment in childhood and aberrant automatic processing of negative emotional expressions in adulthood. Importantly, these findings might in part explain how childhood maltreatment predisposes individuals to development of psychiatric conditions, such as clinical depression, later in life.

Reference: Dannlowski U, Kugel H, Huber F, Stuhrmann A, Redlich R, Grotegerd D, Dohm K, Sehlmeyer K, Konrad C, Baune BT, Arolt V, Heindel W, Zwitserlood P, Suslow T. Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala. Human Brain Mapping (2012) e-publication ahead of print. http://dx.doi.org/10.1002/hbm.22112 

Comparison of monkeys and humans reveals superior temporal sulcus as the region that has evolved for human language processing

It has been often remarked that speech and language represent a highly specialized skill that is unique to humans. It is, however, increasingly recognized that animals do also use acoustic signals to communicate with conspecifics. This suggests that humans and certain other species are closer to each other with respect to evolution of language than what has been traditionally assumed, even though the human language is much more complex and refined than animal communication calls. The species-specific vocalizations of non-human primates constitute a prime example of this, however, there have been relatively few attempts to compare foci of brain responses to non-speech/communicative sounds vs. speech and communication calls in humans vs. non-human primates.

In their recent functional magnetic resonance imaging (fMRI) study, Olivier Joly et al. (2012), presented humans and macaque monkeys with monkey vocalizations, human emotional non-linguistic vocalizations, intelligible speech, non-intelligible speech, bird songs, as well as scrambled control sounds. The authors observed widespread hemodynamic responses in temporal, frontal and parietal cortical areas to vocalizations and scrambled control sounds in both species. Further, non-primary auditory areas in the temporal cortex preferentially responded to the intact sounds. Interestingly, parabelt areas extending into superior temporal gyrus responded to monkey vocalizations in macaques matching areas activated by unintelligible speech and emotional sounds in humans. Further, monkey superior temporal sulcus appeared as not responding to species-specific sounds, thus sharply contrasting with the human superior temporal sulcus (and Broca’s area) that specifically responded to intelligible speech.  

Taken together, the results of this highly interesting study suggest that evolution of language in humans has recruited most of the superior temporal sulcus, whereas in monkeys the much simpler species-specific vocalizations have not required corresponding involvement of this area. Methodologically, this pioneering study very nicely demonstrates how macaque and human brain function can be compared at multiple levels of processing using non-invasive functional magnetic resonance imaging, in addition to shedding light on the highly intriguing question of which brain areas have developed in humans to enable our rich language skills that have to a large part made it possible for human societies to emerge and develop.

Reference: Joly O, Pallier C, Ramus F, Pressnitzer D, Vanduffel W, Orban GA. Processing of vocalizations in humans and monkeys: a comparative fMRI study. Neuroimage (2012) 62: 1376-1389.  http://dx.doi.org/ 10.1016/j.neuroimage.2012.05.070

One year of aerobic exercise enhances white matter integrity in prefrontal and temporal areas in older adults

Aging-related decline in cognitive function is a rapidly increasing societal challenge in nations where the population is aging rapidly such as in European Union countries. With normal aging there are a number of changes in brain structure and function, and degeneration of cerebral white matter (that is composed of connections linking brain areas together) has been consistently observed to take place with aging. This degeneration of brain connectivity has been further observed to correlate with aging-related decline in cognitive functioning. While cardio-respiratory (i.e., aerobic) fitness has been reported to protect against aging-associated cognitive decline, the effects of aerobic fitness on white-matter integrity in aging have remained an open question.

In their recent study, Voss et al. (2012) showed that increased aerobic fitness caused by a one-year walking program predicted enhanced white-matter integrity in prefrontal and temporal lobe areas that are especially susceptible to the adverse effects of aging. Aerobic fitness that resulted from the exercise intervention also predicted short-term memory improvements. These results extend in a very interesting way the scope of applications of diffusion imaging methods and even though the authors failed to see any statistically significant associations between the increased white-matter integrity and short-term memory improvements, these results are nonetheless promising, provide an important contribution to understanding the neuro-cognitive protective effects of aerobic exercise in aging, and suggest that aerobic training is highly important for aging persons. 

Reference: Voss MW, Heo S, Prakash RS, Erickson KI, Alves H, Chaddock L, Szabo AN, Mailey EL, Wojcicki TR, White SM, Gothe N, McAuley E, Sutton BP, Kramer AF. The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention. Human Brain Mapping (2012), e-publication prior to print. http://dx.doi.org/10.1002/hbm.22119

Beta oscillations decrease in left inferior frontal gyrus when a word violates semantic expectations formed by preceding words

The event-related potential N400 response is elicited when a word violates semantic expectations formed by preceding words in a sentence, for example, the word “river” in sentence “Yesterday, I went to the grocery store to buy a river” would elicit an N400 response. Event-related potentials such as the N400 are obtained by averaging tens or even hundreds of electroencephalogram (EEG) or magnetoencephalogram (MEG) epochs time-locked to onset of stimuli (such as words that violate semantic expectations). The rationale behind this is that the much larger background EEG/MEG activity (that has been presumed to be non-interesting noise) is averaged out, thus leaving the signal of interest for scrutiny. Over the last couple of decades, alternative ways to inspect stimulus-related EEG and MEG activity have been steadily gaining popularity; in one of such approaches, instead of averaging the EEG/MEG trials, power as a function of time and frequency is calculated over the trials, thus allowing inspection of EEG/MEG oscillatory activity that is related to, yet not precisely time-locked to onset of, the stimuli. 

In their recent study, Lin Wang and colleagues (Wang et al. 2012) inspected oscillatory activity elicited by semantic violations that resulted in generation of the N400 event-related response. A correlation was observed between the N400 response (that was predominantly generated in auditory cortical areas) and decreased power in the beta frequency band within left-hemisphere inferior frontal gyrus. The authors suggested that beta suppression reflects larger effort within the task-relevant network (consisting of the left inferior frontal gyrus and that is part of the speech motor system and auditory cortical areas in the left superior temporal region) for attempting to integrate the incongruent word with the preceding context. These findings also add to the pool of evidence indicating that speech motor system plays an important role in speech perception, and further stress the importance of inspecting electromagnetic activity not strictly time-locked to onset of stimuli, in addition to assessing event-related responses, in EEG and MEG studies.

Reference: Wang L, Jensen O, van den Brink D, Weder N, Schoffelen J-M, Magyari L, Hagoort P, Bastiaansen M. Beta oscillations relate to the N400m during language comprehension. Human Brain Mapping (2012), e-publication ahead of print.  http://dx.doi.org/10.1002/hbm.21410

Emotions synchronize brain activity across individuals

Emotions are highly contagious and it is often noted that emotional states can spread rapidly through a large crowd such as when a peaceful demonstration turns into a riot. In their recent study Nummenmaa et al. (2012) shed light on the underlying neural mechanisms. The authors showed short (on average ~90 s) movie clips depicting humans experiencing either strong positive or negative emotions (or in control clips a neutral state) to 16 healthy volunteers during 3-Tesla functional magnetic resonance imaging.  Immediately after the scanning session, the subjects were asked to continuously rate their emotional state while watching the movie clips on two scales: emotional valence (varying from negative to positive emotional state) and emotional arousal (varying from drowsy to highly aroused).

The authors calculated 17-s moving average of inter-subject correlations of brain hemodynamic responses. The resulting inter-subject brain synchrony time courses were then predicted with the emotional valence and arousal ratings to probe which brain areas are synchronized by emotional states. While high arousal predicted across-subjects synchronous brain activity in somatosensory and visual cortices and dorsal attention networks (comprising intraparietal sulci and frontal eye fields), negative valence predicted increased inter-subject synchrony in emotion-processing networks and in the so-called default-mode network (i.e., precuneous, temporoparietal junction, medial prefrontal cortex and posterior superior temporal sulcus). In contrast to negative valence, positive valence was not observed to enhance inter-subject synchrony of brain activity.

Based on these results, the authors proposed that high arousal directs attention of individuals to similar features in their environment, and that negative valence (i.e., unpleasant emotional states) synchronizes the brain areas of individuals that give rise to emotional states and support understanding of the actions of others. The authors further suggested that positive emotions did not result in increased inter-subject synchrony of brain activity due to positive emotions triggering planning of novel and exploratory thoughts and behaviors, whilst negative emotions can be surmised to trigger for example fight-or-flight responses that results in narrowing of mental/behavioral repertoires. The authors conclude that by synchronizing brain activity across individuals, emotions may promote social interaction and facilitate interpersonal understanding.

Reference:

Nummenmaa L, Glerean E, Viinikainen M, Jaaskelainen IP, Hari R, Sams M. Emotions promote social interaction by synchronizing brain activity across individuals. PNAS (2012) epublication ahead of print.  http://dx.doi.org/10.1073/pnas.1206095109

Emotions are generated by activity patterns of networks of brain areas

The neural basis of emotions is at the same time one of the most interesting and challenging puzzles in cognitive neuroscience. One of the most topical questions is whether specific brain structures generate six basic emotions (fear, happiness, disgust, anger, surprise, sadness) or whether discrete emotions are generated by some other brain mechanisms. A recent theoretical / meta-analysis paper by Lindquist et al. (2012) provides a comprehensive review and insightful synthesis of recent emotion neuroimaging literature. In their meta-analysis, Lindquist et al. specifically focus on addressing the question of whether the particular brain structures that have been implicated to underlie the basic emotions are consistent and specific in their response to a given emotion category; for instance, whether activation of the amygdala is always—and only—related to fearfulness, or whether some other aspect such as stimulus novelty and/or need to quickly determine potential harmfulness of an external stimulus governs amygdala activity (in which case amygdala would contribute rather differently to emotional experiences).

Based on their literature synthesis, Lindquist et al. propose that there is evidence supporting a so-called psychological constructionist approach, which states that discrete emotion categories are constructed by more general activity patterns of networks of brain areas that are not specific to the basic emotion categories. In contrast, little evidence was found supporting the hypothesis that discrete emotion categories would be consistently and specifically localized to distinct brain regions; as one example of this, amygdala that has been traditionally viewed as responding to fear-eliciting stimuli, does respond to stimuli of other emotion categories, habituates quickly, and does not exhibit activity in persons who are anticipating a fear/anxiety-eliciting situation (e.g., stage performance). Importantly, the solid theoretical framework proposed by Lindquist et al. provides multiple empirically testable hypotheses for future neuroimaging studies on the neural basis of emotions.

Reference: Lindquist KA, Wager TD, Kober H, Bliss-Moreau E, Feldman Barrett L. The brain basis of emotion: a meta-analytic review. Behavioral and Brain Sciences (2012) 35: 121-202. http://dx.doi.org/10.1017/S0140525X11000446

Theory-of-mind engages brain autobiographical memory mechanisms when inferring the mental states of familiar people

Theory of mind refers to one’s ability to infer mental states of other persons (what they think, feel, know and do not know, their intentions etc) that is arguably one of the most fascinating of human cognitive abilities. The constituent processes of theory of mind ability (such as being able to retrieve relevant person-specific information from memory) have remained less well known. Previous neuroimaging studies that have utilized theory-of-mind tasks have reported that there is an overlap between brain regions that are activated during theory-of-mind and autobiographical memory tasks, thus suggesting that one retrieves past personal experiences when inferring mental states of other persons. In contrast, however, brain lesions studies have shown that theory of mind ability is not necessarily disrupted in amnesic patients.

In their recent neuroimaging study, Rabin and Rosenbaum (2012) addressed the question of whether the reliance on autobiographical memory during theory-of-mind tasks depends on whether or not the person about whom inferences are made is personally known. The authors requested healthy volunteers to 1) remember past experiences when presented with personal photos and 2) to imagine experiences of others to photos who were personally familiar vs. 3) unfamiliar. A spatiotemporal partial least squares analysis of the functional magnetic resonance imaging data that were acquired during these tasks revealed neural activation patterns associated with the autobiographical memory, and theory of mind tasks during the personally familiar and unfamiliar conditions.

Interestingly, there was overlap between brain activity patterns in the autobiographical memory condition and in the theory-of-mind condition that involved inference of mental states of personally known others. In contrast, brain regions associated with social semantic memory were activated during inference of mental states of unfamiliar others. Taken together the results of Rabin and Rosenbaum reveal important information about the constituent processes of theory-of-mind ability and the underlying neural mechanisms; it seems that theory-of-mind engages autobiographical memory when personally familiar others are the subjects of mental state inference, and general social semantic memory when the subject of mental state inference is an unknown person.

Reference:

Rabin JS, Rosenbaum RS. Familiarity modulates the functional relationship between theory of mind and autobiographical memory. Neuroimage (2012, available online prior to printed publication). http://dx.doi.org/10.1016/j.neuroimage.2012.05.002

Phase-synchrony metrics allow inspection of inter-subject similarity at high temporal resolution

Recent studies have demonstrated that it is possible to use feature films (see Hasson et al. 2010) and music (Alluri et al. 2012) as highly dynamic naturalistic stimuli in functional magnetic resonance imaging studies. This constitutes a highly significant step forward as it enables one to study cognitive functions that would otherwise be difficult to engage under the neuroimaging laboratory conditions such as emotions, social perception and cognition, and perception of higher-order musical features. Analysis of the resulting highly multidimensional neuroimaging data is not trivial and while functional brain activity under naturalistic viewing conditions has been successfully analyzed by calculating inter-subject correlations of hemodynamic data, inspection of temporal dynamics of inter-subject similarity using inter-subject correlation has been challenging as the correlations have to be calculated over sliding time windows of ~10-20 seconds.

Glerean et al. 2012 show that it is possible to increase temporal resolution by using instantaneous phase synchronization rather than inter-subject correlation as the measure of dynamic (time-varying) functional connectivity. In their study, Glerean et al. applied inter-subject phase-synchrony on a functional magnetic resonance imaging dataset obtained while 12 healthy volunteers watched a feature film. In addition, they compared across-subject similarities of phase-synchrony that take place between brain areas (similarly to the widely used seed-voxel correlation method that also suffers from compromised temporal accuracy), denoting this as seed-based inter-subject phase-synchrony.

The findings of Glerean et al. suggest that the tested phase-synchrony metrics yield results that are consistent with both seed-based correlation and inter-subject correlation methods when inspected over the whole duration of the movie, but provide superior (an order of magnitude better) temporal resolution for estimates of how similarly brains of individual subjects are processing the various features and events of the movie. These results thus provide a significant methodological step forward in making it possible to use highly naturalistic stimuli in neuroimaging studies and remarkably broaden the possibilities of cognitive neuroimaging. The matlab algorithms for calculating the phase-synchrony metrics of functional magnetic resonance imaging data are freely downloadable from http://becs.aalto.fi/bml/software.html

References: 

Alluri V, Toiviainen P, Jääskeläinen IP, Glerean E, Sams M, Brattico E.Large-scale brain networks emerge from dynamic processing of musical timbre, key and rhythm. Neuroimage (2012) 59: 3677-3689. http://dx.doi.org/10.1016/j.neuroimage.2011.11.019

Glerean E, Salmi J, Lahnakoski JM, Jääskeläinen IP, Sams M. FMRI phase synchronization as a measure of dynamic functional connectivity. Brain Connectivity (2012) (epublication ahead of print May 4). http://dx.doi.org/10.1089/brain.2011.0068

Hasson U, Malach R, Heeger DJ. Reliability of cortical activity during natural stimulation. Trends in Cognitive Sciences (2010) 14: 40-48. http://dx.doi.org/10.1016/j.tics.2009.10.011

Inter-individual differences in human dopamine systems predict individual differences in decision-making

Dopamine has been identified in a large number of studies as a neurotransmitter that plays a central role in decision-making. In animal studies, for example, when healthy rats are to choose between freely available less desirable food and exerting effort to obtain more desirable food, they tend to choose the latter; and blocking the dopamine system decreases, and enhancing the dopaminergic system further increases, preference to exert effort to obtain the better-tasting food. What has been less clear is whether inter-individual differences in dopamine function in humans can predict variability in decision-making.

Treadway et al. (2012) recently studied the role of dopamine in effort-based decision-making is healthy humans. In their study, healthy volunteers were scanned with positron emission tomography (using [¹⁸F]fallypride and d-amphetamine) to quantify inter-individual differences in dopaminergic function. The same subjects also underwent a so-called effort expenditure for rewards task. In this task, subjects can choose between high-effort and low-effort trials that require different amounts of speeded button presses. If successful, the participants earn a lower monetary reward in the low-effort condition, and a higher reward in the high-effort condition; however, each successfully completed trial is not rewarded, as there are no-win trials. Before making their choice between the low and high effort conditions, the subjects are indicated the probability of winning (if successful) that varies between “high” (88% of successful trials rewarded), “medium” (50%), and “low” (12%).

The positron emission tomography data showed that there were inter-individual differences in dopamine function in multiple brain structures that correlated with the results of the behavioral task. Inter-individual variation in dopamine function in the left striatum and bilateral ventromedial prefrontal cortex correlated positively with the willingness to exert greater effort to obtain larger rewards in cases where the probability of reward receipt was lower. Insula, in contrast, showed a negative correlation between dopamine function and decision-making. This latter finding is in line with findings in previous studies suggesting that insula plays a central role in processing of response costs. Taken together, these highly interesting findings show that inter-individual differences in dopamine function explain individual differences in cost-benefit decision-making in human volunteers.

Reference: Treadway MT, Buckholtz JW, Cowan RL, Woodward ND, Li R, Ansari MS, Baldwin RM, Schwartzman AN, Kessler RM, Zald DH. Dopaminergic mechanisms of individual differences in human effort-based decision-making. J Neurosci (2012) 32: 6170-6176. http://dx.doi.org/10.1523/JNEUROSCI.6459-11.2012

The six basic emotions are not culturally universal after all

In everyday life we use a plethora of words to describe various emotional states (and facial expressions) such as “upset”, “nervous”, “delighted”, “contended”, and “flabbergasted”. One of the most intriguing questions in emotion research has been which of (and to what extent) these emotions are culturally shaped, and to what extent facial expressions are universal across cultures, driven more by “nature” (i.e., human biology) than “nurture”. To solve this question, emotion researchers have looked for culturally shared basic emotions and it has become a more or less consensual view that there are six culturally universal basic emotions: happy, surprised, fearful, disgusted, angry, and sad.

In their highly interesting study, Jack et al. (in PNAS early view) report findings that challenge the view of culturally universal basic emotions. In their study, Western Caucasian and Eastern Asian subjects perceived 4800 computer-generated random facial expressions (that were based on simulated contractions of facial muscles, for a short video example of a random expression, see http://www.pnas.org/content/suppl/2012/04/12/1200155109.DCSupplemental/sm01.avi). The task of the  subjects was to categorize each of the facial expressions as either one of the six basic emotions or “don’t know” and, in case one of the six basic emotions was detected, also rate the intensity of the emotion. Based on these ratings facial action unit (muscle group) models for the six basic emotions (as well as for emotion intensity) were generated for the two cultures.

Comparison of the Western Caucasian and East Asian models revealed that the two groups perceived the six basic emotions differently and, furthermore, the intensity ratings of the emotional expressions also differed between the cultures. Specifically, Western Caucasian subjects appeared to perceive each of the six basic emotions based on a distinct set of facial muscles (as predicted based on previous studies). In contrast, in the East Asian subjects the emotion categories considerably overlapped; furthermore, for the perceived intensity of emotions, early movements of the eyes appeared to be important cues for Eastern Asian subjects in contrast to the Western Caucasian subjects. For video examples of Western Caucasian and East Asian facial expressions see http://www.psy.gla.ac.uk/~rachael/4D_FoE_Culture/. These results constitute an important step forward in emotion research and potentially also help explain misunderstandings that may arise in social interactions between representatives from different cultural backgrounds.

Reference: Jack RE, Garrod OG, Yu H, Caldara R, Schyns PG. Facial expressions of emotion are not culturally universal. Proc Natl Acade Sci USA (2012). http://dx.doi.org/10.1073/pnas.1200155109

Human visual cortex area V2 is necessary for visual awareness

The human visual cortex (that encompasses posterior parts of the occipital lobes in the very back of the brain) is composed of multiple functionally distinct areas. According to classical hierarchical processing models, neurons in the primary visual cortex (also known as V1) are sensitive to fairly simple visual stimulus features (such as lines of certain orientation), and as one progresses from the V1 to the neighboring area V2 (and from V2 to higher order areas) inputs converge so that neurons begin to respond to increasingly complex visual features, such as perceptual objects (e.g., chairs, cows, hats) in the lateral occipital complex. What has puzzled researchers, however, is the point(s) at which visual awareness takes place in this processing chain; while there are studies indicating that removal of/damage to V1 results in lack of visual awareness, it is possible that this is due to V1 distributing information to higher-order areas, rather than V1 generating visual awareness per se.

Salminen-Vaparanta and colleagues, by inducing currents on the cortical surface using transcranial magnetic stimulation (TMS), specifically disturbed the functioning of area V2 in healthy volunteers (N.B. the disturbance of a cortical area using TMS is highly transient and does not produce any longer-lasting adverse effects). During this transient disruption of area V2, the subjects lost awareness of visual stimuli that were presented to them. Specifically, suppressing the V2 (without concomitant suppression of V1) 44-84 ms from the onset of a visual stimulus resulted in lack of conscious percept of the stimulus. The results of Salminen-Vaparanta thus suggest that area V2 is necessary for conscious visual experience. Methodologically, their study nicely demonstrates how TMS can be utilized to probe the role of various cortical areas in higher-order cognitive functions, such as visual awareness.

Reference: Salminen-Vaparanta N, Koivisto M, Noreika V, Vanni S, Revonsuo A. Neuronavigated transcranial magnetic stimulation suggests that area V2 is necessary for visual awareness. Neuropsychologia (2012). http://dx.doi.org/10.1016/j.neuropsychologia.2012.03.015

Inflammatory state augments orbitofrontal cortex responses to negative pictures

While there have been several interesting studies reporting associations between inflammatory state and clinical depression (see, for instance, Irwin & Miller 2007), the potential underlying neural mechanisms have remained largely unexplored. In a recent study by Jennifer Kullmann et al. published in Human Brain Mapping (currently available online as a pre-publication "early view" article), healthy volunteers were given an injection of either saline or bacterial lipopolysaccharide (0.4 ng/kg) that caused an acute inflammatory reaction, including rise in body temperature, and increase in plasma levels of pro- and anti-inflammatory cytokines and cortisol. The effects of acute inflammation on brain responses to negative-valence aversive pictures vs. emotionally neutral pictures was then investigated using functional magnetic resonance imaging.

The authors observed that the activation to presentation of negative-valence pictures of especially right-hemisphere inferior orbitofrontal cortex (at lower statistical threshold also several other brain structures) was augmented during acute inflammatory response. Given that the orbitofrontal cortex has been in previous studies associated with emotion-regulation (e.g., inhibition of amygdala activity during suppression of emotional responses) and production of affective states in response to emotional stimuli, the authors interpreted their findings as indicating that the subjects were more susceptible to the emotion-inducing effects of the aversive pictorial stimuli during the peripheral inflammatory response. These findings are highly interesting as they disclose a potential mechanism through which inflammatory state modulates affective processing and may thus play a role in the development of mood disorders.

Curiously, a recent Cochrane meta analysis indicated that mirtazapine, an older antidepressant that has antihistaminergic effects (that reduce inflammatory response) in addition to it's effects on various 5-HT receptors, was more effective in the treatment of clinical depression than the newer selective serotonin re-uptake inhibitors (Watanabe N et al. 2011). There are also findings suggesting that co-administration of an anti-inflammatory drug with selective serotonin re-uptake inhibitors improves treatment outcome in patients suffering from clinical depression (Akhondzadeh S et al. 2009). Overall, these findings highlight the important principle that the brain, and thus disorders of brain function, is never quite separate from the rest of the body (or the environment), but rather that brain function is significantly intertwined with bodily functions.

References:

Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depression and Anxiety (2009) 26: 607-611. http://dx.doi.org/10.1002/da.20589

Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain, Behavior, and Immunity (2007) 21: 374-383. http://dx.doi.org/10.1016/j.bbi.2007.01.010

Kullmann JS, Grigoleit JS, Lichte P, Kobbe P, Rosenberger C, Banner C, Wolf OT, Engler H, Oberbeck R, Elsenbruch S, Bingel U, Forsting M, Gizewski ER, Schedlowski M. Neural response to emotional stimuli during experimental human endotoxemia. Human Brain Mapping (2012). http://dx.doi.org/10.1002/hbm.22063

Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA. Mirtazapine versus other antidepressive agents for depression. Cochrane Database of Systematic Reviews (2011) 12. Art. No.: CD006528. http://dx.doi.org/10.1002/14651858.CD006528.pub2

Diffusion imaging reveals anatomical connectivity and microstructural changes due to learning

Diffusion imaging is a method where magnetic resonance imaging is utilized to measure movement of water within the brain; in modern diffusion imaging sequences water movement is measured in several tens of directions. Since the glia cells and neurons that make up the brain tissue obstruct free diffusion of water, there are significant deviations from Brownian (i.e., random) motion in most brain structures (other than ventricles of course). What makes this phenomenon really interesting is that by measuring the directions of local diffusion, it is possible to reconstruct the white matter tracts of the brain (as water flows along the direction of the myelinated neural fibers) and thus inspect anatomical connectivity of the brain. A recent paper by Dr. Wedeen and colleagues published in Science shows how accurately the anatomical connectivity of human brain can be measured non-invasively in healthy volunteers. This paper nicely combines the vast improvements that have recently taken place in both diffusion imaging sequences as well as data analysis methods.

As another highly interesting recent publication on diffusion imaging, it was shown by Sagi et al. in Neuron that there are rapid changes in diffusion properties of focal brain structures that correlate with learning. In this study, diffusion was measured prior to and immediately after volunteers were intensely playing a car-racing game where they had to learn to navigate the racetrack. One control group was playing the same game but with changing racetracks so that their spatial learning was not to the same extent engaged during the gameplay. Compared to pre-game diffusion measures, there were microstructural changes revealed by diffusion imaging after two hours of racing in several brain structures and, furthermore, learning the racetrack correlated with microstructural changes in the right-hemisphere parahippocampus. These results are really fascinating as they suggest that structural imaging can be utilized to measure short-term plastic changes in the human brain.

References:

Sagi Y, Tavor I, Hofstetter S, Tzur-Moryosef S, Blumenfeld-Katzir T, Assaf Y. Learning in the fast lane: new insights into neuroplasticity. Neuron (2012) 73: 1195-1203. http://dx.doi.org/10.1016/j.neuron.2012.01.025

Wedeen VJ, Rosene DL, Wang R, Dai G, Mortazavi F, Hagmann P, Kaas JH, Tseng WY. The geometric structure of the brain fiber pathways. Science (2012) 335: 1628-1634. http://dx.doi.org/10.1126/science.1215280

Cortical network properties predict language learning ability

Findings by Sheppard et al. published in the Journal of Cognitive Neuroscience, reveal interesting brain functional network properties that make it easier for some to learn words of a new language. The authors of this study used functional magnetic resonance imaging to map brain hemodynamic responses of a group of volunteers during a pitch discrimination task. Subsequently, the volunteers participated in another experiment where they were to learn words of an artificial (spoken) language. Interestingly, results of network analysis of brain hemodynamic data obtained during the pitch discrimination task predicted individual differences in spoken language learning ability.

Brain networks were analyzed by the authors by reconstructing the cortical surface of each subject and by dividing the cortex into ~1000 nodes. Person’s correlation coefficients were then calculated between hemodynamic response time series of each of the nodes and correlations exceeding a certain threshold value were considered as a functional connection between two nodes. Network analysis across all the nodes revealed differences between successful and less successful learners. Successful learners had higher global efficiency, meaning that there were, on the average, fewer edges separating the nodes of their cortical networks from each other. On the other hand, local efficiency measure was higher in the less successful learners, suggesting that their local network connectivity was higher than in successful learners. When analyzed across specific anatomical regions, it was further observed that these network differences could be observed in prefrontal and parietal cortical areas bilaterally as well as in the right temporal cortex.

Network analysis offers a powerful alternative method that complements the more traditional functional neuroimaging data analysis methods. With a network analysis it can be effectively measured how cortical areas work together to give rise to perceptual and cognitive functions. In this particular study, it was very nicely observed that network properties of brain function predicted language learning capability, and I anticipate that we will see in the near future a wealth of highly interesting findings in cognitive neuroscience that are based on network analysis methodology. Furthermore, it would be interesting to see whether cortical functional network properties differ between healthy individuals and those suffering from language disorders such as dyslexia.

Reference: Sheppard JP, Wang JP, Wong PC. Large-scale cortical network properties predict future sound-to-word learning success. Journal of Cognitive Neuroscience (2012) 24: 1087-1103. http://dx.doi.org/10.1162/jocn_a_00210

Movies as stimuli in cognitive neuroscience

In 2004, Dr. Uri Hasson and his colleagues published rather amazing findings in Science; they showed that brain hemodynamic activity patterns, measured with non-invasive functional magnetic resonance imaging, were highly replicable across individual volunteers who were freely viewing a 30 min clip from the feature film "The Good, the Bad and the Ugly" (dir. Sergio Leone, 1966). These findings elicited hopes for being able to use feature films in studies of perceptual and cognitive functions and, indeed, it was soon demonstrated that "higher-order" prefrontal cortical areas are also synchronized across subjects when viewing a feature film during brain scanning (Jaaskelainen et al. 2008). 

This week there was another step forward that is making it possible to use feature films in non-invasive cognitive neuroimaging studies. Lahnakoski et al. (2012) showed in their study published in PLoS ONE how annotating stimulus features that occur in a movie can be utilized in the analysis of the highly complex and spatiotemporally overlapping brain responses that are elicited when subjects are watching a movie. The stimulus feature time series were both used in a general linear model and correlated with independent components. The authors report that, taken together, the results encourage use of movie stimuli in non-invasive cognitive neuroimaging studies.

While the advances presented by Lahnakoski et al. are mostly methodological ones, feature films present exciting possibilities to any cognitive neuroscientist; they can be highly involving, capable of eliciting genuine emotions in experimental subjects, and often depict social interactions in a highly realistic manner along with all those subtle social cues that take place in real life. This way, movies can be highly effective in stimulating brain processes that underlie emotions and social cognition, thus potentially helping bridge one of the bigger gaps that still today exist between psychology and neuroscience.

References:

Hasson U, Nir Y, Furhmann G, Malach R. Intersubject synchronization of cortical activity during natural vision. Science (2004) 303: 1634-1640. http://dx.doi.org/10.1126/science.1089506

Jääskeläinen IP, Koskentalo K, Balk MH, Autti T, Kauramäki J, Pomren C, Sams M. Inter-subject synchronization of prefrontal cortex hemodynamic activity during natural viewing. Open Neuroimaging Journal (2008) 2: 14-19. http://dx.doi.org/10.2174/1874440000802010014

Lahnakoski JM, Salmi J, Jääskeläinen IP, Lampinen J, Glerean E, Tikka P, Sams M. Stimulus-related independent component and voxel-wise analysis of human brain activity during free viewing of a feature film. PLoS ONE (2012) 7: e35215. http://dx.doi.org/10.1371/journal.pone.0035215