Treatment of Poststroke Aphasia
Treatment of Poststroke Aphasia
Neuroscience research on language and aphasia has expanded rapidly in recent decades, largely due to advances in neuroimaging and brain stimulation (also called neuromodulation) techniques. Insights from this research about the brain networks disrupted in aphasia and the subsequent reorganization of these networks over the course of recovery has driven interest in biologically based interventions for aphasia, including medications and brain stimulation.
The basic rationale for the use of medications for aphasia is that strokes disrupt neurotransmitter pathways, and enhancement of neurotransmitter availability in partially disrupted pathways may mitigate deficits related to the disruption. Several medications have been studied in single cases, open-label studies, or small randomized controlled trials, either alone or in combination with SLT. The results have been promising for some medications, including piracetam (, although see ), acetylcholinesterase inhibitors, and memantine. In general, these studies have been too small in size or too crude in measuring aphasia outcomes to draw firm conclusions, and larger more definitive trials are needed. Additional studies are also needed to examine which patients benefit most from medications, the ideal timing of administration (e.g., during the acute or chronic phases), and the neurobiological basis of any beneficial effects.
Another new class of experimental treatments for aphasia attempts to focally modulate neuronal activity in a beneficial way. The aim of these approaches is either to directly improve language functions or to enhance plasticity, which may enable more successful natural recovery from aphasia or enhance learning and retention during SLT. The most common techniques use noninvasive mild direct current electrical stimulation (termed transcranial direct current stimulation [tDCS]) or repetitive magnetic pulses (transcranial magnetic stimulation [TMS]). Although the two techniques differ substantially in their characteristics and mechanisms, both can induce localized excitation or inhibition of neuronal populations that can last for minutes to hours after a short session, and both can enhance learning during motor or language training.
Because both techniques induce focal neuromodulation, principled use of either tDCS or TMS for aphasia treatment requires a reasonable understanding of the neurobiological basis of aphasia recovery to guide selection of stimulation targets. The first neuromodulation studies for aphasia adopted a theoretical framework from the motor system often referred to as interhemispheric inhibition. This theory posits that homotopic areas of the two hemispheres compete with one another via transcallosal inhibitory fibers, and that a focal brain injury to one hemisphere releases the uninjured hemisphere from inhibition, causing it to overly suppress the injured side. Because optimal language recovery is thought to occur through restitution of function and reorganization within the injured left hemisphere, the theory of interhemispheric inhibition predicts that overinhibition from the right hemisphere limits successful left-hemisphere recovery in aphasia. Based on this theory, recovery from aphasia could be improved by enhancement of left-hemisphere activity, inhibition of the right hemisphere, or both. Indeed, most of the TMS and tDCS studies in aphasia to date have used one of these strategies either alone or in combination with SLT, often (but not always) based on the theory of interhemispheric inhibition. These studies, mainly observational series and small randomized clinical trials, have shown some beneficial effects of TMS or tDCS in both subacute and chronic aphasia. Benefits on several different language functions have been found, and in some studies, these effects last for months after a few weeks of treatment, even during the chronic phase when lasting effects of SLT without ongoing treatment are unusual. Insufficient evidence is available at this time to support one particular strategy of neuromodulation over others.
Although these early findings regarding neuromodulation have generated a great deal of excitement in the aphasia community, the studies have been too small to draw firm conclusions, and not all studies have yielded positive results. Further, the trials to date have tended not to use functional communication outcomes, making the clinical relevance of the effects somewhat uncertain. At the same time, the theoretical framework of interhemispheric inhibition that many early studies were based on has fallen somewhat out of favor. Newer theories of aphasia recovery are more nuanced with regard to the role of the right hemisphere, posing mixed mechanisms of reorganization, some adaptive, and some potentially maladaptive, depending on the particular region, the specific language function in question, and the characteristics of the individual such as the premorbid lateralization of language and the size of the stroke. Other theories have posited that there is no reorganization in the right hemisphere per se, but only increased reliance on domain general cognitive systems in the right hemisphere in people with aphasia.
Because the individual differences between patients with aphasia are so large, both anatomically and behaviorally, it is very likely that neurobiological reorganization differs between individuals. Understanding these individual differences will be key to developing maximally effective neuromodulatory treatments. As such, a great deal more work is needed to understand longitudinal changes in the organization of brain networks after strokes causing aphasia, and the relationships between these changes and behavioral recovery. Additional work is needed to understand the mechanism of long-term effects of TMS and tDCS, to delineate the population most likely to benefit from treatment, and to identify the ideal dose and timing of treatment, the ideal pairing between particular stimulation paradigms and SLT approaches, and the brain sites that provide the best response. The optimal approach likely varies from individual to individual, depending on stroke location or behavioral deficits. Collection of detailed behavioral and neurobiological outcome measures in neuromodulation trials will be essential in gaining a better understanding of the mechanisms of these treatments and how individual differences relate to any beneficial effects. This information, along with the development of other neuromodulatory techniques that are in early phases of human subjects testing, including high-intensity red light and focused ultrasound, has the potential to lead to more effective and long-lasting treatments for aphasia.
Interesting Developments in the Therapeutic Pipeline
Neuroscience research on language and aphasia has expanded rapidly in recent decades, largely due to advances in neuroimaging and brain stimulation (also called neuromodulation) techniques. Insights from this research about the brain networks disrupted in aphasia and the subsequent reorganization of these networks over the course of recovery has driven interest in biologically based interventions for aphasia, including medications and brain stimulation.
The basic rationale for the use of medications for aphasia is that strokes disrupt neurotransmitter pathways, and enhancement of neurotransmitter availability in partially disrupted pathways may mitigate deficits related to the disruption. Several medications have been studied in single cases, open-label studies, or small randomized controlled trials, either alone or in combination with SLT. The results have been promising for some medications, including piracetam (, although see ), acetylcholinesterase inhibitors, and memantine. In general, these studies have been too small in size or too crude in measuring aphasia outcomes to draw firm conclusions, and larger more definitive trials are needed. Additional studies are also needed to examine which patients benefit most from medications, the ideal timing of administration (e.g., during the acute or chronic phases), and the neurobiological basis of any beneficial effects.
Another new class of experimental treatments for aphasia attempts to focally modulate neuronal activity in a beneficial way. The aim of these approaches is either to directly improve language functions or to enhance plasticity, which may enable more successful natural recovery from aphasia or enhance learning and retention during SLT. The most common techniques use noninvasive mild direct current electrical stimulation (termed transcranial direct current stimulation [tDCS]) or repetitive magnetic pulses (transcranial magnetic stimulation [TMS]). Although the two techniques differ substantially in their characteristics and mechanisms, both can induce localized excitation or inhibition of neuronal populations that can last for minutes to hours after a short session, and both can enhance learning during motor or language training.
Because both techniques induce focal neuromodulation, principled use of either tDCS or TMS for aphasia treatment requires a reasonable understanding of the neurobiological basis of aphasia recovery to guide selection of stimulation targets. The first neuromodulation studies for aphasia adopted a theoretical framework from the motor system often referred to as interhemispheric inhibition. This theory posits that homotopic areas of the two hemispheres compete with one another via transcallosal inhibitory fibers, and that a focal brain injury to one hemisphere releases the uninjured hemisphere from inhibition, causing it to overly suppress the injured side. Because optimal language recovery is thought to occur through restitution of function and reorganization within the injured left hemisphere, the theory of interhemispheric inhibition predicts that overinhibition from the right hemisphere limits successful left-hemisphere recovery in aphasia. Based on this theory, recovery from aphasia could be improved by enhancement of left-hemisphere activity, inhibition of the right hemisphere, or both. Indeed, most of the TMS and tDCS studies in aphasia to date have used one of these strategies either alone or in combination with SLT, often (but not always) based on the theory of interhemispheric inhibition. These studies, mainly observational series and small randomized clinical trials, have shown some beneficial effects of TMS or tDCS in both subacute and chronic aphasia. Benefits on several different language functions have been found, and in some studies, these effects last for months after a few weeks of treatment, even during the chronic phase when lasting effects of SLT without ongoing treatment are unusual. Insufficient evidence is available at this time to support one particular strategy of neuromodulation over others.
Although these early findings regarding neuromodulation have generated a great deal of excitement in the aphasia community, the studies have been too small to draw firm conclusions, and not all studies have yielded positive results. Further, the trials to date have tended not to use functional communication outcomes, making the clinical relevance of the effects somewhat uncertain. At the same time, the theoretical framework of interhemispheric inhibition that many early studies were based on has fallen somewhat out of favor. Newer theories of aphasia recovery are more nuanced with regard to the role of the right hemisphere, posing mixed mechanisms of reorganization, some adaptive, and some potentially maladaptive, depending on the particular region, the specific language function in question, and the characteristics of the individual such as the premorbid lateralization of language and the size of the stroke. Other theories have posited that there is no reorganization in the right hemisphere per se, but only increased reliance on domain general cognitive systems in the right hemisphere in people with aphasia.
Because the individual differences between patients with aphasia are so large, both anatomically and behaviorally, it is very likely that neurobiological reorganization differs between individuals. Understanding these individual differences will be key to developing maximally effective neuromodulatory treatments. As such, a great deal more work is needed to understand longitudinal changes in the organization of brain networks after strokes causing aphasia, and the relationships between these changes and behavioral recovery. Additional work is needed to understand the mechanism of long-term effects of TMS and tDCS, to delineate the population most likely to benefit from treatment, and to identify the ideal dose and timing of treatment, the ideal pairing between particular stimulation paradigms and SLT approaches, and the brain sites that provide the best response. The optimal approach likely varies from individual to individual, depending on stroke location or behavioral deficits. Collection of detailed behavioral and neurobiological outcome measures in neuromodulation trials will be essential in gaining a better understanding of the mechanisms of these treatments and how individual differences relate to any beneficial effects. This information, along with the development of other neuromodulatory techniques that are in early phases of human subjects testing, including high-intensity red light and focused ultrasound, has the potential to lead to more effective and long-lasting treatments for aphasia.