April 27, 2004 Feature

Aphasia Treatment at the Crossroads: A Biological Perspective

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A stroke accompanied by aphasia results in damage to or loss of brain tissue that once played an integral role in communication. Right now we can perform biologically based actions to relieve aphasia.  For example, we are able to increase cerebral blood flow particularly in the acute phase of damage. This increase of blood flow has the potential to affect other regions and increase brain activity. We can also remove agents that impede a patient's recovery and help treat post-stroke depression that occurs in as many as 50%-80% of people with aphasia. Ongoing studies are investigating the treatment of depression in stroke patients.

Current Issues and Challenges

In order to explore the future of aphasia treatment, we must first address some significant problems in the current therapeutic approach. Although the efficacy of aphasia treatment has been demonstrated, the very fact that this demonstration continues to be controversial in some quarters shows that the treatment of aphasia, despite its effectiveness, remains unsatisfactory. There are several reasons why this is happening.

The first issue is poor understanding of the functional changes of the brain during the non-acute stages of stroke. What is actually happening to the brain over the course of recovery is completely unknown. There are many variables involved in the case of each patient, such as age and mode of therapy; we do not know how these individual factors are affecting the brain. Are new synapses forming? If so, where? Are neurotransmitter changes occurring? We currently do not know the answers.

The second issue concerns the treatment options for aphasia. These options are limited by knowledge about neurophysiology and anatomy, and thus treatment is directed at the external manifestations of the damaged structure rather than at the damaged structure itself. Thus, if a patient has Broca aphasia with damage to the left frontal lobe, we attempt to educate the patient by teaching him to form full sentences rather than looking at the brain's anatomy to fix the left frontal lobe.

The third issue evaluates the goals of treatment. The incremental gains that are used in current treatment and social care, although helpful and effective, are far too modest. The best of modern aphasia treatments try to make small restorative or compensatory changes in language behavior. Patients are continually frustrated and disappointed because they are not seeing rapid changes. Furthermore, if there are changes, they are often not the right ones for the patient.

Why do we accept these minor gains? Shouldn't we aim higher and try to cure aphasia? We believe it will be possible.

Why is aphasia therapy as a whole so challenging? Language is the most complex of human cognitive functions, and neither the nature of human language itself nor the brain mechanisms for producing or receiving language are understood. Although there appear to be general principles that hold for language, linguistic observations have had little, if any, impact on the understanding of language disorders or the human brain. Much more is known about the neural circuits underlying sensory and motor function than is known about language function, as they map straightforwardly to the environment. This only magnifies the therapeutic challenge in aphasia.

Animal models have successfully been used to provide information about aphasia. Of course, animals don't use language, but we can use animals to look at the brain's plasticity when it is involved in rehabilitation. One of the earliest studies of stroke recovery in an animal model was done by Michael Merzenich in San Francisco.  Merzenich created experimental lesions in monkeys. But before creating these lesions, he made a map of the monkeys' sensory cortex. He then generated an experimental stroke, causing a small area of damage to the somato-sensory cortex of these animals and, in turn, affecting certain digits. Two months later he remapped the same area. He found that after stroke, there was a tremendous amount of reorganization in the cortical tissue that subserved those fingers (Xerri, Merzenich, Peterson, & Jenkins, 1998).

Randy Nudo followed up Merzenich's study, investigating stroke in the squirrel monkey.  However, Nudo went one step further and taught the monkeys how to do a certain task, thus beginning to address issues having to do with rehabilitation. In the beginning, the monkeys were taught to take food from big buckets. As part of Nudo's therapeutic training, he progressively increased the difficulty of the task by decreasing the size of the buckets. The smaller buckets acted as the rehabilitative device, forcing the monkeys to use their inflexible fingers. When he trained the monkeys differently compared to control groups, he found reorganization again of the motor-cortical map with rehabilitative training (Nudo, Friel, & Delia, 2000). This study relates to the human rehabilitation process; if we can actually use behavioral interventions to change the brain, then we have a future for the biological model.

The Future of Treatment

So what exactly is the future of aphasia treatment? It will comprise two complementary factors. Biological interventions will be used to stimulate or repair the injured brain area, and speech and language treatment will be provided to retrain the new circuitry and integrate it with the preserved, existing tissue. Let's examine each step a little more closely.

Tissue transplantation and electronic prostheses are not yet viable, but may be in coming years. Thus far, transplantation has been accomplished using several different cell types for ischemic injury at several different stages. The most prominent of these trials, using human neurons taken from a cloned embryonal cancer cell line (Trojanowski et al., 1997), has had some success in a rodent model (Borlongan et al., 1998) and has recently been attempted in humans (Spice & Srikameswaran, 1998). Tissue transplantation using neural stem cells might also have a promising role if we can cause new brain structure to develop in the area that is damaged by a stroke. Work in neural prostheses using cortical electrode grids is also in progress around the world.

Pharmacotherapy has not yet fulfilled its promise for aphasia treatment, despite many decades of effort (Linn, 1947; Small, 1994b). Although many studies of aphasia pharmacotherapy have been done, there are not many well-constructed or reliable trials. Bromocriptine, for example, is used in Parkinsonism and helps affect dopamine systems. Although this drug is extremely effective in treating Parkinsonism, it is unclear if it has any direct impact on language and communication ability. Dextro-amphetamine has been tested in a few trials, and may be beneficial (Walker-Batson et al., 1992). There are some trials that used dextro-amphetamine in a more or less controlled fashion. These studies show it works best when it is accompanied by speech and language treatment. In fact, in all cases, pharmacotherapy has been successful only when accompanied by behavioral therapy. Pharmacotherapy alone has never been shown to have any effectiveness.

Finally, we look at the future of speech and language treatment. Although different aphasia treatments are usually considered to be either effective or ineffective in particular settings, they have not generally been thought of as having a potential for harm. Thus, it is perfectly reasonable to try one approach, and if it does not work, to try another, without ever facing a risk of detriment to the patient (other than prolonging recovery). This approach may not be correct.

An aphasia treatment that has the potential to change the brain for the better is likely to have the same potential to change it for worse. That is not true of generally helpful educational strategies, but will be true of carefully constructed therapies to alter brain anatomy and physiology. This radical concept has been studied to a limited degree in the motor system with the notion that some patients develop a "learned nonuse" of a paretic extremity, due to behavioral habits that minimize the use of the extremity.

The Crossroads

The main argument presented here is that aphasia treatment is at a crossroads. Very soon, it will be possible to intervene biologically to replace damaged brain tissue and/or neural transmitters and modulators, and to provide the potential for significant functional recovery. However, we must also be ready to face the behavioral challenge: These neural circuits, damaged and replaced, will need to be integrated not only into a biological organism, but also into a behavioral organism. Further, proper integration into the biological system may require proper behavioral intervention. Given what we know about artificial neural networks in language and aphasia (Harris & Small, 1998; Small, 1994a), it seems likely that transplanted and/or pharmacologically altered natural neural networks will require significant attention to training. A great deal of data exist from the world of modeling to suggest that providing the wrong training to a network can lead both to failures to learn (Elman, 1993) and/or to unlearning of previous material (McCloskey & Cohen, 1989).

Aphasia treatment after biological intervention may thus need to meet new standards-not ones of effectiveness and ineffectiveness, but standards of benefit versus harm. At the present time, a number of different therapeutic methods exist from a wide variety of perspectives (Holland & Forbes, 1993; Small, 1998). Although the efficacy of aphasia treatment itself has been demonstrated (e.g., Robey, 1994; Wertz et al., 1986), treatment success is compared to no treatment. In this new era, aphasia treatments have to be evaluated in terms of both benefit and detriment to biological and behavioral recovery of brain circuits for language (and concomitant functional recovery).

The current options for stroke treatment are limited, the goals too modest, and aphasia treatment is problematical. The solution we propose is to use novel biological treatments to make the brain amenable to more dramatic change in function. However, this will put new responsibilities on clinicians, as speech-language pathology will go through a revolution. The role of the SLP will become even more important. The interventions that will be used will not just be behavioral, but biological as well. Treatment will require a shift from "effective treatment" to specific "beneficial treatments" to achieve particular biological and behavioral goals. This will be of great importance for aphasia treatment because of the complexity of human language, poor understanding of its biology, and limited knowledge about the effects of particular treatments.

The future thus presents both tremendous anticipation and tremendous challenges for aphasia treatment. With careful and successful research, the methodology of our clinical approach may be fundamentally changed for the better. Perhaps we will start looking at aphasia as a syndrome we can cure, rather than one we can simply support, but never cure.

Lauren F. Wineburgh, is a research assistant with Steven Small and Peter Huttenlocher in the Departments of Neurology and Pediatrics at The University of Chicago and at the Brain Research Imaging Center. She performs neuropsychological testing and functional magnetic resonance imaging in adults who had neonatal, perinatal, and early post-natal strokes. Contact her by e-mail at laurenfw@uchicago.edu.

Steven L. Small, is associate professor in the Departments of Neurology and Psychology, a member of the Committees on Neurobiology and Computational Neuroscience at The University of Chicago, and co-directs the University's Brain Research Imaging Center. His research investigates the basic neurobiology and rehabilitation of language disorders and hand motor function. Contact him by e-mail at small@uchicago.edu.

cite as: Wineburgh, L. F.  & Small, S. L. (2004, April 27). Aphasia Treatment at the Crossroads: A Biological Perspective. The ASHA Leader.

References

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Linn, L. (1947). Sodium amytal in treatment of aphasia. Archives of Neurology and Psychiatry, 58, 357-358

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