Transfer of learning: Analysis of dose-response functions from a large-scale, online, cognitive training dataset.

Fundamental to the efficacy of cognitive training (CT) is its dose. Here we used the power and breadth afforded by a large dataset to measure precisely dose-response (D-R) functions for CT and to examine the generality of their magnitude and form. The present observational study involved 107,000 users of Lumosity, a commercial program comprising computer games designed to provide CT over the internet. In addition to training with Lumosity games, these users took an online battery of cognitive assessments (NeuroCognitive Performance Test, NCPT) on two or more occasions separated by at least 10 weeks. Changes in performance on the NCPT between the first and second assessments were examined as a function of the amount of intervening gameplay. The resulting D-R functions were obtained both for overall performance on the NCPT and performance on its eight subtests. Also examined were differences between D-R functions from demographic groups defined by age, gender, and education. Monotonically increasing D-R functions, well fit by an exponential approach to an asymptote, were found consistently for overall performance on the NCPT, performance on seven of the eight subtests, and at each level of age, education, and gender. By examining how individual parameters of the D-R functions varied across subtests and groups, it was possible to measure separately changes in the effects on NCPT performance of 1) transfer from CT and 2) direct practice due to repeated testing. The impact of both transfer and direct practice varied across subtests. In contrast, while the effects of direct practice diminished with age, those of transfer remained constant. Besides its implications for CT by older adults, this latter finding suggests that direct practice and transfer do not involve identical learning processes, with transfer being limited to learning processes that remain constant across the adult lifespan.

Perceptions of Brain Training: Public Expectations of Cognitive Benefits From Popular Activities.

Many popular activities are thought by the general public to improve cognitive function. Such expectations can influence how often people engage in these activities, as well as the scientific evaluation of their putative cognitive benefits, e.g., via placebo effects. Here, we gathered survey data about the public's perceptions of nine different activities commonly thought to be cognitively stimulating, including "brain-training" games. Information was collected about the degree to which participants thought each activity was beneficial for improving cognitive function and how often they engaged in each activity. The patterns of correlation between ratings reveal details about the perception of cognitive benefits and its relation to engagement. They suggest that participants varied with respect to an overarching perception of the entire set of activities, which were perceived also as divided into three clusters. Frequency of engagement and perceived cognitive benefits were positively correlated across participants for each activity considered individually. But, when the activities were compared, the magnitude of their perceived benefits was not a good predictor of their frequency of engagement (and vice versa). Though small, there were systematic demographic differences. Women were more optimistic than men about cognitive benefits. Individual participants differed in the range of their ratings of benefit across activities, and these ranges were greater for younger than older participants, suggesting that perceptions of benefit are more differentiated among the young. Besides contributing to a better understanding of public expectations of cognitive benefits, the findings of this study are relevant to the critical evaluation of such benefits. Our survey can be viewed as providing an interface between expectations held by the general public and the design of studies examining the efficacy of cognitive training. The type of information it provides could be used in the selection of activities performed by an active control group, so that control activities match the treatment intervention as closely as possible with respect to such expectations.

Computerized Cognitive Training by Healthy Older and Younger Adults: Age Comparisons of Overall Efficacy and Selective Effects on Cognition.

Among the non-pharmacological methods under development for maintaining cognitive function across the lifespan is computerized cognitive training (CCT). There has been considerable interest in using CCT to slow or remediate age-related cognitive decline, both normal and pathological. Toward these ends, it would be useful to know how the effects of CCT on cognitive function vary over the course of normal cognitive aging. Are there changes in either 1) the overall efficacy of CCT or 2) which cognitive faculties are affected? To address these two questions, we reanalyzed results from a large online study by Hardy et al. (1) of 4,715 adults between 18 and 80 that examined effects of CCT on both a neuropsychological test battery and self-reported ratings of cognition and affect in daily living. Combined across all participants, Hardy et al. found greater improvement on both types of assessment following 10 weeks of CCT with the commercial program Lumosity, as compared to practice with a control activity involving computerized crossword puzzles. The present study compared the size of these effects on the older (50-80) and younger (18-49) participants. To address the question of overall efficacy, we examined CCT effects (treatment minus control) on overall performance of the test battery and mean rating. No significant difference on either measure was found between the two age cohorts. To address the question of whether the same magnitude of overall effects on both age cohorts was due to equivalent effects on the same set of underlying cognitive functions, we examined the patterns of CCT effects across individual subtests and rated items. These patterns did not differ significantly between the two age cohorts. Our findings suggest that benefits from CCT can occur to a similar degree and in a similar way across an extended part of the adult lifespan. Moreover, the overall effects of CCT delivered over the internet were of the same small to medium size as those typically found in the lab or clinic. Besides improving access and reducing the cost of CCT for older adults, delivery over the internet makes long-term training more practicable, which could potentially yield larger benefits.

Point pressure sensitivity in early stage Parkinson's disease.

A number of sensory changes occur in the earliest stages of Parkinson's disease (PD), some of which precede the expression of the classic motor phenotype by years (e.g., olfactory dysfunction). Whether point pressure sensitivity (PPS), a cutaneous measure of light touch mediated by myelinated Aß fibers, is altered in early PD is not clear. Prior studies on this point are contradictory and are based on non-forced-choice threshold tests that confound the sensitivity measure with the response criterion. While α-synuclein pathology, a defining feature of PD, is present in the skin of PD patients, it is restricted to unmyelinated nerve fibers, suggesting PPS may be spared in this disease. We determined PPS thresholds using a state-of-the-art forced-choice staircase threshold test paradigm in 29 early stage PD patients and 29 matched controls at 11 body sites: the center of the forehead and the left and right forearms, index fingers, palms, medial soles of the feet, and plantar halluces. The patients were tested, in counterbalanced sessions, both on and off dopamine-related medications (DRMs). PPS was not influenced by PD and did not correlate with DRM l-DOPA equivalents, scores on the Unified Parkinson's Disease Rating Scale, side of the major motor disturbances, or SPECT imaging of the striatal dopamine transporter, as measured by technetium-99m TRODAT. However, PPS thresholds were lower on the left than on the right side of the body (p=0.008) and on the upper extremities relative to the toes and feet (ps<0.0001). Positive correlations were evident among the thresholds obtained across all body sectors, even though disparate regions of the body differed in terms of absolute sensitivity. This study indicates that PPS is not influenced in early stage PD regardless of whether patients are on or off DRMs.

Taste function in early stage treated and untreated Parkinson's disease.

Since brain stem regions associated with early Parkinson's disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated whole-mouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue. The PD cohort was tested both on and off dopamine-related medications in counterbalanced test sessions. While whole-mouth taste identification test scores for all stimuli were, on average, nominally lower for the PD patients than for the controls, a trend in the opposite direction was noted for the intensity ratings at the lower stimulus concentrations for all stimuli except caffeine. Moreover, regional testing found that PD subjects tended to rate the stimuli, relative to the controls, as more intense on the anterior tongue and less intense on the posterior tongue. No significant associations were evident between taste test scores and UPDRS scores, L-DOPA medication equivalency values, or [(99m)Tc]TRODAT-1 SPECT imaging of dopamine transporter uptake within the striatum and associated regions. Our findings suggest that suprathreshold measures of taste function are influenced by PD and that this disease differentially influences taste function on anterior (CN VII) and posterior (CN IX) tongue regions. Conceivably PD-related damage to CN IX releases central inhibition on CN VII at the level of the brainstem, resulting in enhanced taste intensity on the anterior tongue.

Suprathreshold odor intensity perception in early-stage Parkinson's disease.

BACKGROUND: Whether Parkinson's disease (PD) influences suprathreshold changes in perceived odor intensity is unknown. In patients with Alzheimer's disease, patients with schizophrenia, and the elderly, such perception is reportedly normal. If generally true, this could reflect a core element of the olfactory system insulated to some degree from age- and disease-related pathological conditions. METHODS: Odor intensity ratings for pentyl acetate were obtained from 29 early-stage PD patients when on and off dopamine-related medications (DRMs) and from 29 matched controls. RESULTS: The ratings were significantly attenuated at the higher odorant concentrations, with the degree of attenuation associated with overall olfactory dysfunction. Ratings were higher on the right than on the left side of the nose of both patients and controls. No associations with DRMs, Unified Parkinson's Disease Rating Scale (UPDRS) scores, or striatal dopamine transporter imaging were found. CONCLUSIONS: Parkinson's disease (PD) influences suprathreshold estimates of perceived odor intensity, negating the notion that such perception might be spared in this disease. No association with dopaminergic processes was apparent.

Profound olfactory dysfunction in myasthenia gravis.

In this study we demonstrate that myasthenia gravis, an autoimmune disease strongly identified with deficient acetylcholine receptor transmission at the post-synaptic neuromuscular junction, is accompanied by a profound loss of olfactory function. Twenty-seven MG patients, 27 matched healthy controls, and 11 patients with polymiositis, a disease with peripheral neuromuscular symptoms analogous to myasthenia gravis with no known central nervous system involvement, were tested. All were administered the University of Pennsylvania Smell Identification Test (UPSIT) and the Picture Identification Test (PIT), a test analogous in content and form to the UPSIT designed to control for non-olfactory cognitive confounds. The UPSIT scores of the myasthenia gravis patients were markedly lower than those of the age- and sex-matched normal controls [respective means (SDs) =20.15 (6.40) & 35.67 (4.95); p<0.0001], as well as those of the polymiositis patients who scored slightly below the normal range [33.30 (1.42); p<0.0001]. The latter finding, along with direct monitoring of the inhalation of the patients during testing, implies that the MG-related olfactory deficit is unlikely due to difficulties sniffing, per se. All PIT scores were within or near the normal range, although subtle deficits were apparent in both the MG and PM patients, conceivably reflecting influences of mild cognitive impairment. No relationships between performance on the UPSIT and thymectomy, time since diagnosis, type of treatment regimen, or the presence or absence of serum anti-nicotinic or muscarinic antibodies were apparent. Our findings suggest that MG influences olfactory function to the same degree as observed in a number of neurodegenerative diseases in which central nervous system cholinergic dysfunction has been documented.

Temporal preparation decreases perceptual latency: evidence from a clock paradigm.

A clock paradigm was employed to assess whether temporal preparation decreases the time to detect the onset of a stimulus-that is, perceptual latency. In four experiments participants watched a revolving clock hand while listening to soft or loud target tones under high or low temporal preparation. At the end of each trial, participants reported the clock hand position at the onset of the target tone. The deviation of the reported clock hand position from the actual position indexed perceptual latency. As expected, perceptual latency decreased with target tone intensity. Most importantly, however, greater temporal preparation decreased perceptual latency in all four experiments, especially for soft tones, which supports rather directly the idea that temporal preparation diminishes the duration of perceptual processing.

The beat goes on: rhythmic modulation of cortical potentials by imagined tapping.

A frequency analysis was used to tag cortical activity from imagined rhythmic movements. Participants synchronized overt and imagined taps with brief visual stimuli presented at a constant rate, alternating between left and right index fingers. Brain potentials were recorded from across the scalp and topographic maps made of their power at the alternation frequency between left and right taps. Two prominent power foci occurred in each hemisphere for both overt and imagined taps, one over sensorimotor cortex and the other over posterior parietal cortex, with homologous foci in opposite hemispheres arising from oscillations 180 degrees out of phase. These findings demonstrate temporal isomorphism at a neural level between overt and imagined movements and illustrate a new approach to studying covert actions.

Paradoxical lateralization of brain potentials during imagined foot movements.

Though each foot is controlled primarily by the contralateral hemisphere, the event-related brain potentials preceding an overt foot movement are largest over the ipsilateral side of the head. Because such "paradoxical lateralization" results from the spatial organization of the motor homunculus, it can provide a sign of motor-cortex activation. We report paradoxical lateralization in the potentials accompanying imagined foot movements, thereby demonstrating a contribution of cortical areas directly involved in movement execution.

On the locus of speed-accuracy trade-off in reaction time: inferences from the lateralized readiness potential.

Lateralized readiness potentials (LRPs) were used to determine the stage(s) of reaction time (RT) responsible for speed-accuracy trade-offs (SATs). Speeded decisions based on several types of information were examined in 3 experiments, involving, respectively, a line discrimination task, lexical decisions, and an Erikson flanker task. Three levels of SAT were obtained in each experiment by adjusting response deadlines with an adaptive tracking algorithm. Speed stress affected the duration of RT stages both before and after the start of the LRP in all experiments. The latter effect cannot be explained by guessing strategies, by variations in response force, or as an indirect consequence of the pre-LRP effect. Contrary to most models, it suggests that SAT can occur at a late postdecisional stage.

Temporal organization of covert motor processes during response selection and preparation.

Onset of a movement-related brain potential (lateralized readiness potential, LRP) was used to divide reaction time (RT) into two intervals: (1) stimulus onset to LRP onset, and (2) LRP onset to onset of the overt response. Effects on these intervals of advance information about the to-be-signaled response and of the mapping between fingers and response buttons were examined. These effects were used to reach conclusions about the organization of response preparation and about the identity of the processes influenced by advance information. In the absence of advance information, response preparation involved two steps. First, two of the four possible response alternatives were prepared, then one of these two was prepared further. Which pair of responses was prepared during the first step depended on the spatial arrangement of the fingers on the buttons, rather than on any common anatomical feature. Advance information about the upcoming response allowed the first step to be performed prior to the response signal, thus removing its contribution to RT. The second step, however, remained unaffected.

Linear spatial integration for single-trial detection in encephalography.

Conventional analysis of electroencephalography (EEG) and magnetoencephalography (MEG) often relies on averaging over multiple trials to extract statistically relevant differences between two or more experimental conditions. In this article we demonstrate single-trial detection by linearly integrating information over multiple spatially distributed sensors within a predefined time window. We report an average, single-trial discrimination performance of Az approximately 0.80 and faction correct between 0.70 and 0.80, across three distinct encephalographic data sets. We restrict our approach to linear integration, as it allows the computation of a spatial distribution of the discriminating component activity. In the present set of experiments the resulting component activity distributions are shown to correspond to the functional neuroanatomy consistent with the task (e.g., contralateral sensorymotor cortex and anterior cingulate). Our work demonstrates how a purely data-driven method for learning an optimal spatial weighting of encephalographic activity can be validated against the functional neuroanatomy.