How facial expressions in a Rett syndrome population are recognised and interpreted by those around them as conveying emotions

Rett syndrome (RTT) is a neurodevelopmental disorder, including autonomic nervous system dysfunctions and severe communication impairment with an extremely limited ability to use verbal language. These individuals are therefore dependent on the capacity of caregivers to observe and interpret communicative signals, including emotional expressions. People in general, including therapists tend to focus on changes in facial expressions to interpret a person's emotional state or choices, but with this population it is difficult to know if the interpretations are correct. The aims of this study were to investigate if the Facial Action Coding System (FACS) could be used to identify facial expressions, and differentiate between those that expressed emotions and those that were elicited by abnormal brainstem activation in RTT. The sample comprised 29 participants with RTT and 11 children with a normal developmental pattern, exposed to six different musical stimuli during non-invasive registration of autonomic brainstem functions. The results indicate that FACS makes it possible both to identify facial expressions and to differentiate between those that stem from emotions and those caused by abnormal brainstem activation. This knowledge may be a great help to an uninitiated observer, who otherwise might incorrectly interpret the latter as an expression of emotion.     

Multidimensional scaling of emotional responses to music in patients with temporal lobe resection

The present study investigated emotional responses to music by using multidimensional scaling (MDS) analysis in patients with right or left medial temporal lobe (MTL) lesions and matched normal controls (NC). Participants were required to evaluate emotional dissimilarities of nine musical excerpts that were selected to express graduated changes along the valence and arousal dimensions. For this purpose, they rated dissimilarity between pairs of stimuli on an eight-point scale and the resulting matrices were submitted to an MDS analysis. The results showed that patients did not differ from NC participants in evaluating emotional feelings induced by the musical excerpts, suggesting that all participants were able to distinguish refined emotions. We concluded that the ability to detect and use emotional valence and arousal when making dissimilarity judgments was not strongly impaired by a right or left MTL lesion. This finding has important clinical implications and is discussed in light of current neuropsychological studies on emotion. It suggests that emotional responses to music can be at least partially preserved at a non-verbal level in patients with unilateral temporal lobe damage including the amygdala.     

A little goes a long way: how the adult brain is shaped by musical training in childhood

Playing a musical instrument changes the anatomy and function of the brain. But do these changes persist after music training stops? We probed this question by measuring auditory brainstem responses in a cohort of healthy young human adults with varying amounts of past musical training. We show that adults who received formal music instruction as children have more robust brainstem responses to sound than peers who never participated in music lessons and that the magnitude of the response correlates with how recently training ceased. Our results suggest that neural changes accompanying musical training during childhood are retained in adulthood. These findings advance our understanding of long-term neuroplasticity and have general implications for the development of effective auditory training programs.     

Anterior cingulate and medial prefrontal cortex response to systematically controlled tonal dissonance during passive music listening

Several studies have attempted to investigate how the brain codes emotional value when processing music of contrasting levels of dissonance; however, the lack of control over specific musical structural characteristics (i.e., dynamics, rhythm, melodic contour or instrumental timbre), which are known to affect perceived dissonance, rendered results difficult to interpret. To account for this, we used functional imaging with an optimized control of the musical structure to obtain a finer characterization of brain activity in response to tonal dissonance. Behavioral findings supported previous evidence for an association between increased dissonance and negative emotion. Results further demonstrated that the manipulation of tonal dissonance through systematically controlled changes in interval content elicited contrasting valence ratings but no significant effects on either arousal or potency. Neuroscientific findings showed an engagement of the left medial prefrontal cortex (mPFC) and the left rostral anterior cingulate cortex (ACC) while participants listened to dissonant compared to consonant music, converging with studies that have proposed a core role of these regions during conflict monitoring (detection and resolution), and in the appraisal of negative emotion and fear‐related information. Both the left and right primary auditory cortices showed stronger functional connectivity with the ACC during the dissonant portion of the task, implying a demand for greater information integration when processing negatively valenced musical stimuli. This study demonstrated that the systematic control of musical dissonance could be applied to isolate valence from the arousal dimension, facilitating a novel access to the neural representation of negative emotion.     

Importance of the left auditory areas in chord discrimination in music experts as demonstrated by MEG

The brain basis behind musical competence in its various forms is not yet known. To determine the pattern of hemispheric lateralization during sound‐change discrimination, we recorded the magnetic counterpart of the electrical mismatch negativity (MMNm) responses in professional musicians, musical participants (with high scores in the musicality tests but without professional training in music) and non‐musicians. While watching a silenced video, they were presented with short sounds with frequency and duration deviants and C major chords with C minor chords as deviants. MMNm to chord deviants was stronger in both musicians and musical participants than in non‐musicians, particularly in their left hemisphere. No group differences were obtained in the MMNm strength in the right hemisphere in any of the conditions or in the left hemisphere in the case of frequency or duration deviants. Thus, in addition to professional training in music, musical aptitude (combined with lower‐level musical training) is also reflected in brain functioning related to sound discrimination. The present magnetoencephalographic evidence therefore indicates that the sound discrimination abilities may be differentially distributed in the brain in musically competent and naïve participants, especially in a musical context established by chord stimuli: the higher forms of musical competence engage both auditory cortices in an integrative manner.     

Using eye movement responses to index auditory comprehension: An adaptation of the Revised Token Test

Background: Tracking spontaneous eye movement responses may improve the accuracy of comprehension assessment in patients with neurological impairments. Eye movement methods provide an on-line response mode that does not require an overt planned motoric response, tax participants' understanding of instructions, or interrupt the comprehension process with intervening instructions or prompts. Aims: The purpose of this study was to examine an adaptation of a standardised test of auditory comprehension for adults with neurological impairments, using eye movement responses. Individuals with normal language comprehension should demonstrate a consistent pattern of eye movement responses indicating comprehension. Methods & Procedures: Nineteen adults with no history of neurological involvement were presented with auditory comprehension stimuli from the Revised Token Test (RTT) (McNeil & Prescott, 1978) in each of three conditions: traditional, pointing, and eye movement. In the traditional condition, the standardised version of the RTT was administered. In the pointing condition, RTT stimuli were manipulated to fit a multiple-choice format; participants responded to modified verbal stimuli for each item by pointing to one of four images shown in a printed test manual. In the eye movement condition, participants viewed the same stimuli presented in the multiple-choice pointing version, shown on a computer monitor rather than in a test manual. A remote pupil centre/corneal reflection system was used to monitor eye movements. Participants were not instructed to look at anything in particular, and were not told that there were target images within the displays. The eye movement condition was presented first to avoid participants/ perceptions that they were expected to select a target image with their eyes. Dependent variables included the proportion of total viewing time that participants fixated on target images and non-target foils. Outcomes & Results: Traditional RTT scores indicated normal comprehension for all participants, according to published norms. Likewise, pointing condition scores indicated good comprehension. For each of the subtests in the eye movement condition, the proportional amount of time that fixations were allocated to target images significantly exceeded chance expectations.     

Comparing social reciprocity in preserved speech variant and typical Rett syndrome during the early years of life

This study compared early markers of social reciprocity in children with typical Rett syndrome (RTT) and in those with the preserved speech variant (PSV) of RTT. Retrospective video analysis of 10 toddlers with typical RTT and five with PSV investigated participants’ orientation to their name being called between the ages of 5 and 24 months, prior to their diagnosis. From analysis of the recordings two distinct profiles were apparent. Although response rate was higher in girls with typical RTT than PSV at 5 to 8 months this noticeably reversed from 9 to 12 months onwards. By two years of age there was a markedly higher rate and range of responses from girls with PSV. This study contributes to the delineation of different profiles for the variants of RTT.     

Shared neural mechanisms for processing emotions in music and vocalizations

The neural mechanisms involved in the processing of vocalizations and music were compared, in order to observe possible similarities in the encoding of their emotional content. Positive and negative emotional vocalizations (e.g. laughing, crying) and violin musical stimuli digitally extracted from them were used as stimuli. They shared the melodic profile and main pitch/frequency characteristics. Participants listened to vocalizations or music while detecting rare auditory targets (bird tweeting, or piano's arpeggios). EEG was recorded from 128 sites. P2, N400 and Late positivity responses of ERPs were analysed. P2 peak was earlier in response to vocalizations, while P2 amplitude was larger to positive than negative stimuli. N400 was greater to negative than positive stimuli. LP was greater to vocalizations than music and to positive than negative stimuli. Source modelling using swLORETA suggested that, among N400 generators, the left middle temporal gyrus and the right uncus responded to both music and vocalizations, and more to negative than positive stimuli. The right parahippocampal region of the limbic lobe and the right cingulate cortex were active during music listening, while the left superior temporal cortex only responded to human vocalizations. Negative stimuli always activated the right middle temporal gyrus, whereas positively valenced stimuli always activated the inferior frontal cortex. The processing of emotional vocalizations and music seemed to involve common neural mechanisms. Notation obtained from acoustic signals showed how emotionally negative stimuli tended to be in Minor key, and positive stimuli in Major key, thus shedding some lights on the brain ability to understand music.     

Rett syndrome: A preliminary analysis of stereotypy,stress, and negative affect

Rett syndrome (RTT) is a neurodevelopmental disorder primarily affecting females. It is characterized by apparently normative development of motor and communicative abilities followed by deterioration in these domains. Stereotypic hand movements are one of the core diagnostic criteria for RTT. There is some anecdotal but limited scientific evidence that changes in hand stereotypy may be a sign of increased anxiety or arousal (i.e., a ‘stress response’) in RTT. Understanding stress responsivity is difficult in RTT because almost all individuals are nonverbal or otherwise severely communicatively impaired. This study used direct behavioral observation to quantify and compare the frequency of hand stereotypy and signs of negative affect during presumed periods of high and low stress associated with functional analysis conditions (negative reinforcement [‘escape’] and control [‘free play’], respectively) for 5 females with RTT (mean age = 17.8; range 4–47). Negative affect was more likely to occur during negative reinforcement (‘stress’) conditions for each participant whereas hand stereotypies did not differ across conditions for any of the participants. Although preliminary, the results suggest that hand stereotypy may not be a valid behavioral ‘stress-response’ indicator in females with RTT. Alternatively, the approach we used may have been limited and not sufficient to evoke a stress response. Either way, more work with direct relevance to improving our understanding of hand stereotypy and anxiety in RTT in relation to social context appears warranted.     

Priming paradigm reveals harmonic structure processing in congenital amusia

Deficits for pitch structure processing in congenital amusia has been mostly reported for melodic stimuli and explicit judgments. The present study investigated congenital amusia with harmonic stimuli and a priming task. Amusic and control participants performed a speeded phoneme discrimination task on sung chord sequences. The target phoneme was sung either on a functionally important chord (tonic chord, referred to as "related target") or a less important one (subdominant chord, referred to as "less-related target"). Correct response times were faster when the target phoneme was sung on tonic chords rather than on subdominant chords, and this effect was less pronounced, albeit significant, in amusic participants. These data report for the first time a deficit in congenital amusia for chord processing, but also provide evidence that, despite this deficit, amusic individuals have internalized sophisticated syntactic-like functions of chords in the Western tonal musical system. This finding suggests that thanks to this musical knowledge, amusic individuals could develop expectancies for musical events, and, presumably, follow the tension-relaxation schemas in Western tonal music, which also influence emotional responses to music.     

Normal reactions to orthostatic stress in Rett syndrome

The aim of this study was to investigate orthostatic reactions in females with Rett syndrome (RTT), and also whether the severity of the syndrome had an impact on autonomic reactions. Based on signs of impaired function of the central autonomic system found in RTT, it could be suspected that orthostatic reactions were affected. The orthostatic reactions in 21 females with RTT and 14 normally developed females matched by age were investigated when they rose from a sitting position, and during standing for 3 min. Reactions of the heart, the blood pressure and the time for recovery of systolic blood pressure, were studied in real time, heartbeat by heartbeat, simultaneously. There was no difference between participants with RTT and the normally developed controls regarding general orthostatic reactions (heart rate, systolic and diastolic blood pressure, and mean arterial pressure) when getting up from a sitting position, and when standing erect for 3 min. In the specific immediate response by the heart to standing up, the 30:15 ratio, significantly lower values were found for females with RTT. In the RTT group, the maximum fall of systolic blood pressure showed a tendency to a larger decrease, and the initial decrease in systolic blood pressure was significantly faster. The time for recovery of systolic blood pressure from standing erect did not differ between groups. At baseline the females with RTT had significantly lower systolic blood pressure and a tendency to a higher heart rate. The results do not indicate any autonomic limitations for people with RTT in getting up from a sitting position and standing. The participants with RTT had normal orthostatic reactions indicated by the heart and blood pressure responses when standing erect for 3 min. A faster initial drop in systolic blood pressure in people with RTT was notable.     

Impairments in musical abilities reflected in the auditory brainstem: evidence from congenital amusia

Congenital amusia is a neurogenetic condition, characterized by a deficit in music perception and production, not explained by hearing loss, brain damage or lack of exposure to music. Despite inferior musical performance, amusics exhibit normal auditory cortical responses, with abnormal neural correlates suggested to lie beyond auditory cortices. Here we show, using auditory brainstem responses to complex sounds in humans, that fine‐grained automatic processing of sounds is impoverished in amusia. Compared with matched non‐musician controls, spectral amplitude was decreased in amusics for higher harmonic components of the auditory brainstem response. We also found a delayed response to the early transient aspects of the auditory stimulus in amusics. Neural measures of spectral amplitude and response timing correlated with participants' behavioral assessments of music processing. We demonstrate, for the first time, that amusia affects how complex acoustic signals are processed in the auditory brainstem. This neural signature of amusia mirrors what is observed in musicians, such that the aspects of the auditory brainstem responses that are enhanced in musicians are degraded in amusics. By showing that gradients of music abilities are reflected in the auditory brainstem, our findings have implications not only for current models of amusia but also for auditory functioning in general.     

A functional MRI study of happy and sad affective states induced by classical music

The present study investigated the functional neuroanatomy of transient mood changes in response to Western classical music. In a pilot experiment, 53 healthy volunteers (mean age: 32.0; SD = 9.6) evaluated their emotional responses to 60 classical musical pieces using a visual analogue scale (VAS) ranging from 0 (sad) through 50 (neutral) to 100 (happy). Twenty pieces were found to accurately induce the intended emotional states with good reliability, consisting of 5 happy, 5 sad, and 10 emotionally unevocative, neutral musical pieces. In a subsequent functional magnetic resonance imaging (fMRI) study, the blood oxygenation level dependent (BOLD) signal contrast was measured in response to the mood state induced by each musical stimulus in a separate group of 16 healthy participants (mean age: 29.5; SD = 5.5). Mood state ratings during scanning were made by a VAS, which confirmed the emotional valence of the selected stimuli. Increased BOLD signal contrast during presentation of happy music was found in the ventral and dorsal striatum, anterior cingulate, parahippocampal gyrus, and auditory association areas. With sad music, increased BOLD signal responses were noted in the hippocampus/amygdala and auditory association areas. Presentation of neutral music was associated with increased BOLD signal responses in the insula and auditory association areas. Our findings suggest that an emotion processing network in response to music integrates the ventral and dorsal striatum, areas involved in reward experience and movement; the anterior cingulate, which is important for targeting attention; and medial temporal areas, traditionally found in the appraisal and processing of emotions.     

Neuropathology and immunohistochemistry of brains with Rett syndrome

To clarify critical lesions and pathomechanism of Rett syndrome (RTT), we studied the followings: (1) neuropathological observation of RTT, (2) Comparison of neurotransmitter expression between RTT and controls, and developmental immunohistology of MeCP2, the product of the causative gene of RTT in control brains using the ABC immunohistochemical technique. In the RTT brainstem, there were lesions in the substantia nigra, periaquaductal gray and locus ceruleus, in which catecholaminergic neurons were markedly reduced. MeCP2 expression, was detectable in all neurons of fetal brain until 20 gestational weeks (GW). The expression disappeared in the cerebrum after 20 GW and in the brainstem after perinatal or infantile periods, but re-appeared in the brainstem after adolescence. These findings suggest that the period and location of MeCP2 expression may play an important role in the pathogenesis of RTT. The lack of MeCP2 in the specific periods and regions may lead to the dysfunction of catecholaminergic neurons in RTT brains.     

The effect of the presentation of visual and auditory stimuli on the breathing patterns of two girls with Rett syndrome

The respiration patterns of individuals with Rett syndrome are known to be dysrhythmic during wakefulness, suggesting cortical involvement of brainstem respiratory control. To investigate this involvement further, the waking breathing patterns of two girls with Rett syndrome were analysed during three phases: a quiet phase, and two phases during which visual and auditory stimuli were presented in controlled intervals. Differences were noted between the two subjects’ respiratory patterns in both the quiet and stimulation phases. The usual quiet respiration patterns became more dysrhythmic for both girls during stimulation, with shortened breathing cycles and lengthened apmoeic pauses for the one subject, and increased numbers of apnoeic pauses and shallower breaths for the other. These results suggest that the cyclical brainstem control of breathing patterns in Rett syndrome may be subject to disruption as a result of cortical influences, including arousal subsequent to the engagement of attention.     

Early behavior characteristics and sleep disturbance in Rett syndrome

This paper reviews the early features of Rett syndrome (RTT). The behavioral characteristics of RTT were analyzed retrospectively by taking history and asking about early infancy behaviors. The earliest behavioral characteristics are thought to be autistic features and hypotonia of trunkal muscles. Analysis of sleep-wake rhythm and all-night polysomnography suggested that the initial lesion is serotonergic and noradrenargic hypofunction at brainstem level. Dopaminergic (DA) hypofunction associated with DA receptor supersensitivity follows as the brain matures. Characteristic symptoms developing at specific age ranges are based on the neuronal connections of the brainstem aminergic neurons and DA neurons with the pedunculo-pontine nuclei, projecting to specific cortical areas.     

Interaction between musical emotion and facial expression as measured by event-related potentials

We examined the integrative process between emotional facial expressions and musical excerpts by using an affective priming paradigm. Happy or sad musical stimuli were presented after happy or sad facial images during electroencephalography (EEG) recordings. We asked participants to judge the affective congruency of the presented face–music pairs. The congruency of emotionally congruent pairs was judged more rapidly than that of incongruent pairs. In addition, the EEG data showed that incongruent musical targets elicited a larger N400 component than congruent pairs. Furthermore, these effects occurred in nonmusicians as well as musicians. In sum, emotional integrative processing of face–music pairs was facilitated in congruent music targets and inhibited in incongruent music targets; this process was not significantly modulated by individual musical experience. This is the first study on musical stimuli primed by facial expressions to demonstrate that the N400 component reflects the affective priming effect.     

Enhanced brainstem encoding predicts musicians' perceptual advantages with pitch

Important to Western tonal music is the relationship between pitches both within and between musical chords; melody and harmony are generated by combining pitches selected from the fixed hierarchical scales of music. It is of critical importance that musicians have the ability to detect and discriminate minute deviations in pitch in order to remain in tune with other members of their ensemble. Event-related potentials indicate that cortical mechanisms responsible for detecting mistuning and violations in pitch are more sensitive and accurate in musicians as compared with non-musicians. The aim of the present study was to address whether this superiority is also present at a subcortical stage of pitch processing. Brainstem frequency-following responses were recorded from musicians and non-musicians in response to tuned (i.e. major and minor) and detuned (± 4% difference in frequency) chordal arpeggios differing only in the pitch of their third. Results showed that musicians had faster neural synchronization and stronger brainstem encoding for defining characteristics of musical sequences regardless of whether they were in or out of tune. In contrast, non-musicians had relatively strong representation for major/minor chords but showed diminished responses for detuned chords. The close correspondence between the magnitude of brainstem responses and performance on two behavioral pitch discrimination tasks supports the idea that musicians' enhanced detection of chordal mistuning may be rooted at pre-attentive, sensory stages of processing. Findings suggest that perceptually salient aspects of musical pitch are not only represented at subcortical levels but that these representations are also enhanced by musical experience.     

Modulation of corticospinal activity by strong emotions evoked by pictures and classical music: a transcranial magnetic stimulation study

Using transcranial magnetic stimulation and skin conductance responses, we sought to clarify if, and to what extent, emotional experiences of different valences and intensity activate the hand-motor system and the associated corticospinal tract. For that purpose, we applied a newly developed method to evoke strong emotional experiences by the simultaneous presentation of musical and pictorial stimuli of congruent emotional valence. We uncovered enhanced motor-evoked potentials, irrespective of valence, during the simultaneous presentation of emotional music and picture stimuli (Combined conditions) compared with the single presentation of the two modalities (Picture/Music conditions). In contrast, vegetative arousal was enhanced during both the Combined and Music conditions, compared with the Picture conditions, again irrespective of emotional valence. These findings strongly indicate that arousal is a necessary, but not sufficient, prerequisite for triggering the motor system of the brain. We offer a potential explanation for this discrepant, but intriguing, finding in the paper.     

Rett syndrome diagnostic criteria: lessons from the Natural History Study

Analysis of 819 participants enrolled in the Rett syndrome (RTT) Natural History Study validates recently revised diagnostic criteria. 765 females fulfilled 2002 consensus criteria for classic (653/85.4%) or variant (112/14.6%) RTT. All participants classified as classic RTT fulfilled each revised main criterion; supportive criteria were not uniformly present. All variant RTT participants met at least 3 of 6 main criteria in the 2002, 2 of 4 main criteria in the current format, and 5 of 11 supportive criteria in both. This analysis underscores the critical role of main criteria for classic RTT; variant RTT requires both main and supportive criteria.