Effect of Audio Training on executive dysfunction in patients with stroke Zhang Jingjing, Chen Changxiang. College of Nursing and Rehabilitation, North China University of Science and Technology; Tangshan Rehabilitation Medical Center, Hebei Province Tangshan 063000, China Corresponding author: Chen Changxiang, Email: firstname.lastname@example.org Abstract: Objective To investigate the effect of Tomatis audio training on executive dysfunction in patients with stroke. Methods A total of 80 stroke patients from the Rehabilitation Branch, Tangshan Workerâ&#x20AC;&#x2122;s Hospital were enrolled prospectively. They were divided into either a music group or a control group (n=40 in each group) according to random number table. On the basis of conventional rehabilitation training, both groups received music training. The patients of the control group received conventional music training (conventional frequency music without audio processing); the patients of the music group received Tomatis audio training. Both groups were trained at the same time, once a day for 60-90 min, and they were trained for 2 cycles. The first cycle was 14 days and the second one was 10 days, the interval of the 2 cycles was 30 days (a total of 54 days). The Behavioral Assessment of Dys-executive Syndrome (BADS) was used to assess their executive dysfunction before and after music training. Results The 6 sub-projects of BADS in the music group after music training: the rule shift cards test, action program test, key seek test, temporal judgment test, zoo map test, modified six elements, and total standard score (median [P25, P75]) 2.0 (1.2, 2.7), 2.0 (1.0, 2.0), 2.0 (1.0, 2.0), 2.0 (1.0, 2.0), 2.0 (2.0, 2.0), 2.0 (2.0, 3.0), and 11.0 (11.0, 12.0), respectively). They were compared with those of the control group (1.0[1.0, 2.0]), 1.0 [1.0, 2.0], 1.0 [1.0, 2.0], 1.0 [1.0, 2.0], 1.0 [1.0, 2.0], 1.0 [1.0, 1.0], and 8.0 [8.0, 10.0], respectively). There were significant differences between the 2 groups (all P < 0.05). Conclusion Tomatis audio training may effectively improve the executive function in patients with stroke. Key words: Stroke; Executive function disorders; Rehabilitation; Tomatis audio training
The incidence of executive function disorders after stroke is as high as 66% , while the executive dysfunction has the most obvious impact on the life of patients and also seriously affects the later rehabilitation . Researched and developed by the French scientific research institutions  , Tomatis audio training uses music that went through audio processing and can produce effective music stimulation on brain to improve brain function. Tomatis audio training has been used for treatment of psychological and cognitive function disorders in foreign countries . The author applied Tomatis audio training to executive dysfunction after stroke to investigate the effect.
1. Objects and methods 1.1 Objects A total of 80 stroke patients [52 males and 28 females; mean age: (57± 9) (range: 35~75)] admitted into the Rehabilitation Branch, Tangshan Worker’s Hospital from June to December 2015 were enrolled prospectively. They were randomly divided into two groups according to random number table: 40 cases in the control group and 40 cases in the music group. This study had been approved by the hospital ethics committee. The differences in general condition, course of disease, stroke location, stroke type and disease side were not statistically significant (P >0. 05), so the two groups are comparable. See table 1. Inclusion criteria: (1) patient who was in accordance with the stroke diagnosis standard formulated in the Fourth National Conference on Cerebrovascular Diseases  and was diagnosed with stroke in clinical examination; (2) aged 35 ~ 75 years old; (3) Brnnnstrom score > grade Ⅲ and the standing balance ≥ grade Ⅱ ; (4) without moderate or severe brain atrophy or leukoaraiosis; (5) first onset and the course of disease within three months; (6)
patient who has cognitive dysfunction by Montreal Cognitive Assessment (MoCA) scale (MoCA < 26 scores); (7) patient who has a certain cultural foundation and can recognize and understand common words and language; (8) no disturbance of consciousness and pregnancy. Exclusion criteria: (1) with severe abnormalities in visual, auditory and expression ability; (2) with a history of craniocerebral diseases or obvious hypophrenia appeared before onset; (3) with a history of past mental disorder, serious heart, lung and renal insufficiency and malignant tumor or other serious diseases; (4) with severe arthropathy; (5) length of hospitalization < 2 months; (6) with drug and alcohol dependence; (7) patients who do not sign the informed consent form. 1.2 Methods 1.2.1 Intervention methods: Routine rehabilitation training was performed in both groups, including occupational therapy, physical therapy, transcutaneous electrical nerve stimulation, neural network plasticity therapy, acupuncture treatment and so on. Music Group: Tomatis hearing training was offered on the basis of conventional rehabilitation training. The test instrument was “Talks Up”, which was researched and developed by French Tomatis scientific research institution in 2015 (model: SN: 150103-0000472 and produced by Austria Tomatis Development Agency); this machine included 2 hosts equipped with touch control panel (the host with green sign was the host with audio processing function and the host with red sign was the one without audio processing function), 2 wireless signal transmitters matched with the host and wireless earphone with air conduction and bone conduction technology (allow multiple persons to receive hearing training at the same time). Concrete training method: patients were
gathered in the range covered by the wireless signal transmitter (about 30m radius), 10 to 16 individuals once. Trainers turned on the earphone switch, adjusted the volume to a proper level and helped patients wear the wireless earphone (pay attention to left and right side), making the bone conduction device at the top of the earphone close to the center of the patient's calvarium. The music program was programmed for this test by the neurocognitive expert of University of Marseille (France), which included a series of Mozart Music and Gregoria chants. Trainers replaced the music program everyday in accordance with the order and daily music content was different, including one or more Mozart's music and Gregoria chants. Audio processing principle: the audio processing principle of Tomatis audio training instrument is to control the alternate conversion between the high-frequency air conduction (AC1) channel, bone conduction (BC1) channel, low frequency air conduction (AC2) channel and bone conduction (BC2) channel using gating system, to achieve the change of audio between 16,000 and 20 Hz. Wherein, the conversion speed of bone conduction signal from BC1 to BC2 is "delaying", the conversion speed of air conduction signal from AC1 to AC2 is â&#x20AC;&#x153;advancingâ&#x20AC;? and the sum of delaying and advancing speed is called the gating speed. The regular bi-directional conversion is used to stimulate the muscles on both sides of the ear, excite the brain and excite the central nervous system . Audio change law: (1) The first cycle (T Program) was composed of the programs of 35% non-filtered music (MU), 26% mixed sound or Gregoira chants (GC), 21% low pass filter music (frequency: 6,000 Hz) and
18% ordinary band-pass (frequency: 500 ~ 3,000 Hz), once a day, 60 min once for the first to third day and 90 min once for the fourth to fourteenth day (a total of 14 days). It was the adaptive phase, in which the audio changed gradually to prepare for the implementation of the second cycle . (2) The interval was 30 days. The brain can exhibit change only after intensive and repetitive stimuli and also needed non-stimulation phase to integrate the changes and let the body have a break . (3) The second cycle (F Program) was composed of the programs of 60% MU (high pass filter with a frequency of 500 ~2,500 Hz), 25% GC and 15% low pass filter music (with a frequency of 6,000 Hz), 90 min, once a day for 10 days. The control group: the music and tests same as those of the music group were given, using the host with the red mark and conventional frequency music without audio processing. 1.2.2 Assessment method: the executive function of both groups were tested with behavioral assessment of dysex-excutive syndrome (BADS)  before and after the intervention. BADS included six sub-items: rule shift cards test (RSCT), action program test (APT), key seek test (KST), temporal judgement test (TJT), zoo map test (ZMT) and modified six elements test (MSET). Subjects were asked to complete the assigned tasks within 10 minutes in accordance with the rules. The original score was converted to. the standard score for each item. The standard score of each term was 0 to 4, and the total standard score was 0 to 24. The lower the score was, the worse the executive function was. .
Control group Music group Test value P value Group
Table 1 Comparison of balance of general condition between the two groups [n (%)] Cases Male Education Course of disease (month) Age (x±s, 1 2 3 Elementary High years and junior school old) Illiteracy high and school above 40 57+8 27(67.5) 14(35.0) 19(47.5) 7(17.5) 16(40.0) 16(40.0) 8(20.0) 40 56+8 25(62.5) 15(37.5) 17(42.5) 8(20.0) 12(30.0) 18(45.0) 10(25.0) -0.149a 0.220b 0.212c -0.787c 0.637 0.815 0.899 0.634 Cases
Diseased region Basal Others nucleus
Onset side Stroke type Cerebral Left Right Both Cerebral side side sides infarction hemorrhage Control group 40 32(80.0) 8(20.0) 17(42.5) 16(40.0) 7(17.5) 25(62.5) 15(37.5) Music group 40 27(67.5) 13(32.5) 15(37.5) 19(47.5) 6(15.0) 30(75.0) 10(25.0) Test value 1.614b 0.459b 1.455b P value 0.209 0.795 0.335 Note: MoCA is Montreal cognitive assessment scale; a is the t value, b is the x 2 value and c is the Z value.
MoCA (x±s, score) 13 ±3 14±3 0.616a 0.539
1.3 Statistical analysis SPSS 17.0 statistical software was used for analysis. The measurement data of normal distribution were expressed by x ± s, and t test was adopted for comparison between groups; the measurement data of non-normal distribution were expressed by median and quartile [M (P25, P75)] and rank sum test was employed for comparison between groups. The count data were expressed by cases and percentage; and χ２ test was applied for comparison between groups and rank sum test for comparison of ranked data between groups. The difference was considered statistically significant if P < 0.05. 2 Results 2.1 Comparison of BADS scores between the two groups before music training The differences between scores of each sub-item of BAD and total standard scores of music group and control group before music training were not statistically significant (P > 0.05) .See table 2. 2.2 Comparison of BADS scores between the two groups after music training Each sub-item score of BAD and total standard score of the music group were higher than those of the control group after music training and the differences were statistically significant (P < 0.05). See table 3.
Table 2 Comparison of executive dysfunction syndrome behavioral scores of two groups of patients with stroke before intervention [M (P25, P75), score) Total standard score
1.0(1.0,2.0) 1.0(1.0,2.0) 1.0(1.0,2.0) 1.0(1.0,2.0) 1.0(1.0,2.0)
1.0(0.0,1.7) 1.0(0.2,1.0) 1.0(0.0,2.0) 1.0(1.0,1.7) 1.0(1.0,2.0)
Note: RSCT is rule shift cards test, APT is action program test, KST i s k e y seek test, judgement test, ZMT is zoo map test, MSET is modified six elements test.
Table 3 Comparison of executive dysfunction syndrome behavioral scores of two groups of patients with stroke after intervention [M (P25, P75), score] Group
Total standard score
1.0(1.0,2.0) 1.0(1.0,2.0) 1.0(1.0,2.0) 1.0(1.0,2.0) 1.0(1.0,2.0)
Note: the same as table 2
3 Discussions Executive dysfunction is the most common cognitive impairment after stroke. Executive functions include the abilities of concentrating, processing unfamiliar conditions, selectively participating, planning, and implementing as well as many functional regions affecting human behavior, cognition, movement and emotion , which play an important role in functional recovery. The limbic system, basal ganglia, and prefrontal cortex, which are responsible for executive function, are impaired due to brain tissue injury after stroke, resulting in impaired executive function . However, the central nervous system has structural and functional plasticity after injury, and their structures and functions can be strengthened and consolidated through continuous learning and training . Mozart music can make the brain more
active and "activate" related functional areas to neural cortical circuits, while Gregoria chants can relieve autonomic nervous system  . This trial results showed that the scores of 6 sub-items of BAD and total standard score of music group were higher than those of the control group (P < 0.05), suggesting that Tomatis audio training can effectively improve executive function in patients with stroke. These were consistent with the findings of foreign study that the audio training of a certain period can improve the cognitive function . The effective mechanisms of Tomatis training to improve executive ability in patients with stroke are as following: (1) earphone possessing the characteristics of bone conduction and air conduction can make patients receive sound more quickly and effectively . (2) The mutual conversion between the processed high-low frequency sound and high-low frequency can stimulate the limbic system in
the cerebral central region through the auditory neural system. This area is responsible for emotion, executive function, memory and learning, etc. Executive dysfunction is closely related to the impairment of limbic system, basal ganglia and prefrontal cortex , and high frequency sound stimulation makes the cochlea in the middle ear discharge to the cerebral cortex and affects the limbic system and prefrontal cortex. High-low frequency processing is set for the test objects, based on years of scientific research experiences of French Tomatis institutions, and meets the safety range of patients with stroke. (3) Mozart music is able to "activate" the cognitive function related to the neural cortical circuit  . (4) Different Mozart and Gregoria chants are used in Tomatis audio training, featuring beautiful melody and easy acceptance, and novel method, thus avoiding fatigue due to long course of treatment. The frequency processing of each track is different so that the brain can receive stimulation with different frequencies each day, which plays a good role in helping recover executive function of patients. Tomatis audio training offers a relatively relaxing environment to patients and doesnâ&#x20AC;&#x2122;t require complex coordination, which effectively reduces the pessimal stimulus generated by the treatment. The wireless devices can be used simultaneously by multiple persons, which lowers the costs. However, sample size of this trial is small and the period is short. Subsequent trials with larger sample size and longer training period are expected, in order to better observe the long-term effect of the Tomatis audio training.
References  Kamtchum Tatuene J, Allali G, Saj A, et al. Incidence,risk factors and anatomy of peripersonal visuospatial neglect in acute stroke [ J]. Eur Neurol,2016,4(3/4):157-163.  Carlson MC, Xue QL, Zhou Jďź&#x152;et al. Executive decline and dysfunction precedes declines in memory: the Women's Health and Aging Study II [J].J Gerontol A Biol Sci Med Sci, 2009,64(1):110-117.  Brosch H. Sound therapy according to Alfred Tomatis [J]. Kinderkrankenschwester, 2000,19(10): 412414.  Corbett BA, Shickman K, Ferrer E. Brief report: the effects of Tomatis sound therapy on language in children with autism [J]. Autism Dev Disord, 2008, 38(3): 562-564.  The Chinese Neuroscience Society, the Chinese Neurosurgery Society. Key points of diagnosis for cerebrovascular diseases [J].Chinese Journal of Neurology, 1996, 29(6):379-383.  Shi Fengying. Rehabilitation Nursing [M]. Version 2. Beijing: People's Medical Publishing House, 2008:34-84.  Hu Xiquan. Evaluation and recovery of cognitive disorder caused by stroke [J]. Chinese Journal of Practical Internal Medicine, 2013, 33 (8): 598-601.  Burgess PW, Alderman N, Evans J, et al. The ecological validity of tests of executive function [J]. J Int Neuropsy-chol Soc, 1998, 4(6): 547-558.  Rozental-Iluz C, Zeilig G, Weingarden H, et al. Improving executive function deficits by playing interactive video- games; a
secondary analysis of a randomized controlled trial for individuals with chronic stroke [J]. Eur J Phys Rehabil Med, 2016, In press.  Kluding PM, Tseng BY, Billinger SA. Exercise and executive function in individuals with chronic stroke: a pilot study [J]. J Neurol Phys Ther, 2011, 35(1): 11-17.  Rand D, Eng JJ, Liu-Ambrose T, et al. Feasibility of a 6-month exercise and recreation program to improve executive functioning and memory inindividuals with chronic stroke [J]. Neurorehabil Neural Repair, 2010, 24(8): 722-729.  Verrusio W, Ettorre E, Vicenzini E. The Mozart effect: a quantitative EEG study [J]. Conscious Cogn, 2015, 9 ( 35 ): 150-154.  McBride M, Tran P, Pollard KA, et al. Effects of bone vibrator position on auditory spatial perception tasks [J].Hum Factors, 015, 7(8): 1443-1458.  Fukushima A, Yagi R, Kawai N. Frequencies of inaudible high-frequency sounds differentially affect brain activity: positive and negative hypersonic effects [J]. PLoS One, 2014, (4): 95464.