Enjoying Sad Music: What’s Going On In the Brain?

Post by Anastasia Sares

What's the science?

There are many components to an emotional response, such as whether it is pleasant or unpleasant, the intensity of an emotion, and our aesthetic enjoyment of the experience. This can lead to situations where we experience a “negative” emotion (like in response to a sad piece of music) but enjoy it at the same time. In addition, emotions are dynamic, but many carefully controlled studies focus on short stimuli and static responses. This week in NeuroImage, Sachs and colleagues dynamically tracked the neural responses of people listening to a sad (but enjoyable) piece of music in order to separate out different aspects of emotional cognition.

How did they do it?

Thirty-six participants first listened to three musical pieces passively in an MRI scanner. The pieces were unfamiliar, wordless, and validated for emotional content by prior testing. After the MRI, they were asked to complete a rating task, using a sliding scale to continuously track their emotional states while listening to the same pieces again. They listened to each song twice, separately evaluating their enjoyment of the song and its emotional quality/intensity (how happy/sad it was). Participants also completed questionnaires about musicality, empathy, anxiety, and depression.

One sad piece, in particular, was chosen for the fMRI analysis: Discovery of the Camp by Michael Kamen. It clocks in at 11 minutes, which gave ample opportunity to examine emotions unfolding over time. The idea of the analysis was to find parts of the brain that acted in synchrony across individuals—meaning that they were probably responding to some aspect of the stimulus. The authors did this by recording the brain activity at many points in the brain (voxels) and calculating the correlation of the signals between participants at each voxel using a process called inter-subject correlation. They also looked for brain regions where inter-subject correlations were predicted by changes in the emotion and enjoyment ratings.

What did they find?

Signals from auditory brain regions and some motor brain regions were correlated across participants while listening to the music. Most of these were likely driven by the auditory signal itself. However, signals were also correlated in the insula, which is involved in processing the body’s own internal changes and the emotional states of other people. Both sadness and enjoyment involved synchronization in striatal regions. The intensity of sadness ratings was additionally related to dynamic synchronization in the limbic network, while enjoyment ratings were related to auditory, orbitofrontal, and default mode networks. This shows the separation between the emotion communicated by the piece (processed in the limbic system) and the participant’s enjoyment (aesthetic evaluation and reward, processed in other regions).

One subcategory of the empathy questionnaire, fantasy, measures how transported a person is by a story or narrative and has previously been associated with the enjoyment of sad music. The authors, therefore, divided the participants into a high-fantasy and low-fantasy group to see whether their brain synchronization differed as a function of empathy. The high-fantasy group demonstrated more correlated activity in the left auditory cortex, extending to the middle temporal gyrus, frontal areas, and some visual areas. The low-fantasy group had more correlated activity in posterior auditory and parietal areas as well as the insula and caudate. The authors interpret the group differences in the following manner: high-fantasy participants may focus on reflecting, understanding, and visualizing emotions during music listening, and thus may enjoy sad music, while low-fantasy participants may have a more intense emotional response.

What's the impact?

This study separates the emotions communicated by a piece of music from the enjoyment of that music, showing that different brain networks are involved in processing various aspects of our emotional experience. Individual differences in empathy also play a role in our reaction to emotional stimuli. This is a step forward, but we are still only scratching the surface of the rich and complex nature of human emotion.

Sachs et al. Dynamic intersubject neural synchronization reflects affective responses to sad music. NeuroImage (2019). Access the original scientific publication here.

The Relationship Between Vitamin D and Brain Morphology in Children

Post by Kasey Hemington

What's the science?

Maternal vitamin D deficiencies during gestation have been associated with cognitive or neuropsychiatric disorders in offspring, such as autism, lower IQ, and schizophrenia. However, the neurobiological basis of these links (for example, between autism and low vitamin D) remain unclear. Further, our understanding of how gestational vitamin D affects brain morphology during development is limited. In animal studies lower gestational vitamin D has been associated with smaller brain volumes, however, there have been no investigations of the effects of vitamin D on brain morphology in human children. This week in NeuroImage, Zou and colleagues used different structural magnetic resonance imaging (MRI) techniques to examine the relationship between gestational vitamin D levels in human mothers and the brain morphology of their offspring.

How did they do it?

As part of the prospective cohort Generation R study (Rotterdam, the Netherlands), the authors included data from 2597 mother-child dyads, where gestational vitamin D concentration information and structural MRI brain scans of the children (aged between 9-11 years) were available. Vitamin D concentration information was obtained via maternal blood-samples at mid-pregnancy, and at birth from the umbilical cord. Some dyads only had vitamin D concentration data at one of the time points and 1536 dyads had data at both time points. In their statistical analysis of the relationship between vitamin D concentration and different measures of brain morphology, the authors also included data on factors that could potentially confound the relationship: maternal age, ethnicity, socioeconomic factors, alcohol and drug use, vitamin supplement use, and the season at which the vitamin D concentration was sampled. Vitamin D concentration was studied both as a continuous variable and as a categorical variable, where categories were defined as ‘deficient’ (<25 nmol/L) ‘insufficient’ (25-50 nmol/L) and ‘sufficient’ (>50 nmol/L).

The authors assessed 1) The relationship between gestational vitamin D concentrations at mid-pregnancy and the child’s total brain volume, cortical grey matter volume, cortical white matter volume and cerebellar volume using multiple linear regression, 2) Whether having sufficient vitamin D concentration at only one time point or both time points was associated with different brain volumes, 3) The relationship between gestational vitamin D concentration and the brain volume of subcortical structures and brain ventricles, and 4) The relationship between vitamin D concentration and surface-based brain metrics: cortical thickness, surface area, and gyrification (the curvature or folding of the brain’s cortical surface). For each regression analysis, the authors created one model (‘Model 1’) with age at MRI scan and the child’s sex as covariates, and a second model (‘Model 2’) which included the other potential confounders described above.

What did they find?

Vitamin D concentration at mid-pregnancy and at birth was positively associated with the children’s total brain volume, total grey matter, and total white matter in Model 1, but not when other potential confounders were included (Model 2). Vitamin D concentration was positively associated with cerebellar volume in both models 1 and 2, but this relationship did not survive when the authors corrected their statistical analysis for multiple statistical comparisons. There was no association between vitamin D concentration category (deficient, insufficient, sufficient) and any measures of brain volume in model 1 or 2. However, smaller cerebral grey matter volumes were found in children who were ‘consistently insufficient’ or ‘consistently deficient’ (not sufficient at either time point) versus children who were ‘consistently sufficient’ children after correction for multiple statistical comparisons. Smaller total brain cerebral white matter volumes were also seen in ‘consistently deficient’ children compared to the ‘consistently sufficient’ group. No relationships were found between subcortical or ventricle volume and vitamin D concentration. Finally, when the authors assessed cortical thickness, surface area, and gyrification in other groups compared to the ‘consistently sufficient’ group, they found smaller surface area of temporal region of the right hemisphere of the brain in children with ‘consistently insufficient’ vitamin D concentrations and smaller frontal and occipital surface area in the right hemisphere and less gyrification in the left hemisphere in those ‘consistently deficient’ in models 1 and 2.

What's the impact?

This study, which is the first longitudinal study to assess the relationship between brain morphology in children and gestational vitamin D levels, found that consistently low vitamin D levels were associated with smaller brain volumes and different brain surface area and gyrification in children. Studies such as this could help to provide insight on the link between vitamin D deficiencies and neurodevelopment or neuropsychiatric abnormalities. 

Zou et al. A prospective population-based study of gestational vitamin D status and brain morphology in preadolescents. NeuroImage (2020). Access the original scientific publication here.

Pairing Vagus Nerve and Tactile Stimulation Improves Somatosensory Function Following Nerve Injury

Post by Elisa Guma

What's the science?

Sensory dysfunction is a common consequence of injury to the nervous system due to nerve damage or stroke. Sensory training using tactile stimulation in affected areas is the most common form of rehabilitation for these patients, but most are left with sensory loss. Promising clinical data has identified a potential novel therapy involving pairing stimulation of the vagus nerve with tactile rehabilitation; this is thought to enhance synaptic plasticity and facilitate recovery of sensory function. This week in Annals of Neurology, Darrow and colleagues rigorously test this hypothesis in a rodent model of nerve damage.

How did they do it?

To create a model of chronic sensory loss in rodents, rats underwent transection followed by repair of the median and ulnar nerves in the forelimb, which produces lasting deficits in somatosensation in spite of reinnervation. This injury results in a denervation of mechanoreceptors on the ventral (but not dorsal) surface of the forepaw. Typically, reinnervation does occur over time, however animals still experience long lasting impairments in somatosensation and have disruptions in nerve morphology. The rats were also implanted with stimulating cuff electrode on the left cervical vagus nerve.

Sixteen weeks after the injury, animals were randomized to receive either 1) a tactile rehabilitation paradigm consisting of the presentation of various mechanical stimuli to the surface of the paw, or 2) a tactile rehabilitation paradigm with 0.5 s bursts of vagus nerve stimulation paired with the presentation of each tactile stimulus, daily for 6 weeks. The tactile stimuli included a paintbrush, a 10g filament, a copper rod, and a puff of air to the affected ventral forepaw. Mechanosensory thresholds were measured at baseline, weekly throughout the therapy, and every two weeks for 8 weeks after the cessation of therapy to see if benefits were long-lasting. Given that sensory and motor function are highly related, additional measures of forelimb sensorimotor function were recorded including the spontaneous use of the injured forelimb during exploration, grip strength, placement of the forelimb in a horizontal ladder rung task, and toe spread analysis.

What did they find?

The authors found that pairing tactile rehabilitation with vagus nerve stimulation improved recovery of somatosensation in the forelimbs of animals with chronic sensory deficits compared to tactile rehabilitation alone. Improvements were already detectable in the first week of therapy and were maintained up to 2 months after the cessation of therapy. Furthermore, the animals that received paired vagus nerve and tactile stimulation therapy also had improved motor function in the injured forelimb, observable in exploratory behaviour, as well as reducing the length of toe spread during normal walking, and decreased missed placements and slips in the horizontal ladder task. The only motor behaviour that the paired therapy did not improve was for grip strength, where no difference between treatment groups were observed. 

What's the impact?

This study, motivated by recent clinical findings, provides compelling evidence for the efficacy of pairing tactile stimulation with vagus nerve stimulation for restoring somatosensation and motor function in a rodent model of sensory loss. This paired therapy could be a promising new approach for recovery from neurological injury. Future studies are needed to validate this strategy in other clinical populations, as well as to uncover the precise mechanisms supporting recovery.

Michael J Darrow et al. Restoration of somatosensory function by pairing nerve stimulation with tactile rehabilitation. Annals of Neurology (2019). Access the original scientific publication here.