Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. SIGNIFICANCE STATEMENT: In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function.

Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.

Processing of hierarchical syntactic structure in music.

Hierarchical structure with nested nonlocal dependencies is a key feature of human language and can be identified theoretically in most pieces of tonal music. However, previous studies have argued against the perception of such structures in music. Here, we show processing of nonlocal dependencies in music. We presented chorales by J. S. Bach and modified versions in which the hierarchical structure was rendered irregular whereas the local structure was kept intact. Brain electric responses differed between regular and irregular hierarchical structures, in both musicians and nonmusicians. This finding indicates that, when listening to music, humans apply cognitive processes that are capable of dealing with long-distance dependencies resulting from hierarchically organized syntactic structures. Our results reveal that a brain mechanism fundamental for syntactic processing is engaged during the perception of music, indicating that processing of hierarchical structure with nested nonlocal dependencies is not just a key component of human language, but a multidomain capacity of human cognition.

Differential effects of early life stress on hippocampus and amygdala volume as a function of emotional abilities.

Early life stress (ELS) is known to have considerable influence on brain development and affective functioning. Previous studies in clinical populations have shown that hippocampus and amygdala, two central structures of limbic emotion processing circuits, are predominantly affected by early stress exposure. Given the inconsistent findings on ELS-related effects in healthy populations and the associations of ELS and affective functioning, the question arises which additional emotion-relevant variables need to be considered to better understand the effects of ELS. We, therefore, investigated the volume of hippocampus and amygdala in 25 high alexithymic (h-ALEX) and 25 low alexithymic (l-ALEX) individuals, which were matched with regard to ELS, but significantly differed in their degree of emotional functioning. Volumetric analyses were performed using FSL-FIRST, a method to automatically segment subcortical structures on T1-weighted magnetic resonance images. Alexithymia was assessed using the Toronto Alexithymia Scale and Bermond-Vorst Alexithymia Questionnaire. ELS was assessed by Childhood Trauma Questionnaire (CTQ) and Early Trauma Inventory. Our data showed that ELS was negatively associated with right hippocampus volume in h-ALEX individuals, while there was no such association in the l-ALEX group. Furthermore, ELS was positively associated with left amygdala volume in l-ALEX individuals, but not in individuals with high levels of alexithymia. The present study emphasizes a substantial relationship between intrapersonal factors, such as alexithymia and neural alterations related to the experience of ELS. Longitudinal study designs are necessary to pursue the question of how emotional abilities interact with individual adaptations to early stress exposure on the neural level.

Normative development of white matter tracts: similarities and differences in relation to age, gender, and intelligence.

The white matter of the brain undergoes a range of structural changes throughout development; from conception to birth, in infancy, and onwards through childhood and adolescence. Several studies have used diffusion magnetic resonance imaging (dMRI) to investigate these changes, but a consensus has not yet emerged on which white matter tracts undergo changes in the later stages of development or what the most important driving factors are behind these changes. In this study of typically developing 8- to 16-year-old children, we use a comprehensive data-driven approach based on principal components analysis to identify effects of age, gender, and brain volume on dMRI parameters, as well as their relative importance. We also show that secondary components of these parameters predict full-scale IQ, independently of the age- and gender-related effects. This overarching assessment of the common factors and gender differences in normal white matter tract development will help to advance understanding of this process in late childhood and adolescence.

Neural correlates of statistical learning in developmental dyslexia: An electroencephalography study.

The human brain extracts statistical regularities from the surrounding environment in a process called statistical learning. Behavioural evidence suggests that developmental dyslexia affects statistical learning. However, surprisingly few studies have assessed how developmental dyslexia affects the neural processing underlying this type of learning. We used electroencephalography to explore the neural correlates of an important aspect of statistical learning - sensitivity to transitional probabilities - in individuals with developmental dyslexia. Adults diagnosed with developmental dyslexia (n = 17) and controls (n = 19) were exposed to a continuous stream of sound triplets. Every so often, a triplet ending had a low transitional probability given the triplet's first two sounds ("statistical deviants"). Furthermore, every so often a triplet ending was presented from a deviant location ("acoustic deviants"). We examined mismatch negativity elicited by statistical deviants (sMMN), and MMN elicited by location deviants (i.e., acoustic changes). Acoustic deviants elicited a MMN which was larger in the control group than in the developmental dyslexia group. Statistical deviants elicited a small, yet significant, sMMN in the control group, but not in the developmental dyslexia group. However, the difference between the groups was not significant. Our findings indicate that the neural mechanisms underlying pre-attentive acoustic change detection and implicit statistical auditory learning are both affected in developmental dyslexia.

Unpredictability of the "when" influences prediction error processing of the "what" and "where".

The capability to establish accurate predictions is an integral part of learning. Whether predictions about different dimensions of a stimulus interact with each other, and whether such an interaction affects learning, has remained elusive. We conducted a statistical learning study with EEG (electroencephalography), where a stream of consecutive sound triplets was presented with deviants that were either: (a) statistical, depending on the triplet ending probability, (b) physical, due to a change in sound location or (c) double deviants, i.e. a combination of the two. We manipulated the predictability of stimulus-onset by using random stimulus-onset asynchronies. Temporal unpredictability due to random onsets reduced the neurophysiological responses to statistical and location deviants, as indexed by the statistical mismatch negativity (sMMN) and the location MMN. Our results demonstrate that the predictability of one stimulus attribute influences the processing of prediction error signals of other stimulus attributes, and thus also learning of those attributes.

Self-Compassion and Its Association With Ruminative Tendencies and Vagally Mediated Heart Rate Variability in Recurrent Major Depression.

Background: Recurrent Major Depressive Disorder (MDD) is one of the most disabling mental disorders in modern society. Prior research has shown that self-compassion protects against ruminative tendencies, a key feature of recurrent MDD. In addition, self-compassion has been found to be positively related to higher psychophysiological flexibility (indexed by a higher vagally mediated heart rate variability; vmHRV) in young, healthy adults. To our knowledge, there is a lack of studies on how self-compassion relates to vmHRV in patients with recurrent MDD. The aim of the current study was to investigate whether higher self-compassion would associate with (1) lower ruminative tendencies and (2) higher vmHRV in a sample of adults with recurrent MDD. Methods: We included a sample of 63 patients (46 females) between 20 and 71 years old (M = 40.24, SD = 12.8) with a history of three or more depressive episodes. They filled out the Self-Compassion Scale (SCS), Beck Depression Inventory (BDI), and Rumination Rating Scale (RRS). ECG (used to derive vmHRV) was acquired while resting and the square root of the mean squared differences of successive RR interval values (RMSSD) was calculated as measure of vmHRV. Results: As hypothesized, self-compassion was associated with lower ruminative tendencies. However, self-compassion was not associated with level of vmHRV. Several confounding variables were controlled for in the statistical analyses, and higher age predicted lower vmHRV across all statistical analyses. Conclusion: The results confirmed our hypothesis that higher self-compassion would be associated with lower ruminative tendencies in recurrent MDD. Contrary to our expectation, we did not find that the tendency to be more self-compassionate was associated with higher vmHRV. As such, higher self-compassion seems to relate with a lower tendency to ruminate about past mistakes and events but does not seem to relate to a flexible autonomic stress response (as indexed by higher vmHRV). Other potential explanatory factors for lower vmHRV in recurrent MDD is suggested as focus for exploration in future studies.

Neocortical substrates of feelings evoked with music in the ACC, insula, and somatosensory cortex.

Neurobiological models of emotion focus traditionally on limbic/paralimbic regions as neural substrates of emotion generation, and insular cortex (in conjunction with isocortical anterior cingulate cortex, ACC) as the neural substrate of feelings. An emerging view, however, highlights the importance of isocortical regions beyond insula and ACC for the subjective feeling of emotions. We used music to evoke feelings of joy and fear, and multivariate pattern analysis (MVPA) to decode representations of feeling states in functional magnetic resonance (fMRI) data of n = 24 participants. Most of the brain regions providing information about feeling representations were neocortical regions. These included, in addition to granular insula and cingulate cortex, primary and secondary somatosensory cortex, premotor cortex, frontal operculum, and auditory cortex. The multivoxel activity patterns corresponding to feeling representations emerged within a few seconds, gained in strength with increasing stimulus duration, and replicated results of a hypothesis-generating decoding analysis from an independent experiment. Our results indicate that several neocortical regions (including insula, cingulate, somatosensory and premotor cortices) are important for the generation and modulation of feeling states. We propose that secondary somatosensory cortex, which covers the parietal operculum and encroaches on the posterior insula, is of particular importance for the encoding of emotion percepts, i.e., preverbal representations of subjective feeling.

The illusion of absence: how a common feature of magic shows can explain a class of road accidents.

The purpose of the present note is to draw attention to the potential role of a recently discovered visual illusion in creating traffic accidents. The illusion consists in a compelling and immediate experience that the space behind an occluding object in the foreground is empty. Although the illusion refers to a region of space, which is invisible due to occlusion (a blind spot), there is evidence to suggest that it is nevertheless driven by visual mechanisms and that it can be just as deceptive and powerful as ordinary visual illusions. We suggest that this novel illusion can make situations involving blind spots in a road user's field of view even more dangerous than one would expect based on the lack of visibility by itself. This could be because it erroneously makes the road user feel that (s)he has actually seen everything there is to see, and thus has verified that the blind spot is empty. This hypothesis requires further testing before definitive conclusions can be drawn, but we wish to make researchers and authorities involved in the analysis of traffic accidents and on-the-spot crash investigations aware of its potential role in order to encourage registration of relevant data and facilitate further research.

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

Differences in electric brain responses to melodies and chords.

The music we usually listen to in everyday life consists of either single melodies or harmonized melodies (i.e., of melodies "accompanied" by chords). However, differences in the neural mechanisms underlying melodic and harmonic processing have remained largely unknown. Using EEG, this study compared effects of music-syntactic processing between chords and melodies. In melody blocks, sequences consisted of five tones, the final tone being either regular or irregular (p = .5). Analogously, in chord blocks, sequences consisted of five chords, the final chord function being either regular or irregular. Melodies were derived from the top voice of chord sequences, allowing a proper comparison between melodic and harmonic processing. Music-syntactic incongruities elicited an early anterior negativity with a latency of approximately 125 msec in both the melody and the chord conditions. This effect was followed in the chord condition, but not in the melody condition, by an additional negative effect that was maximal at approximately 180 msec. Both effects were maximal at frontal electrodes, but the later effect was more broadly distributed over the scalp than the earlier effect. These findings indicate that melodic information (which is also contained in the top voice of chords) is processed earlier and with partly different neural mechanisms than harmonic information of chords.

Volume reduction of caudate nucleus is associated with movement coordination deficits in patients with hippocampal atrophy due to perinatal hypoxia-ischaemia.

Acute sentinel hypoxia-ischaemia in neonates can target the hippocampus, mammillary bodies, thalamus, and the basal ganglia. Our previous work with paediatric patients with a history of hypoxia-ischaemia has revealed hippocampal and diencephalic damage that impacts cognitive memory. However, the structural and functional status of other brain regions vulnerable to hypoxia-ischaemia, such as the basal ganglia, has not been investigated in these patients. Furthermore, it is not known whether there are any behavioural sequelae of such damage, especially in patients with no diagnosis of neurological disorder. Based on the established role of the basal ganglia and the thalamus in movement coordination, we studied manual motor function in 20 participants exposed to neonatal hypoxia-ischaemia, and a group of 17 healthy controls of comparable age. The patients' handwriting speed and accuracy was within the normal range (Detailed Assessment of Speed of Handwriting), and their movement adaptation learning (Rotary Pursuit task) was comparable to the control group's performance. However, as a group, patients showed an impairment in the Grooved Pegboard task and a trend for impairment in speed of movement while performing the Rotary Pursuit task, suggesting that some patients have subtle deficits in fine, complex hand movements. Voxel-based morphometry and volumetry showed bilateral reduction in grey matter volume of the thalamus and caudate nucleus. Reduced volumes in the caudate nucleus correlated across patients with performance on the Grooved Pegboard task. In summary, the fine movement coordination deficit affecting the hand and the wrist in patients exposed to early hypoxic-ischaemic brain injury may be related to reduced volumes of the caudate nucleus, and consistent with anecdotal parental reports of clumsiness and coordination difficulties in this cohort.

Musical training modulates the development of syntax processing in children.

The question of how musical training can influence perceptual and cognitive abilities of children has been the subject of numerous past studies. However, evidence showing which neural mechanisms underlie changes in cognitive skills in another domain following musical training has remained sparse. Syntax processing in language and music has been shown to rely on overlapping neural resources, and this study compared the neural correlates of language- and music-syntactic processing between children with and without long-term musical training. Musically trained children had larger amplitudes of the ERAN (early right anterior negativity), elicited by music-syntactic irregularities. Furthermore, the ELAN (early left anterior negativity), a neurophysiological marker of syntax processing in language, was more strongly developed in these children, and they furthermore had an enlarged amplitude of a later negativity, assumed to reflect more sustained syntax processing. Thus, our data suggest that the neurophysiological mechanisms underlying syntax processing in music and language are developed earlier, and more strongly, in children with musical training.

When the statistical MMN meets the physical MMN.

How do listeners respond to prediction errors within patterned sequence of sounds? To answer this question we carried out a statistical learning study using electroencephalography (EEG). In a continuous auditory stream of sound triplets the deviations were either (a) statistical, in terms of transitional probability, (b) physical, due to a change in sound location (left or right speaker) or (c) a double deviants, i.e. a combination of the two. Statistical and physical deviants elicited a statistical mismatch negativity and a physical MMN respectively. Most importantly, we found that effects of statistical and physical deviants interacted (the statistical MMN was smaller when co-occurring with a physical deviant). Results show, for the first time, that processing of prediction errors due to statistical learning is affected by prediction errors due to physical deviance. Our findings thus show that the statistical MMN interacts with the physical MMN, implying that prediction error processing due to physical sound attributes suppresses processing of learned statistical properties of sounds.

Author Correction: When the statistical MMN meets the physical MMN.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Heroic music stimulates empowering thoughts during mind-wandering.

It is generally well-known, and scientifically well established, that music affects emotions and moods. However, only little is known about the influence of music on thoughts. This scarcity is particularly surprising given the importance of the valence of thoughts for psychological health and well-being. We presented excerpts of heroic- and sad-sounding music to n = 62 individuals, and collected thought probes after each excerpt, assessing the valence and the nature of thoughts stimulated by the music. Our results show that mind-wandering emerged during listening to either type of music (heroic, sad), and that the type of music strongly influenced the thought contents during mind-wandering. Heroic-sounding music evoked more positive, exciting, constructive, and motivating thoughts, while sad-sounding music evoked more calm or demotivating thoughts. The results thus indicate that music has a strong effect on the valence of thought contents during mind-wandering, with heroic music evoking more empowering and motivating thoughts, and sad music more relaxing or depressive thoughts. These findings have important implications for the use of music in everyday life to promote health and well-being in both clinical populations and healthy individuals.

The Association Between Juvenile Onset of Depression and Emotion Regulation Difficulties.

Juvenile onset of Major Depressive Disorder (MDD) is associated with increased likelihood of recurrent episodes of depression and more detrimental clinical trajectories. The aim of the current study was to investigate the effect of juvenile onset of MDD on emotion regulation as measured by self-report and Heart Rate Variability (HRV). Furthermore, we wanted to assess whether juvenile onset impacted the association between rumination and depressive symptoms. Sixty-four individuals with at least three prior episodes of MDD were recruited and filled out self-report questionnaires measuring rumination and emotion regulation abilities. In addition, electrocardiographic assessments were used to calculate HRV. Based on self-reported age of MDD onset, individuals were divided in two groups: Juvenile onset of MDD (first MDD episode before the age of 18, n = 30) and adult onset of MDD (first MDD episode after the age of 18, n = 34). Results showed that individuals whose first depressive episode occurred in childhood and adolescence reported more rumination and less emotional clarity compared to individuals who had their first episode of MDD in adulthood. Moreover, the tendency to ruminate was strongly associated with depressive symptoms in the juvenile onset of MDD group, whereas no such association was found in the adult onset group. There was no significant group difference for HRV. The findings are discussed in light of existing literature, in addition to suggesting how our findings may inform clinical practice and future research. We conclude that juvenile onset of MDD may lead to difficulties in emotion regulation and that these difficulties may increase depressive symptoms and vulnerability for relapse in this particular subgroup.

Short-term effects of processing musical syntax: an ERP study.

We investigated influences of short-term experience on music-syntactic processing, using a chord-sequence paradigm in which sequences ended on a harmony that was syntactically either regular or irregular. In contrast to previous studies (in which block durations were rather short), chord sequences were presented to participants for around 2 h while they were watching a silent movie with subtitles. Results showed that the music-syntactically irregular chord functions elicited an early right anterior negativity (ERAN), and that the ERAN amplitude significantly declined over the course of the experiment. The ERAN has previously been suggested to reflect the processing of music-syntactic irregularities, and the present data show that the cognitive representations of musical regularities are influenced by the repeated presentation of unexpected, irregular harmonies. Because harmonies were task-irrelevant, the data suggest that cognitive representations of musical regularities can change implicitly, i.e., even when listeners do not attend to the harmonies, and when they are presumably oblivious of the changes of such representations. Although the ERAN amplitude was significantly reduced, it was still present towards the end of the experiment at the right anterior electrodes, indicating that cognitive representations of basic music-syntactic regularities cannot easily be erased.

EEG correlates of moderate intermittent explosive disorder.

OBJECTIVE: We investigated electroencephalographic (EEG) correlates of moderate intermittent explosive disorder (mIED), which is characterized by uncontrollable, impulsive attacks that either manifest in aggressive outbursts of temper, or in implosive, auto-aggressive behaviour. METHODS: In two Experiments, EEG data were recorded during rest conditions, and while subjects were presented with auditory and visual stimuli. Additionally, scores of the I7 impulsivity scale (designed to capture acting on impulse) were obtained. RESULTS: In Experiment 1, individuals with mIED showed a stronger increase in the power of oscillatory activity in the beta band, along with a stronger power decrease in the theta band in response to both visual and auditory stimuli. Based on discriminant function analysis, a model of discriminant functions was derived that clearly separated the mIED group from the control group. In Experiment 2, subjects were categorized into either of two groups (supposedly without mIED, with mIED) based on this model of discriminant functions. Results showed that I7 impulsivity scores clearly differed between groups. CONCLUSIONS: The present data show a relation between oscillatory brain activity and mIED. They indicate that this brain activity is related to the impulsivity facet of impulsive action, and suggest that mIED can be assessed based on the analysis of electrophysiological data. SIGNIFICANCE: To our knowledge, this is the first study on EEG correlates of (m)IED. Results open up new perspectives for future investigations on disorders characterized by substantial impulsivity.