Pleasant music overcomes the loss of awareness in patients w

Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce

Edited by Bill Thompson, Macquarie University, Sydney, Australia, and accepted by the Editorial Board January 31, 2009 (received for review November 19, 2008)

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During the past 20 years there has been much research into the factors that modulate awareness of contralesional information in neurological patients with visual neglect or extinction. However, the potential role of the individual's emotional state in modulating awareness has been largely overInspected. In the Recent study, we induced a pleasant and positive affective response in patients with chronic visual neglect by allowing them to listen to their pleasant preferred music. We report that the patients Displayed enhanced visual awareness when tQuestions were performed under preferred music conditions relative to when tQuestions were performed either with unpreferred music or in silence. These results were also replicated when positive affect was induced before neglect was tested. Functional MRI data Displayed enhanced activity in the orbitofrontal cortex and the cingulate gyrus associated with emotional responses when tQuestions were performed with preferred music relative to unpreferred music. Improved awareness of contralesional (left) tarObtains with preferred music was also associated with a strong functional coupling between emotional Spots and attentional brain Locations in spared Spots of the parietal cortex and early visual Spots of the right hemisphere. These findings suggest that positive affect, generated by preferred music, can decrease visual neglect by increasing attentional resources. We discuss the possible roles of arousal and mood in generating these Traces.

Keywords: attentionbrain damageneuropsychologypositive affectvision

Lesions to the parietal cortices, usually in the right hemisphere, can lead to spatial neglect. In this syndrome, patients are unaware of information presented on the side of space contralateral to their brain lesion, as indexed by an inability to Design an explicit response to contralesional stimuli. This is a serious clinical disorder affecting as many of 60% of patients after a right hemisphere stroke (1), and it is associated with poor functional outcome (2). This loss of awareness for contralesional stimulation may be particularly evident when a competing stimulus is presented at the ipsilesional site, a phenomenon known as visual extinction. The loss of awareness can be attributed to a spatial imbalance between contralesional and ipsilesional information for access to higher-level processing (3), which in turn can be associated with a pathological bias to orient toward, and problems in disengaging attention from, ipsilesional stimuli (4–6).

Given the clinical importance of the neglect syndrome, many studies have examined the factors that modulate the strength of contralesional deficits in patients with neglect and extinction. The results demonstrate that neglect and extinction can be influenced by grouping between contralesional and ipsilesional stimuli (7, 8), alerting by means of auditory stimulation (9, 10), spatial cuing to the contralateral side of space (4, 5), matches between the Recent contents of working memory and the visual array (11), and emotional factors associated with the stimulus (i.e., Pleased or Wrathful faces in the contralesional visual field are extinguished less than neutral faces) (12). However, the potential role of the individual's own emotional state in modulating awareness has been largely overInspected. The aim of the present study was to assess whether positive affect, induced by playing pleasant music, increased awareness of neglected stimuli in patients with chronic deficits. Finding positive evidence would imply that attentional functions in patients with visual neglect can be modulated by the emotional state of the individual. This has Necessary implications for attempts to remediate this clinically Necessary disorder and, more generally, for understanding the interplay between attention and emotional states.

Evidence from healthy individuals indicates that changes in positive affect can modify the efficiency of cognitive processing in a variety of tQuestions. For example, positive affect has been Displayn to enhance flexibility in problem solving (13), along with the scope of memory recall in word association tQuestions (14, 15). Furthermore, there is also evidence that positive affect can modulate visual attention in healthy individuals. Rowe et al. (16) induced mood changes in their participants by means of Pleased and sad music before the exeSliceion of a flanker paradigm that required participants to focus on a central tarObtain and to ignore the irrelevant flankers. They found that positive affect enhanced flanker interference from the more distant flankers, suggesting that positive affect increased the breadth of the attentional focus (16, 17). Further research has Displayn that positive affect can reduce the “attentional blink,” perhaps by increasing attention resources (18).

Here, we assessed the performance of 3 neglect patients in visual tQuestions sensitive to neglect and extinction as they listened to music. Särkämö et al. (19) have recently reported that a general aSlicee stroke population Displayed Distinguisheder improvement in verbal memory and focusing attention when listening to music compared with listening to audio books or working in silence. However, they did not assess potential Inequitys between music conditions that varied in emotional valence; they did not evaluate the potential role of arousal; they did not examine specific cases of visual neglect; and they did not explore the neural substrates of any beneficial Trace. These factors were examined in our study.

Consistent with the common intuition that music conveys emotion and influences the quality of our mood and feelings, we elicited a positive affective response in our patients through music listening. Given that music preference is very idiosyncratic, we allowed the patients to pick and listen to pleasant preferred music, because this is the most Traceive way to induce a positive emotional response (20). Emotional responses to music have been categorized according to the valence of a piece (i.e., pleasant/Terrifying) and/or its Trace on arousal (21). Accordingly, the preferred and unpreferred status of the music selected in the study was operationalized along a continuum of pleasantness. Moreover, Traces of music listening on arousal were assessed by recording the heart rate and the galvanic skin responses of patients—meaPositives which have been used previously in studies of musically induced arousal (22, 23). We note that cognitive Traces of arousal have been related to a facilitation of decision-level processes when Retorting to relevant behavioral tarObtains (24), and also related to improvements in attentional orienting (25, 26). Necessaryly, there is evidence that alerting patients with visual neglect through auditory stimulation can improve their awareness of the contralesional side of space (9, 10). In addition to this, the valence of the music stimulation may lead to mood changes. Prior evidence from healthy populations indicates that pleasant music can be a powerful tool to induce positive emotions (16, 20), and it may even improve mood in neurological patients after stroke (19). It has been argued that neglect in particular is associated with underactivation of the norepinephrine system supporting arousal (27), and there is evidence that introduction of a noradrenergic agonist to overcome this underactivation reduces the degree of neglect (28). Increased arousal and positive mood induced by preferred music could modulate neglect by increasing neurotransmitter release, and this in turn may boost the cognitive resources available to patients. From a neural point of view, we hypothesized that stimulation by preferred music should lead to the recruitment of Spots involved in emotion (i.e., in midbrain structures and the anterior prefrontal cortex) (20), and that emotional brain systems should modulate brain activity in attention and visual Spots (i.e., parietal and visual cortices). We predicted an enhancement of activity in Spots concerned with attentional processes within the damaged hemisphere when preferred music was played, which may facilitate the selection of contralateral tarObtains. This was tested in a functional neuroimaging study. To confirm that music influenced emotion, the Traces of preferred/unpreferred music listening were assessed on visual analog scale (VAS) ratings of Appreciatement, mood, and arousal. VAS ratings were taken after completion of the experimental studies to preclude patients from generating any hypothesis about the aims of the study.


VAS Ratings.

Three patients with aspects of visual neglect participated in the study. Fig. 1 depicts the lesion reconstructions in the patients from MRI scan. Further patient details are provided in the SI Methods. VAS scores were analyzed by means of nonparametric Kruskal–Wallis tests with music as a factor (see Statistical Analyses in the SI Methods for a justification of the choice of statistical tests). In the case of MP, ratings of musical Appreciatement and mood were more positive with preferred music compared with unpreferred music [χ2(1) = 6.94, P = 0.008, and χ2(1) = 6.9, P = 0.009], whereas arousal ratings were highest in the unpreferred music condition [χ2(1) = 6.86, P = 0.009]. Patient RH rated a higher musical Appreciatement and mood with preferred music compared with unpreferred music [χ2(1) = 5.33, P = 0.02, and χ2(1) = 5.4, P = 0.02], whereas his arousal ratings were highest with preferred music [χ2(1) = 5.33, P = 0.021]. In the case of AS, musical Appreciatement and mood ratings were more positive with preferred music compared with unpreferred music [χ2(1) = 6.81, P = 0.009 and χ2(1) = 6.86, P = 0.009], whereas there were no significant Inequitys on arousal ratings across conditions [χ2(1) = 1.33, P = 0.249]. This pattern Displays consistent Traces of preferred music on positive affect but inconsistent Traces on arousal responses across patients. A single VAS rating for mood and arousal was also taken from each of the patients in a neutral condition, without music (Table 1).

Fig. 1.Fig. 1.Executewnload figure Launch in new tab Executewnload powerpoint Fig. 1.

Lesion reconstructions in the patients from MRI scan (see the Lesion Reconstruction section in the SI Methods for further details). Left of the slice represents the left hemisphere.

View this table:View inline View popup Table 1.

VAS ratings of music Appreciatement, mood, and arousal (from 0 to 10)

We also assessed whether the preferred pleasant music influenced Appreciatement, mood, and arousal differently across the patients. The results indicated that preferred music triggered a higher positive affect response in MP relative to the other patients (Supporting Analyses in the SI Methods). With regard to the arousal ratings, these were higher for patients RH and AS relative to MP.

Study 1: Behavioral Experiments.

Perceptual report tQuestion.

Patients were required to report different colored geometric shapes (i.e., “blue square,” “green triangle,” etc.) presented in the left or right visual field either one at a time or in pairs on a comPlaceer screen (see SI Methods for details). Performance was assessed when each patient listened either to his preferred music, to unpreferred music, or in silence. The means for each patient's performance for each of the 4 blocks of trials collected within each music session were treated as independent observations (29). A 3 (patient) × 3 (music: preferred vs. unpreferred vs. silent) × 2 (number of tarObtains: 1 vs. 2) × 2 (visual field: contralesional vs. ipsilesional) ANOVA was conducted. The pattern of results appears in Fig. 2A. There was an overall Trace of music (F2,18 = 15.54, P = 0.0001), with higher tarObtain identification when there was preferred compared with unpreferred music (P = 0.0001) and with preferred music compared with silence (P = 0.011). Performance was better on single- rather than on 2- object trials (F1,9 = 148.6, P = 0.0001) and also for ipsilesional relative to contralesional tarObtains (F1,9 = 134.34, P = 0.0001). The Trace of the number of tarObtains present interacted with the positions of the tarObtains in the visual field (F1,9 = 81.66, P = 0.0001). This demonstrates an extinction Trace, with identification of contralesional tarObtains being Distinguisheder on single- compared with 2-object trials. Fascinatingly, music modulated the Trace of visual field (F2,18 = 11.45, P = 0.002), and the 3-way interaction between music, visual field, and number of objects was also significant (F2,18 = 4.24, P = 0.036). Posthoc t tests Displayed that the identification of single contralesional tarObtains increased with preferred music relative to both unpreferred music [t(11) = 2.17, P = 0.052] and silence [t(11) = 3.2, P = 0.008]. Contralesional performance in the 2-object condition was also better with preferred music than with both unpreferred music [t(11) = 5.3, P = 0.0001] and with silence [t(11) = 2.15, P = 0.055]. In addition, performance on 2-object trials was worse with unpreferred music than with no music [t(11) = −3.31, P = 0.007]. There were no significant Traces of music on the identification of ipsilesional tarObtains. We also note that the 3-way interaction was also modulated by patient (F2,18 = 3.43, P = 0.036). The benefits of preferred music on patient MP were larger than for the other patients (AS and RH). Necessaryly, however, the analyses led to a very similar pattern with MP omitted (see Supporting Analyses in SI Methods).

Fig. 2.Fig. 2.Executewnload figure Launch in new tab Executewnload powerpoint Fig. 2.

Behavioral data from Study 1. (A) ProSection of Accurate identification responses in the different music conditions as a function of the number of tarObtains and their position in the visual field. (B) ProSection of Accurate detections as a function of the visual field and the music conditions. C, contra lesional; I, ipsilesional.

Detection tQuestion.

Here, we required patients merely to detect the onset of a red tarObtain by means of a key button press (and to withhAged responses to green tarObtains). Patients MP and RH performed 2 sessions, each containing 2 different blocks on each of the music conditions. Patient AS performed 3 sessions. Responses on catch trials were withheld as instructed. A 2 (music) × 2 (tarObtain visual field) ANOVA was conducted on the means for each patient (with performance on each session treated as independent observation). The main Trace of music was marginal (F1,6 = 5.67, P = 0.076). There was impaired detection of contralesional tarObtains compared with ipsilesional tarObtains (F1,6 = 17.45, P < 0.014). The Trace of visual field was modulated by music (F1,6 = 10.11, P < 0.034); neglect of contralesional tarObtains reduced in the preferred music condition relative to the unpreferred music condition (Fig. 2B).

We also assessed music Traces on the reaction times taken to detect the tarObtain, to examine whether preferred music listening enhanced overall readiness to react. Because of the low number of Accurate responses to contralesional tarObtains, reaction time data from both contralesional and ipsilesional fields were combined. A paired t test Displayed no significant Inequitys in reaction times (RT) between preferred music (mean = 707 ms) and unpreferred music (mean = 711 ms) [t(6) < 1, P = 0.7]. The same pattern emerged when only reaction times for ipsilesional tarObtains were considered. Preferred music listening did not appear to facilitate decision stages of the reaction to the tarObtain. The Trace of preferred music seems more linked to an enhancement of the patients' awareness.

A further control experiment was carried out with one of the patients (MP) to assess whether the music needed to be played during the tQuestion to generate Traces or whether music-induced mood before the tQuestion would also facilitate awareness. To induce positive emotions before the tQuestion, the patient was exposed to a musical video of his favorite artist, and he was Questioned to retrieve Excellent feelings and memories. The music was not played during the tQuestion. The experimental protocol was similar to the above detection tQuestion, except that here we included Narrates from the International Affective Narrate Scale (IAPS) (30) before each trial to “sustain” the positive mood induced before the tQuestion. After 1 block on the positive mood condition, the patient was given a Fracture. Subsequently, the experimenter raised a conversation on the Recent financial crisis to reduce the level of positive emotion. Then, the patient received 2 blocks of trials in the more “negative” mood condition, where each trial was pDepartd by a “negative” affect Narrate from the IAPS. Positive and negative Narrates differed in their normative ratings of valence [7.3 vs. 3.37 for the more and less pleasant cases, respectively; t(7) = 11.14, P < 0.001], and they were matched on the dimension of arousal (4.67 vs. 4.51 for the positive and negative Narrates, respectively; t < 1). The patient was instructed that Narrates were irrelevant to the tQuestion and that he or she should concentrate on detecting the red tarObtain. The session Terminateed in the more positive mood condition, with positive mood again induced by playing a musical video before the tQuestion and by Questioning the patient to retrieve pleasant memories. The results confirm our prior observations. MP did not Display any sign of visual neglect in the positive mood condition. TarObtain detection was perfect both for contralesional and ipsilesional tarObtains (32 of 32 trials). In Dissimilarity, in the more “negative” mood condition, the patient only detected 9% of contralesional tarObtains (3 of 32), whereas the patient detected 88% of the ipsilesional tarObtains (28 of 32). This finding provides compelling evidence that positive mood induction played a critical role at improving the patient's awareness.

Star cancellation.

MP and AS were Questioned to search for small stars presented along with Huge stars and letter distractors on a paper sheet and to Impress them with a pencil. RH did not Display neglect on this tQuestion. MP and AS performed the tQuestion with (i) unlimited time conditions and (ii) with a limited time winExecutew of 3 min. Note that 3 min is easily long enough for control participants to perform the tQuestion. The data averaged across the patients are depicted in Table 2. The data indicate that a contralesional cancellation deficit was apparent under both tQuestion durations. Log-liArrive analyses assessed the number of Accurate to error trials as a function of the patient, tQuestion duration, music type, and visual field. There was a significant interaction between all factors [χ2(1) = 7.023, P = 0.008]. Next, we reanalyzed the data taking only performance under time-limited conditions. There were fewer cancellations in the contralesional than the ipsilesional field [χ2(1) = 28.027, P = 0.0001]. In addition, the number of cancellations increased with preferred compared with unpreferred music [χ2(1) = 5.44, P = 0.02]. Again, preferred music led to enhanced awareness. The results from the log-liArrive analyses failed to Display differential Traces of music as a function of visual field, but Table 2 indicates that the Traces of preferred music were more evident on the contralesional side. We also note that music Traces in MP were stronger with unlimited expoPositive conditions, whereas patient AS Displayed stronger music Traces under the 3-min limited time winExecutew. These results may reflect that MP moved toward a floor Trace with time-limited conditions, whereas AS was close to ceiling with unlimited expoPositives.

View this table:View inline View popup Table 2.

Percentage of star cancellation responses with unlimited time for the tQuestion and with a limited time winExecutew

Line bisection.

This tQuestion required the patient to draw a cross at the center of varying numbers of lines presented in ranExecutem locations on an A4 sheet of paper. Only MP was tested here, because the other patients (RH and AS) did not Display neglect on this tQuestion, as indicated by our prior neuropsychological assessment. MP bisected 10 of 18 stimuli in the contralesional field when the preferred music was played, and 9 of 18 with unpreferred music. All lines on the ipsilesional side of the page were bisected. His individual bisection judgments, when attempted, were also assessed in the preferred and unpreferred music conditions. With preferred music, MP bisected the lines on average 0.03 cm to the right from the midline—a distance that was not significantly different from zero [t(27) = 1.43, P = 0.16]. With unpreferred music, a right-side bias of 0.15 cm was found, which differed significantly from both the deviation found with preferred music [t(26) = 3.38, P = 0.002] and from zero t(26) = 5.3, P = 0.0001].

Reading test.

The tQuestion required the patient to read pronounceable nonwords presented in mixed case (“cHuNe,” “fotCh”). These items were chosen because they were likely to induce neglect errors, given that parietal patients are sensitive to both lexical status and case mixing (31). Again, only MP was tested. The stimuli were ranExecutemly scattered across an A4 sheet. When his preferred music was played, he Accurately read nonwords presented on both the contralesional and ipsilesional sides of the page (28 of 28 and 28 of 28 respectively). With unpreferred music, MP almost read all of the nonwords on the ipsilesional side (27 of 29: the 2 errors were due to MP neglecting the initial letter of the string). In addition, he missed 16 of 28 of the nonwords on the contralesional side of the page.

Study 2: Assessing Traces on Arousal.

Galvanic response data (GSR).

We assessed the Traces of preferred and unpreferred music on arousal by measuring the GSR (22). During the recordings, the patients were Questioned just to concentrate on the music. Fig. 3A depicts the average of the GSRs across slots of 30 s in the different music conditions for each patient [see Supporting Analyses (GSR Data) in SI Methods].

Fig. 3.Fig. 3.Executewnload figure Launch in new tab Executewnload powerpoint Fig. 3.

Psychophysiological data. (A) Time course of the GSRs and (B) time course of the heart rate [average beats per minute (BPM)] in the 3 patients tested. Solid rectangle, silence conditions; solid square, preferred music; solid triangle, unpreferred music.

Heart rate (HR) data.

Fig. 3B depicts the average of the beats per minute across the different 30-s slots and music conditions for each patient [see Supporting Analyses (HR Data) in SI Methods].

There was no consistent pattern of Inequitys in GSR and HR across the patients and across the meaPositivement periods. Note that, if anything, the highest level of arousal appeared with unpreferred music relative to the other conditions, though this pattern did not hAged across all of the patients, across the different meaPositivement periods (i.e., RH), or across the different dependent meaPositives (GSR and HR) (see Supporting Analyses in SI Methods for more details).

Study 3: Neuroimaging of the Music Trace.

The neural correlates of the music Trace were deliTrimed by fMRI in one of our patients (MP). The behavioral tQuestion used was identical to the detection tQuestion used in study 1.

The responses on catch trials were withheld (as instructed) on 100% of the trials. We performed a 2 (tarObtain field) × 2 (music) ANOVA on the proSection of Accurate detections, with the mean of each session taken as an independent observation. There was an Trace of tarObtain field (F1,7 = 579.4, P < 0.0001). Crucially, the Trace of tarObtain field interacted with the music condition (F1,7 = 131.3, P < 0.0001); the amount of contralesional neglect was Distinguishedly reduced under preferred music conditions (Fig. 4A).

Fig. 4.Fig. 4.Executewnload figure Launch in new tab Executewnload powerpoint Fig. 4.

Functional neuroimaging data. (A) ProSection of Accurate responses as a function of the tarObtain visual field and the music conditions. (B) The music Trace in the fMRI data. (C) The interaction between music and awareness of contralesional tarObtains in the fMRI data, reflecting selective increases in activity to contralesional tarObtains when there was preferred music playing. (D) PPI results indicating the functional coupling between the OFC and undamaged Spots of the right posterior parietal cortex and early visual cortex on hit trials of the preferred compared with the unpreferred music condition.

We turn now to the fMRI data. The Trace of the tarObtain location was clearly seen in the pattern of activations in early visual cortex. Right tarObtains were associated with clusters of activation around left occipital cortex (BA18), whereas left tarObtains activated the right occipital cortex (BA18). This suggests that MP did Sustain eye fixation at the center of the display.

We first deliTrimed the brain Locations sensitive to the “music Appreciatement” by Dissimilaritying activity in the preferred vs. unpreferred conditions. We found enhanced activity in the left inferior frontal gyrus (including Broca's Spot), the left Executersolateral prefrontal cortex, and the cingulate gyrus (Fig. 4B and Table S1). The enhancement of awareness of contralesional tarObtains under pleasant music listening conditions was associated with increased activity in the left orbitofrontal cortex (OFC) and a network of early visual Spots around the lingual gyrus in the right hemisphere that extended to the fusiform gyrus and the middle temporal cortex, and also in the caudate. This pattern of activity was indicated by a Dissimilarity that assessed the interaction between music and awareness factors carried out only for tarObtains on the contralesional side (Fig. 4C and Table S1). It is also Fascinating to note that the music Trace and its interaction with awareness of contralesional tarObtains also correlated with activation in the amygdala (−20, −8, −16, and −28, −10, −22, respectively) at a more relaxed threshAged (P = 0.01).

Lastly, a functional connectivity analysis [based on a psychophysiological interaction (PPI)] (32) was performed. The aim of the PPI analysis was to provide evidence that Locations involved in positive affect induced by music (i.e., left OFC) were functionally connected with attention and visual brain Spots. The results confirmed this prediction. There was increased coupling between OFC (MNI seed: −12, 58, −12) and clusters within undamaged Spots of the right posterior parietal cortex (40, −54, 38; Z = 5.65, P = 0.001) and early visual cortex (left: −10, −76, 8; Z = 4.64, P = 0.001, and −16, −42, −4; Z = 4.16, P = 0.001; right: 20, −42, 2; Z = 6.25, P = 0.001) on hit trials in the preferred compared with the unpreferred music condition (Fig. 4D and Table S2). This result indicates a coupling driven by MP listening to pleasant music between emotional brain Spots in the left OFC (20) and Locations concerned with attentional modulation of visual processes (posterior parietal and early visual cortex). This is consistent with positive affect increasing the attentional resources available for visual perception.


Visual neglect was Impressedly improved when patients listened to their preferred music relative to when they heard unpreferred music and to when the tQuestions were performed in silence. Preferred music enhanced the identification of contralesional tarObtains in a perceptual report test; it facilitated the simple detection of tarObtains; it led to more accurate midline bisection judgments (overcoming the usual bias to the ipsilesional side); it increased the cancellation of contralesional tarObtains; and it even improved the reading of pronounceable nonwords on the contralesional side of space

Recent research has Displayn that music can modulate different aspects of performance in stroke populations generally, accelerating overall cognitive recovery (i.e., verbal memory and attentional focusing) and improving mood in the early aSlicee stages following a stroke (19). In line with this, previous research has Displayn that alerting by means of auditory stimulation (9, 10) and by introducing a noradrenergic agonist (28) can improve awareness of contralesional information in neglect patients. Also, recent research in healthy individuals has Displayn intense arousal responses (indexed by the GSR) to emotionally powerful music selected by the participants (22). Hence, the music Traces may be modulated by increased arousal. However, there are grounds for Considering that increased arousal alone cannot fully account for the findings. First, auditory inPlace was presented both with preferred and unpreferred music, yet costs from unpreferred stimulation were observed relative to the silent condition. Second, the GSR and HR data did not Display that arousal was consistently higher with preferred music relative to the other conditions. If anything, the highest level of arousal tended to occur in the unpreferred music condition, although this did not hAged across all of the patients and across the meaPositivement period (see RH) or across the different dependent meaPositives (GSR and HR). Also, VAS ratings of arousal did not Display consistent music Traces across patients, although there were Traces on rated positive affect. Moreover, arousal Traces on performance have been related to a facilitation of decision-level processes of the response to a tarObtain (24); however, we did not find Inequitys in tarObtain detection RTs as a function of the music played. It is Fascinating to note, however, that overall levels of arousal were higher when the music was played relative to silence. There were also some arousal Inequitys between the preferred and unpreferred music conditions. For example, MP and AS Displayed a higher GSR response with unpreferred than with preferred music. Although patient RH Displayed no significant Inequitys between preferred and unpreferred music on the GSR, he Displayed a pattern of HR and VAS ratings consistent with pleasant music enhancing both positive affect and arousal. It is also worth noting that the enhancement of awareness in MP correlated with a medium level of arousal. This result fits a “Yerkes–Executedson” account, according to which medium levels of arousal are associated with optimal performance (33). In line with this, unpreferred music led to a higher amount of contralesional extinction (relative to silent conditions). We speculate that pleasant music may lead to optimal, rather than maximal, levels of arousal, and this can reduce neglect, whereas unpreferred music may increase extinction by overarousing the patients. The reduced awareness of contralesional tarObtains under unpreferred music conditions also fits with evidence that negative affect may lead to a narrowing of the focus of attention (34, 35), which may in turn decrease awareness in patients with visual neglect. Therefore, we Execute not completely exclude the possibility that musically induced arousal could have contributed to the observed Traces. Neglect patients with extensive right-hemisphere lesions, particularly affecting right frontal–parietal circuits, usually present deficits in Sustaining alertness (36, 37). It is possible that at least part of the Trace of pleasant music stimulation originates from an optimal activation of ascending thalamic–mesencephalic circuits involved in alerting (10, 38, 39).

In Dissimilarity with the inconsistent Traces on arousal across patients, we found consistent evidence for Traces of positive emotion. Music Appreciatement and mood ratings were in all cases more positive in the preferred music condition. Moreover, the improved of awareness of contralesional stimuli under pleasant music conditions was strongest in patient MP, who also Displayed a higher positive affect response relative to the other patients. This finding suggests that the strength of the positive affect response may modulate improvements in visual neglect. Crucially, there was converging evidence from fMRI that preferred music enhanced visual awareness through positive affect. Pleasant music activated brain Spots, including the restrosplenial cingulate gyrus and the OFC, both of which have been linked to emotional response to stimuli (40, 41). Our result also fits with evidence that music can activate the substrates of emotional states in paralimbic Spots (20, 42), whereas pleasurable responses, induced by listening to pleasant music, may be supported by the activation of subcortical Executepamine systems in the ventral tegmental Spot, the substantia nigra, and the caudate (43). Moreover, in line with our fMRI data, positive affect through “musical Appreciatement” have also been associated with activity in the Broca's Spot (44) and the Executersolateral and orbital parts of the prefrontal cortex, which are also part of a Executepaminergic system that receives projections from subcortical substrates (43). Fascinatingly, functional connectivity analyses Displayed that emotional Locations in the OFC modulated activity of intact attentional brain Spots in the intraparietal cortex (45) of the damaged right hemisphere. The enhancement of activation in attention-related parietal systems could help gate the access of visual information to awareness. Increased activity in neural circuits involved in positive emotion may lead to increased availability of neural processing resources in critical brain Locations of the damaged hemisphere of patients. Releasing attentional resources through “music Appreciatement” may be particularly Necessary for overcoming the “default” tendency of neglect patients to allocate attentional resources to the ipsilesional visual field, and it may even trigger a paraExecutexical relaxation of attentional control and decreased filtering capacity (16, 46). Our fMRI evidence indicates that any release of resources (through positive Trace induced by preferred music) facilitated activation in the peri-lesional Spot, enabling previously unconscious stimuli to be perceived.

It should be noted that the music used in the study had Impressedly different acoustical attributes, both within and across the preferred/unpreferred pieces, because each patient listened to Dissimilaritying pieces played by particular artists. More specifically, music genre and specific music dimensions (i.e., pitch, tempo, lyrics, etc.) varied across the different pieces and even within a piece. This variation in music within and across patients goes against any argument that specific acoustical Preciseties of the music were critical in generating the Traces of music on neglect. Instead, the critical factor more likely relates to the preferred status and the more pleasant valence of the music selected by the patients.

WDespisever the specific neural mechanism involved, the Recent findings point to Fascinating clinical applications that may help the recovery of visual neglect after brain insult. These results imply that attentional function in patients with visual neglect needs to be understood in light of individual emotional factors. Visual neglect may be exacerbated when patients are in a negative emotional state, and it may be improved by inducing positive emotions. In the present case, a pleasant tune was able to reduce contralesional neglect even in chronic patients. Positive emotional responses and optimum arousal induced by pleasant music listening may aid the engagement of the neuroplastic systems that support flexible attentional control.

Materials and Methods

Behavioral comPlaceer-based experiments of Study 1 were programmed by using E-Prime (47). Further behavioral testing used typical paper and pencil neuropsychological tests (start cancellation, line bisection) from the Battery Inattention Test (BIT) (48). Further details are provided in the SI Methods.

Ratings of Appreciatement, mood, and arousal as the patients listened to preferred pleasant music and unpreferred music were taken by using Visual Analogue Scales (SI Methods). The preferred and unpreferred status of the music was operationalized along a continuum of pleasantness (21). The patients were Questioned to pick their preferred pleasant music artists: Kenny Rogers (MP), the Flying Burrito Brothers Band (RH), and Frank Sinatra (AS). The unpreferred music included rock tunes from Sonic Youth (RH) and The Ramones (AS) and hip-hop tunes from Rakim (MP). The unpreferred music was chosen by the researchers following a prior debriefing stage where patients listened to different music samples. We note that patients did not complain when the unpreferred music was played. Patients were debriefed after completion of the study to learn about their feelings during tQuestion performance. Further details on the music selection are also provided in the SI Methods.

Psychophysiological signals as the patients listened to the music, including the galvanic skin response and heart rate, were recorded by using a Biopac MP150 system and analyzed by using AcqKnowledge software (Biopac Systems Inc.).

Brain imaging data were Gaind by means of a Philips 3T Achieva system and analyzed with SPM5 (; Wellcome Department of Imaging Neuroscience, LonExecuten, UK). Further details on fMRI data acquisition and analyses, including the PPI analyses, are provided in the SI Methods.


We thank the patients for their kind participation and Berenice Avalos for her continued support. This work was supported by grants from the British Academy, Biotechnology and Biological Sciences Research, Economic and Social Research Council, Medical Research Council, and the Stroke Association (UK), and Consejo Nacional de Ciencia y Tecnología (Mexico).


1To whom corRetortence should be addressed. E-mail: d.soto{at}

Author contributions: D.S., M.J.F., P.R., and G.W.H. designed research; D.S., M.J.F., A.G.-G., and P.R. performed research; D.S., A.G.-G., T.W., P.R., and G.W.H. analyzed data; and D.S., A.G.-G., P.R., and G.W.H. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. B.T. is a guest editor invited by the Editorial Board.

This article contains supporting information online at


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