This work was funded by the foundation Vontobel-Stiftung Zurich.

The clinical protocol follows the ethical guidelines of the University Hospital at Zurich. All methods and techniques are based on the described approach of CMT in the NICU and are recommended to be provided by music therapists specially trained in CMT (CMT training or the Rhythm Breath and Lullaby training with CMT modules39,40,41). CMT can be delivered when the infant is clinically stable, as defined by nurses and doctors of the neonatal team, 2-3 times per week, for approximately 20 min each session.
1. Preparation
<ol>
	<li>Before initiating music therapy, conduct an in-depth assessment with team members of the unit (e.g., doctors, nurses, psychologists) and as soon as possible with the parents to identify the needs of the infant and parents. Based on these needs create therapeutic objectives oriented towards the principles of neonatal music therapy and family-integrated care approaches42,43,44.</li>
	<li>Introduce music therapy to the parents. Assess their needs, resources, musical heritage, and culture. Assess what song or music they wish for as well as their natural vocal range. Assess if they already provided music to their infant during pregnancy, and if so, integrate this music in the therapy procedures referred to as &#34;song of kin&#34;45.</li>
	<li>Supply the parents with empowering intercultural music material (e.g., the lullaby book &#34;Wiegenlieder f&#252;r die Kleinsten. Ausgew&#228;hlte Lieder von Eltern f&#252;r Eltern fr&#252;hgeborener Kinder&#34; [Lullabies for the most little ones. Songs of parents for parents of preterm infants])46. Parents of preterm infants sang all the international songs in this book and framed each song with their written experiences on why and how they sang to empower and to motivate other parents to sing for their infant as well47. Alternatively, provide further information (e.g., a flyer) to motivate parents to engage in vocal interaction with their infant.</li>
	<li>Continue to assess the infants&#39; and parents&#39; needs during their clinical trajectory over time by attending interdisciplinary neonatal rounds and or meetings regularly and by intensifying the dialogue with the parents. Continue to adapt to these families&#39; needs to facilitate a needs-, and resource-based therapeutic process.</li>
	<li>Identify a reasonable time frame with the neonatal staff and the parents in which to conduct the music therapy session to minimize the chance of interfering with healthcare routines, treatments, emergencies, infant resting periods, and needs of the parents.</li>
	<li>Discuss with neonatal staff and/or parents if the session should take place at the incubator or bedside only with the infant or together with the parents. For example, when the parents spend a lot of time in the NICU and enjoy the shared sessions, conduct as many joint sessions as possible, mostly and preferably during KC. When parents have less time, fewer possibilities to visit, or are not accountable, offer music therapy with other caregivers or just the infant as well.</li>
	<li>Before providing CMT, seek the latest meaningful clinical information on the infant and its family as well as approval of the neonatal team. Tune the monochord in the key of the unit (the most dominant and frequent monitor beeping tone of the unit) if the instrument is needed for the session48.</li>
	<li>Before conducting each music therapy session and entering the patient zone, disinfect hands, arms, and the instrument by following the hygiene guidelines of the neonatal unit and the individual infant. Disinfect and prepare a chair at the bedside of the infant or next to the parents.</li>
</ol>
2. Creative Music Therapy with the Preterm Infant at the Bedside or Incubator
<ol>
	<li>When the infant tolerates touch, start with initial touch by touching the infant at the head and feet and change it into therapeutic touch by lightly laying one hand on the chest or the back49,50. While touching the infant connect with the infant, notice any increased or decreased muscle tension, any voluntary or involuntary movement, and support the breathing movements and patterns by adapting the pressure and weight of the hand on the chest or back to these patterns.</li>
	<li>After a period of observation, start with infant-directed humming entrained to the infant&#39;s breathing pattern, incorporating the infant&#39;s signs of mimicry and movements to attune to the infant&#39;s needs and to support or regulate breathing. Fade in the music: Start with a few long and calm notes proceeding in small steps with a high degree of repetitions and continuity.</li>
	<li>Develop the melody slowly over time. Often this occurs synchronously: for example, when the infant&#39;s eyebrows lift, move the melodic pitch and tempo upwards16. In contrast, when the infant is overly aroused, reduce the melody&#39;s span of pitches and pitch range and shift it downwards, slow the tempo, and repeat the closing notes to soothe the infant.</li>
	<li>Hum to sooth and sing to activate, synchronize and interact with older infants, or infants who open their eyes and mouth and/or start &#34;mouthing&#34; (i.e., shaping their mouth to make &#34;oh&#34; and &#34;ah&#34; sounds and tongue play) and/or move their fingers or arms smoothly50.</li>
	<li>Hum and sing simply in lullaby style in order not to overwhelm the infant: Keep the voice calm, slow, simple, predictable, repetitive, and contingent with the pitch range of children&#39;s songs based on the guidelines of neonatal music therapy24,43,44. Hum with flowing breath and a free natural voice full of overtones and total ease.</li>
	<li>Incorporate the &#34;song of kin&#34;25 in lullaby style in the individualized, attuned improvisation. If necessary, attune to environmental sounds to integrate and thereby mitigate disturbing noises such as a monitor beeping50 oriented towards environmental music therapy approaches4,48.</li>
	<li>After ~15-20 min (adapt the duration to the individual needs of the infant) fade the humming or singing slowly out by reducing the notes, the tempo, the rhythms, and conclude by repeating the last note51.</li>
	<li>Hold the infant some seconds longer before removing hands slowly and cautiously.</li>
</ol>
3. Creative Music Therapy with the Parents During Skin-to-skin Care
<ol>
	<li>Assess the current needs of the parents (e.g., assess if they would like to listen and relax during the music therapy session or if they would like to sing along).</li>
	<li>Invite the parents to sit or lie down comfortably. Position the monochord next to the side chair of the parent with the infant in KC. Place the instrument next to the elbow or arm of the parents so that the relaxing vibrations can transmit to their body.</li>
	<li>If appropriate, invite the parents to breathe in and out deeply. Invite the parents to close their eyes, to focus on their breathing, and afterward to focus on feeling their infant. Alternatively, invite the parents to observe and interact with their infant, as they prefer. This procedure may be appropriate as preparation for the joint music therapy session and/or during the session accompanied by monochord sounds and singing and/or speaking.</li>
	<li>After a short period of observing the parent-infant dyad, start with long, calm sound waves on the monochord, entrained to the infant&#39;s breathing pattern (e.g., three sets of infant inhalations and exhalations = one long continuous strum on the monochord). Fade the sound in smoothly.</li>
	<li>After a while (~90 s) hum along with the monochord sound, as described above, or accompany and support the parental humming/singing for their infant.
	<ol>
		<li>Attune and tailor the humming and singing to the affects, rhythms, and needs of the infant and environmental sounds as described above and additionally to the parents&#39; needs (compare previous publication23,47).</li>
		<li>Hum or sing within the parents&#39; vocal range to facilitate parental humming or singing. To honor the family&#39;s musical and cultural heritage integrate their favorite music in the singing23,25.</li>
	</ol>
	</li>
	<li>After ~15-20 min (adapt the duration to the individual needs of the infant), fade the humming or singing slowly out by reducing the notes, the tempo, the rhythms, and repeating the last note. Continue to play the monochord for 1 or 2 min more and fade the monochord sound smoothly out. Hold the moment of reverberation and silence some seconds longer before removing the instrument slowly and cautiously.</li>
	<li>If appropriate, ask the parents how they experienced the music therapy session for themselves and how they perceived their infant&#39;s reactions. If appropriate, share perceptions of the infant&#39;s behavioral state and reactions (e.g., smiling, finger movements, if occurred). Give feedback about observations and thereby encourage and value observed appropriate parental and infant behavior as well as appropriate parental-infant interactions to promote parental self-efficacy and parent-infant attachment.</li>
	<li>Encourage the parents to use their voice to connect with their infant in their daily NICU routine. Encourage the parents to use infant-directed speech with &#34;motherese&#34;52,53 and humming and singing, as preferred by the parents.</li>
	<li>When therapeutically indicated, invite the parents to engage in song writing, a widely used music therapy method to express and validate experiences, to externalize emotions and thoughts54, and to intensify and personalize the parent-infant interactions in neonatal music therapy in particular30,55,56. Invite the parents to write about their musical experiences in their dairy (or the diary pages of the lullaby book &#34;Wiegenlieder f&#252;r die Kleinsten&#34;) and to quote their song.</li>
</ol>
4. Creative Music Therapy with Additional Family Members
<ol>
	<li>Prepare and adapt to the current needs of the infant and parents as described above, but assess the needs of siblings, grandparents, or other significant caregivers, if and how they wish to participate in the music therapy sessions. Assess well-known family songs and model the song in lullaby style for the preterm infant.</li>
	<li>Assess the context, history, and heritage of the chosen songs and invite the family to share their associations and emotions regarding the chosen music. Sing the song for or with the family based on the infant&#39;s and family&#39;s current needs. Sing and or accompany as described above or let the family members sing for the infant and accompany or listen and coach them. Encourage the family to use infant-directed speech or singing when they visit the infant as well.</li>
</ol>
5. Follow-up
<ol>
	<li>Make a new appointment with the parents, if appropriate. Upon exiting the patient zone, disinfect following the neonatal hygiene guidelines.</li>
	<li>Document the sessions as described elsewhere16. Give feedback to and discuss with neonatal staff and parents (if available). Attend integrative rounds and continuously assess the needs of the team and parents to incorporate these needs in the therapeutic process.</li>
	<li>Write a final patient report before hospital discharge and advise parents on how to use music at home, including written recommendations. If appropriate, give the parents a call 2 weeks after discharge to inquire how they are doing and to recommend further musical support.</li>
</ol>

The authors have nothing to disclose.

The therapeutic, responsive, empowering, and creative use of music in CMT may be of great potential for preterm infants, their parents, and the parent-infant attachment. Individually tailored soft music, shared affects attunement, and joint attention may support relaxation, development, and the bonding process even in the stressful and artificial environment of an intensive care unit.
However, music therapy plays a subordinated and complementary role in the lifesaving priority setting of medical treatment and intensive care. Mostly, CMT should be delivered when the infants are clinically stable and do not suffer severe or life-threatening instability as defined by the neonatal team. Nonetheless, music therapists can provide CMT as palliative care as well when recommended by the neonatal team and or requested by the parents61. CMT with parental integration can only occur when the parents are present and willing to participate. Often, the music therapist has to reschedule planned sessions so as not to interfere with healthcare routines, treatments, emergencies, and infant resting periods. Sometimes, planned joint music therapy sessions in KC have to be changed to sessions at the bedside of the infant because the infant is too medically unstable for KC. The needs of the infant are of highest priority in all decision-making processes because the preterm infant is the most vulnerable component of the parent-infant-environment triad, even when this may evoke parental feelings of disappointment. This priority setting is warranted for the whole music therapy process as well.
When working with the parents, the aim is to enable intuitive parental roles to emerge through interactions with their infants, more than to explicitly teach new skills. While working with the family, the music therapist should act as a facilitator and collaborator, rather than as an educator or expert teaching parents how to use their voice and or sing since many parents experience helplessness, dependence on NICU experts, and a lack of self-control, self-confidence, and autonomy as primary caregivers9,62. Therefore, the role of the therapist is to advice by supporting the parental role as primary caregiver rather than compromising it. The task of the therapist is to integrate the cultural heritage of the family because supporting parents in their cultural identity is argued to be particularly empowering and may build transcultural bridges47,63,64. Because infant-directed humming is characterized by musical parameters across cultures such as slower tempo, higher pitch, and a distinctive style of humming and singing65, these musical parameters can be used to facilitate communication and interaction with the parent-infant dyad even beyond potential cultural and language barriers66. In cases when parents are not accountable (e.g., due to severe mental health issues or drug addiction), CMT should aim to integrate other potential caregivers of the infant. Moreover, the overarching challenge of the music therapist is to assess steadily the interweaving and constantly changing needs of the infant, parents, and neonatal intensive care environment in order to be flexible, creative, and therapeutically responsive. Therefore, only specially trained music therapists are recommended to provide CMT in neonatal care by following the described step-by-step protocol.
Nowadays, CMT is aligned with key principles of family-centered care: e.g., empowering each child and family, honoring choices and cultures, adapting to caregivers&#39; needs, and collaborating with parents in treatment24. CMT draws further on the elements of family-integrated care by integrating parents as partners and primary and most meaningful (vocal) caregiver as soon as possible11.
CMT may enhance the widely used approach of KC by reducing stress, promoting relaxation, and intensifying feelings of safety and connectedness38,67. CMT may be of particular significance not least because of providing meaningful, socio-emotional, joyful, and playful &#34;moments of meeting&#34; which are argued to foster a secure relationship between the parent-infant dyad9,68. CMT aims at relaxing, stimulating, and coregulating premature infants at a time when many other interventions are still at risk to overwhelm the vulnerable patient group. Particularly in the first weeks after preterm birth when very preterm infants are sometimes too unstable for KC, infant-directed humming can facilitate nurturing connectedness. Additionally, the music therapist can provide CMT during sleep without awakening but stimulating the infant50.
Socio-emotional experiences and early auditory experiences make an impact on brain development as suggested by human and animal studies69,70,71. Because preterm infants are in the most rapid and vulnerable period of brain development, auditory and socio-emotional experiences may influence the plasticity of auditory and cortical brain regions72,73.
We may speculate that the enriched musical and socio-emotional experience in CMT may promote brain development, notably functional and structural connectivity, as well as emotional and cognitive development74. Rigorously designed trials are required to evaluate short and longitudinal effects of music therapy on brain development in preterm infants and psychosocial adaption. In Switzerland, such a study is implemented, and a multicenter study is prepared17. In conclusion, CMT may be a promising and feasible family-integrated therapy involving communicative musicality to promote neurodevelopment, parental psychosocial adaption, and mutual socioemotional connectedness from the very beginning.

Preterm infants represent a growing population in health care, and many infants suffer neurodevelopmental impairments that persist into later life (e.g., motor dysfunction, cognitive and behavioral problems)1,2. In addition to other risk factors, sensory deprivation (e.g., the lack of the intrauterine multisensory experience of the regular maternal heartbeat and the maternal voice) and the stressful sensory overload of the NICU, or neonatal intensive care unit (e.g., monitor beeping, mechanical noises), may negatively impact brain maturation3,4.
Preterm birth is a stressful and traumatic event for preterm infants and their parents5. Infants and parents are separated too early, and the parents lack their autonomy as primary caregivers, which can impede the development of healthy bonding between parents and their infants6. Parents may suffer from feelings of disappointment, ambivalence, helplessness, anxiety, and guilt7. Unresolved psychological trauma is linked to parental stress, thereby compromising parental well-being, attitudes, and behaviors, potentially adversely impacting the attachment process between infants and their parents8,9,10.
Family-integrated early interventions are warranted to decrease these adverse consequences of preterm birth and to actively involve parents as primary caregivers as soon as possible11. Music therapy in neonatal care is exactly that: an early and promising intervention to stabilize and nurture the infant as well as to promote connectedness at a time when many other interventions are still at risk to overwhelm the fragile infant. CMT for preterm infants and their parents has emerged as one of these interactive music therapy approaches in the NICU12,13,14. CMT is an individualized and interactive approach, resource and needs-oriented15,16,17. CMT is related to Nordoff-Robbins music therapy18, which assumes that being responsive to music is an intrinsic quality to being human, regardless how handicapped or even premature a human being is19,20. CMT directs the trained music therapist to assess the meaning of the infant&#39;s breathing rhythms, facial expressions, and gesticulations, and to construct a musical response15,21. The therapist hums or sings in an infant-directed improvised lullaby style, continually coregulating the infant&#39;s behavioral states (affects, emotion, arousal22). CMT aims to relax the infant as well as to offer individualized interaction, meaningful stimulation, and entrained rhythms (e.g., to facilitate stable and regular breathing rhythm and suck-swallow-breath rhythm)23,24.
Based on the principles of family-integrated care11, the family is incorporated individually in the therapeutic process, namely by delivering CMT during KC when the infant is placed chest-to-chest or skin-to-skin on the chest of the parents to enhance parental feelings of security and thereby prevent their retraumatization5. The music is tailored continuously to the affects, rhythms, and needs of the infants as well. CMT aims to honor the family&#39;s musical and cultural heritage and to integrate their favorite music or song to empower the family in their cultural identity23 similar to the &#34;song of kin&#34; techniques of Loewy et al.25. CMT further aims to promote parental self-confidence and autonomy and to enhance the parent-infant attachment process. The music therapist generates the parent&#39;s awareness to reconnect with their musical self and their infant via vocal interaction by supporting parental infant-directed speaking and/or singing in a responsive and attuned way. During KC the therapist may accompany the voice with a monochord, a single-stringed wooden instrument (~30 strings tuned to one base tone with octaves and fifth generating vibroacoustic sounds of overtones). It may evoke the deep-frequency sounds and vibroacoustic of the womb. It generates an open, nurturing sound that may be inviting to sing along with in all musical keys and styles, as proposed by the parents. Techniques such as positioning the instrument against the parent&#39;s elbow allows its vibrations to convey relaxation. The monochord has proven itself effective in inducing relaxation and lending a feeling of intensity to parent-infant encounters26. Parents in the NICU reported after CMT that particularly the monochord sound generated the feelings of security, relaxation, and increased physical closeness to their infant27. Additionally, KC itself is a natural technique for enhancing the multisensory bonding experience between mother (or father) and infant and has become standard routine in many NICU units28.
Even among siblings, premature birth is challenging. Siblings may struggle with feelings of neglect, envy, and sometimes grief, which can lead them to refuse to accept their preterm sibling29. Consequently, CMT also aims to include preterm infants&#39; siblings by letting them choose a song for their prematurely born sister or brother and by singing it together, for example. Generally speaking, CMT aims to facilitate communicative musicality to promote parent-infant connectedness. Music is the pathway for each family to engage in a meaningful ongoing relationship &#34;to support the infant coming into being, the parents into parenthood, and the triad into bonding&#34;30.
Several systematic reviews and a meta-analysis31,32,33 suggest favorable effects of music therapy in neonatal care (e.g., physiological parameters, behavior state, respiration). The meta-analysis, including 964 preterm infants and 266 parents, showed a beneficial effect of music therapy on the infants&#39; respiratory rate and maternal anxiety31. The authors highlight the need for neonatal music therapy provided by specially trained music therapists31. Equally, the authors of a multicenter randomized controlled trial (RCT)13, a mixed-method study34, and a qualitative study35, call for the informed use of music in a therapeutic relationship by certified music therapists. Several trials revealed that music therapy, and particularly entrained music therapy13, has a favorable impact on preterm infants&#39; respiratory rate, and quiet alert and sleep states13,31. Integrating parental-preferred lullabies in the live music therapy process was associated with enhanced bonding and decreased parental stress and anxiety13,34.
Researchers have further investigated if live music therapy during KC may affect the well-being and stress levels of parents more than KC alone. Two randomized studies from Israel demonstrated that active harp music therapy during KC may reduce maternal anxiety more than KC alone36 and that a mother&#39;s anxiety may decrease when singing while holding the baby in KC and increase calmness in preterm infants more than KC alone37. Similarly, researchers from Finland38 suggest that live music therapy combined with KC may have more relaxing effects than KC alone. Although these results have to be confirmed with more extensive trials, they already indicate the potentials and possible advantages of music therapy over other nonpharmacological interventions such as KC and call for family-integrated music therapy in neonatal care. In this manuscript, we present a detailed step-by-step protocol on how to use CMT as a family-integrated, needs-oriented, and individualized live music therapy approach in the NICU to empower preterm infants and their parents from the very beginning.

<table><tbody><tr><td>K&amp;ouml;rpermonochord</td><td>Saitenklang</td><td></td><td>http://www.saitenklang.ch/koerpermonochord/</td></tr></tbody></table>

clinical practice protocol of creative music therapy for preterm infants and their parents in the neonatal intensive care unit

Creative music therapy for preterm infants and their parents (CMT) has emerged as a promising family-integrated early intervention involving communicative musicality to improve infant development, parental well-being, and bonding. It aims at relaxing and nurturing the infant as well as promoting safety and social interaction for the parent-infant dyad. A music therapist specially trained in CMT hums or sings in an infant-directed, improvised, lullaby style continually adjusting to the individual needs, expressions, and breathing pattern of the preterm infant. Based on the principles of family-integrated care, the family is incorporated individually in the therapeutic process, namely by delivering CMT during kangaroo care (KC) and by motivating and facilitating parental vocal interaction with their infant to strengthen the parent-infant bonding. CMT aims at relaxing, stimulating, and coregulating premature infants at a time when many other interventions are still risky and can overwhelm the vulnerable patient group. CMT may be advantageous not by educating and teaching parents, but rather by uncovering the intuitive capacities of parenting that are often overshadowed by the traumatic experience of preterm birth. However, CMT can only be provided when the infants are clinically stable. CMT with parental integration is feasible when parents are available and receptive to participate. This paper presents a detailed protocol on how to use CMT to empower preterm infants and their families.

A microanalysis of video material (122 videos) collected for a qualitative, grounded-theory-based, multiperspective study of CMT23,50, identified three central interaction categories: 1) responsiveness of the therapist and parents, 2) resulting in communicative musicality with the infant, and 3) infants&#39; and parents&#39; empowerment as a consequence of categories 1 and 2 (Figure 1). The study results suggest that the therapists&#39; prevailing attitude of responsiveness via musical attunement and entrainment may facilitate shared communicative musicality (e.g., interactional synchrony, moment of meeting, interplay). By experiencing this relatedness in music, parents and infants may be supported to relax and to engage in mutual relationship. However, preterm infants still act and re-act with most subtle facial expressions and movements23.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/60412/60412fig1.jpg" /> 
Figure 1: Logic diagram of categories inherent in the CMT process. This figure has been modified from Haslbeck23. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
In this context, responsiveness means the therapist`s ability to observe, interpret, and respond reasonably with musical capacity57. The video microanalysis revealed that when the infant is aroused, the therapist sings as simple and repetitive as possible to calm down the infant. The therapist softly hums only two long holding notes centering around the tonic of the scale to provide a musical holding, stability, and safety (Figure 2, blue circle voice line, 0:21-0:55). The therapist continually entrains the singing to the breathing rhythms of the infant (Figure 2-4: infant`s breathing and therapist`s voice line continuously rhythmically entrained).
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/60412/60412fig2.jpg" /> 
Figure 2: Transcription of responsiveness and therapist-infant synchronization. Detailed transcription of music therapy session with Melissa by using conservative music notation with Finale 2011 notation software50 including three layers on the same timescale: 1) environment, 2) infant behavior (four layers: a) behavioral state b) gestures c) mimicry d) breathing pattern, if visible) and 3) therapist`s voice. This figure has been modified from Haslbeck50. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Further responsiveness involves attuning to the environmental sounds such as the monitor beeping. The therapist sings in the key of the monitor alarms (Figure 3, blue arrows, 1:00-1:07) to integrate sudden stressful digital sounds in the music and thereby to mitigate disturbing noises. Consequently, &#34;Melissa&#34; remains calm (Figure 3, blue rectangles, 1:04-1:10) after the sudden alarm during music therapy (Figure 3, red star, 1:04) in contrast to beeping noise evoked stressed reactions without music therapy50. The therapist continuously tailors the singing to the facial expressions and gestures of the infant (Figure 3, orange arrows, 0:58, 1:09). For instance, when Melissa smiles and rises her fingers the therapist rises the melody, tempo and dynamics synchronously (Figure 4, blue circle: compare voice line with breathing, mimic mouth and gesture line, 1:30-1:45).
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/60412/60412fig3.jpg" /> 
Figure 3: Transcription of responsiveness, entrainment, therapist-infant synchronization, and integrating of monitor alarm. Detailed transcription of music therapy session with Melissa as described in Figure legend 2. This figure has been modified from Haslbeck50. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/60412/60412fig4.jpg" /> 
Figure 4: Transcription of communicative musicality and therapist-infant synchronization. Detailed transcription of music therapy session with Melissa as described in Figure legend 2. This figure has been modified from Haslbeck50. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Communicative musicality acts like the intuitive affect attunement of a healthy caregiver-infant relationship. This sharing of emotional experiences is like a dance, like a musical performance52,58,59,60. Through shared rhythms, tempi, and affects, communicative musicality may support the infants&#39; coregulation and stabilization and may transform the arrhythmic intensive care environment into a relational environment required for healthy socio-emotional development and growth59. The video microanalysis50 implies that CMT may enhance relaxation, participation, self-regulation, and engagement in premature infants through experienced communicative musicality. Communicative musicality can evolve through interactional synchronization of affects. In Figure 2, at first, Melissa synchronizes her stressed movements with the tension in the music. She splays her fingers synchronously with the higher more suspenseful note or in the tense pause (Figure 2, red arrows, 0:24-0:37). After synchronizing with the tension in the music, she may then be able to synchronize with the relaxation of the music. When the first musical phrase ends, she relaxes her body and moves her arms and fingers smoothly down (Figure 2, orange lines, 0:38-0:44). Throughout the session, Melissa remains in this relaxed behavioral state and engages with increasing smooth facial reactions and finger movements (Figure 3, orange arrows, 0:58 -1:09). When the melody rests with the ritardando (rit.), she sighs deeply (Figure 4, blue circle, orange arrow, 2:03) interpreted as a sign of relaxation. When the melody, dynamics, and intensity ascend, she raises her finger and smiles (Figure 4, blue circle, orange arrows, 2:03-2:05) interpreted as engagement in communicative musicality.
By relaxing and engaging the parents in meaningful, sensitive interactions with the infant, the parents may experience self-confidence, self-efficacy, and autonomy. They may thereby be empowered in their role as primary caregivers and participants. In this context, empowerment means to facilitate self-regulation in the infant and to uncover intuitive parental capacities for parental responsiveness that are often overshadowed by anxiety and stress23,47. Parents reported in the qualitative interviews of the study that they could relax and relate more intense to their infant through music therapy: &#34;I notice when I can relax that I am much more connected, much more intense, much more closely connected with my daughter because of the music, because of the singing.&#34;23
The video microanalysis revealed that mothers who were stressed and distanced connected with their infants through meaningful vocal interaction. Figure 5 &#38; Figure 6 show the microanalysis of shared mother-infant rhythms of a previously stressed and detached mother. The mother entrains her singing to the sucking rhythms of her daughter. She sings with &#34;motherese&#34; (infant-directed, with a loving tone and free voice, responsive with facial expression and gestures) rocking the infant in the rhythm of the song. &#34;Emila&#34; begins with her sucking pattern precisely at the beginning of the musical phrase of her mother (Figure 5 &#38; Figure 6, orange arrows) except in bar 9 (Figure 5, red circle, 0:26). The mother immediately recognizes, interprets correctly, reacts appropriately and promptly with sensitivity as referred to as appropriate bonding behavior23. She reduces and ceases her singing to hold and readjust (Figure 5 &#38; Figure 6, blue circle, 0:26-0:28). After this moment of readjustment, she begins the musical phrase again in synchrony with the sucking pattern of Emila (Figure 6, blue circle, 0:28 following). Mother and daughter meet once more within communicative musicality in shared pulse and quality. They connect in a mutual gaze at the end of the musical phrase, and the mother smiles (Figure 5, 0:28 following). Mother and daughter meet in a &#34;neonatal moment of meeting&#34; described as tender moments after birth to generate the attachment bond and the mother&#39;s self-confidence in her role as primary caregiver23. Immediately after this singing episode, the mother expressed her love and empowerment by picturing herself as a lion mother. She phrases her self-confidence and autonomy by the sentences&#39; causal dependence (underlined): &#34;If I would not have so much love, right? Then my daughter would have no chance to survive. I am like a lion.&#34;23
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/60412/60412fig5.jpg" /> 
Figure 5: Mother-infant synchronization. Detailed transcription of mother`s singing for her daughter Emila by using conservative music notation with Finale 2011 notation software50 including three layers on the same timescale: 1) Emila`s nutritive sucking pattern, 2) mother`s behavior and 3) mother`s singing. This figure has been modified from Haslbeck23. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/60412/60412fig6.jpg" /> 
Figure 6: Mother-infant synchronization and moment of meeting. Detailed transcription of mother`s singing for her daughter Emila as described in Figure legend 5. This figure has been modified from Haslbeck23. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig6large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
First results of a mixed-method pilot trial underline these results. The study revealed that parental depressive symptoms decreased and physical closeness increased across hospitalization time in the CMT group compared to the control group27. The parents reported that CMT evoked feelings of relaxation and joy and empowerment to interact more profoundly with their infant27.

Watch this Scientific Journal Video about Clinical Practice Protocol of Creative Music Therapy for Preterm Infants and Their Parents in the Neonatal Intensive Care Unit at JoVE.com

Clinical Practice Protocol of Creative Music Therapy for Preterm Infants and Their Parents in the Neonatal Intensive Care Unit

Creative music therapy for preterm infants and their parents has emerged as a promising family-integrated early intervention. We present a detailed protocol on how to use vocal interaction, humming, or singing to empower preterm infants and their families.

Creative music therapy for preterm infants and their parents (CMT) has emerged as a promising family-integrated early intervention involving communicative ...

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26.0K Views.  University of Zurich. Creative music therapy for preterm infants and their parents has emerged as a promising family-integrated early intervention. We present a detailed protocol on how to use vocal interaction, humming, or singing to empower preterm infants and their families.

Video: Clinical Practice Protocol of Creative Music Therapy for Preterm Infants and Their Parents in the Neonatal Intensive Care Unit

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant.  The NICU Network Neurobehavioral Scale ...

Behavior

Infant Auditory Processing and Event-related Brain Oscillations

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral and temporal changes that are characteristic of human language. These abilities lay the foundation for effective language acquisition; allowing infants to hone in on the sounds of their native language. Invasive procedures in animals and scalp-recorded potentials from human adults suggest that simultaneous, rhythmic activity (oscillations) between and within brain regions are fundamental to sensory development; determining the resolution with which incoming stimuli are parsed. At this time, little is known about oscillatory dynamics in human infant development. However, animal neurophysiology and adult EEG data provide the basis for a strong hypothesis that rapid auditory processing in infants is mediated by oscillatory synchrony in discrete frequency bands. In order to investigate this, 128-channel, high-density EEG responses of 4-month old infants to frequency change in tone pairs, presented in two rate conditions (Rapid: 70 msec ISI and Control: 300 msec ISI) were examined. To determine the frequency band and magnitude of activity, auditory evoked response averages were first co-registered with age-appropriate brain templates. Next, the principal components of the response were identified and localized using a two-dipole model of brain activity. Single-trial analysis of oscillatory power showed a robust index of frequency change processing in bursts of Theta band (3 - 8 Hz) activity in both right and left auditory cortices, with left activation more prominent in the Rapid condition. These methods have produced data that are not only some of the first reported evoked oscillations analyses in infants, but are also, importantly, the product of a well-established method of recording and analyzing clean, meticulously collected, infant EEG and ERPs. In this article, we describe our method for infant EEG net application, recording, dynamic brain response analysis, and representative results.

High-density electroencephalography (dEEG) is being used increasingly to study brain development and plasticity in the early years of life. Here we present an application of sophisticated analysis techniques that builds on traditional EEG recording to understand the oscillatory dynamics of rapid auditory processing in the infant brain.

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral ...

A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing &#8220;in action and in context&#8221;. This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.

This protocol presents a novel methodology for the neural decoding of intent from freely-behaving infants during unscripted social interaction with an actor. Neural activity is acquired using non-invasive high-density active scalp electroencephalography (EEG). Kinematic data is collected with inertial measurement units and supplemented with synchronized video recording.

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental ...

Experience is Instrumental in Tuning a Link Between Language and Cognition: Evidence from 6-  to 7- Month-Old Infants' Object Categorization

At birth, infants not only prefer listening to human vocalizations, but also have begun to link these vocalizations to cognition: For infants as young as three months of age, listening to human language supports object categorization, a core cognitive capacity. This precocious link is initially broad: At 3 and 4 months, vocalizations of both humans and nonhuman primates support categorization. But by 6 months, infants have narrowed the link: Only human vocalizations support object categorization. Here we ask what guides infants as they tune their initially broad link to a more precise one, engaged only by the vocalizations of our species. Across three studies, we use a novel exposure paradigm to examine the effects of experience. We document that merely exposing infants to nonhuman primate vocalizations enables infants to preserve the early-established link between this signal and categorization. In contrast, exposing infants to backward speech &#8212; a signal that fails to support categorization at any age &#8212; offers no such advantage. Our findings reveal the power of early experience as infants specify which signals, from an initially broad set, they will continue to link to cognition.

At 3-4 months, listening to human and nonhuman primate vocalizations boosts infants&#39; cognition; by 6 months, only human vocalizations exert this cognitive advantage. We describe an exposure manipulation that reveals the powerful shaping role of experience as infants specify which sounds to link to cognition and which to tune out.

At birth, infants not only prefer listening to human vocalizations, but also have begun to link these vocalizations to cognition: For infants as young as ...

A Novel Method for Involving Women of Color at High Risk for Preterm Birth in Research Priority Setting

Involvement of patients and the public is now recognized to be essential for the good conduct of research. Patient and public involvement in research priority setting and funding decisions is only beginning to be recognized as important, and methods for doing so are nascent. This protocol describes the Research Prioritization by Affected Communities (RPAC) protocol and findings from its use with women at high socio-demographic risk for preterm birth. The goal was to directly involve these women in identifying and prioritizing their unanswered questions about pregnancy, birth and neonatal care, and treatment so that their views could be included in research priority setting by funders and researchers. The RPAC protocol may be used to meaningfully involve under-represented groups at high-risk for specific health problems, or those who face disproportionate burden of disease, in research strategy and funding priority setting.

This manuscript describes the Research Prioritization by Affected Communities (RPAC) protocol and findings from its use with women at risk for preterm birth. Using the protocol, women identified and prioritized their unanswered questions about pregnancy, birth and neonatal care aimed at influencing research priority setting by funders and researchers.

Involvement of patients and the public is now recognized to be essential for the good conduct of research. Patient and public involvement in research ...

Preterm EEG: A Multimodal Neurophysiological Protocol

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. 
In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked.
In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

This video explains the background theory of the neonatal EEG activity and the sensory responses, followed by a live demonstration of their recording in neonatal intensive care unit.

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and ...

Neuroscience

Transcutaneous Microcirculatory Imaging in Preterm Neonates

Microcirculatory imaging (MI) is a relatively new research tool mainly used in the intensive care setting. MI provides a clear view of the smallest capillaries, arterioles and venules. The magnifying effect visualizes the flow pattern of erythrocytes through these vessels.
It's non-invasive character makes it suitable to apply in (preterm) neonates, even in cardiorespiratory unstable patients. In adults and children, MI is mainly performed sublingually, but this is not possible in preterm infants as these cannot cooperate and the size of the probe is problematic. In preterm infants, MI is therefore performed transcutaneously. Their thin skin makes it possible to obtain high quality images of peripheral microcirculation. 
In this manuscript we will demonstrate the method of transcutaneous MI in preterm infants. We will focus on the different techniques and provide tips to optimize image quality. The highlights of software settings, safety and offline analysis are also addressed.

Microcirculatory imaging (MI) is used to monitor peripheral perfusion in critically ill or preterm neonates. This manuscript and video demonstrates the optimal approach for obtaining high-quality images.

Microcirculatory imaging (MI) is a relatively new research tool mainly used in the intensive care setting. MI provides a clear view of the smallest ...

Application of an Amplitude-integrated EEG Monitor (Cerebral Function Monitor) to Neonates

Amplitude-integrated EEG (aEEG) is an easily accessible technique to monitor the electrocortical activity in preterm and term infants in neonatal intensive care units (NICUs). This method was first used to monitor newborns after asphyxia, providing information about future neurological outcomes. The aEEG is also helpful to select newborns who benefit from cooling. The aEEG monitoring of preterm infants is becoming more widespread, as various studies have shown that neurodevelopmental outcome is related to early aEEG tracings. Here, we demonstrate the application of the aEEG monitoring system and present typical patterns that depend upon gestational age and pathophysiological conditions. Furthermore, we mention pitfalls in the interpretation of the aEEG, as this method requires accurate fixation and localization of the electrodes. Additionally, the raw EEG can be used to detect neonatal seizures or to identify aEEG application problems. In conclusion, aEEG is a safe and generally well-tolerated method for the bedside monitoring of neonatal cerebral function; it can even provide information about long-term outcome.

Application of an Amplitude-integrated EEG Monitor Cerebral Function Monitor to Neonates

Here, we show how to apply amplitude-integrated electroencephalography to monitor cerebral function in neonates.

Amplitude-integrated EEG (aEEG) is an easily accessible technique to monitor the electrocortical activity in preterm and term infants in neonatal ...

A Detailed Protocol for Physiological Parameters Acquisition and Analysis in Neurosurgical Critical Patients

Intracranial pressure (ICP) monitoring is now widely used in neurosurgical critical patients. Besides mean ICP value, the ICP derived parameters such as ICP waveform, amplitude of pulse (AMP), the correlation of ICP amplitude and ICP mean (RAP), pressure reactivity index (PRx), ICP and arterial blood pressure (ABP) wave amplitude correlation (IAAC), and so on, can reflect intracranial status, predict prognosis, and can also be used as guidance of proper treatment. However, most of the clinicians focus only on the mean ICP value while ignoring these parameters because of the limitations of the current devices. We have recently developed a multimodality monitoring system to address these drawbacks. This portable, user-friendly system will use a data collecting and storing device to continuously acquire patients&#39; physiological parameters first, i.e., ABP, ICP, and oxygen saturation, and then analyze these physiological parameters. We hope that the multimodality monitoring system will be accepted as a key measure to monitor physiological parameters, to analyze the current clinical status, and to predict the prognosis of the neurosurgical critical patients.

Recently, we have developed a portable multimodality monitoring system for the monitoring of various physiological parameters in neurosurgical critical patients. Detailed protocols on how to use this multimodality monitoring system are presented here.

Intracranial pressure (ICP) monitoring is now widely used in neurosurgical critical patients. Besides mean ICP value, the ICP derived parameters such as ...

A Modified Sonographic Algorithm for Image Acquisition in Life-Threatening Emergencies in the Critically Ill Newborn

The use of routine point-of-care ultrasound (POCUS) is increasing in neonatal intensive care units (NICUs), with several centers advocating for 24 h equipment availability. In 2018, the sonographic algorithm for life-threatening emergencies (SAFE) protocol was published, which allows the assessment of neonates with sudden decompensation to identify abnormal contractility, tamponade, pneumothorax, and pleural effusion. In the study unit (with a consulting neonatal hemodynamics and POCUS service), the algorithm was adapted by including consolidated core steps to support at-risk newborns, aiding clinicians in managing cardiac arrest, and adding views to verify correct intubation. This paper presents a protocol that can be applied in the NICU and the delivery room (DR) in relation to three scenarios: cardiac arrest, hemodynamic deterioration, or respiratory decompensation. 
This protocol can be performed with a state-of-the-art ultrasound machine or an affordable handheld device; the image acquisition protocol is carefully detailed. This method was designed to be learned as a general competence to obtain the timely diagnosis of life-threatening scenarios; the method aims to save time but does not represent a substitute for comprehensive and standardized hemodynamic and radiological analyses by a multidisciplinary team, which might not universally be on call but needs to be involved in the process. From January 2019 to July 2022, in our center, 1,045 hemodynamic consultation/POCUS consults were performed with 25 patients requiring the modified SAFE protocol (2.3%), and a total of 19 procedures were performed. In five cases, trained fellows on call resolved life-threatening situations. Clinical examples are provided that show the importance of including this technique in the care of critical newborns.

Here, we present a protocol that can be applied in the neonatal intensive care unit and the delivery room in relation to three scenarios: cardiac arrest, hemodynamic deterioration, or respiratory decompensation. This protocol can be performed with a state-of-the-art ultrasound machine or an affordable handheld device; an image acquisition protocol is carefully detailed.

The use of routine point-of-care ultrasound (POCUS) is increasing in neonatal intensive care units (NICUs), with several centers advocating for 24 h ...