Basal Ganglia and Thalamic Contributions to Language Function: Insights from A Parallel Distributed Processing Perspective.

Cerebral representations are encoded as patterns of activity involving billions of neurons. Parallel distributed processing (PDP) across these neuronal populations provides the basis for a number of emergent properties: 1) processing occurs and knowledge (long term memories) is stored (as synaptic connection strengths) in exactly the same networks; 2) networks have the capacity for setting into stable attractor states corresponding to concepts, symbols, implicit rules, or data transformations; 3) networks provide the scaffold for the acquisition of knowledge but knowledge is acquired through experience; 4) PDP networks are adept at incorporating the statistical regularities of experience as well as frequency and age of acquisition effects; 5) networks enable content-addressable memory; 6) because knowledge is distributed throughout networks, they exhibit the property of graceful degradation; 7) networks intrinsically provide the capacity for inference. This paper details the features of the basal ganglia and thalamic systems (recurrent and distributed connectivity) that support PDP. The PDP lens and an understanding of the attractor trench dynamics of the basal ganglia provide a natural explanation for the peculiar dysfunctions of Parkinson's disease and the mechanisms by which dopamine deficiency is causal. The PDP lens, coupled with the fact that the basal ganglia of humans bears strong homology to the basal ganglia of lampreys and the central complex of arthropods, reveals that the fundamental function of the basal ganglia is computational and involves the reduction of the vast dimensionality of a complex multi-dimensional array of sensorimotor input into the optimal choice from a small repertoire of behavioral options - the essence of reactive intention (automatic responses to sensory input). There is strong evidence that the sensorimotor basal ganglia make no contributions to cognitive or motor function in humans but can cause serious dysfunction when pathological. It appears that humans, through the course of evolution, have developed cortical capacities (working memory and volitional and reactive attention) for managing sensory input, however complex, that obviate the need for the basal ganglia. The functions of the dorsal tier thalamus, however, even viewed with an understanding of the properties of population encoded representations, remain somewhat more obscure. Possibilities include the enabling of attractor state constellations that optimize function by taking advantage of simultaneous input from multiple cortical areas; selective engagement of cortical representations; and support of the gamma frequency synchrony that enables binding of the multiple network representations that comprise a full concept representation.

Using Radiological Data to Estimate Ischemic Stroke Severity.

BACKGROUND: Risk-adjusted poststroke mortality has been proposed for use as a measure of stroke care quality. Although valid measures of stroke severity (e.g., the National Institutes of Health Stroke Scale [NIHSS]) are not typically available in administrative datasets, radiology reports are often available within electronic health records. We sought to examine whether admission head computed tomography data could be used to estimate stroke severity. MATERIALS AND METHODS: Using chart review data from a cohort of acute ischemic stroke patients (1998-2003), we developed a radiographic measure ([BIS]) of stroke severity in a two-third development set and assessed in a one-third validation set. The retrospective NIHSS was dichotomized as mild/moderate (<10) and severe (≥10). We compared the association of this radiographic score with NIHSS and in-hospital mortality at the patient level. RESULTS: Among 1348 stroke patients, 86.5% had abnormal findings on initial head computed tomography. The c-statistic for the BIS for modeling severe stroke (development, .581; validation, .579) and in-hospital mortality (development, .623; validation, .678) were generated. CONCLUSIONS: Although the c-statistics were only moderate, the BIS provided significant risk stratification information with a 2-variable score. Until administrative data routinely includes a valid measure of stroke severity, radiographic data may provide information for use in risk adjustment.

Body-weight-supported treadmill rehabilitation after stroke.

BACKGROUND: Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. METHODS: We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. RESULTS: At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). CONCLUSIONS: Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

Cognitive effects of treatment of depression with repetitive transcranial magnetic stimulation.

BACKGROUND AND OBJECTIVE: We previously reported a randomized, sham-controlled trial of 5 Hz dorsolateral prefrontal left- and right-side repetitive transcranial magnetic stimulation (rTMS) in 48 participants with a medically refractory major depressive disorder. Depression improved most with right-side cranial stimulation, both rTMS and sham, and to a lesser degree with left rTMS. Because depression is often associated with cognitive impairment, in this study we sought to determine whether our earlier participants had treatment-induced changes in cognition, which cognitive domains (language, executive, visuospatial, verbal episodic memory, attention) were affected, and whether treatment-induced cognitive changes were related either to improvement in depression or to other treatment variables, such as right versus left treatment and rTMS versus sham. METHODS: We used hierarchical regression analyses to determine how variables measured at baseline or associated with treatment affected changes in neuropsychological functions. The variables were neuropsychological function in the 5 domains, severity of depression, change in depression with treatment, rTMS versus sham, laterality of stimulation, and rTMS-laterality interaction. RESULTS: Compared to sham, right rTMS was associated with 1.24 standard deviations greater gain in language function, 1.09 standard deviations greater gain in visuospatial function, and 2.38 standard deviations greater gain in verbal episodic memory than left rTMS. These improvements did not appear to be directly related to the relief from depression. CONCLUSIONS: Our results suggest that disorders of cognition and mood in depression may have different mechanisms, but right rTMS may treat both. We propose potential mechanisms underlying the right-side rTMS effect. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT00711568.

Lecanemab Questions.

The recently published results of the 18-month randomized controlled trial of lecanemab, reporting the efficacy of the drug in slowing the progression of early Alzheimer disease, quickly led to approval by the FDA and widespread acceptance of lecanemab treatment. However, there are a number of matters that deserve further consideration. The success of blinding was not assessed, even as infusion reactions and the cerebral pathology underlying amyloid-related imaging abnormalities could have signaled to many participants that they were on drug, potentially exerting a potent placebo effect. The value of the outcome to participants is not defined in the absolute terms necessary for clinical decision-making, and the difference attributable to lecanemab was between 18% and 46% of estimates of the minimal clinically important difference on the Clinical Dementia Rating Scale Sum of Boxes. The attenuation of change on the Alzheimer's Disease Assessment Scale-Cognitive 14 achieved by lecanemab at 18 months was 50% of that achieved by donepezil at 6 months. Lecanemab treatment imposes a high treatment burden. The fact that the burden commences at the initiation of lecanemab treatment, whereas the benefit accrues years later requires us to take into account value discounting over time, which would significantly reduce the benefit/burden ratio. Finally, treatment with monoclonal antibodies to cerebral amyloid has consistently been associated with progressive cerebral atrophy. At the least, these issues should be raised in treatment discussions with patients. They also suggest a need to very seriously reconsider how we evaluate clinical trial results preparatory to translating them into clinical practice. Some suggestions are provided.

Robot-assisted therapy for long-term upper-limb impairment after stroke.

BACKGROUND: Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. METHODS: In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. RESULTS: At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], -0.23 to 4.58) and worse than that for patients receiving intensive comparison therapy (difference, -0.14 points; 95% CI, -2.94 to 2.65), but the differences were not significant. The results on the Stroke Impact Scale were significantly better for patients receiving robot-assisted therapy than for those receiving usual care (difference, 7.64 points; 95% CI, 2.03 to 13.24). No other treatment comparisons were significant at 12 weeks. Secondary analyses showed that at 36 weeks, robot-assisted therapy significantly improved the Fugl-Meyer score (difference, 2.88 points; 95% CI, 0.57 to 5.18) and the time on the Wolf Motor Function Test (difference, -8.10 seconds; 95% CI, -13.61 to -2.60) as compared with usual care but not with intensive therapy. No serious adverse events were reported. CONCLUSIONS: In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy. In secondary analyses, robot-assisted therapy improved outcomes over 36 weeks as compared with usual care but not with intensive therapy. (ClinicalTrials.gov number, NCT00372411.)

Does exercise tolerance testing at 60 days poststroke predict rehabilitation performance?

OBJECTIVE: To assess the relationship between exercise tolerance test (ETT) performance at 6 weeks poststroke and subsequent performance in a treadmill and overground locomotor training program (LTP). DESIGN: Prospective cohort study. SETTING: Exercise testing laboratory in either a primary care hospital or outpatient clinic. PARTICIPANTS: Community-dwelling individuals (N=469), 54.9±19.0 days poststroke, enrolled in the Locomotor Experience Applied Post-Stroke randomized controlled trial. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: For participants randomly assigned to LTP, the number of sessions needed to attain the training goal of 20 minutes of treadmill stepping was determined. Regression analyses determined the contribution of ETT performance (cycling duration), age, and 6-minute walk test (6MWT) distance to attainment of the stepping duration goal. RESULTS: Age, 6MWT, and ETT performance individually accounted for 10.74%, 10.82%, and 10.76%, respectively, of the variance in the number of sessions needed to attain 20 minutes of stepping. When age and 6MWT were included in the model, the additional contribution of ETT performance was rendered nonsignificant (P=.150). CONCLUSIONS: To the extent that ETT performance can be viewed as a measure of cardiovascular fitness rather than neurologic impairment, cardiovascular fitness at the time of the ETT did not make a significant unique contribution to the number of sessions needed to achieve 20 minutes of stepping. The 6MWT, which involves less intensive exercise than the ETT and therefore is likely to be predominantly affected by neurologic impairment and muscular condition, appeared to account for as much variance as the ETT.

Management of chronic non-cancer pain: a framework.

Aim: Since publication of the CDC 2016 Guideline, opioid-related mortality in the USA has doubled and a crisis has developed among the 15-20 million Americans with chronic, moderate-to-severe, noncancer pain. Our aim was to develop a comprehensive alternative approach to management of chronic pain. Methods: Analytic review of the clinical literature. Results: Published science provides a solid framework for the management of chronic non-cancer pain, detailed here, even as it leaves many knowledge gaps, which we fill with insights from clinical experience. Conclusion: There is a sufficient basis in science and in clinical experience to achieve adequate control of chronic pain in nearly all patients in a way that adequately balances benefits and potential harms.

Opioid-related mortality in the USA continues to increase rapidly despite the decline in opioid prescriptions achieved by the CDC 2016 Guideline. This Guideline has also created a crisis among the 15­20 million Americans with chronic, moderate-to-severe, noncancer pain. We offer a detailed framework for an alternative approach to management of chronic pain. We also offer some suggestions for solving the problem of illicit drug use, which now accounts for 84% of opioid-related deaths. To the extent possible, we have relied upon published science. However, we also identify many knowledge gaps that we address with insights from clinical experience and thousands of interactions with patients. These knowledge gaps will ultimately need to be addressed by further research.

The Challenge of Achieving Greater Generalization in Phonological Treatment of Aphasia.

Background: Stimulus selection is important to anomia treatment because similarity between trained and untrained words in the mental lexicon may influence treatment generalization. We focused on phonological similarity between trained and untrained words from a clinical trial of Phonomotor Treatment (PMT) that showed gains in confrontation naming accuracy of untrained words post-treatment. One way to capture the amount of similarity between the trained and untrained words is to consider the phonological network path distance between words. We posited that the distance between trained and untrained words in a phonological network could account for the improvement in confrontation naming accuracy post-treatment. Aim: To define the phonological network distance between trained and untrained words that influences change in confrontation naming accuracy post-treatment. Methods and procedures: We retrospectively analyzed data from 28 people with aphasia who received PMT as part of a clinical trial. Participants completed confrontation naming (baseline, post-treatment, and 3-months post-treatment) of words varying in phonological distance to the treatment stimuli. We used a phonological network to calculate the average shortest path length (ASPL), defined by number of phoneme differences, between an untrained word and all trained words. We used mixed effects regression models to predict change in confrontation naming accuracy of untrained words post-treatment from ASPL. Several post-hoc analyses were also conducted. Outcomes and results: We found no effect of ASPL on change in confrontation naming accuracy of untrained words immediately post- and 3-months post-treatment. However, post-hoc analyses indicated significant subject heterogeneity and limitations in observable path distance between trained and untrained words. Conclusion: Despite the clinical trial report that confrontation naming of untrained words improved after PMT, we found no overall effect of ASPL on the amount of improvement. We discuss further investigation of the entire domain of phonological sequence knowledge (the phonological sequence knowledge landscape) and its influence on treatment generalization, and the potential importance of identifying predictors of treatment response to enhance the effects of treatment generalization.

Emotional and Neuropsychiatric Disorders Associated with Alzheimer's Disease.

Alzheimer's disease is associated with impairments in emotional communication including comprehension and production of facial emotional expressions, comprehension of affective prosody, and alexithymia. It is also associated with disorders of emotional experience including mood disorders (depression and anxiety), agitation/aggression, and psychosis. Agitation/aggression and psychosis are particularly disruptive, are associated with earlier institutionalization, and pose a major challenge to institutional management. Treatment of disorders of emotional experience has been primarily pharmacologic (reviewed here in detail) and has relied heavily on antipsychotic medications despite the small effect sizes demonstrated in a large number of randomized controlled trials and the prevalence of serious side effects associated with these drugs. Recent studies suggest that treatment with pimavanserin, an antipsychotic without activity at dopamine receptors, may represent an important advance for treatment of psychotic manifestations, even as the drug appears to pose significant risk. Dextromethorphan/quinidine may represent an important advance in the treatment of agitation/aggression. There is also compelling evidence that sleep disorders, which are common among patients with Alzheimer's disease and are readily treatable, may potentiate psychotic manifestations and agitation/aggression, but further studies are needed.

Language and Aphasias.

PURPOSE OF REVIEW: This article reveals how it is possible for a brain composed of 100 billion highly interconnected, lipid-encased, reticular electrochemical devices to support complex functions such as language and how language disorders can be understood as a reflection of degradation of one or more domains of knowledge. RECENT FINDINGS: Ongoing research, building on landmark work regarding parallel distributed processing (PDP), provides the basis for understanding cognitive functions as a manifestation of the activity of populations of millions or billions of neurons in various highly interconnected networks. Population encoding networks have the following intrinsic properties that provide an orderly explanation for normal and degraded language: (1) a capacity for settling into stable "attractor" states; (2) processing occurs in and knowledge (long-term memories) is stored in exactly the same network; (3) a capacity for incorporating statistical regularities of experience, frequency, and age of acquisition; (4) support of content-addressable memory; and (5) graceful degradation, such that lesions increase the probability of errors but do not fundamentally transform network operations. Knowledge in parallel distributed processing networks resides in the strength of connections between units (synapses in the brain). Aphasia, whether stemming from stroke or dementing disorders, can be understood in terms of the degradation of one or more domains of knowledge. SUMMARY: Understanding the brain as a population encoding machine incorporating vast interconnectivity provides an orderly explanation for language function, both normal and abnormal.

Treatment of disorders of emotional comprehension, expression, and emotional semantics.

Neurological disease can impair emotional communication by several means: damaging the networks important in understanding the meaning of emotional stimuli (emotional semantics); damaging networks important in the perceptual recognition and production of emotional stimuli, and damaging the connections between networks supporting emotional semantics and recognition/production networks. Disorders of emotional expression, comprehension, and emotional semantics may improve with pharmacological or behavioral treatments. Pharmacological treatments can be used to redress naturally occurring or disease-related alterations in the computational properties of target neural systems. No drug treatment can replace a loss of cerebral knowledge related to the pathological loss of neural connectivity. Behavioral treatments that benefit either comprehension or expression of specific emotions may be of value if these emotions are particularly important in enabling human social interaction. However, behavioral treatments that achieve generalization, that is, improve performance with untrained exemplars and in daily life, are much to be preferred, even as they pose the greatest methodological challenges. This chapter will discuss possible mechanisms of generalization and then review what is known about the treatment of expressive and receptive affective aprosodia, deficits in recognition of facial emotions, and pseudobulbar affect. The final section of the chapter is devoted to a discussion of three disorders of emotional semantics, apathy, alexithymia, and impaired empathy.

Neural mechanisms of emotions, alexithymia, and depression.

This chapter brings the powerful conceptual tools of the science of parallel distributed processing (PDP) to bear on the cognitive neuroscience of emotions discussed in this book. Cerebral representations are encoded as patterns of activity involving billions of neurons. PDP across these neuronal populations provides the basis for a number of emergent properties: (1) processing occurs and knowledge (long term memories) is stored (as synaptic connection strengths) in exactly the same networks; (2) networks have the capacity for setting into stable attractor states corresponding to concepts, symbols, implicit rules, or data transformations; (3) networks provide the scaffold for the acquisition of knowledge, but knowledge is acquired through experience; (4) PDP networks are adept at incorporating the statistical regularities of experience as well as frequency and age of acquisition effects; (5) networks enable content-addressable memory; (6) because knowledge is distributed throughout networks, they exhibit the property of graceful degradation; (7) networks intrinsically provide the capacity for inference. With this perspective, I propose a new model of emotional function that reasonably accounts for the effects of focal lesions at various points (insula, orbitofrontal cortex, convexity cortex, and intervening white matter) due to stroke, trauma, surgery, and degenerative disease, as reflected in disorders of affective prosody, facial emotional comprehension and expression, emotional behavior, and personality. I consider a modification of the James Lange theory that takes into account the role of a lifetime of subjective knowledge acquisition by the orbitofrontal cortex. Alexithymia is conceptualized as a disorder of the insula/orbitofrontal cortex/dorsolateral prefrontal cortex (DL-PFC) system, the function of which can be disrupted by degradation of knowledge at a number of different locations. Finally, I consider the possibility that depression reflects pathological learning involving the medial and lateral orbitofrontal cortices such that there is a pathologic engagement of the two regions, as suggested by Rolls. I conclude with a consideration of the peculiar responsivity of depression to serotonergic and noradrenergic agents, as well as to surgical orbitofrontal undercutting, and what that might be telling us about the mechanisms of depression and its treatment.

Opioids and Chronic Pain: An Analytic Review of the Clinical Evidence.

We conducted an analytic review of the clinical scientific literature bearing on the use of opioids for treatment of chronic non-cancer pain in the United States. There is substantial, albeit not definitive, scientific evidence of the effectiveness of opioids in treating pain and of high variability in opioid dose requirements and side effects. The estimated risk of death from opioid treatment involving doses above 100 MMED is ~0.25%/year. Multiple large studies refute the concept that short-term use of opioids to treat acute pain predisposes to development of opioid use disorder. The prevalence of opioid use disorder associated with prescription opioids is likely <3%. Morbidity, mortality, and financial costs of inadequate treatment of the 18 million Americans with moderate to severe chronic pain are high. Because of the absence of comparative effectiveness studies, there are no scientific grounds for considering alternative non-pharmacologic treatments as an adequate substitute for opioid therapy but these treatments might serve to augment opioid therapy, thereby reducing dosage. There are reasons to question the ostensible risks of co-prescription of opioids and benzodiazepines. As the causes of the opioid crisis have come into focus, it has become clear that the crisis resides predominantly in the streets and that efforts to curtail it by constraining opioid treatment in the clinic are unlikely to succeed.

Right and left dorsolateral pre-frontal rTMS treatment of refractory depression: a randomized, sham-controlled trial.

We conducted a prospective, randomized, sham-controlled, double blind, parallel group study of right or left pre-frontal rTMS in 48 subjects with medication-resistant depression. Two thousand (50x8-s trains of 5Hz) stimuli at MEP threshold were delivered each weekday for 2weeks. We employed a sham coil and simultaneous electrical stimulation of the scalp to simulate rTMS. Mean (+/-S.D.) reductions in the HAMD-24 from baseline to 3-months were not significantly different between rTMS and sham treatment groups. However, right cranial stimulation (sham or rTMS) was significantly more effective than left cranial stimulation (sham or rTMS) (P=0.012). Mean (+/-S.D.) reductions in the HAMD from baseline to 3 months were: left: 28.1 (+/-5.36) to 19.2 (+/-11.2); and right 27.2 (+/-4.2) to 11.5 (+/-9.4). Left rTMS achieved a reduction in HAMD 9.5 points greater than that achieved by left sham, a benefit greater than that reported in a recent multi-center Phase III trial of rTMS (O'Reardon et al., 2007), albeit not statistically significant. These results suggest that somatosensory stimuli that repeatedly engage the left hemisphere may be important to the achievement of therapeutic effect.

Neural Population Dynamics and Cognitive Function.

Representations in the brain are encoded as patterns of activity of large populations of neurons. The science of population encoded representations, also known as parallel distributed processing (PDP), achieves neurological verisimilitude and has been able to account for a large number of cognitive phenomena in normal people, including reaction times (and reading latencies), stimulus recognition, the effect of stimulus salience on attention, perceptual invariance, simultaneous egocentric and allocentric visual processing, top-down/bottom-up processing, language errors, the effect of statistical regularities of experience, frequency, and age of acquisition, instantiation of rules and symbols, content addressable memory and the capacity for pattern completion, preservation of function in the face of noisy or distorted input, inference, parallel constraint satisfaction, the binding problem and gamma coherence, principles of hippocampal function, the location of knowledge in the brain, limitations in the scope and depth of knowledge acquired through experience, and Piagetian stages of cognitive development. PDP studies have been able to provide a coherent account for impairment in a variety of language functions resulting from stroke or dementia in a large number of languages and the phenomenon of graceful degradation observed in such studies. They have also made important contributions to our understanding of attention (including hemispatial neglect), emotional function, executive function, motor planning, visual processing, decision making, and neuroeconomics. The relationship of neural network population dynamics to electroencephalographic rhythms is starting to emerge. Nevertheless, PDP approaches have scarcely penetrated major areas of study of cognition, including neuropsychology and cognitive neuropsychology, as well as much of cognitive psychology. This article attempts to provide an overview of PDP principles and applications that addresses a broader audience.

Errorless practice as a possible adjuvant to donepezil in Alzheimer's disease.

Six individuals with probable Alzheimer's disease (AD) participated in a phase 1 study employing a repeated measures, parallel baseline design testing the hypothesis that error-free experience during word production practice combined with an acetyl cholinesterase inhibitor would improve confrontation naming ability. While acetyl cholinesterase inhibitors are safe and delay cognition decline associated with AD, improvement over baseline cognition is less evident; clinically significant cognitive deficits persist and progress. Both animal and clinical research strongly implicate acetylcholine in learning, a form of neuroplasticity. In clinical practice, however, people with AD are given cholinergic medications without concomitant systematic/targeted retraining. In this study six participants with probable AD and taking donepezil participated in targeted word production practice using an errorless learning strategy. Results showed that combining behavioral enrichment training and an acetyl cholinesterase inhibitor resulted in significant improvements in verbal confrontation naming of trained items for three of six participants. Differences in baseline dementia severity, living conditions, and medications may have influenced the training response. Detection of substantial treatment effects in 50% of subjects suggests further language treatment studies in AD in combination with an acetyl cholinesterase inhibitor are warranted and provide useful information on inclusion/exclusion criteria for use in subsequent studies.

Phonomotor Versus Semantic Feature Analysis Treatment for Anomia in 58 Persons With Aphasia: A Randomized Controlled Trial.

Purpose The ultimate goal of anomia treatment should be to achieve gains in exemplars trained in the therapy session, as well as generalization to untrained exemplars and contexts. The purpose of this study was to test the efficacy of phonomotor treatment, a treatment focusing on enhancement of phonological sequence knowledge, against semantic feature analysis (SFA), a lexical-semantic therapy that focuses on enhancement of semantic knowledge and is well known and commonly used to treat anomia in aphasia. Method In a between-groups randomized controlled trial, 58 persons with aphasia characterized by anomia and phonological dysfunction were randomized to receive 56-60 hr of intensively delivered treatment over 6 weeks with testing pretreatment, posttreatment, and 3 months posttreatment termination. Results There was no significant between-groups difference on the primary outcome measure (untrained nouns phonologically and semantically unrelated to each treatment) at 3 months posttreatment. Significant within-group immediately posttreatment acquisition effects for confrontation naming and response latency were observed for both groups. Treatment-specific generalization effects for confrontation naming were observed for both groups immediately and 3 months posttreatment; a significant decrease in response latency was observed at both time points for the SFA group only. Finally, significant within-group differences on the Comprehensive Aphasia Test-Disability Questionnaire (Swinburn, Porter, & Howard, 2004) were observed both immediately and 3 months posttreatment for the SFA group, and significant within-group differences on the Functional Outcome Questionnaire (Glueckauf et al., 2003) were found for both treatment groups 3 months posttreatment. Discussion Our results are consistent with those of prior studies that have shown that SFA treatment and phonomotor treatment generalize to untrained words that share features (semantic or phonological sequence, respectively) with the training set. However, they show that there is no significant generalization to untrained words that do not share semantic features or phonological sequence features.

Bilateral arm training with rhythmic auditory cueing in chronic stroke: not always efficacious.

OBJECTIVE: Bilateral arm training with rhythmic auditory cueing (BATRAC) has been reported to be efficacious in promoting upper-extremity (UE) recovery in chronic stroke. We tested a modified form of BATRAC (modBATRAC) in a new group of participants with a condensed treatment regime to determine whether we could replicate these reported results. METHODS: Fourteen subjects with chronic stroke completed 2 weeks of 2.25 hours per session, 4 sessions per week of modBATRAC. RESULTS: No significant changes were observed in UE Fugl-Meyer or Wolf Motor Function Test scores. Subjects did report increased paretic UE use on the Motor Activity Log (mean change, 0.50; SD = 0.70). CONCLUSIONS: The results of this study offer only partial support for the efficacy of modBATRAC. As in previous trials, modBATRAC facilitated increased use of the paretic arm, but unlike previous trials, it did not increase motor performance. These differences may reflect a more temporally condensed training schedule and less impaired patients.

Phoneme-based rehabilitation of anomia in aphasia.

This study investigated the effects of phonologic treatment for anomia in aphasia. We proposed that if treatment were directed at the level of the phonologic processor, opportunities for naming via a phonological route, as opposed to a strictly whole word route, would be enhanced, thereby improving naming. The participants, ten people with anomia and aphasia due to left hemisphere stroke, received 96 h of phoneme based treatment in 12 weeks. To learn if treatment improved naming, a single-subject, repeated probe design with replication was employed. The primary outcome measure was confrontation naming. Secondary outcome measures included phonologic production, nonword repetition and discourse production. Results suggest a positive treatment effect (confrontation naming), improvements in phonologic production and nonword repetition, and generalization to discourse production. When tested 3 months after the completion of treatment the effects appeared to be maintained.