Daniel J. Levitin

A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks

Cognitively demanding tasks that evoke activation in the brains central-executive network (CEN) have been consistently shown to evoke decreased activation (deactivation) in the default-mode network (DMN). The neural mechanisms underlying this switch between activation and deactivation of large-scale brain networks remain completely unknown. Here, we use functional magnetic resonance imaging (fMRI) to investigate the mechanisms underlying switching of brain networks in three different experiments. We first examined this switching process in an auditory event segmentation task. We observed significant activation of the CEN and deactivation of the DMN, along with activation of a third network comprising the right fronto-insular cortex (rFIC) and anterior cingulate cortex (ACC), when participants perceived salient auditory event boundaries. Using chronometric techniques and Granger causality analysis, we show that the rFIC-ACC network, and the rFIC, in particular, plays a critical and causal role in switching between the CEN and the DMN. We replicated this causal connectivity pattern in two additional experiments: (i) a visual attention “oddball” task and (ii) a task-free resting state. These results indicate that the rFIC is likely to play a major role in switching between distinct brain networks across task paradigms and stimulus modalities. Our findings have important implications for a unified view of network mechanisms underlying both exogenous and endogenous cognitive control.

The rewards of music listening: response and physiological connectivity of the mesolimbic system.

Although the neural underpinnings of music cognition have been widely studied in the last 5 years, relatively little is known about the neuroscience underlying emotional reactions that music induces in listeners. Many people spend a significant amount of time listening to music, and its emotional power is assumed but not well understood. Here, we use functional and effective connectivity analyses to show for the first time that listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the nucleus accumbens (NAc) and the ventral tegmental area (VTA), as well as the hypothalamus and insula, which are thought to be involved in regulating autonomic and physiological responses to rewarding and emotional stimuli. Responses in the NAc and the VTA were strongly correlated pointing to an association between dopamine release and NAc response to music. Responses in the NAc and the hypothalamus were also strongly correlated across subjects, suggesting a mechanism by which listening to pleasant music evokes physiological reactions. Effective connectivity confirmed these findings, and showed significant VTA-mediated interaction of the NAc with the hypothalamus, insula, and orbitofrontal cortex. The enhanced functional and effective connectivity between brain regions mediating reward, autonomic, and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences.

Social Modulation of Pain as Evidence for Empathy in Mice

Empathy is thought to be unique to higher primates, possibly to humans alone. We report the modulation of pain sensitivity in mice produced solely by exposure to their cagemates, but not to strangers, in pain. Mice tested in dyads and given an identical noxious stimulus displayed increased pain behaviors with statistically greater co-occurrence, effects dependent on visual observation. When familiar mice were given noxious stimuli of different intensities, their pain behavior was influenced by their neighbors status bidirectionally. Finally, observation of a cagemate in pain altered pain sensitivity of an entirely different modality, suggesting that nociceptive mechanisms in general are sensitized.

Musical structure is processed in “language” areas of the brain: a possible role for Brodmann Area 47 in temporal coherence

The neuroanatomical correlates of musical structure were investigated using functional magnetic neuroimaging (fMRI) and a unique stimulus manipulation involving scrambled music. The experiment compared brain responses while participants listened to classical music and scrambled versions of that same music. Specifically, the scrambled versions disrupted musical structure while holding low-level musical attributes constant, including the psychoacoustic features of the music such as pitch, loudness, and timbre. Comparing music to its scrambled counterpart, we found focal activation in the pars orbitalis region (Brodmann Area 47) of the left inferior frontal cortex, a region that has been previously closely associated with the processing of linguistic structure in spoken and signed language, and its right hemisphere homologue. We speculate that this particular region of inferior frontal cortex may be more generally responsible for processing fine-structured stimuli that evolve over time, not merely those that are linguistic.

The neurochemistry of music

Music is used to regulate mood and arousal in everyday life and to promote physical and psychological health and well-being in clinical settings. However, scientific inquiry into the neurochemical effects of music is still in its infancy. In this review, we evaluate the evidence that music improves health and well-being through the engagement of neurochemical systems for (i) reward, motivation, and pleasure; (ii) stress and arousal; (iii) immunity; and (iv) social affiliation. We discuss the limitations of these studies and outline novel approaches for integration of conceptual and technological advances from the fields of music cognition and social neuroscience into studies of the neurochemistry of music.

Current Advances in the Cognitive Neuroscience of Music

The study of music perception and cognition is one of the oldest topics in experimental psychology. The last 20 years have seen an increased interest in understanding the functional neuroanatomy of music processing in humans, using a variety of technologies including fMRI, PET, ERP, MEG, and lesion studies. We review current findings in the context of a rich intellectual history of research, organized by the cognitive systems underlying different aspects of human musical behavior. We pay special attention to the perception of components of musical processing, musical structure, laterality effects, cultural issues, links between music and movement, emotional processing, expertise, and the amusias. Current trends are noted, such as the increased interest in evolutionary origins of music and comparisons of music and language. The review serves to demonstrate the important role that music can play in informing broad theories of higher order cognitive processes such as music in humans.

Neural Correlates of Auditory Perception in Williams Syndrome: An fMRI Study

Williams syndrome (WS), a neurogenetic developmental disorder, is characterized by a rare fractionation of higher cortical functioning: selective preservation of certain complex faculties (language, music, face processing, and sociability) in contrast to marked and severe deficits in nearly every other cognitive domain (reasoning, spatial ability, motor coordination, arithmetic, problem solving). WS people are also known to suffer from hyperacusis and to experience heightened emotional reactions to music and certain classes of noise. We used functional magnetic resonance imaging to examine the neural basis of auditory processing of music and noise in WS patients and age-matched controls and found strikingly different patterns of neural organization between the groups. Those regions supporting music and noise processing in normal subjects were found not to be consistently activated in the WS participants (e.g., superior temporal and middle temporal gyri). Instead, the WS participants showed significantly reduced activation in the temporal lobes coupled with significantly greater activation in the right amygdala. In addition, WS participants (but not controls) showed a widely distributed network of activation in cortical and subcortical structures, including the brain stem, during music processing. Taken together with previous ERP and cytoarchitectonic studies, this first published report of WS using fMRI provides additional evidence of a different neurofunctional organization in WS people than normal people, which may help to explain their atypical reactions to sound. These results constitute an important first step in drawing out the links between genes, brain, cognition, and behavior in Williams syndrome.

Patterns of pain: Meta-analysis of microarray studies of pain

&NA; Existing microarray gene expression profiling studies of tonic/chronic pain were subjected to meta‐analysis to identify genes found to be regulated by these pain states in multiple, independent experiments. Twenty studies published from 2002 to 2008 were identified, describing the statistically significant regulation of 2254 genes. Of those, a total of 79 genes were found to be statistically significant “hits” in 4 or more independent microarray experiments, corresponding to a conservative P < 0.01 overall. Gene ontology‐based functional annotation clustering analyses revealed strong evidence for regulation of immune‐related genes in pain states. A multi‐gene quantitative real‐time polymerase chain reaction experiment was run on dorsal root ganglion (DRG) and spinal cord tissue from rats and mice given nerve (sciatic chronic constriction; CCI) or inflammatory (complete Freund’s adjuvant) injury. We independently confirmed the regulation of 43 of these genes in the rat‐CCI‐DRG condition; the genetic correlates in all other conditions were largely and, in some cases, strikingly, independent. However, a handful of genes were identified whose regulation bridged etiology, anatomical locus, and/or species. Most notable among these were Reg3b (regenerating islet‐derived 3 beta; pancreatitis‐associated protein) and Ccl2 (chemokine [C–C motif] ligand 2), which were significantly upregulated in every condition in the rat. Gene expression profiling (microarray) studies of chronic pain were subjected to meta‐analysis. Two genes were identified that are consistently upregulated in chronic pain states.

Neural Dynamics of Event Segmentation in Music: Converging Evidence for Dissociable Ventral and Dorsal Networks

The real world presents our sensory systems with a continuous stream of undifferentiated information. Segmentation of this stream at event boundaries is necessary for object identification and feature extraction. Here, we investigate the neural dynamics of event segmentation in entire musical symphonies under natural listening conditions. We isolated time-dependent sequences of brain responses in a 10 s window surrounding transitions between movements of symphonic works. A strikingly right-lateralized network of brain regions showed peak response during the movement transitions when, paradoxically, there was no physical stimulus. Model-dependent and model-free analysis techniques provided converging evidence for activity in two distinct functional networks at the movement transition: a ventral fronto-temporal network associated with detecting salient events, followed in time by a dorsal fronto-parietal network associated with maintaining attention and updating working memory. Our study provides direct experimental evidence for dissociable and causally linked ventral and dorsal networks during event segmentation of ecologically valid auditory stimuli.

Characterizing the Musical Phenotype in Individuals With Williams Syndrome

Williams Syndrome (WS), a neurodevelopmental genetic disorder, is characterized by peaks and valleys in mental function: substantial impairments in cognitive domains such as reasoning, arithmetic ability, and spatial cognition, alongside relatively preserved skills in social domains, face processing, language, and music. We report the results of a comprehensive survey on musical behaviors and background administered to the largest sample of individuals with WS to date (n = 118, mean age = 20.4), and compare the results to those obtained from a control group of typically developing normal individuals (n = 118, mean age = 20.9) and two groups of individuals with other neurodevelopmental genetic disorders, Autism (n = 30, mean age = 18.2) and Down Syndrome (n = 40, mean age = 17.2). Individuals with WS were found to be rated higher in musical accomplishment, engagement, and interest than either of the comparison groups, and equivalent on most measures to the control group. Compared to all other groups including the controls, the WS individuals displayed greater emotional responses to music, manifested interest in music at an earlier age, and spent more hours per week listening to music. In addition, the effects of music listening (whether positive or negative) tended to last longer in the WS group. A factor analysis extracted seven principal components that characterize the musical phenotype in our sample, and discriminant function analysis of those factors was able to successfully predict group membership for the majority of cases. We discuss the neurobiological implications of these findings.