Can Crossover and Altered Magnitude Estimation in Neglect Be Explained by Contextual Effects?

Three studies that used experimental manipulations of stimulus context and correlational analyses were conducted to examine how contextual effects influence magnitude estimation and the crossover effect on line bisection. Previous work had shown that although orienting attention to one end of a line prior to bisection determines the direction in which crossover occurs, bias in magnitude estimation actually produces the crossover effect. The influence of contextual effects on magnitude estimation, however, was not examined in these previous models of crossover. Consequently, the purpose of the present investigation was to examine these effects. Subjects in the current studies were healthy controls and people who had right and left hemisphere injury due to stroke, both with and without spatial neglect. Study 1 examined the crossover effect for lines bisected with and without a stimulus context. Study 2 examined both stimulus order as well as response order context effects on magnitude estimation. Study 3 examined how much variance in magnitude estimation was accounted for by stimulus contextual effects and how stimulus context influenced the crossover effect. The results showed that contextual bias was ubiquitous but relatively small in the magnitude estimates of normal subjects. Contextual bias was exaggerated to a similar degree in subjects with right or left hemisphere injury due to stroke, but the amount of variance accounted by contextual bias was still quite small. A novel finding of study 2 was that contextual effects can be induced by previous responses to stimuli as well as by the magnitude of preceding stimuli in subjects with unilateral brain injury. This may be a contextual effect related to response perseveration. Finally, studies 1 and 3 indicated that contextual effects strengthened the crossover effect on line bisection, primarily on relatively short lines. Contextual effects, however, cannot fully account for the crossover effect, because crossover bisections were observed also in the absence of a stimulus context. It is concluded that the crossover effect is explained by biases in attentional orientation and magnitude estimation. Contextual effects represent one source of bias in magnitude estimation that influences the crossover effect by promoting contralateral errors on short line lengths (<2 cm).

Stimulation Induced Changes in Ratio Scaling Between and Within Hemispheres.

OBJECTIVES: This paper examines if ratio scaling, the principle behind the psychophysical Power Law, is similarly performed by the left and right cerebral hemispheres and how magnitude estimates derived in each hemisphere are integrated. METHOD: Three models of hemispheric integration were tested (dominance, summation, and inhibition) using a cross-modal matching procedure in right-handed, male subjects. Visual stimuli were presented to one or both hemispheres using a tachistoscopic method to test each model. Olfactory stimuli were also presented to one or both nares (hemispheres) to test the dominance and summation models. RESULTS: A dominance model was not supported as there was little difference in ratio scaling between hemispheres for either visual or olfactory stimuli. A summation model was supported for olfactory but not visual integration. Inter-hemispheric inhibition did not account for hemispheric integration. CONCLUSIONS: The most interesting findings stemmed from a comparison of experimental conditions within rather than between hemispheres. Ratio scaling parameters, the sizes of the exponents and constants, appeared to be driven by the amount of stimulation provided to a hemisphere - a greater amount being associated with higher exponents and lower constants. Variability in ratio scaling, how well data fit power functions, corresponded to whether the hemispheres received equal amounts of stimulation - equal stimulation producing a better fit than unequal stimulation. We conclude that stimulus induced cerebral activation influences the form of power functions; whereas equivalency of stimulation between hemispheres influenced the fit.

Lateralized Effects in Troxler Fading and Parvo and Magnocellular Processing Tasks after Localized 1Hz rTMS.

Troxler Fading (TF) is a complex visual phenomenon with uncertain mechanisms. This study was performed to test hypotheses concerning the contributions of parvocellular and magnocelluar processing in extrastriate pathways to TF. The study used low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) delivered at target sites in the parietal, temporal and dorsolateral frontal cortex to alter performance on a TF paradigm and on tests sensitive to parvocellular and magnocellular processing. Nine, right-handed, healthy subjects completed 3 tasks, TF, Texture Detection (TD), and Motion Detection (MD), at baseline and after undergoing 15 minutes of low-frequency rTMS at each cortical site on separate occasions. Results revealed lateralized effects of rTMS on each test. Left temporal stimulation slowed the parvocellular, TD task and it accelerated TF. Right parietal stimulation markedly accelerated TF whereas left parietal stimulation slowed TF. Right frontal stimulation accelerated performance on the magnocellular, MD task. Taken together and in the context of other research studies, the findings suggest hemispheric specialization both for TF and for the parvocellular and magnocellular processing tasks.

A Randomized Placebo Controlled Clinical Trial Demonstrating Safety & Efficacy of EnXtra® in Healthy Adults.

Objective: The present randomized, placebo-controlled study aimed to assess the long-term safety and perceivable mental acuity benefits of EnXtra® in healthy individuals.Methods: Study participants were administered EnXtra® with or without caffeine for a period of 12 weeks. The cardiovascular safety was evaluated by assessing change in QT interval, blood pressure and heart rate. Further, other efficacy variables evaluated were change in perceived alertness and calmness by Bond and Lader mood scales, Sleep disturbance by Pittsburgh sleep quality Index and daytime sleepiness by Epworth sleepiness scale.Results: None of the study group showed any significant change in the ECG or haemodynamic parameters as compared to baseline (p > 0.05). Post consumption, alertness and calmness scores were significantly increased in the EnXtra®, and EnXtra® plus caffeine group (p < 0.001) as compared to placebo. Daytime sleep scores decreased in the EnXtra® group however change was not significant. Sleep quality remained undisturbed in all three arms.Conclusion: The findings demonstrated the psychostimulant efficacy of EnXtra® with no safety concerns on long-term usage.

On How Psychophysical Thresholds are Altered by Unilateral Brain Injury Due to Stroke.

OBJECTIVE: This study examined whether and how the absolute thresholds and the just noticeable difference thresholds for eleven, sensory/perceptual continua are altered by unilateral left and right hemisphere lesions due to stroke relative to healthy subjects. METHODS: The three subject groups were those with unilateral right hemisphere lesions (n=21), with unilateral left hemisphere lesions (n=13), and age-matched control subjects (n=76). Absolute thresholds of sensory detection and just noticeable difference thresholds were assessed for perceptual continua spanning the visual, tactile, proprioceptive, thermal, and gustatory sensory modalities. For stroke subjects, brain lesions were analyzed using subtraction techniques and volume analysis with the MRIcro and MRIcroN software programs. Stroke subjects also complete tests for spatial neglect, stroke severity and functional independence. RESULTS: There was no significant difference among subject groups regarding gender, race, hand dominance, age, or educational composition. There was no significant difference between subjects with right and left hemisphere lesions on measures of function, stroke severity, or lesion volume except for those with spatial neglect. The RHL group had a higher percentage of impaired perceptual continua (16%) than both normal controls (4%) and the LHL group (9%). If a stoke subject had an impaired threshold on one side of the body, they were ~5 times more likely to have an impaired threshold on the other side of the body. This result was more consistent and even exaggerated (~8 times more likely) in the small percentage of normal control subjects who demonstrated "impaired" sensory thresholds. Lesion volume was positively correlated with stroke severity and sensory threshold impairment, and it was negatively correlated with functional independence. CONCLUSIONS: When subjects, have difficulty detecting and discriminating sensory experiences, they tend to do so on both sides of the body. Unilateral right hemisphere stroke appeared to increase the relative frequency of altered thresholds occurring on the contralesional side of the body even though they made errors on both sides.

Transcranial Direct Current Stimulation (tDCS) Can Alter Cortical Excitability of the Lower Extremity in Healthy Participants: A Review and Methodological Study.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has been used to alter cortical excitability of the lower extremity (LE) and to influence performance on LE tasks like ankle tracking accuracy; but no study, to our knowledge, ever reported a significant change in cortical excitability relative to sham-tDCS. Additionally, because several different electrode montages were used in previous studies, it is difficult to know how stimulation should be applied to achieve this effect. Our objective was to determine whether active-tDCS alters cortical excitability of the LE and ankle tracking accuracy relative to sham-tDCS in healthy participants. The efficacy of two electrode montages and two conductance mediums were compared. METHODS: A triple-blind, fully randomized, within-subjects study was conducted with healthy participants (N=18, 24.2 (6.6) years). Cortical recruitment curves and measures of ankle tracking accuracy for the dominant lower extremity were obtained before and after participants received active-tDCS at 2 milliamps for 20 minutes using montage-medium combinations of M1-SO:Saline, M1-SO:Gel, C1-C2:Saline, and C1-C2:Gel and a sham-tDCS condition (M1-SO: Saline). RESULTS: The motor evoked potential maximum of the recruitment curve was significantly lower for active than sham-tDCS, but only for the M1-SO:Saline combination. No other significant differences in the recruitment curve parameters or in ankle tracking were found. CONCLUSIONS: This is the first study to our knowledge to demonstrate a significant difference in cortical excitability of the LE between active and sham-tDCS conditions. Given the order in which the experimental procedures occurred, the result is consistent with the concept of a homeostatic plasticity response.

Repetitive transcranial magnetic stimulation for apathy in mild cognitive impairment: A double-blind, randomized, sham-controlled, cross-over pilot study.

Apathy is a common and disabling behavioral concomitant of many neurodegenerative conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked with heightened rates of conversion to Alzheimer's disease. Improving apathy may slow the neurodegenerative process. The objective was to establish the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross-over study was conducted in nine subjects (66 ± 9 years) with apathy and MCI. Subjects were randomized to rTMS or sham treatment (5 days/week) for 2 weeks following which they underwent a 4-week treatment-free period. Subjects then crossed-over to receive the other treatment for 2 weeks. The primary (apathy (AES-C)) and secondary (cognition (3MS & MMSE), executive function (TMT-A & TMT-B), and clinical global impression (CGI)) outcomes were assessed at baseline, 2, 6, and 8 weeks. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment at 2 weeks. There was significantly greater improvement in 3MS, MMSE, TMT-A, and CGI-I with rTMS compared to the sham treatment. This study establishes that rTMS is efficacious in improving apathy in subjects with MCI.

Effect of Alpinia galanga on Mental Alertness and Sustained Attention With or Without Caffeine: A Randomized Placebo-Controlled Study.

OBJECTIVE: Although Alpinia galanga has been reported to improve cognitive performance in animals, it has not been thoroughly studied for its potential psychostimulant effect in humans. A randomized, double-dummy, double-blind, placebo-controlled cross-over study was conducted to determine the effect of A galanga on mental alertness and sustained attention in comparison with caffeine and placebo in participants with a habitual caffeine intake. METHODS: Fifty-nine participants (18-40 years and body mass index of ≥18.5 and <25.00 kg/m2) with moderate caffeine consumption were enrolled. The participants had a Generalized Anxiety Disorder-7 score ≤7, Patient Health Questionnaire-9 score ≤14 and a Jin Fan's Attention Network Test alertness score of 50 ± 20 ms. The interventional product (placebo, A galanga proprietary extract [E-AG-01], caffeine, and a combination of E-AG-01 with caffeine) was administered to the participants, followed by sequential administration of the remaining interventions on the consecutive study visits; the effects on mental alertness, sustained attention, and sleep architecture, along with safety and tolerability, were analyzed by validated methods. RESULTS: In the E-AG-01 group, the alertness score was increased by 11.65 ± 23.94, 12.50 ± 19.73, and 12.62 ± 0.68 ms from baseline at 1, 3 (p = 0.042), and 5 hours, respectively, indicating its efficacy to enhance mental alertness and the increase in alertness score as compared to placebo. In the composite group (E-AG-01 with caffeine), mean response time was significantly reduced, by 15.55 ms (p = 0.026) at 3 hours. CONCLUSIONS: A galanga (E-AG-01) induces a beneficial effect in mental alertness and the combination of A galanga with caffeine impedes the caffeine crash and improves sustained attention at 3 hours. Thus, these stimulant effects might yield a new usage for A galanga as a key ingredient in energy drinks or similar products.

Effects of functional electrical stimulation on gait recovery post-neurological injury during inpatient rehabilitation.

This stage 2 trial investigated the therapeutic effect of single channel, peroneal functional electrical stimulation (FES) for improving gait and muscle activity in people with neurological injuries who were enrolled in an inpatient rehabilitation program. Twenty-six patients (16 male; M age = 51.3 yr., SD = 16.2; 2-33 days post-injury) completed the study. Participants were randomly assigned to an experimental group (n = 13) or control group (n = 13). The experimental group received FES and the control group received sensory stimulation during 45-min. gait training sessions three times a week for the duration of their stay in a rehabilitation facility (average of four sessions for both groups). Changes in gait speed, tibialis anterior muscle electromyography (EMG), and FIM™ locomotion scores were compared between groups. No significant differences were found, as both groups demonstrated similar improvements. The current results with this small sample suggest a low dose of gait training with single channel FES did not augment gait nor EMG activity beyond gait training with sensory stimulation; therefore, clinicians will likely be better served using a larger dose of FES or multichannel FES in this clinical population.

Recruitment and Retention of Smokers Versus Nonsmokers in an rTMS Study.

Repetitive transcranial magnetic stimulation (rTMS) is a new frontier in the examination of addictive behaviors and perhaps the development of new interventions. This study examined differences in recruitment, eligibility, and retention among smokers and nonsmokers in an rTMS study. We modeled participant eligibility and study completion among eligible participants accounting for demographic differences between smokers and nonsmokers. Nonsmokers were more likely than smokers to remain eligible for the study after the in-person screen (84.2% versus 57.4%; OR 4.0 CI: 1.0, 15.4, p=0.05) and to complete the study (87.5% versus 59.3%; OR=43.9 CI: 2.8, 687.2, p=0.007). The preliminary findings suggest that careful screening for drugs of abuse and brain abnormalities among smokers prior to administering rTMS is warranted. More research is needed concerning the prevalence of brain abnormalities in smokers. Smokers might need to be informed about a higher risk of incidental MRI findings.

Effects of topical nasal anesthetic on fiberoptic endoscopic examination of swallowing with sensory testing (FEESST).

Objections to the use of topical nasal anesthesia (TNA) during fiberoptic endoscopic evaluation of swallowing (FEES) with sensory testing (FEESST) have been raised, primarily because of the possibility of desensitizing the pharyngeal and laryngeal mucosa and affecting both the sensory and motor aspects of the swallow. Furthermore, it has been suggested that TNA is not necessary during FEES as it does not improve patient comfort or make the procedure easier for the endoscopist. The purpose of this double-blind, randomized, controlled, crossover clinical trial was to determine how gel TNA during flexible endoscopic evaluation of swallowing with sensory testing affects sensation, swallowing, and comfort rating scores in healthy non-dysphagic participants. Laryngopharyngeal sensory thresholds and swallowing durations were compared between two conditions: TNA and sham. Transition duration decreased statistically significantly during the TNA condition compared to the sham for 10 ml only (p < 0.05). All other swallowing measures did not change between the conditions. Laryngopharyngeal sensory thresholds and perceptions did not change between conditions. No change was observed for subject comfort scores, ease of exam, or quality of view. Future studies should evaluate TNA administration variables, including concentration, dosage amount, and method of application, to determine the optimal strategy for providing comfort while avoiding altered swallowing.

Focal electrical stimulation as an effective sham control for active rTMS and biofeedback treatments.

A valid sham control is important for determining the efficacy and effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an experimental and clinical tool. Given the manner in which rTMS is applied, separately or in combination with self-regulatory approaches, and its intended impact on brain states, a valid sham control of this type may well serve as a meaningful control for biofeedback studies, where efforts to develop a credible control have often been less than ideal. This study examined the effectiveness of focal electrical stimulation of the frontalis muscle as a sham technique for blinding participants to high-frequency rTMS over the dorso-lateral prefrontal cortex (DLPFC) at durations, intensities, and schedules of stimulation similar to many clinical applications. In this within-subjects single blind design, 19 participants made guesses immediately after receiving 54 counterbalanced rTMS sessions (sham, 10 Hz, 20 Hz); 7 (13 %) of the guesses were made for sham, 31 (57 %) were made for 10 Hz, and 16 (30 %) were made for 20 Hz. Participants correctly guessed the sham condition 6 % (CI 1, 32 %) of the time, which is less than the odds of chance (i.e., of guessing at random, 33 %); correctly guessed the 10 Hz condition 66 % (CI 43, 84 %) of the time, which was greater than chance; and correctly guessed the 20 Hz condition 41 % (CI 21, 65 %) of the time, which was no different than chance. Focal electrical stimulation therefore can be an effective sham control for high-frequency rTMS of the DLPFC, as well as for active biofeedback interventions. Participants were unaware that electrical stimulation was, in fact, sham rTMS.

Neuromodulation of delay discounting, the reflection effect, and cigarette consumption.

Cigarette smokers and substance users discount the value of delayed outcomes more steeply than non-users. Higher discounting rates are associated with relapse and poorer treatment outcomes. The left dorsolateral prefontal cortex (DLPFC) exerts an inhibitory influence on impulsive or seductive choices. Greater activity in the prefrontal cortex is associated with lower discounting rates. We hypothesized that increasing activity in the left DLPFC with high frequency repetitive transcranial magnetic stimulation (HF rTMS) would decrease delay discounting and decrease impulsive decision-making in a gambling task as well as decrease cigarette consumption, similar to other studies. In this single-blind, within-subjects design, smokers with no intention to quit (n = 47) and nonsmokers (n = 19) underwent three counterbalanced sessions of HF rTMS (20 Hz, 10 Hz, sham) delivered over the left DLPFC. Tasks were administered at baseline and after each stimulation session. Stimulation decreased discounting of monetary gains (F([3,250]) = 4.46, p < .01), but increased discounting of monetary losses (F([3,246]) = 4.30, p < .01), producing a reflection effect, normally absent in delay discounting. Stimulation had no effect on cigarette consumption. These findings provide new insights into cognitive processes involved with decision-making and cigarette consumption and suggest that like all medications for substance dependence, HF rTMS is likely to be most effective when paired with cognitive-behavioral interventions.

Hypnosis in the right hemisphere.

Speculations about the neural substrates of hypnosis have often focused on the right hemisphere (RH), implying that RH damage should impair hypnotic responsiveness more than left-hemisphere (LH) damage. The present study examined the performance of a patient who suffered a stroke destroying most of his LH, on slightly modified versions of two hypnotizability scales. This patient was at least modestly hypnotizable, as indicated in particular by the arm rigidity and age regression items, suggesting that hypnosis can be mediated by the RH alone - provided that the language capacities normally found in the LH remain available. A further study of 16 patients with unilateral strokes of the LH or RH found no substantial differences in hypnotizability between the two groups. Future neuropsychological studies of hypnosis might explore the dorsal/ventral or anterior/posterior dichotomies, with special emphasis on the role of prefrontal cortex.

Measurement of reaction time in the home for people with dementia: a feasibility study.

BACKGROUND: Cognitive decline is the cardinal symptom of dementia. Accurate measurement of changes in cognition, while essential for testing interventions to slow cognitive decline, can be challenging in people with dementia (PWD). For example, the laboratory environment may cause anxiety and negatively affect performance. MATERIAL AND METHOD: In healthy people, researchers measure one aspect of cognition, attention, via assessing reaction times in a laboratory environment. This repeated-measures study investigated the feasibility of reaction time measurement in participants' homes using the computerized psychomotor vigilance task (PVT) for PWD. Research questions were (a) Can laboratory controls be replicated in the home? (b) Where do PWD perform PVT trials optimally? and (c) What are the preferences of PWD and their caregivers? Two groups that differed by sequence of testing location completed 12 reaction time assessments over 2 days. Caregiver and person with dementia dyad preferences were examined in a follow-up phone interview. RESULTS: Complete data were collected from 14 dyads. Although there were slight differences in lighting between settings, the time of day, temperature, and sound did not differ. There were no significant differences in PVT performance between the two locations, but the group who tested in the home on Day 1 performed better than the group who tested in the lab on Day 1. All participants preferred home examination. DISCUSSION: It is feasible to measure reaction times in the home. Home testing contributes to optimal performance and participants preferred the home.

Methodological aspects of clinical trials in tinnitus: a proposal for an international standard.

Chronic tinnitus is a common condition with a high burden of disease. While many different treatments are used in clinical practice, the evidence for the efficacy of these treatments is low and the variance of treatment response between individuals is high. This is most likely due to the great heterogeneity of tinnitus with respect to clinical features as well as underlying pathophysiological mechanisms. There is a clear need to find effective treatment options in tinnitus, however, clinical trials differ substantially with respect to methodological quality and design. Consequently, the conclusions that can be derived from these studies are limited and jeopardize comparison between studies. Here, we discuss our view of the most important aspects of trial design in clinical studies in tinnitus and make suggestions for an international methodological standard in tinnitus trials. We hope that the proposed methodological standard will stimulate scientific discussion and will help to improve the quality of trials in tinnitus.

Improvement in arousal, visual neglect, and perception of stimulus intensity following cold pressor stimulation.

The relationship between arousal, perception, and visual neglect was examined in this case study. Cold pressor stimulation (CPS: immersing the foot in iced water) was used to manipulate arousal and to determine its effects on contralesional neglect, perception of stimulus intensity (magnitude estimation), reaction time, and an electrophysiological correlate of ascending reticular activating system activity (i.e., the P50 potential). Measures that normalized from baseline following CPS included contralesional neglect on a clock drawing test, perception of stimulus magnitude, and P50 amplitude. The P50 amplitude returned to its abnormally low baseline level 20 min after CPS ended, indicating that CPS increased arousal.

Cold pressor stimulation diminishes P50 amplitude in normal subjects.

The present study examined how cold pressor stimulation influences electrophysiological correlates of arousal. We measured the P50 auditory evoked response potential in two groups of subjects who immersed their foot in either cold (0-2°C) or room temperature (22-24°C) water for 50 seconds. The P50, which was recorded before and after stimulation, is sleep-state dependent and sensitive to states of arousal in clinical populations. We found a significant reduction in P50 amplitude after exposure to cold, but not room temperature water. In comparison with other studies, these results indicate that cold pressor stimulation in normal subjects may evoke a regulatory process that modulates the P50 amplitude, perhaps to preserve the integrity of sensory perception, even as autonomic and subjective aspects of arousal increase.

Pervasive cognitive impairment in acute rehabilitation inpatients without brain injury.

OBJECTIVE: To establish feasibility for the hypothesis that patients in acute rehabilitation who are hospitalized for disorders not known to involve cerebral injury can have significant cognitive impairment. DESIGN: A comparison of performances on neuropsychological tests between 2 samples of subjects: inpatients in an acute rehabilitation hospital without known cerebral disease and normal community-dwelling persons. SETTING: Acute inpatient rehabilitation hospital. PATIENTS AND PARTICIPANTS: Nineteen hospitalized patients without delirium who were screened for pre-existing cerebral and psychiatric illness, dementia, and dependency in basic self-care skills before hospitalization. Eighteen community-dwelling persons who were not different in terms of age and education served as the control group. METHODS: Participants completed 10 commonly used neuropsychological tests of executive, language, and memory functions. Data were analyzed by using multivariate analysis of variance. MAIN OUTCOME MEASUREMENTS: Raw scores on the 10 neuropsychological tests. RESULTS: Hospitalized patients performed significantly worse on 9 of 10 tests than community-dwelling participants. Older hospitalized participants had significantly greater cognitive impairment than younger hospitalized participants, which suggested increased susceptibility to effects of hospitalization on cognition. CONCLUSIONS: Patients hospitalized without brain injury, and especially elderly patients, should be carefully monitored for cognitive deficits that may affect posthospitalization quality of living. Further research is needed to determine whether the cognitive deficits in such patients persist after discharge and affect functional independence, and to identify mechanisms for the deficits. Furthermore, the use of hospitalized participants without brain injury as control subjects in neuropsychological studies of brain injury should be balanced with an additional comparison group of matched, neurologically healthy, normal subjects who live in the community to control for cognitive impairments that are associated with acute hospitalization.