From: Subject: =?Windows-1252?Q?Music_listening_enhances_cognitive_recovery_and_mood_aft?= =?Windows-1252?Q?er_middle_cerebral_artery_stroke_--_S=E4rk=E4m=F6_et_a?= =?Windows-1252?Q?l._131_=283=29:_866_--_Brain?= Date: Wed, 27 Aug 2008 10:29:53 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C9082F.D7A88340" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C9082F.D7A88340 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://brain.oxfordjournals.org/cgi/content/full/131/3/866 Music listening enhances cognitive recovery and mood = after middle cerebral artery stroke -- S=E4rk=E4m=F6 et al. 131 (3): 866 = -- Brain

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Brain Advance=20 Access originally published online on February 20, 2008 =
Brain 2008 131(3):866-876;=20 doi:10.1093/brain/awn013
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=A9 2008 The=20 Author(s)
This is an Open Access article distributed under the terms = of the=20 Creative Commons Attribution Non-Commercial License=20 (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits = unrestricted=20 non-commercial use, distribution, and reproduction in any medium, = provided the=20 original work is properly cited.

Music listening enhances cognitive recovery and mood after middle = cerebral=20 artery stroke

Teppo S=E4rk=E4m=F61, = Mari=20 Tervaniemi1, Sari Laitinen2,=20 Anita Forsblom2, Seppo = Soinila3,=20 Mikko Mikkonen1, Taina = Autti4,=20 Heli M. Silvennoinen4, Jaakko=20 Erkkil=E42, Matti Laine5, = Isabelle=20 Peretz6 and Marja Hietanen3=20

1Cognitive Brain Research Unit, Department = of=20 Psychology, University of Helsinki, and Helsinki Brain Research Centre,=20 Helsinki, 2Department of Music, University of Jyv=E4skyl=E4, = Jyv=E4skyl=E4,=20 3Department of Neurology and 4Department of = Radiology,=20 Helsinki University Central Hospital, Helsinki, 5Department = of=20 Psychology, =C5bo Akademi University, Turku, Finland and = 6Department of=20 Psychology, University of Montreal, Montreal, Canada

Correspondence to: Teppo S=E4rk=E4m=F6, MA, Cognitive = Brain Research=20 Unit, Department of Psychology, PO Box 9 (Siltavuorenpenger 20 C), = FIN-00014=20 University of Helsinki, Finland E-mail: teppo.sarkamo{at}helsinki.fi


3D"   =20 Summary
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Top
3D"Summary
= Introduction
= Methods
= Results
= Discussion
= References
 
W= e know=20 from animal studies that a stimulating and enriched = environment can=20 enhance recovery after stroke, but little is known about the = effects=20 of an enriched sound environment on recovery from neural = damage in=20 humans. In humans, music listening activates a wide-spread = bilateral=20 network of brain regions related to attention, semantic = processing,=20 memory, motor functions, and emotional processing. Music = exposure=20 also enhances emotional and cognitive functioning in healthy = subjects=20 and in various clinical patient groups. The potential role of = music=20 in neurological rehabilitation, however, has not been = systematically=20 investigated. This single-blind, randomized, and controlled = trial was=20 designed to determine whether everyday music listening can=20 facilitate the recovery of cognitive functions and mood after = stroke.=20 In the acute recovery phase, 60 patients with a left or right = hemisphere middle cerebral artery (MCA) stroke were randomly = assigned=20 to a music group, a language group, or a control group. = During=20 the following two months, the music and language groups = listened=20 daily to self-selected music or audio books, respectively, = while=20 the control group received no listening material. In = addition,=20 all patients received standard medical care and = rehabilitation.=20 All patients underwent an extensive neuropsychological = assessment,=20 which included a wide range of cognitive tests as well as = mood=20 and quality of life questionnaires, one week (baseline), 3 = months,=20 and 6 months after the stroke. Fifty-four patients completed=20 the study. Results showed that recovery in the domains of = verbal=20 memory and focused attention improved significantly more in = the=20 music group than in the language and control groups. The = music group=20 also experienced less depressed and confused mood than the = control=20 group. These findings demonstrate for the first time that = music=20 listening during the early post-stroke stage can enhance = cognitive=20 recovery and prevent negative mood. The neural mechanisms = potentially=20 underlying these effects are discussed.

Key Words: stroke; rehabilitation; music; cognition; = emotions

Abbreviations: FLAIR, fluid-attenuated inversion = recovery;=20 MCA, middle cerebral artery; MRI, magnetic resonance imaging; QOL, = quality of=20 life; RT, reaction time

Received September 18, 2007. Revised=20 January 9, 2008. Accepted January 14, = 2008.


3D"   =20 Introduction
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Top
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Summary
3D"Introduction
= Methods
= Results
= Discussion
= References
 
D= uring the=20 first weeks and months of recovery after a stroke, the brain = can=20 undergo dramatic plastic changes (Witte, 1998<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Kreisel et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) that can be further enhanced by stimulation = provided=20 by the environment. Post-stroke motor and somatosensory = environmental=20 enrichment (Johansson, 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Nithianantharajah and Hannan, 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), virtual environments (You et al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), and electrical cortical and peripheral = stimulation=20 (Hummel and Cohen, 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) have all been shown to improve motor recovery.=20 Interestingly, multimodal stimulation, including auditory, = visual=20 and olfactory stimuli, combined to the enriched motor = environment=20 enhanced motor and cognitive recovery more than the enriched=20 motor environment alone (Maegele et al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Evidence from developmental animal studies = also=20 suggests that an enriched sound environment can enhance = auditory=20 cortical functions (Engineer et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) as well as learning and memory (Chikahisa et = al.,=20 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Kim et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Angelucci et al., 2007a). In humans, the effects of an enriched sound = environment on recovery from neural damage have, however, not = been=20 systematically studied.

In the human brain, one of the most powerful sources of auditory = stimulation is provided by music (Sacks, 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Listening to music is a complex process for = the=20 brain, since it triggers a sequel of cognitive and emotional=20 components with distinct neural substrates (Peretz and = Zatorre,=20 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Recent brain imaging studies have shown = that neural=20 activity associated with music listening extends well beyond = the=20 auditory cortex involving a wide-spread bilateral network of = frontal,=20 temporal, parietal and subcortical areas related to = attention,=20 semantic and music-syntactic processing, memory and motor = functions=20 (Bhattacharya et al., 2001; Janata et al., 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Koelsch et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Popescu et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), as well as limbic and paralimbic regions related = to=20 emotional processing (Blood et al., 1999<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Blood and Zatorre, 2001; Brown et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Koelsch et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Menon and Levitin, 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Music has a well-documented effect on alleviating = anxiety,=20 depression and pain in patients with a somatic illness = (Cassileth=20 et al., 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Cepeda et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Siedliecki and Good, 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Recent cognitive and neuropsychological = studies=20 suggest that it may also enhance a variety of cognitive = functions,=20 such as attention, learning, communication and memory, both = in=20 healthy subjects (Wallace, 1994<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Thompson et al., 2001<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Thompson et al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Schellenberg et al., 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and in clinical conditions, such as dyslexia = (Overy,=20 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), autism (Gold et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), schizophrenia (Talwar et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), multiple sclerosis (Thaut et al., = 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), coronary artery disease (Emery et al., 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and dementia (Brotons and Koger, 2000<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Foster and Valentine, 2001<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Van de Winckel et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). In stroke rehabilitation, elements of music = have=20 previously been used as a part of physiotherapy (Thaut et = al.,=20 1997<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and speech therapy (Belin et al., 1996) to enhance the recovery of motor and speech = functions.=20 In addition, nonverbal auditory stimuli have been shown to=20 temporarily ameliorate left visual neglect after stroke = (Hommel et=20 al., 1990<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). However, the knowledge about the long-term = effects of=20 everyday music listening itself on the recovery of cognitive = and=20 emotional functions after stroke is very limited.

The purpose of this single-blind, randomized and controlled = trial=20 was to determine whether regular self-directed music listening = during=20 the first months after middle cerebral artery (MCA) stroke = can=20 enhance the recovery of cognitive functions and mood. Since = the brain=20 areas involved in music processing are mainly supplied by the = MCA=20 (Ayotte et al., 2000) we hypothesized that, in addition to = engaging=20 cognitive and emotional networks, music listening would also=20 stimulate both the perilesional and healthy brain areas that = normally=20 show increased excitability and adaptability in this subacute = recovery phase (Kreisel et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), and thereby enhance and speed up the = spontaneous=20 recovery process. As listening to real music, especially if = it=20 contains lyrics, activates the brain bilaterally, we also=20 hypothesized that it would facilitate the recovery from = unilateral=20 stroke more than listening to purely verbal material, which = activates=20 primarily the left hemisphere (Zatorre et al., 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Tervaniemi and Hugdahl, 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Thus, we compared the effect of music listening = both=20 to the effect of listening to audio books and to normal = spontaneous=20 recovery.


3D"   =20 Methods
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Top
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Summary
= Introduction
3D"Methods
= Results
= Discussion
= References
 
<= STRONG>Subjects=20 and procedure
Subjects (n =3D 60) were stroke = patients=20 recruited between March 2004 and May 2006 from the Department = of=20 Neurology of the Helsinki University Central Hospital (HUCH) = after=20 been admitted to the hospital for treatment of acute stroke.=20 Following inclusion criteria were used: (1) an acute = ischaemic MCA=20 stroke in the left or right temporal, frontal, parietal or=20 subcortical brain regions, (2) no prior neurological or = psychiatric=20 disease, (3) no drug or alcohol abuse, (4) no hearing = deficit, (5)=20 right-handed, (6) 3D≤=2075 years = old, (7)=20 Finnish-speaking and (8) able to co-operate. Eligible = patients were=20 randomly assigned to one of three groups: a music group, a = language=20 group or a control group (n =3D 20 in each) as soon as = possible=20 after hospitalization. Randomization was performed with a = random=20 number generator by a researcher not involved in the patient=20 enrollment. The study was approved by the HUCH Ethics = Committee, and=20 all patients signed an informed consent. All patients = received=20 standard treatment for stroke in terms of medical care and=20 rehabilitation. All patients underwent a clinical = neuropsychological=20 assessment and a magnetoencephalographic (MEG) measurement 1 = week=20 (baseline), 3 months and 6 months post-stroke, and magnetic = resonance=20 imaging (MRI) within 2 weeks of the stroke and 6 months = post-stroke.=20 The results from the MEG part of the study will be presented = in=20 another paper.

Of the 60 subjects originally recruited in to the study, 55=20 completed the study up to the 3-month follow-up (music group=20 n =3D 19, language group n =3D 19 and control group = n =3D=20 17). Of the five drop-outs, one was due to false diagnosis=20 (transient ischaemic attack), one due to a new stroke, one = due to=20 dementia and two due to refusal. One further subject died = from=20 myocardial infarction before the 6-month follow-up (music = group=20 n =3D 18, language group n =3D 19 and control = group=20 n =3D 17 at the 6-month stage).

Interventions
After agreeing to participate in = the study,=20 all patients were individually contacted by a music therapist = (author=20 S.L. or A.F.) who interviewed them about their pre-stroke = leisure=20 activities and hobbies, such as music listening and reading, = and=20 informed them about the group allocation. The music = therapists=20 provided the patients in the music group with portable CD = players=20 and CDs of their own favourite music in any musical genre.=20 Similarly, they provided the patients in the language group = with=20 portable cassette players and narrated audio books on = cassette=20 selected by the patients from a collection of the Finnish = Celia=20 library for the visually impaired (http://www.celialib.fi/). The = patients=20 in both groups were then trained in using the players and = were=20 instructed to listen to the material by themselves daily = (minimum=20 1 h per day) for the following 2 months while still in the = hospital=20 or at home. The patients were also asked to keep a listening=20 diary. During the 2-month period, the music therapists kept=20 close weekly contact with the patients to encourage = listening,=20 to provide more material, and to give practical aid in using=20 the equipment, if needed. Also nursing staff of the hospital=20 wards and relatives of the patients were informed about the=20 study, and were asked to help the patients in using the = equipment,=20 if needed. The protocol in the music and language groups was=20 therefore identical with the only difference being the type = of=20 listening material used. The control group was not given any=20 listening material. All patients were interviewed about their = leisure=20 activities again after the 2-month intervention and at the = 6-month=20 follow-up.

In order to test for differences between the emotional responses = and preferences to music and verbal material, a short = behavioural=20 listening experiment was also performed by the music = therapists=20 at the acute stage, before the intervention. In this = experiment,=20 two short musical pieces and narrated poems, which were = either=20 happy or sad (as judged by the therapists), were first = presented=20 to the patients. Thereafter they were interviewed about the=20 emotions, thoughts and memories evoked by those. From these=20 qualitative data, we scored individually for each patient = whether=20 the stimulus (happy or sad) evoked any emotions, and which = stimulus=20 type (music or poems) was preferred.

Structural brain imaging
MRI was performed within = 2 weeks=20 of stroke onset and 6 months post-stroke using the 1.5 T = Siemens=20 Vision scanner of the HUCH Department of Radiology. The first = MRI was=20 used to verify the stroke diagnosis and the second to = evaluate the=20 size and location of the lesion without the interfering = effect of the=20 acute stage oedema. Size was evaluated from fluid-attenuated=20 inversion recovery (FLAIR) images by measuring the maximum = diameter=20 of the lesion, or in case of multiple lesions the sum of the=20 diameters, in the sagittal, coronal or horizontal plane. = Following=20 subcategories were used in classifying the location(s) of the = lesion(s) within the damaged hemisphere: frontal lobe, = temporal lobe,=20 parietal lobe, insula and subcortical structures or white=20 matter.

Outcome measures
Clinical neuropsychological = assessment=20 was performed on all patients at the baseline (1 week from = stroke=20 onset), and repeated again 3 months and 6 months post-stroke. = The=20 researchers involved in these studies (authors T.S. and M.M.) = were=20 blinded to the group allocation of the patients. An extensive = neuropsychological test battery was used to evaluate the = following=20 cognitive domains: verbal memory, short-term and working = memory,=20 language, visuospatial cognition, music cognition, executive=20 functions, focused attention and sustained attention. Summary = scores=20 of the tests measuring each cognitive domain were used in the = statistical analyses. Parallel test versions of the memory = tests were=20 used in different testing occasions to minimize practice = effects.=20 Reaction time (RT) tests were always performed using the = better,=20 non-paretic hand. All assessments were carried out in a quiet = room=20 reserved for neuropsychological studies. The baseline = assessment=20 was carried out in two or three testing sessions to avoid=20 interference due to fatigue.

Verbal memory was evaluated with the story recall subtest = from=20 the Rivermead Behavioural Memory Test (RBMT; Wilson et = al.,=20 1985<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and an auditory list-learning task. In the story = recall,=20 both immediate and delayed recall scores were used. In the=20 list-learning task, a 10-word list was presented orally three = times,=20 and after each presentation the subjects were requested to = recall as=20 many words as they could. Total score of the three trials and = delayed recall score were used. Short-term and working = memory=20 was assessed with the digit span subtest from the Wechsler = Memory=20 Scale=97Revised (WMS-R; Wechsler, 1987<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and a memory interference task, in which the = subjects=20 were first orally presented with three words, then asked to = perform a=20 short mental arithmetic or verbal task, and then asked to = recall the=20 words again. Language was evaluated with the word and = sentence=20 repetition and reading subtests from the Finnish version = (Laine et=20 al., 1997<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) of the Boston Diagnostic Aphasia Examination = (BDAE;=20 Goodglass and Kaplan, 1983<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), the verbal fluency and naming subtests from = the CERAD=20 battery (Morris et al., 1989<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), and a shortened version of the Token Test (De = Renzi=20 and Faglioni, 1978<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Visuospatial cognition was assessed = with a=20 clock task (Lezak et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), in which both setting clock hands and = recognition of=20 time was evaluated; a copying task (Lezak et al., = 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), in which copying of four geometric drawings = (triangle, flag, cube, cross) was evaluated; a shortened = version of=20 the Benton Visual Retention Test (BVRT; Benton, 1974); and subtest B from the Balloons Test = (Edgeworth et=20 al., 1998<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Music cognition was evaluated with = the scale=20 and rhythm subtests from the shortened version of the = Montreal=20 Battery of Evaluation of Amusia (MBEA; Peretz et al., = 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), which was administered at baseline and 3 = months=20 post-stroke. Executive functions were assessed with = the=20 Frontal Assessment Battery (FAB; Dubois et al., 2000<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Attention was evaluated with the = CogniSpeed=A9=20 reaction time software (Revonsuo and Portin, 1995<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), which has previously been used, for = example, in=20 studies of multiple sclerosis (Kujala et al., 1994<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and brain tumors (Lilja et al., 2001<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Focused attention, the executive = ability to=20 control and perform mental operations and resolve conflicts = among=20 responses (Raz and Buhle, 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), was assessed with summed correct responses = and summed=20 RTs of the mental subtraction and Stroop subtests. = Sustained=20 attention, the ability to achieve and maintain an alert = state=20 (Raz and Buhle, 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), was evaluated with the percentage of = correct=20 responses in the vigilance subtest and summed RTs in the = vigilance=20 and simple reaction time subtests.

In addition to cognitive functions, also mood was evaluated = at=20 baseline and 3 and 6 months post-stroke using the shortened = Finnish=20 version (H=E4nninen, 1989<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) of the Profile of Mood States (POMS; McNair = et=20 al., 1981<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). It contains 38 items that form following = eight=20 subscales: tension, depression, irritability, vigor, fatigue, = inertia, confusion and forgetfulness. Also quality of life = (QOL) was=20 assessed 3 and 6 months post-stroke with both a self-reported = and a=20 proxy-reported Stroke and Aphasia Quality Of Life Scale-39 = (SAQOL-39;=20 Hilari et al., 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) questionnaire.

Data analysis
Group differences in the baseline=20 characteristics of the patients and in the amount of = rehabilitation=20 received during the follow-up were analysed with one-way = analyses of=20 variance (ANOVA), Kruskal=96Wallis tests, t-tests and = chi-square=20 tests. Group differences in mood and QOL 3 and 6 months = post-stroke=20 were analysed with one-way ANOVAs. Recovery in the cognitive = domains=20 and mood was analysed using a mixed-model ANOVA with a=20 within-subjects factor of time (baseline, 3-month stage and = 6-month=20 stage) and between-subjects factors of group (music, language = and=20 control) and lesion laterality (left and right). The=20 Greenhouse=96Geisser epsilon was used to correct for = sphericity. Main=20 effects of time and group as well as time x group and time x=20 group x lesion laterality = interactions=20 are reported. All post hoc analyses were performed with=20 Tukey's honestly significant difference test. For the = mixed-model=20 ANOVA, post hoc tests were performed on change scores = from the=20 baseline to the 3-month stage and from the baseline to the = 6-month=20 stage. Relationships between the cognitive domains were also=20 analysed with Pearson's correlation coefficients. The level = of=20 statistical significance was set at P < 0.05. All=20 statistical analyses were performed using SPSS (version = 14.0).=20 Missing values in test scores were considered missing at = random.=20


3D"   =20 Results
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Top
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Summary
= Introduction
= Methods
3D"Results
= Discussion
= References
 
T= here were=20 no statistically significant differences between the groups = in the=20 baseline demographic or clinical variables or in relevant = leisure=20 activities prior to stroke (Ta= ble=20 1). There were also no significant group differences in = the=20 baseline cognitive performance or mood (Ta= ble=20 2). The groups did not differ significantly in the = antidepressant=20 medication received at the acute stage or in rehabilitation = received=20 in public health care during the follow-up period (Ta= bles=20 1 and 3<= /A>). In=20 the short pre-intervention listening experiment, emotions = were=20 evoked in the majority of both music and language group = patients=20 after both music listening (63% versus 81%; 3D{chi}=202(Yates=92=20 correction) =3D 0.3, P =3D 0.567) and poem listening = (72% versus=20 94%; 3D{chi}2 (Yates=92 correction) =3D 1.4, = P =3D 0.233),=20 and the proportion of patients who preferred music was highly = similar=20 in both groups (50% versus 56%; 3D{chi}=202 =3D 0.1,=20 P =3D 0.716). Thus, the emotional response to and = preference for=20 music and verbal material were comparable at baseline. =


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  		Table 1 Baseline = demographic and=20 clinical characteristics of the three patient groups =

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  		Table 2 Baseline = cognitive=20 performance and mood in the three patient groups =

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  		Table 3 Music and audio = book=20 listening and other rehabilitation in the three patient = groups at=20 the three month and the six month post-stroke stage =

 = ;
There=20 were, however, highly significant differences between the = groups in=20 the frequency of listening to music and audio books both at = the=20 3-month and at the 6-month post-stroke stage (Ta= ble=20 3): the music group listened to music more than the language=20 group or the control group, whereas the language group = listened=20 to audio books more than the music group or the control group = (P < 0.005 in all pair-wise comparisons). This = indicates=20 that the study protocol worked well. One might expect that = the=20 patients with damage to the language-dominant hemisphere = would=20 have more difficulties in listening to audio books than = music,=20 and would thus spend less time listening to them. However, a=20 further group comparison within the left hemisphere-lesioned=20 patients showed that the amount of daily listening (hours per = day) in the music group (M =3D 1.6, SD =3D 0.7) and in the=20 language group (M =3D 1.3, SD =3D 0.5) did not differ=20 significantly [t(13) =3D 0.68, P =3D 0.511]. = Analysis of=20 the listening diaries kept by the music group patients showed = that=20 62% of all music selections were popular music (pop, rock or = rhythm=20 and blues), 10% was jazz, 8% was folk music and 20% was = classical or=20 spiritual music. All in all, 63% of the music contained = lyrics in a=20 language that the patients could understand (mostly Finnish = or=20 English).

Fi= gure=20 1 illustrates the recovery in the 10 cognitive domains in = all=20 three patient groups. In a mixed-model ANOVA, the within-subjects=20 main effect of time was significant in the domains of verbal=20 memory [F(2, 96) =3D 56.5, P < 0.001], short-term = and=20 working memory [F(2, 90) =3D 8.7, P < = 0.001], language=20 [F(1.2, 51.9) =3D 26.5, P < 0.001], = visuospatial=20 cognition [F(1.4, 58.5) =3D 18.6, P < = 0.001], focused=20 attention (correct responses) [F(1.6, 59.3) =3D 3.5, = P =3D=20 0.045], focused attention (RT) [F(1.2, 45.7) =3D 15.7, = P=20 < 0.001], sustained attention (correct responses) = [F(1.3,=20 57.3) =3D 8.8, P =3D 0.002], sustained attention (RT) = [F(1.2,=20 51.4) =3D 8.5, P =3D 0.003], music cognition [F(1, = 47) =3D 20.6,=20 P < 0.001] and executive functions [F(1.8, = 82.8) =3D=20 30.6, P < 0.001]. The between-subjects main effect = of group=20 was not significant in any cognitive domain.



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  		Fig. 1 Changes in the 10 = cognitive=20 domains (mean =B1 SEM) from the baseline (BL; 1-week = post-stroke=20 stage) to the 3-month (3 m) and the 6-month (6 m) = post-stroke stage=20 (baseline score subtracted from the values) in the three = patient=20 groups. **P < 0.01, *P < 0.05 by = mixed-model=20 ANOVA. =

 = ;
The=20 time x group interaction was, = however,=20 significant in the domains of verbal memory [F(4, 96) = =3D 4.7,=20 P =3D 0.002] and focused attention (correct responses) = [F(3.2, 59.3) =3D 3.9, P =3D 0.012]. Post = hoc tests=20 of the change scores showed that at the 3-month stage verbal = memory=20 recovery was significantly better in the music group than in = the=20 control group (P =3D 0.049) or in the language group = (P =3D=20 0.006). Focused attention recovery was significantly better = in the=20 music group than in the control group (P =3D 0.049) = and also=20 marginally better in the music group than in the language = group=20 (P =3D 0.058). At the 6-month stage, verbal memory recovery = was=20 significantly better in the music group than in the language = group=20 (P =3D 0.006), and focused attention recovery was = significantly=20 better in the music group than in the control group (P =3D=20 0.008) or in the language group (P =3D 0.016). A = further=20 analysis also showed that, across all patients, the = correlation=20 between the focused attention (correct responses) score and = the=20 verbal memory score was significant at baseline (r =3D = 0.32,=20 P =3D 0.037) and at the 3-month (r =3D 0.54, = P <=20 0.001) and 6-month (r =3D 0.49, P < 0.001)=20 stages.

In addition, the time x group = x lesion laterality interaction = was=20 significant in focused attention (correct responses) [F(3.2, = 59.3) =3D 4.1, P =3D 0.009]. Separate mixed-model ANOVAs = for the=20 left hemisphere-lesioned patients and the right = hemisphere-lesioned=20 patients showed that the time x group=20 interaction was significant only in the left = hemisphere-lesioned=20 patients [F(3.0, 25.7) =3D 4.5, P =3D 0.011]. = Post=20 hoc tests of the change scores showed that in the left=20 hemisphere-lesioned patients focused attention recovery was=20 significantly better in the music group than in the language = group=20 (P =3D 0.019), and also marginally better in the music = group=20 than in the control group (P =3D 0.092) at the 3-month = stage. At=20 the 6-month stage, recovery was significantly better in the = music=20 group than in the language group (P =3D 0.036) or in = the control=20 group (P =3D 0.041).

Fi= gure=20 2 illustrates the 3- and 6-month post-stroke POMS scores = in the=20 three patient groups. No significant time x=20 group or time x group = x lesion laterality interactions were = observed=20 in a mixed-model ANOVA (P =3D 0.378=960.859 in all = subscales),=20 indicating, thus, that the intervention did not induce = systematic=20 changes on mood from the baseline to the 3- and 6-month = stages.=20 However, the emotional reactions of the patients are = typically=20 highly variable in the acute post-stroke stage, encompassing=20 sadness, passivity, withdrawal, crying, catastrophic = reactions,=20 lack of adaptation, disinhibition, anosognosia and = aggressiveness=20 (Bogousslavsky, 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Consequently, the emotional status of the = patients=20 can change rapidly during the first days and weeks after the = stroke.=20 Thus, the changes that take place between the acute and the = 3-month=20 post-stroke stage vary considerably between patients, and = more stable=20 effects on mood, such as post-stroke depression, appear = usually=20 later, only about 3=964 months after the stroke (Carota et = al.,=20 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Therefore, directly comparing mood assessed = with POMS=20 at the acute and at the 3- and 6-month stages may not be = reliable due=20 to the emotional lability of the patients at the acute stage. = For=20 this reason, we also analysed group differences in mood=20 cross-sectionally from the 3- and 6-month post-stroke POMS = scores. At=20 the 3-month stage, there were significant group differences = in the=20 depression [F(2, 51) =3D 3.7, P =3D 0.031] and = confusion=20 [F(2, 51) =3D 3.3, P =3D 0.045] scores. Post = hoc=20 tests indicated that the depression score was significantly = lower in=20 the music group than in the control group (P =3D = 0.024). Also=20 the confusion score was marginally lower in the music group = than in=20 the control group (P =3D 0.061). At the 6-month stage, = the group=20 differences in depression [F(2, 50) =3D 2.6, P = =3D 0.086]=20 and confusion [F(2, 50) =3D 2.9, P =3D 0.064] = were still=20 marginally significant with post hoc tests showing a = tendency=20 for the music group to experience less depressed (P = =3D 0.071)=20 and confused (P =3D 0.064) mood than the control group. = There=20 were no significant group differences in self-rated or = proxy-rated=20 QOL at the 3-month stage or at the 6-month stage (P = =3D=20 0.094=960.987 in all domains).



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  		Fig. 2 Profile of Mood = States=20 (POMS) scale scores (mean =B1 SEM) in the three patient = groups at the=20 3-month (3 m) and the 6-month (6 m) post-stroke stage.=20 *P < 0.05, #P < 0.1 by = one-way=20 ANOVA. =

 = ;

3D"   =20 Discussion
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Top
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Summary
= Introduction
= Methods
= Results
3D"Discussion
= References
 
T= he novel=20 main finding of this study was that regular self-directed = music=20 listening during the early post-stroke stage can enhance = cognitive=20 recovery and prevent negative mood. Specifically, after the = 2-month=20 intervention period, patients who listened to their favourite = music=20 1=962 h a day showed greater improvement in focused attention = and=20 verbal memory than patients who listened to audio books or = received=20 no listening material. Moreover, patients who listened to = music also=20 experienced less depressed and, to a lesser extent, confused = mood=20 after the intervention than patients who received no = listening=20 material. Since the patient groups did not differ in = demographic and=20 clinical variables at the baseline or in antidepressant = medication=20 and rehabilitation received during the intervention, and = since any=20 non-specific effects of therapeutic attention were controlled = for,=20 these differences observed in cognitive recovery can be = directly=20 attributed to the effect of listening to music. Furthermore, = the fact=20 that most of the music also contained lyrics, would suggest = that=20 it is the musical component (or the combination of music and=20 voice) that plays a crucial role in the observed recovery of=20 these cognitive functions.

By its very nature, music has strong connections to both = attention=20 and memory systems. Brain imaging studies have shown that = listening=20 to real polyphonic music calls for rule-based analysis and=20 combination of sound patterns from multiple auditory streams, = which=20 naturally recruits bilateral temporal, frontal and parietal = neural=20 circuits underlying multiple forms of attention, working = memory,=20 semantic and syntactic processing, and imagery (Janata et = al.,=20 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Peretz and Zatorre, 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Recent evidence suggests that listening to = music that=20 is enjoyable but unrelated to the cognitive task may even = temporarily=20 improve performance in tests of spatial-temporal abilities = (Thompson=20 et al., 2001<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), attention (Schellenberg et al., = 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), verbal fluency (Thompson et al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and creativity (Schellenberg et al., = 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) in healthy subjects. Moreover, auditory = stimulation=20 with music has also temporarily improved performance in tests = of=20 autobiographical recall in dementia patients (Foster and = Valentine,=20 2001<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and in tests of visual neglect in stroke = patients=20 (Hommel et al., 1990<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Furthermore, in healthy subjects (Wallace, = 1994<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and in multiple sclerosis patients (Thaut et=20 al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) verbal material presented in a musical modality = (as=20 song lyrics) is learned and retrieved more efficiently than = one=20 presented verbally. It can also increase the coherence of = frontal EEG=20 oscillations during learning more than verbally presented = material=20 (Thaut et al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Peterson and Thaut, 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Moreover, aphasic patients repeat and recall more = words=20 from novel songs when singing than speaking along an auditory = model (Racette et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Randomized controlled trials have also = shown that=20 active music therapy or music-based exercise improves general = cognition and verbal fluency in dementia patients (Van de = Winckel=20 et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), symptom scores in schizophrenia patients = (Talwar=20 et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), and communication skills in autistic = children (Gold=20 et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Similar studies that have used a = within-subject=20 design have also shown that music improves phonological and = spelling=20 skills in dyslexic children (Overy, 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), speech content and fluency in dementia patients=20 (Brotons and Koger, 2000<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), and verbal fluency in cardiac rehabilitation = patients=20 (Emery et al., 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Collectively, these findings provide = evidence that=20 music engages and facilitates a wide range of cognitive=20 functions.

Music is also closely linked to emotions and arousal. Evidence=20 suggests that music listening modulates emotional arousal as=20 indexed by changes in electrodermal, cardiovascular and = respiratory=20 activity (Khalfa et al., 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Bernardi et al., 2006; Gomez and Danuser, 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Listening to pleasant and relaxing music = also=20 enhances the recovery of cardiovascular and respiratory = functions and=20 decreases cortisol levels after stress (Khalfa et al., = 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Leardi et al., 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Sokhadze, 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Music therapy has been shown to reduce = anxiety and=20 depression in patients with a somatic illness (Cassileth = et=20 al., 2003<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Siedliecki and Good, 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and anecdotally also in neurological patients = (Magee=20 and Davidson, 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). These findings suggest that music has an = analgesic=20 effect in reducing anxiety and directing attention away from = the=20 negative experience, thus helping to cope with emotional = stress.=20

In summary, music listening can facilitate a wide variety of=20 cognitive and emotional functions. Whether these effects are=20 truly specific to music, are selective to a few cognitive = functions,=20 and are long-lasting is, however, not known due to = methodological=20 limitations of most prior studies. Here, we used a = single-blind,=20 randomized, longitudinal experimental design with two control = groups and extensive neuropsychological outcome measures to=20 evaluate a wide range of cognitive functions. Our results = indicate=20 that music, when applied during the most dynamic period of = recovery=20 from neural damage, can induce long-term changes on cognition = that is indexed by enhanced recovery of focused attention and = verbal memory. Interestingly, the facilitating effect of = music=20 on focused attention was more pronounced in patients with = damage=20 to the language-dominant hemisphere. This most likely = reflects=20 the strong verbal component (mental arithmetic and color-word = processing) in the tasks we used to evaluate focused = attention.=20 Moreover, music listening was associated with less depressed=20 and confused mood, suggesting that music may help to cope = with=20 the emotional stress brought about by sudden and severe = neurological=20 illness. Here, the possible effect of non-specific = therapeutic=20 attention can not, however, be entirely ruled out, since the=20 difference in mood between the music group and the language=20 group was not significant.

An important and difficult question still pertains to the neural = mechanisms that can account for the beneficial effect of = music=20 on cognition. Most previous studies have attributed the = effect=20 to a general positive affective state or enhanced arousal and = attention, which, given the wide variability of reported = benefits,=20 seems a plausible mechanism. The focused attention and verbal = memory scores in our study were also significantly = correlated,=20 suggesting that the effect is mostly related to enhanced = attention.=20 Thus, current evidence suggests that music has a rather = general,=20 non-specific effect on cognition. This is in line with the = arousal=20 and mood hypothesis (Thompson et al., 2001<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), which states that any enjoyable stimuli, = such as=20 music, that induces positive affect and heightened arousal = can lead=20 to improved performance on cognitive tasks. Recent animal = studies and=20 functional neuroimaging studies in humans have shed some = light on the=20 neural mechanisms that mediate these effects. Listening to = pleasant=20 music activates an interconnected network of subcortical and = cortical=20 brain regions, which includes the ventral striatum, nucleus=20 accumbens (NAc), amygdala, insula, hippocampus, hypothalamus, = ventral tegmental area (VTA), anterior cingulate, = orbitofrontal=20 cortex and ventral medial prefrontal cortex (Blood and = Zatorre,=20 2001; Brown et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Menon and Levitin, 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Koelsch et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). VTA produces dopamine and has direct projections to = the=20 locus ceruleus (LC), amygdala, hippocampus, anterior = cingulate=20 and prefrontal cortex (Ashby et al., 1999). The VTA-NAc responses are suggested to be = related to=20 suppression of aversive stimuli and pain (Menon and Levitin, = 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), which would account for the effect of music = on coping=20 with stress, whereas LC and hypothalamus mediate arousal. = Together,=20 this dopaminergic mesocorticolimbic system is crucial for = mediating=20 arousal, emotion, reward, motivation, memory, attention and = executive=20 functioning (Ashby et al., 1999). In animals, music listening leads to = increased=20 dopamine synthesis in the brain (Panksepp and Bernatzky, = 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Sutoo and Akiama, 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Increased dopamine directly enhances alertness, = speed=20 of information processing, attention, and memory in healthy=20 humans (Sch=FCck et al., 2002<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and also global cognitive functioning in = patients with=20 cognitive impairment (Nagaraja and Jayashree, 2001<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). It is, thus, possible that the music-related = enhanced=20 cognitive recovery seen in our study was mediated by positive = mood=20 induced by music, and hence the dopaminergic mesocorticolimbic=20 system, especially since the music the patients listened to = was=20 their own favourite music and concurrent effects on mood were = also=20 observed.

A related topic concerns the pleasurability of listening to = music=20 and stories. When comparing the effects of music and narrated = story=20 listening on healthy subjects, Nantais and Schellenberg = (1999<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) found that listeners performed better on a = cognitive=20 task following the listening condition they preferred. In our = study, the music and language groups liked music and story = listening=20 to the same degree before the intervention, the material used = in both groups was self-selected, and the groups listened to = it=20 equally often. This suggests that preference to the type of = material=20 did not play a significant role. In general, also anecdotal = evidence=20 from the patients=92 reports indicated that both music and = language=20 groups enjoyed the intervention, although music listening was = experienced as easier and less demanding, especially in the = early=20 recovery phase. Moreover, it is possible that some aphasic = patients=20 in the language group had difficulties in listening to the = audio=20 books due to comprehension deficits, and, thus, did not find = the=20 intervention as enjoyable as patients in the music = group.

In addition to the effect on cognition and mood, music may also=20 have general effects on brain plasticity after stroke. Since=20 our patients had a unilateral MCA stroke, and the brain = regions=20 involved in music processing are mainly supplied by the MCA=20 bilaterally (Ayotte et al., 2000), listening to music may well have further = stimulated=20 both the peri-infarct regions in the damaged hemisphere as = well as=20 regions in the contralesional, healthy hemisphere that = normally show=20 increased plasticity at this recovery stage (Witte, 1998<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Kreisel et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). The fact that listening to music, = especially with=20 lyrics, is associated with activity of a more widely and = bilaterally=20 distributed neural network than listening to verbal material = alone=20 (Callan et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), would also account for the observed superiority of = music=20 stimulation over purely verbal stimulation, especially in = left=20 hemisphere-lesioned patients (D=E9monet et al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Animal studies have shown that an enriched=20 post-stroke recovery environment can induce many structural = plastic=20 changes in the recovering brain such as decreased infarct = volume and=20 increased dendritic branching, spine density, neurotrophic = factors,=20 cell proliferation and neurogenesis (Johansson, 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Nithianantharajah and Hannan, 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Although the effect of an enriched sound = environment=20 on recovery from neural damage has not been directly studied, = recent=20 developmental animal studies have shown that exposure to = music during=20 development improves auditory cortical functions, learning, = and=20 memory (Engineer et al., 2004<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Chikahisa et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Kim et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Angelucci et al., 2007a). Importantly, exposure to music also = enhances brain=20 plasticity by increasing neurogenesis in the hippocampus (Kim = et=20 al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), modifying the expression of glutamate = reseptor GluR2=20 in the auditory cortex and in the anterior cingulate (Xu = et=20 al., 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), increasing brain-derived neurotrophic = factor (BDNF)=20 levels in the hippocampus (Angelucci et al., = 2007a) and in the hypothalamus (Angelucci et = al.,=20 2007b), and also increasing the levels of tyrosine kinase = receptor B (TrkB), a BDNF receptor, in the cortex (Chikahisa=20 et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). Changes in glutamate transmission in the = peri-infarct=20 area (Centonze et al., 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) and increased BDNF levels (Sch=E4bitz et = al.,=20 2007<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>) are also crucial plasticity mechanisms that = contribute=20 to recovery from stroke. Thus, it is possible that the = music-related=20 enhanced cognitive recovery seen in our study was also due to = structural plastic changes induced by music stimulation in = the=20 recovering brain. At present, this suggestion is, however, = tentative,=20 and further research is clearly needed to elucidate the = potential=20 effects of a musically enriched recovery environment on brain = plasticity after stroke.

In conclusion, the results of the present study demonstrate, = to=20 our knowledge for the first time, that regular self-directed = music=20 listening during the 2-month subacute phase of MCA stroke = recovery=20 enhanced the recovery of verbal memory and focused attention, = and=20 also prevented depressed and confused mood. According to a = recent=20 study conducted in European stroke rehabilitation centers (De = Wit=20 et al., 2005<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>), stroke patients typically spend >72% of = their=20 daily time in non-therapeutic activities, mostly in their = rooms,=20 inactive and without any interaction, even though from a = plasticity=20 standpoint this time-window is ideal for rehabilitative = training=20 (Witte, 1998<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>; Kreisel et al., 2006<= IMG=20 height=3D7 alt=3DGo = src=3D"http://brain.oxfordjournals.org/icons/fig-down.gif" width=3D8=20 border=3D1>). We suggest that everyday music listening = during early=20 stroke recovery offers a valuable addition to the patients=92 = care,=20 especially if other active forms of rehabilitation are not = yet=20 feasible at this stage, by providing an individually = targeted,=20 easy-to-conduct and inexpensive means to facilitate cognitive = and=20 emotional recovery.


3D"   =20 Acknowledgements
 
We = wish to express=20 our gratitude to the staffs of the HUCH Department of = Neurology and=20 other rehabilitation hospitals in the Helsinki metropolitan = area for=20 their generous collaboration, and especially to the patient = subjects=20 and their families for their participation and effort. This = work was=20 supported by Academy of Finland (project no 77322), Jenny and = Antti=20 Wihuri Foundation (Helsinki, Finland), National Graduate = School of=20 Psychology and Neurology Foundation (Helsinki, Finland). = Funding to=20 pay the Open Access publication charges for this article was = provided=20 by Cognitive Brain Research Unit, Department of Psychology,=20 University of Helsinki, Finland.


3D"   =20 References
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Top
<= IMG=20 height=3D9 alt=3D" " hspace=3D5=20 src=3D"http://brain.oxfordjournals.org/icons/toc/uarrow.gif" = width=3D11=20 border=3D0>Summary
= Introduction
= Methods
= Results
= Discussion
3D"References
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i < this._headers.length; i++) {=0A= if (header =3D=3D '*' || this._headers[i].h =3D=3D header) {=0A= ret +=3D this._headers[i].h + ': ' + this._headers[i].v + '\n';=0A= }=0A= }=0A= return ret;=0A= };=0A= this.getResponseHeader =3D function(header) {=0A= var ret =3D getAllResponseHeader(header);=0A= var i =3D ret.indexOf('\n');=0A= if (i !=3D -1) {=0A= ret =3D ret.substring(0, i);=0A= }=0A= return ret;=0A= };=0A= this.setRequestHeader =3D function(header, value) {=0A= this._headers[this._headers.length] =3D {h:header, v:value};=0A= };=0A= this.open =3D function(method, url, async, user, password) {=0A= this.method =3D method;=0A= this.url =3D url;=0A= this._async =3D true;=0A= this._aborted =3D false;=0A= this._headers =3D [];=0A= if (arguments.length >=3D 3) {=0A= this._async =3D async;=0A= }=0A= if (arguments.length > 3) {=0A= opera.postError('XMLHttpRequest.open() - user/password not = supported');=0A= }=0A= this.readyState =3D 1;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= };=0A= this.send =3D function(data) {=0A= if (!navigator.javaEnabled()) {=0A= alert("XMLHttpRequest.send() - Java must be installed and = enabled.");=0A= return;=0A= }=0A= if (this._async) {=0A= setTimeout(this._sendasync, 0, this, data);=0A= // this is not really asynchronous and won't execute until the = current=0A= // execution context ends=0A= } else {=0A= this._sendsync(data);=0A= }=0A= }=0A= this._sendasync =3D function(req, data) {=0A= if (!req._aborted) {=0A= req._sendsync(data);=0A= }=0A= };=0A= this._sendsync =3D function(data) {=0A= this.readyState =3D 2;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= // open connection=0A= var url =3D new java.net.URL(new = java.net.URL(window.location.href), this.url);=0A= var conn =3D url.openConnection();=0A= for (var i =3D 0; i < this._headers.length; i++) {=0A= conn.setRequestProperty(this._headers[i].h, this._headers[i].v);=0A= }=0A= this._headers =3D [];=0A= if (this.method =3D=3D 'POST') {=0A= // POST data=0A= conn.setDoOutput(true);=0A= var wr =3D new = java.io.OutputStreamWriter(conn.getOutputStream(), this._getCharset());=0A= wr.write(data);=0A= wr.flush();=0A= wr.close();=0A= }=0A= // read response headers=0A= // NOTE: the getHeaderField() methods always return nulls for me :(=0A= var gotContentEncoding =3D false;=0A= var gotContentLength =3D false;=0A= var gotContentType =3D false;=0A= var gotDate =3D false;=0A= var gotExpiration =3D false;=0A= var gotLastModified =3D false;=0A= for (var i =3D 0; ; i++) {=0A= var hdrName =3D conn.getHeaderFieldKey(i);=0A= var hdrValue =3D conn.getHeaderField(i);=0A= if (hdrName =3D=3D null && hdrValue =3D=3D null) {=0A= break;=0A= }=0A= if (hdrName !=3D null) {=0A= this._headers[this._headers.length] =3D {h:hdrName, = v:hdrValue};=0A= switch (hdrName.toLowerCase()) {=0A= case 'content-encoding': gotContentEncoding =3D true; break;=0A= case 'content-length' : gotContentLength =3D true; break;=0A= case 'content-type' : gotContentType =3D true; break;=0A= case 'date' : gotDate =3D true; break;=0A= case 'expires' : gotExpiration =3D true; break;=0A= case 'last-modified' : gotLastModified =3D true; break;=0A= }=0A= }=0A= }=0A= // try to fill in any missing header information=0A= var val;=0A= val =3D conn.getContentEncoding();=0A= if (val !=3D null && !gotContentEncoding) = this._headers[this._headers.length] =3D {h:'Content-encoding', v:val};=0A= val =3D conn.getContentLength();=0A= if (val !=3D -1 && !gotContentLength) = this._headers[this._headers.length] =3D {h:'Content-length', v:val};=0A= val =3D conn.getContentType();=0A= if (val !=3D null && !gotContentType) = this._headers[this._headers.length] =3D {h:'Content-type', v:val};=0A= val =3D conn.getDate();=0A= if (val !=3D 0 && !gotDate) this._headers[this._headers.length] = =3D {h:'Date', v:(new Date(val)).toUTCString()};=0A= val =3D conn.getExpiration();=0A= if (val !=3D 0 && !gotExpiration) = this._headers[this._headers.length] =3D {h:'Expires', v:(new = Date(val)).toUTCString()};=0A= val =3D conn.getLastModified();=0A= if (val !=3D 0 && !gotLastModified) = this._headers[this._headers.length] =3D {h:'Last-modified', v:(new = Date(val)).toUTCString()};=0A= // read response data=0A= var reqdata =3D '';=0A= var stream =3D conn.getInputStream();=0A= if (stream) {=0A= var reader =3D new java.io.BufferedReader(new = java.io.InputStreamReader(stream, this._getCharset()));=0A= var line;=0A= while ((line =3D reader.readLine()) !=3D null) {=0A= if (this.readyState =3D=3D 2) {=0A= this.readyState =3D 3;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= }=0A= reqdata +=3D line + '\n';=0A= }=0A= reader.close();=0A= this.status =3D 200;=0A= this.statusText =3D 'OK';=0A= this.responseText =3D reqdata;=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onload) {=0A= this.onload();=0A= }=0A= } else {=0A= // error=0A= this.status =3D 404;=0A= this.statusText =3D 'Not Found';=0A= this.responseText =3D '';=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onerror) {=0A= this.onerror();=0A= }=0A= }=0A= };=0A= };=0A= }=0A= // ActiveXObject emulation=0A= if (!window.ActiveXObject && window.XMLHttpRequest) {=0A= window.ActiveXObject =3D function(type) {=0A= switch (type.toLowerCase()) {=0A= case 'microsoft.xmlhttp':=0A= case 'msxml2.xmlhttp':=0A= case 'msxml2.xmlhttp.3.0':=0A= case 'msxml2.xmlhttp.4.0':=0A= case 'msxml2.xmlhttp.5.0':=0A= return new XMLHttpRequest();=0A= }=0A= return null;=0A= };=0A= }=0A= ------=_NextPart_000_0000_01C9082F.D7A88340 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://brain.oxfordjournals.org/javascript/ajax/utility.js /************************************************************************= *****=0A= * javascript/ajax/utility.js=0A= *=0A= * Utility functions for working with XMLHttpRequest data.=0A= *=0A= * Copyright 2006 Board of Trustees of the Leland Stanford Junior = University.=0A= = *************************************************************************= ***/=0A= =0A= /*=0A= * Copy XML nodes into an HTMLElement. This effectively=0A= * clones XML markup which uses XHTML naming conventions=0A= * into an HTML DOM.=0A= */=0A= function copy_xml_to_html(src, dst) {=0A= if (src.nodeType =3D=3D 1) { /* Node.ELEMENT_NODE */=0A= var e =3D document.createElement(src.nodeName);=0A= for (var i =3D 0; i < src.childNodes.length; i++) {=0A= copy_xml_to_html(src.childNodes[i], e);=0A= }=0A= for (var i =3D 0; i < src.attributes.length; i++) {=0A= var n =3D src.attributes[i].name;=0A= var v =3D unescape_xml_string(src.attributes[i].value); =0A= e.setAttribute(n, v);=0A= if (n =3D=3D "class") {=0A= e.className =3D v;=0A= }=0A= else if (n =3D=3D "style") {=0A= set_css_style(v, e, "");=0A= }=0A= }=0A= dst.appendChild(e);=0A= }=0A= else if (src.nodeType =3D=3D 3) { /* Node.TEXT_NODE */=0A= dst.appendChild(document.createTextNode(src.nodeValue));=0A= }=0A= }=0A= =0A= /* =0A= * It is unclear that this is the right thing to be calling=0A= * from copy_xml_to_html, but it appears that Safari decides=0A= * to convert & to the NCR #, and then encodes that=0A= * NCR to &%26%2338;. So, I'm going to treat the DOM Attr=0A= * value as a plain string, and run our XML string input=0A= * through the decoding routine below.=0A= */=0A= function unescape_xml_string(s) {=0A= return s.replace(/'/g, "'")=0A= .replace(/'/g, "'")=0A= .replace(/"/g, "\"")=0A= .replace(/"/g, "\"")=0A= .replace(/>/g, ">")=0A= .replace(/>/g, ">")=0A= .replace(/</g, "<")=0A= .replace(/</g, "<")=0A= .replace(/&/g, "&")=0A= .replace(/&/g, "&");=0A= }=0A= =0A= /*=0A= * Parse set of CSS rules and apply them to an element.=0A= * This is quite horrifying, but I'm unable to determine=0A= * how else to handle this with IE 6. FireFox and other=0A= * sane browsers let you simply set the style attribute=0A= * or use e.style.setProperty(rule, value, priority),=0A= * IE 6 appears to have neither of these capabilities..=0A= */=0A= function set_css_style(css, e, priority) {=0A= var rules =3D css.split(";");=0A= for (var i =3D 0; i < rules.length; i++) {=0A= var nvpair =3D rules[i].split(":");=0A= if (nvpair.length =3D=3D 2) {=0A= try {=0A= var name =3D nvpair[0]; /* style attribute */=0A= var value =3D nvpair[1]; /* attribute value */=0A= =0A= /*=0A= * For each possible style attribute, set the=0A= * appropriate style property in the element.=0A= */=0A= if (name =3D=3D "background") {=0A= e.style.background =3D value;=0A= }=0A= else if (name =3D=3D "background-attachment") {=0A= e.style.backgroundAttachment =3D value;=0A= }=0A= else if (name =3D=3D "background-color") {=0A= e.style.backgroundColor =3D value;=0A= }=0A= else if (name =3D=3D "background-image") {=0A= e.style.backgroundImage =3D value;=0A= }=0A= else if (name =3D=3D "background-position") {=0A= e.style.backgroundPosition =3D value;=0A= }=0A= else if (name =3D=3D "background-position-x") {=0A= e.style.backgroundPositionX =3D value;=0A= }=0A= else if (name =3D=3D "background-position-y") {=0A= e.style.backgroundPositionY =3D value;=0A= }=0A= else if (name =3D=3D "background-repeat") {=0A= e.style.backgroundRepeat =3D value;=0A= }=0A= else if (name =3D=3D "behavior") {=0A= e.style.behavior =3D value;=0A= }=0A= else if (name =3D=3D "border") {=0A= e.style.border =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom") {=0A= e.style.borderBottom =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-color") {=0A= e.style.borderBottomColor =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-style") {=0A= e.style.borderBottomStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-width") {=0A= e.style.borderBottomWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-collapse") {=0A= e.style.borderCollapse =3D value;=0A= }=0A= else if (name =3D=3D "border-color") {=0A= e.style.borderColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left") {=0A= e.style.borderLeft =3D value;=0A= }=0A= else if (name =3D=3D "border-left-color") {=0A= e.style.borderLeftColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left-style") {=0A= e.style.borderLeftStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-left-width") {=0A= e.style.borderLeftWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-right") {=0A= e.style.borderRight =3D value;=0A= }=0A= else if (name =3D=3D "border-right-color") {=0A= e.style.borderRightColor =3D value;=0A= }=0A= else if (name =3D=3D "border-right-style") {=0A= e.style.borderRightStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-right-width") {=0A= e.style.borderRightWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-style") {=0A= e.style.borderStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top") {=0A= e.style.borderTop =3D value;=0A= }=0A= else if (name =3D=3D "border-top-color") {=0A= e.style.borderTopColor =3D value;=0A= }=0A= else if (name =3D=3D "border-top-style") {=0A= e.style.borderTopStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top-width") {=0A= e.style.borderTopWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-width") {=0A= e.style.borderWidth =3D value;=0A= }=0A= else if (name =3D=3D "bottom") {=0A= e.style.bottom =3D value;=0A= }=0A= else if (name =3D=3D "clear") {=0A= e.style.clear =3D value;=0A= }=0A= else if (name =3D=3D "clip") {=0A= e.style.clip =3D value;=0A= }=0A= else if (name =3D=3D "color") {=0A= e.style.color =3D value;=0A= }=0A= else if (name =3D=3D "cssText") {=0A= e.style.Sets =3D value;=0A= }=0A= else if (name =3D=3D "cursor") {=0A= e.style.cursor =3D value;=0A= }=0A= else if (name =3D=3D "direction") {=0A= e.style.direction =3D value;=0A= }=0A= else if (name =3D=3D "display") {=0A= e.style.display =3D value;=0A= }=0A= else if (name =3D=3D "font") {=0A= e.style.font =3D value;=0A= }=0A= else if (name =3D=3D "font-family") {=0A= e.style.fontFamily =3D value;=0A= }=0A= else if (name =3D=3D "font-size") {=0A= e.style.fontSize =3D value;=0A= }=0A= else if (name =3D=3D "font-style") {=0A= e.style.fontStyle =3D value;=0A= }=0A= else if (name =3D=3D "font-variant") {=0A= e.style.fontVariant =3D value;=0A= }=0A= else if (name =3D=3D "font-weight") {=0A= e.style.fontWeight =3D value;=0A= }=0A= else if (name =3D=3D "height") {=0A= e.style.height =3D value;=0A= }=0A= else if (name =3D=3D "ime-mode") {=0A= e.style.imeMode =3D value;=0A= }=0A= else if (name =3D=3D "layout-flow") {=0A= e.style.layoutFlow =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid") {=0A= e.style.layoutGrid =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-char") {=0A= e.style.layoutGridChar =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-line") {=0A= e.style.layoutGridLine =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-mode") {=0A= e.style.layoutGridMode =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-type") {=0A= e.style.layoutGridType =3D value;=0A= }=0A= else if (name =3D=3D "left") {=0A= e.style.left =3D value;=0A= }=0A= else if (name =3D=3D "letter-spacing") {=0A= e.style.letterSpacing =3D value;=0A= }=0A= else if (name =3D=3D "line-break") {=0A= e.style.lineBreak =3D value;=0A= }=0A= else if (name =3D=3D "line-height") {=0A= e.style.lineHeight =3D value;=0A= }=0A= else if (name =3D=3D "list-style") {=0A= e.style.listStyle =3D value;=0A= }=0A= else if (name =3D=3D "list-style-image") {=0A= e.style.listStyleImage =3D value;=0A= }=0A= else if (name =3D=3D "list-style-position") {=0A= e.style.listStylePosition =3D value;=0A= }=0A= else if (name =3D=3D "list-style-type") {=0A= e.style.listStyleType =3D value;=0A= }=0A= else if (name =3D=3D "margin") {=0A= e.style.margin =3D value;=0A= }=0A= else if (name =3D=3D "margin-bottom") {=0A= e.style.marginBottom =3D value;=0A= }=0A= else if (name =3D=3D "margin-left") {=0A= e.style.marginLeft =3D value;=0A= }=0A= else if (name =3D=3D "margin-right") {=0A= e.style.marginRight =3D value;=0A= }=0A= else if (name =3D=3D "margin-top") {=0A= e.style.marginTop =3D value;=0A= }=0A= else if (name =3D=3D "min-height") {=0A= e.style.minHeight =3D value;=0A= }=0A= else if (name =3D=3D "overflow") {=0A= e.style.overflow =3D value;=0A= }=0A= else if (name =3D=3D "overflow-x") {=0A= e.style.overflowX =3D value;=0A= }=0A= else if (name =3D=3D "overflow-y") {=0A= e.style.overflowY =3D value;=0A= }=0A= else if (name =3D=3D "padding") {=0A= e.style.padding =3D value;=0A= }=0A= else if (name =3D=3D "padding-bottom") {=0A= e.style.paddingBottom =3D value;=0A= }=0A= else if (name =3D=3D "padding-left") {=0A= e.style.paddingLeft =3D value;=0A= }=0A= else if (name =3D=3D "padding-right") {=0A= e.style.paddingRight =3D value;=0A= }=0A= else if (name =3D=3D "padding-top") {=0A= e.style.paddingTop =3D value;=0A= }=0A= else if (name =3D=3D "page-break-after") {=0A= e.style.pageBreakAfter =3D value;=0A= }=0A= else if (name =3D=3D "page-break-before") {=0A= e.style.pageBreakBefore =3D value;=0A= }=0A= else if (name =3D=3D "pixelBottom") {=0A= e.style.pixelBottom =3D value;=0A= }=0A= else if (name =3D=3D "pixelHeight") {=0A= e.style.pixelHeight =3D value;=0A= }=0A= else if (name =3D=3D "pixelLeft") {=0A= e.style.pixelLeft =3D value;=0A= }=0A= else if (name =3D=3D "pixelRight") {=0A= e.style.pixelRight =3D value;=0A= }=0A= else if (name =3D=3D "pixelTop") {=0A= e.style.pixelTop =3D value;=0A= }=0A= else if (name =3D=3D "pixelWidth") {=0A= e.style.pixelWidth =3D value;=0A= }=0A= else if (name =3D=3D "posBottom") {=0A= e.style.posBottom =3D value;=0A= }=0A= else if (name =3D=3D "posHeight") {=0A= e.style.posHeight =3D value;=0A= }=0A= else if (name =3D=3D "position") {=0A= e.style.position =3D value;=0A= }=0A= else if (name =3D=3D "posLeft") {=0A= e.style.posLeft =3D value;=0A= }=0A= else if (name =3D=3D "posRight") {=0A= e.style.posRight =3D value;=0A= }=0A= else if (name =3D=3D "posTop") {=0A= 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quoted-printable Content-Location: http://brain.oxfordjournals.org/javascript/entrez/callback.js /************************************************************************= *****=0A= * javascript/entrez/callback.js=0A= *=0A= * Entrez Linking callback to populate content box.=0A= *=0A= * Copyright 2006 Board of Trustees of the Leland Stanford Junior = University.=0A= = *************************************************************************= ***/=0A= =0A= /*=0A= * Execute callback to fill content box with Entrez Linking information.=0A= */=0A= function entrez_callback(pmid, callback_url) {=0A= /*=0A= * MSIE 5.5 and below have issues with the JavaScript=0A= * used for Entrez Linking. For now we have to disable=0A= * the callback until we can track down a proper fix=0A= * (or everybody sanely upgrades to version 6 or 7!).=0A= */=0A= if (navigator) {=0A= var appname =3D navigator.appName;=0A= if (appname =3D=3D "Microsoft Internet Explorer") {=0A= var userAgent =3D navigator["userAgent"];=0A= var s =3D "MSIE ";=0A= var n =3D -1; =0A= if ((n =3D userAgent.indexOf(s)) !=3D -1) {=0A= var v =3D parseFloat(userAgent.substring(n+s.length));=0A= if (v < 6) {=0A= return;=0A= }=0A= }=0A= }=0A= }=0A= =0A= /*=0A= * Acquire table row element to update, initiate callback=0A= * to update table with Entrez Links.=0A= */=0A= var tr =3D document.getElementById('entrez_callback_'+pmid);=0A= if (!tr) {=0A= return;=0A= }=0A= var req =3D new XMLHttpRequest();=0A= if (!req) {=0A= return;=0A= }=0A= req.onreadystatechange =3D function() {=0A= if (req.readyState =3D=3D 4 && (req.status =3D=3D 200 || req.status = =3D=3D 304)) {=0A= var src =3D req.responseXML.documentElement;=0A= var dst =3D document.createDocumentFragment();=0A= for (var i =3D 0; i < src.childNodes.length; i++) {=0A= copy_xml_to_html(src.childNodes[i], dst);=0A= }=0A= var tbl =3D tr.parentNode;=0A= tbl.replaceChild(dst, tr);=0A= }=0A= }=0A= req.open('GET', callback_url, true);=0A= req.send(null);=0A= }=0A= ------=_NextPart_000_0000_01C9082F.D7A88340--