Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study

Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.

One, two, or many mechanisms? The brain's processing of complex words

The heated debate over whether there is only a single mechanism or two mechanisms for morphology has diverted valuable research energy away from the more critical questions about the neural computations involved in the comprehension and production of morphologically complex forms. Cognitive neuroscience data implicate many brain areas. All extant models, whether they rely on a connectionist network or espouse two mechanisms, are too underspecified to explain why more than a few brain areas differ in their activity during the processing of regular and irregular forms. No one doubts that the brain treats regular and irregular words differently, but brain data indicate that a simplistic account will not do. It is time for us to search for the critical factors free from theoretical blinders.

CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors

Interaction between brain endocannabinoid (EC) and serotonin (5-HT) systems was investigated by examining 5-HT-dependent behavioural and biochemical responses in CB1 receptor knockout mice. CB1 knockout animals exhibited a significant reduction in the induction of head twitches and paw tremor by the 5-HT2A receptor selective agonist ()DOI, as well as a reduced hypothermic response following administration of the 5-HT1A receptor agonist (±)-8-OH-DPAT. Additionally, exposure to the tail suspension test induced enhanced despair responses in CB1 knockout mice. However, the tricyclic antidepressant imipramine and the 5-HT selective reuptake inhibitor fluoxetine induced similar decreases in the time of immobility in the tail suspension test in CB1 receptor knockout and wild-type mice. No differences were found between both genotypes with regard to 5-HT2A receptor and 5-HT1A receptors levels, measured by autoradiography in different brain areas. However, a significant decrease in the ability of the 5-HT1A receptor agonist (±)-8-OH-DPAT to stimulate 35SGTPS binding was detected in the hippocampal CA1 area of CB1 receptor knockout mice. This study provides evidence that CB1 receptors are involved in the regulation of serotonergic responses mediated by 5-HT2A and 5-HT1A receptors, and suggests that a reduced coupling of 5-HT1A receptors to Gi/o proteins in the hippocampus might be involved in these effects.

Lack of CB1 receptor activity impairs serotonergic negative feedback

Serotonergic and endocannabinoid systems are important substrates for the control of emotional behavior and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB1 cannabinoid receptor impaired serotonergic negative feedback in mice. Thus, in vivo microdialysis experiments revealed increased basal 5-HT extracellular levels and attenuated fluoxetine-induced increase of 5-HT extracellular levels in the prefrontal cortex of CB1 knockout compared to wild-type mice. These observations could be related to the significant reduction in the 5-HT transporter binding site density detected in frontal cortex and hippocampus of CB1 knockout mice. The lack of CB1 receptor also altered some 5-HT receptors related to the 5-HT feedback. Extracellular recordings in the dorsal raphe nucleus revealed that the genetic and pharmacological blockade of CB1 receptor induced a 5-HT1A autoreceptor functional desensitization. In situ hybridization studies showed a reduction in the expression of the 5-HT2C receptor within several brain areas related to the control of the emotional responses, such as the dorsal raphe nucleus, the nucleus accumbens and the paraventricular nucleus of the hypothalamus, whereas an overexpression was observed in the CA3 area of the ventral hippocampus. These results reveal that the lack of CB1 receptor induces a facilitation of the activity of serotonergic neurons in the dorsal raphe nucleus by altering different components of the 5-HT feedback as well as an increase in 5-HT extracellular levels in the prefrontal cortex in mice.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Virtual milgram : empathic concern or personal distress? Evidence from functional MRI and dispositional measures

One motive for behaving as the agent of another"s aggression appears to be anchored in as yet unelucidated mechanisms of obedience to authority. In a recent partial replication of Milgram"s obedience paradigm within an immersive virtual environment, participants administered pain to a female virtual human and observed her suffering. Whether the participants" response to the latter was more akin to other-oriented empathic concern for her well-being or to a self-oriented aversive state of personal distress in response to her distress is unclear. Using the stimuli from that study, this event-related fMRI-based study analysed brain activity during observation of the victim in pain versus not in pain. This contrast revealed activation in pre-defi ned brain areas known to be involved in affective processing but not in those commonly associated with affect sharing (e.g., ACC and insula). We then examined whether different dimensions of dispositional empathy predict activity within the same pre-defi ned brain regions: While personal distress and fantasy (i.e., tendency to transpose oneself into fi ctional situations and characters) predicted brain activity, empathic concern and perspective taking predicted no change in neuronal response associated with pain observation. These exploratory fi ndings suggest that there is a distinct pattern of brain activity associated with observing the pain-related behaviour of the victim within the context of this social dilemma, that this observation evoked a self-oriented aversive state of personal distress, and that the objective"reality" of pain is of secondary importance for this response. These fi ndings provide a starting point for experimentally more rigorous investigation of obedience.

Theta EEG oscillatory activity and auditory change detection

The mismatch negativity is an electrophysiological marker of auditory change detection in the event-related brain potential and has been proposed to reflect an automatic comparison process between an incoming stimulus and the representation of prior items in a sequence. There is evidence for two main functional subcomponents comprising the MMN, generated by temporal and frontal brain areas, respectively. Using data obtained in an MMN paradigm, we performed time-frequency analysis to reveal the changes in oscillatory neural activity in the theta band. The results suggest that the frontal component of the MMN is brought about by an increase in theta power for the deviant trials and, possibly, by an additional contribution of theta phase alignment. By contrast, the temporal component of the MMN, best seen in recordings from mastoid electrodes, is generated by phase resetting of theta rhythm with no concomitant power modulation. Thus, frontal and temporal MMN components do not only differ with regard to their functional significance but also appear to be generated by distinct neurophysiological mechanisms.

Functional neuroanatomy of meaning acquisition from context

An important issue in language learning is how new words are integrated in the brain representations that sustain language processing. To identify the brain regions involved in meaning acquisition and word learning, we conducted a functional magnetic resonance imaging study. Young participants were required to deduce the meaning of a novel word presented within increasingly constrained sentence contexts that were read silently during the scanning session. Inconsistent contexts were also presented in which no meaning could be assigned to the novel word. Participants showed meaning acquisition in the consistent but not in the inconsistent condition. A distributed brain network was identified comprising the left anterior inferior frontal gyrus (BA 45), the middle temporal gyrus (BA 21), the parahippocampal gyrus, and several subcortical structures (the thalamus and the striatum). Drawing on previous neuroimaging evidence, we tentatively identify the roles of these brain areas in the retrieval, selection, and encoding of the meaning.

An fMRI Study of Emotional engagement in decicion-making

It has been suggested that decisionmaking depends on sensitive feelings associatedwith cognitive processing rather than cognitiveprocessing alone. From human lesions, we knowthe medial anterior inferior-ventral prefrontalcortex processes the sensitivity associated withcognitive processing, it being essentiallyresponsible for decision making.In this fMRI (functional Magnetic ResonanceImage) study 15 subjects were analyzed usingmoral dilemmas as probes to investigate the neuralbasis for painful-emotional sensitivity associatedwith decision making. We found that a networkcomprising the posterior and anterior cingulateand the medial anterior prefrontal cortex wassignificantly and specifically activated by painfulmoral dilemmas, but not by non-painful dilemmas.These findings provide new evidence that thecingulate and medial anterior prefrontal areinvolved in processing painful emotionalsensibility, in particular, when decision makingtakes place. We speculate that decision makinghas a cognitive component processed by cognitivebrain areas and a sensitivity component processedby emotional brain areas. The structures activatedsuggest that decision making depends on painfulemotional feeling processing rather than cognitiveprocessing when painful feeling processinghappens

Constitutive expression of FGF4 disrupts the development of the eye and the anterior CNS during mouse embryogenesi, but does not influence the expressionof shh in these areas.

The biological consequences of constitutive fibroblast growth factor-4 (fgf4) expression have been analysed during anterior CNS development of mouse chimeric embryos. Severe mutant embryos exhibit exencephaly, absence of eye development and anomalous differentiation of neuropithelium. These embryos also show ectopic limb buds resembling the early phases of limb development. Because our results show that anterior CNS in those chimeric embrios does not express shh ectopically, we suggest that malformations may be due to interference between the ectopic expression of fgf4 in the cephalic area and the receptors for the members of the FGF family that regulate brain and eye development, namely fgf8. If this is correct, the results indirectly suport the crucial role of fgf8 in patterning the anterior CNS.

The psychosocial difficulties in brain disorders that explain short term changes in health outcomes.

BACKGROUND: This study identifies a set of psychosocial difficulties that are associated with short term changes in health outcomes across a heterogeneous set of brain disorders, neurological and psychiatric. METHODS: Longitudinal observational study over approximately 12 weeks with three time points of assessment and 741 patients with depression, bipolar disorders, multiple sclerosis, parkinson's disease, migraine, traumatic brain injury and stroke. The data on disability was collected with the checklist of the International Classification of Functioning, Disability and Health. The selected health outcomes were the Short Form 36 and the World Health Organization Disability Assessment Schedule. Multilevel models for change were applied controlling for age, gender and disease severity. RESULTS: The psychosocial difficulties that explain the variability and change over time of the selected health outcomes were energy and drive, sleep, and emotional functions, and a broad range of activities and participation domains, such as solving problems, conversation, areas of mobility and self-care, relationships, community life and recreation and leisure. CONCLUSIONS: Our findings are of interest to researchers and clinicians for interventions and health systems planning as they show that in addition to difficulties that are diagnostic criteria of these disorders, there are other difficulties that explain small changes in health outcomes over short periods of time.

Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in rat brain: an autoradiography study.

Previous studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and killed them on day 11 to perform [125I]epibatidine binding autoradiograms on serial coronal slices. Results showed significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory cortex, motor cortex, auditory cortex, retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei. These increases ranged from 3% (retrosplenial cortex) to 30 and 33% (amygdala and substantia nigra). No increased α4 subunit immunoreactivity was found in up-regulated areas compared with saline-treated rats, suggesting a post-translational mechanism as occurs with nicotine. The percentage of up-regulation correlated positively with the density of serotonin transporters, according to the serotonergic profile of MDMA. The heteromeric nAChR increase in concrete areas could account, at least in part, for the reinforcing, sensitizing and psychiatric disorders observed after long-term treatment with MDMA.

Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in rat brain: an autoradiography study.

Previous studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and killed them on day 11 to perform [125I]epibatidine binding autoradiograms on serial coronal slices. Results showed significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory cortex, motor cortex, auditory cortex, retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei. These increases ranged from 3% (retrosplenial cortex) to 30 and 33% (amygdala and substantia nigra). No increased α4 subunit immunoreactivity was found in up-regulated areas compared with saline-treated rats, suggesting a post-translational mechanism as occurs with nicotine. The percentage of up-regulation correlated positively with the density of serotonin transporters, according to the serotonergic profile of MDMA. The heteromeric nAChR increase in concrete areas could account, at least in part, for the reinforcing, sensitizing and psychiatric disorders observed after long-term treatment with MDMA.