Projects

Behavioral and Brain Effects of Intonation-based and Non-intonation-based Aphasia Therapies

Aphasia is a common and devastating complication of stroke that causes severe communication difficulties for tens of thousands of adults each year. One of the few accepted treatments for severe non-fluent aphasic patients is Melodic Intonation Therapy (MIT). The technique was inspired by the common clinical observation that some severely aphasic patients are better at singing the lyrics of songs than they are at speaking the same words. MIT emphasizes the prosody of speech by using slow, pitched vocalization (singing), and has been shown to lead to significant improvements in naming and propositional language beyond the actual treatment period. It has been hypothesized that this effect is due to the gradual recruitment of right-hemispheric language regions for normal speech production, and this is further supported by our own functional magnetic resonance imaging (fMRI) pilot data. Although the MIT-induced treatment effect has been shown in several small case series, it is not clear whether the effect is due to the intensity of the treatment or to the unique, components of MIT that are not found in other, non-intonation-based interventions. Thus, our overall aim is to test our hypothesis that MIT's rehabilitative effect is achieved by using its melodic and rhythmic elements to engage and/or unmask the predominantly right-hemipsheric brain regions capable of supporting expressive language function. In order to test this hypothesis, we have developed an experimental design that includes the randomization of chronic stroke patients with persistent, moderate to severe non-fluent aphasia into three parallel groups receiving 1) 75 sessions of Melodic Intonation Therapy (approximately 8 weeks), 2) 75 sessions of an equally intensive, alternative verbal treatment method developed for this study (Speech Repetition Therapy), or 3) an equal period of No Therapy. All patients will undergo two pre-therapy and two post-therapy behavioral assessments in addition to the pre- and post-therapy fMRI studies examining the neural correlates of overtly spoken and sung words and phrases.This design allows us to 1) examine the efficacy of MIT over No Therapy, 2) examine the effects of elements specific to MIT (e.g., melodic intonation and rhythmic tapping) by comparing it to a control intervention (SRT) that is similar in structure and intensity of treatment, 3) compare post-therapy effects with pre-therapy baseline variations, and 4) examine post-treatment maintenance effects. Our primary speech outcome measure will be the number of Correct Information Units (CIU)/min produced during spontaneous speech. Secondary outcome measures include correctly named items on standard picture naming tests, timed automatic speech, and linguistically-based measures of phrase and sentence analysis.

Patients should be between 21-80 years old (patients less than 21 years of age may be considered on a case by case basis) with impaired speech production but relatively normal comprehension. If you or someone you know would like more information or is interested in participating in this study, please contact us at aphasia_recovery@yahoo.com

Neural Correlates of Singing and Speaking

Recent studies have challenged the classical view of the existence of distinct cerebral modules for music and language processing by showing activation of language specific areas with musical tasks. However, this sharing of neural substrates between musical and language tasks conflicts somewhat with clinical reports that emphasize a double dissociation between singing and speaking. For instance, it has been reported that patients with Broca's aphasia are able to sing the lyrics of a song better than they can speak the same words. It has been argued that one of the reasons this phenomenon occurs is due to the fact that the left hemisphere is more engaged in propositional speech while the right hemisphere shows greater involvement with automatic or non-propositional speech such as counting or singing familiar songs. This suggests that there could be two possible routes to the articulation of words: 1) a normal language-based route via the left hemisphere, and 2) a singing-based or melodically-intoned route that is either bihemispheric or via the right hemisphere.The major aims of our research in this area are to examine the shared and distinct neural substrates of overt singing and speaking employing a modified sparse temporal sampling method that allows us to effectively use production tasks (overt speaking and singing) in the MR scanner environment. Furthermore, we are interested in the plasticity of the neural elements that control speaking and singing by comparing professional singers to non-singers.

Tone Deafness / Congenital Amusia and Auditory-Motor Interactions

Although we all know one or more individuals who can't sing in tune, the neural correlates of this disorder and what it might reveal about models of communication control remain elusive. In addition to an inability to sing in tune, one characteristic marker of tone-deafness is an abnormally large psychophysical pitch discrimination threshold of more than one semitone. The inability to discriminate fine pitch differences may be an epiphenomenon of the disorder, or it could be related to the presumed auditory-motor dysfunction that underlies disabled production of vocal pitch. Pilot and previous data from morphometric, functional imaging, and Event-Related Potential (ERP) studies point towards functional and structural abnormalities in regions involved in auditory feedback control and sound-motor mapping, rather than dysfunctions in primary auditory cortex. In considering that the inability to sing might be reflective of problems in auditory-motor integration including feedforward and feedback control mechanisms, the present theoretical framework allows us to generalize existing models of speech perception and production to the domain of singing as an instance of "intoned-speech". Our general hypothesis is that tone-deafness is a result of dysfunction in a network of brain regions involved in auditory feedback and feedforward control of vocal pitch production. We plan to test this hypothesis by first identifying the behavioral and neural substrates of tone-deafness. By combining neuroimaging and psychophysical experiments of pitch production, including the use of pitch-shifted auditory feedback, we will test the neural mechanisms responsible for auditory feedback control and sound-motor mapping as well as the interaction of these two systems. We will then reverse-engineer the perceptuomotor pathway by creating temporary regional dysfunctions using a new method of non-invasive brain stimulation (transcranial direct current stimulation - TDCS). Based on pilot pitch production results, brain stimulation can temporarily induce tone-deafness in normal individuals, thus allowing us to assess our regional hypotheses using psychophysical measures that have been evaluated in experiments from the first aim. Examining the neural correlates of tone-deafness and creating a tone-deaf equivalent in normal subjects will offer new insights into the interactions of auditory and motor systems in the brain in normal and disordered speech as well as in non-speech communication. We are looking for individuals that consider themselves as tonedeaf or poor singers. Please contact us through one of our telephone numbers or e-mail addresses.

If you are interested in taking a tone-deaf test, please click on the following link.

Motor Recover Studies

Cerebrovascular disease is the third leading cause of death in the United States and a major cause of adult disability. Most patients that survive an ischemic or hemorrhagic stroke have persistent and disabling deficits. The mechanisms of recovery following stroke are poorly understood and therefore poorly manipulated by therapeutic interventions. Good functional outcome has been associated with smaller size and specific location of the stroke, particularly important is the integrity of the pyramidal system. However, the precise brain areas and physiological processes that are important to enable recovery have not been determined. We are currently conducting two studies in the field of motor recovery:

Using MRI, voxel-based lesion mapping, diffusion tensor imaging, and TMS to study natural recovery from Stroke and Predictors of Stroke Recovery

We are interested in studying natural stroke recovery and in determining recovery predictors in stroke patients by using combinations of functional magnetic resonance imaging (fMRI) while patients perform movements of their affected and non-affected arm, voxel-based lesion mapping, diffusion tensor imaging, and transcranial magnetic stimulation (TMS). These studies are designed to determine not only where neuroplastic changes take place but also to understand their physiological significance and functional importance.This will ultimately help us to develop and design better protocols to facilitate stroke recovery beyond the natural recovery potential.

Facilitating Motor Recovery using combinations of Transcranial Direct Current Stimulation (TDCS) and Occupational Therapy

This protocol investigates the effects of weak Transcranial Direct Current Stimulation (TDCS) applied to the motor cortex in order to facilitate motor recovery in chronic stroke patients with incomplete motor recovery. Previous studies have used functional neuroimaging tools such as functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) to understand the neural correlates of recovery. One interesting observation noted in these studies is the recruitment of the contralesional hemisphere during the affected hand motor tasks. However, further studies reported that this contralesional hemisphere activation is not directly responsible for motor recovery and that in fact, the return of activity in the lesioned hemisphere heralds recovery. Extending the finding of the existence of transcallosal inhibition in normal subjects, we and others proposed that the contralesional activation in patients recovering from stroke might most likely represent a phenomenon of disinhibition in that hemisphere, due to the infarction in the opposite hemisphere. Interestingly, previous research using TDCS has shown that anodal and cathodal TDCS stimulation selectively enhances or reduces cortical excitability respectively. In light of this finding, it is logical to hypothesize that cathodal TDCS stimulation of the contralesional hemisphere should inhibit firing in that hemisphere and result in reduced transcallosal inhibition, thus leading to greater neural activity in the affected hemisphere. This is supported by the evidence that repetitive Transcranial Magnetic Stimulation (rTMS) to the contralesional hemisphere in stroke patients enhanced motor performance in the affected hand. Similarly, anodal TDCS stimulation of the affected hemisphere should increase excitability, promote return of neural firing in that hemisphere and facilitate recovery. If by clinical examination and objective assessment methods we find improvement in motor function in chronic stroke patients following TDCS, we may conclude that TDCS has the potential to be used for motor recovery. The experiment proposed here will compare motor performance / skills in patients at baseline (before any TDCS), after real TDCS, and after "sham" TDCS. Scores on motor assessments in all three groups - affected hemisphere, non-affected hemisphere and sham TDCS will be compared to determine the effects of stimulation. If these results hold, TDCS, which is a non-invasive brain stimulation technique with fewer known risks and less discomfort for participants, can be identified as a safer alternative to Transcranial Magnetic Stimulation (TMS).

Our overall aim is to determine the effect of applying real (anodal, cathodal, and both) versus sham TDCS to the primary motor cortex while simultaneously providing occupational therapy to examine whether the combination of central stimulation with periphyeral sensorimotor activities improve motor function more than occupational therapy by itself in chronic stroke patients. If you or someone you know would like more information or is interested in participating in this trial, please contact us at stroke_recovery@yahoo.com

Music and Emotions

Music is ubiquitous in our daily lives. Whether we are getting up or going to bed, driving, studying, working, or meeting with friends, we like to listen to music at the same time. Furthermore, our everyday experiences suggest that we also listen to music for the emotions that music can elicit and for its effect on our moods. Music has the power to elicit a wide range of emotions in the listener, both conscious and unconscious. In this study, we will test the hypothesis that sounds/music are capable of affecting/modulating measures of peripheral and central nervous system activity by systematically varying lower level acoustical and higher level structural features of music such as tempo, dynamics, mode, timbre, consonance, dissonance, instrumentation, built-up of tension and release of tension etc. will have an effect on subjects' rating of arousal and emotional valence for a given stimulus. Our aims are to determine whether we can reliably influence peripheral nervous system activity as measured by alterations in heart rate, breathing rate and skin conductance response by varying musical features; to determine whether elements of sounds/music known to elicit certain emotions influence brain activity in regions known to process non-musical emotional stimuli; to determine whether musical excerpts with known arousal and valence information can modulate behavior, mood, and cognition.

Using Music Making to Facilitate Improvement in Language and Communication Skills in Autistic Children

One characteristic of Autism Spectrum Disorders (ASD), perhaps the most heartbreaking, is the deficiency in communication skills. Unfortunately, interventions aimed at improving verbal output and/or communication skills are relatively few and have had limited success. However, since autistic children who often respond to music better than spoken language enjoy engaging in music making, treatment methods that use music-based activities may provide an effective alternative or complement to traditional interventions for facilitating speech. The observation that many autistic children can sing, even when unable to speak, is strikingly similar to the disassociation seen in patients with Broca's aphasia who can sing the lyrics of a song better than they can speak the same words. Since singing requires neural coupling of sounds with motor actions, it is possible that a singing-based intervention together with motor-sound activities might be capable of engaging a 'hearing/doin' network, and thus, may offer an alternative therapeutic option for improving language and communication skills in ASD children. Previous results in an autistic child has shown that an intervention such as ours might help children in verbal production. Given this evidence and our extensive experience treating patients with Broca's aphasia, we propose the use of a specific music-based speech intervention to build upon the musical strengths observed in autistic individuals and facilitate communication skills in children with ASD.

The Effects of Instrumental Music Making on Brain and Cognitive Development in Children

There are quite striking structural differences in the brains of professional musicians compared to non-musicians (e.g., larger corpus callosum, larger motor and auditory regions). We do not know whether these differences are caused by the intensive training musicians undergo, beginning typically in early childhood, or whether individuals who choose to study music in early childhood have "atypical" brain structures from birth, which predisposes them to music or whether these differences are due to a combination of both. Most cross-sectional studies comparing the brains of adult musicians with those of matched non-musicians, have used either age of commencement of musical training or intensity/duration of practice throughout a musician's career as predictors of regional differences suggesting that the longer and the more intensely musicians practiced, the more pronounced the between-group differences were lending further support to the notion that these differences are a result of structural brain plasticity.

Research by several groups has also demonstrated that music training in children results in long-term enhanced visual-spatial reasoning (e.g., better performance in reconstructing or assembling individual pieces to form a single object), enhanced verbal memory, as well as enhanced mathematical performance. However, the underlying brain basis of such enhancements is unknown. It is possible that changes in brain structure are induced by long-term learning and practicing a musical instrument and that these changes might have cross-modal effects if other cognitive operations draw on brain regions that could be altered by long-term music making.

In an ongoing longitudinal study, we are studying the development of three groups of children over the course of several years. The children in the Instrumental Music Group are receiving individual instructions on either a string or keyboard instrument. The children in the Non-Instrumental Music Group are receiving a special in-school program of 30 minutes of music exposure four days a week beginning in kindergarten. The children in this group are not studying an instrument. The children in the Basic Music Group are receiving the basic amount of music exposure that children receive in typical American public schools - one class per week. Children who enroll in our study are between 5-7 years of age at study onset and undergo several MRI studies at predefined time points throughout the study period as well as behavioral/cognitive testing batteries which include auditory and motor tests as well as vocabulary/verbal reasoning tests, math tests, visual-spatial, memory, attention, and non-verbal reasoning tests.

Non-invasive Brain Stimulation Studies

Transcranial Direct Current Stimulation (TDCS), a portable, safe, non-invasive, brain stimulation technique, is capable of modulating the excitability of targeted brain regions by altering neuronal membrane potentials based on the polarity of the current transmitted through the scalp via sponge electrodes. Unlike Transcranial Magnetic Stimulation (TMS), TDCS only alters the likelihood that neurons will fire by hyper- or hypo-polarizing brain tissue. "Anodal" stimulation increases cortical excitability while "cathodal" stimulation decreases it. We and others have observed corresponding behavioral effects if the behavior tested draws on the region stimulated. TDCS has enormous clinical potential for use in stroke recovery and other neurological/psychiatric disorders because of its easy of use, its non-invasiveness, its safety (does not provoke seizures), its sham mode (important for controlled clinical trials), and the possibility to combine it with other stimulation/stroke recovery enhancing methods (e.g., simultaneous occupational therapy to enhance brain plasticity in stroke recovery). In various ongoing studies we will address technical aspects of the stimulation by assessing the effects of various current attenuators on how much current actually reaches the brain and how it distributes in the brain. Furthermore, we will examine the effects of different electrode montage on brain activity and behavioral/cognitive performance. For our brain activity measures, we use a non-invasive blood flow techniques and an MRI compatible stimulation device. For our behavioral assessments we use either a motor sequencing task, various memory tasks, or language tasks.

Studying Skill Acquisition and Expert Knowledge Comparing Musicians with Non-Musicians

We are conducting several MRI and behavioral studies to examine the neural correlates of short-term auditory learning in musicians and nonmusicians, the neural correlates of music processing in musically naïve and musically experienced subjects, and adaptation effects in the brain as a result of long-term music making. We are also studying the effects that the use of different instruments (e.g., keyboard players, string players, singers) might have on brain plasticity.

Neural Correlates of Absolute Pitch

Absolute Pitch is defined as the ability to identify a particular pitch of the Western musical scale without any external reference tone and independent of frequency range or timbre. Musicians with absolute pitch are able to perceive tones as beloing to pitch categories and have learned to assign labels/note names to these categories (Siegel, 1974; Burns and Ward, 1978; Burns and Campbell, 1994; Miyazaki et al.,1988; Rakowski et al., 1993). It is our opinion that the ability the perceive tones categorically is the critical component of AP, while the ability to assign note names might be a learned skill. Miyazaki (1988) found that the boundaries for these pitch classes were very reliable within each AP musician and very similar across different individuals with AP. In contrast to absolute pitch, relative pitch is the ability to identify a tone in relation to another tone, or absolutely if a reference tone is provided. This ability can be "perfect" (through intense training) which is the reason that the colloquial term "perfect pitch" is not a good term to describe absolute pitch ability. Typically, there is a good correlation between self-report of AP and the actual test results for AP (Zatorre and Beckett, 1989; Schlaug et al., 1995; Keenan et al., 2001). AP musicians were not found to be better in tone discrimination than non-AP musicians (Bachem 1954; Burns and Campbell, 1994; Levitin, 1996), or octave register (Miyazaki, 1988) or musical interval identification (Miyazaki, 1993). For people with absolute pitch, naming a note is as simple and immediate as naming a color of an object for others. No particular effort is associated with this and AP subjects do not have to make a conscious comparison with an internal template, although they can if they want to. Many great musicians had absolute pitch (e.g., Bach, Mozart, Beethoven) but there are also many famous musicians and composers who did not have it. Absolute pitch does not seem to have a relevance to musicianship or musicality, although it is useful for music theory classes in college and university. AP ability can even be a hindrance in some circumstances and it is known that AP musicians sometimes try to suppress their AP ability when they are making music with others (e.g., singing in a choir).

The neuroanatomical basis as well as the perceptual/cognitive processes that underlie the AP ability are not fully known. We are conducting several studies investigating neural correlates of absolute pitch. These studies include region-based and voxel-based morphometric studies comparing brains from AP subjects with matched non-AP controls as well as several functional imaging studies examining the brain regions that are involved in the specific AP behavior. We are also exploring differences in brain connections comparing AP with non-AP subjects using diffusion-tensor imaging. In addition, we are exploring the incidence and neural basis of absolute pitch in families with more than one member that has AP and the incidence of AP in certain neurological disorders.

Acute Stroke Studies

Stroke is the third leading cause of death and the leading cause of adult morbidity in the United States. Recent thrombolytic trials using tissue-plasminogen activator (t-PA) have established new treatment options for acute stroke patients, however, a benefit has only been shown if t-PA can be given within three hours after the onset of a new ischemic stroke. No overall benefit for the study groups has been shown beyond the three-hour time window. However, there was evidence in recent studies that t-PA might helpful even beyond the three hour time window if appropriate selection criteria could be established to determine which patients would have the greatest benefit and which patients might be at risk for harmful side effects from thrombolytic therapy. Those selection criteria have to incorporate information on tissue pathophysiology and not solely on a ticking clock. Multimodality magnetic resonance imaging is able to provide the pathophysiological basis for selecting patients presumed to have the highest benefit from thrombolytic therapy and for identifying those patients at greatest risk for adverse side effects.

We are evaluating MR imaging based treatment rules to predict patients most likely to benefit from t-PA beyond the three-hour time window. Furthermore, we are assessing the safety and tissue efficacy of intravenous and intraarterial t-PA in patients with certain MR imaging patterns. This will help us to tailor appropriate therapeutic interventions such as giving potentially harmful thrombolytic medications to only those patients that may have the greatest benefit from it based on data determined in this study. We are currently involved in several experimental treatment trials assessing the use of innovative neuroimaging techniques in making treatment decisions.