The impact of gamma transcranial alternating current stimulation (tACS) on cognitive and memory processes in patients with mild cognitive impairment or Alzheimer's disease: A literature review.

BACKGROUND: Transcranial alternating current stimulation (tACS)-a noninvasive brain stimulation technique that modulates cortical oscillations through entrainment-has been demonstrated to alter oscillatory activity and enhance cognition in healthy adults. TACS is being explored as a tool to improve cognition and memory in patient populations with mild cognitive impairment (MCI) and Alzheimer's disease (AD). OBJECTIVE: To review the growing body of literature and current findings obtained from the application of tACS in patients with MCI or AD, highlighting the effects of gamma tACS on brain function, memory, and cognition. Evidence on the use of brain stimulation in animal models of AD is also discussed. Important parameters of stimulation are underscored for consideration in protocols that aim to apply tACS as a therapeutic tool in patients with MCI/AD. FINDINGS: The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These data demonstrate the potential for tACS as an interventional stand-alone tool or alongside pharmacological and/or other behavioral interventions in MCI/AD. CONCLUSIONS: While the use of tACS in MCI/AD has evidenced encouraging results, the effects of this stimulation technique on brain function and pathophysiology in MCI/AD remains to be fully determined. This review explores the literature and highlights the need for continued research on tACS as a tool to alter the course of the disease by reinstating oscillatory activity, improving cognitive and memory processing, delaying disease progression, and remediating cognitive abilities in patients with MCI/AD.

Inconsistency of performance on neglect subtype tests following acute right hemisphere stroke.

Hemispatial neglect has been conceptualized as having dissociable and potentially clinically relevant subtypes. However, the question of whether patient performance on neglect subtype measures is consistent over time remains largely unanswered. We examined changes in performance over time on measures of motor, perceptual, and personal neglect in 21 patients with neglect from acute right hemisphere stroke. Patients were assessed on three occasions, separated by at least one week, using a lateralized target test, lateralized response test, and modified fluff test. Across three testing timepoints, 18 (85.7%) patients changed subtype performance patterns at least once. In 13 (61.9%) of these patients, inconsistency between timepoints was not adequately accounted for by recovery. On initial testing, seven, patients (33.3%) demonstrated more than one neglect subtype symptom; by the third testing timepoint none of the patients demonstrated multiple symptoms. In the setting of acute stroke, performance on three measures of neglect symptoms is inconsistent across time. However, the distribution of neglect subtype symptoms appears to become more discrete over time. These findings complicate our understanding of the pathophysiology and potential prognostic value of neglect subtypes, and suggest that treatment decisions based on subtype performance assessed at a single timepoint, may be of limited utility.

Tactile spatial resolution in blind braille readers.

OBJECTIVE: To determine if blind people have heightened tactile spatial acuity. BACKGROUND: Recently, studies using magnetic source imaging and somatosensory evoked potentials have shown that the cortical representation of the reading fingers of blind Braille readers is expanded compared to that of fingers of sighted subjects. Furthermore, the visual cortex is activated during certain tactile tasks in blind subjects but not sighted subjects. The authors hypothesized that the expanded cortical representation of fingers used in Braille reading may reflect an enhanced fidelity in the neural transmission of spatial details of a stimulus. If so, the quantitative limit of spatial acuity would be superior in blind people. METHODS: The authors employed a grating orientation discrimination task in which threshold performance is accounted for by the spatial resolution limits of the neural image evoked by a stimulus. The authors quantified the psychophysical limits of spatial acuity at the middle and index fingers of 15 blind Braille readers and 15 sighted control subjects. RESULTS: The mean grating orientation threshold was significantly (p = 0.03) lower in the blind group (1.04 mm) compared to the sighted group (1.46 mm). The self-reported dominant reading finger in blind subjects had a mean grating orientation threshold of 0.80 mm, which was significantly better than other fingers tested. Thresholds at non-Braille reading fingers in blind subjects averaged 1.12 mm, which were also superior to sighted subjects' performances. CONCLUSION: Superior tactile spatial acuity in blind Braille readers may represent an adaptive, behavioral correlate of cortical plasticity.

Hand response differences in a self-face identification task.

Evidence has indicated that the right frontal cortex is preferentially involved in self-face recognition. To test this further, we employed a face identification task and examined hand response differences (N=10). Pictures of famous faces were combined with pictures of the participants' faces (self) and their co-workers' faces (familiar). These images were presented as a 'movie' in which one face transformed into another. Under the first instruction set, the movies began with either the participant's face or a co-worker's face, and the sequences gradually morphed into a famous face. When told to stop the movie when the face in the sequence became famous, a significantly later 'frame' was identified when the movies were composed of self-faces and the participants responded with their left hand. When the movies started with the famous faces and participants had to stop the movie when it became their own or their familiar co-worker's image (Instruction set 2), a significantly earlier frame was identified in the 'Self: Left hand' condition. The data suggest that participants are inclined to identify images as their own when the right hemisphere is preferentially accessed.

Cortical plasticity associated with Braille learning.

Blind subjects who learn to read Braille must acquire the ability to extract spatial information from subtle tactile stimuli. In order to accomplish this, neuroplastic changes appear to take place. During Braille learning, the sensorimotor cortical area devoted to the representation of the reading finger enlarges. This enlargement follows a two-step process that can be demonstrated with transcranial magnetic stimulation mapping and suggests initial unmasking of existing connections and eventual establishment of more stable structural changes. In addition, Braille learning appears to be associated with the recruitment of parts of the occipital, formerly `visual', cortex (V1 and V2) for tactile information processing. In blind, proficient Braille readers, the occipital cortex can be shown not only to be associated with tactile Braille reading but also to be critical for reading accuracy. Recent studies suggest the possibility of applying non-invasive neurophysiological techniques to guide and improve functional outcomes of these plastic changes. Such interventions might provide a means of accelerating functional adjustment to blindness.

Trends in pediatric cardiac pacing.

OBJECTIVE: To review retrospectively a 31-year experience with pediatric cardiac pacing at the University of Toronto, with an emphasis on the changing trends in pacemaker implantation in infants and children. DATA SOURCE: Data were obtained from the pediatric pacemaker follow-up clinic at The Hospital for Sick Children, Toronto, Ontario or from the referring pediatric centre. Follow-up was normally continued until the death of the child or referral to an adult hospital at age 18 years. PATIENT SELECTION: The study comprised 397 children (under 18 years of age) who underwent initial pacemaker implantation at The Hospital for Sick Children between January 1962 and December 31, 1992. Follow-up was 99% complete (five children lost) and ranged from one month to 32 years (mean 6.5 years). DATA SYNTHESIS: The use of endocardial versus epicardial leads increased significantly over time (P < 0.001). In addition, significantly more children receiving pacemakers had sick sinus syndrome (P < 0.001). No difference in survival was found between children paced by endocardial versus epicardial leads or between children paced for sick sinus syndrome versus atrioventricular block. The frequency of exit block, by lifetable analysis, did not differ between children who received epicardial versus endocardial leads. CONCLUSIONS: Guidelines for permanent pacemaker implantation in children continue to evolve as developments in lead technology alter trends in pediatric cardiac pacing.

Clinical correlation of the venom-specific IgG antibody level during maintenance venom immunotherapy.

Allergen immunotherapy is associated with a significant increase of specific IgG antibodies that have been suggested as a mechanism of action and as a marker of efficacy for immunotherapy. The value of venom-specific IgG antibody determinations as a measure of clinical protection against sting anaphylaxis has been difficult to prove in individual patients. We performed 211 insect sting challenges in 109 patients over a 4-year period to determine the significance of venom IgG levels 3 micrograms/ml or lower. Systemic symptoms occurred in only 1.6% of those with venom IgG more than 3 micrograms/ml, but in 16% of those with less than 3 micrograms/ml IgG, and notably in 26% of patients with low venom IgG who had received less than 4 years of treatment. The venom IgG level had no predictive value in patients who had received more than 4 years of therapy. Honeybee sting data were inconclusive because of the small number of subjects. We conclude that low venom-specific IgG levels are associated with an elevated risk of treatment failure during the first 4 years of immunotherapy with yellow jacket or mixed vespid venoms.

Falling and postural deficits due to acute unilateral basal ganglia lesions.

Nine patients presented with sudden falling events to one side while sitting, standing, or walking. All were initially unaware of their severe postural deficit, and five were obfuscated. The observed falls were a distinctly slow, tilting motion in a stereotypic lateral or diagonal trajectory, literally "like a falling log." The events occurred with eyes opened and were exacerbated with eye closure, but no patient had evidence of cerebellar, vestibular, or posterior column dysfunction or significant motor weakness. Unilateral basal ganglia hemorrhages or lacunar infarcts contralateral to the side of the fall were demonstrated by computed tomographic scans. The overall prognosis was favorable; eight of nine patients regained independent ambulation within 3 to 6 weeks. Our findings indicate that a distinct loss of postural balance arises contralaterally to unilateral pallidal-putaminal lesions.

A cephalometric, tomographic, and dental cast evaluation of Fränkel therapy.

The purpose of this study was to evaluate the skeletal, dental, and condylar positional changes induced by Fränkel FR-2 therapy. The pre- and posttreatment cephalometric, tomographic, and dental cast records of 25 consecutively treated cases were evaluated. Results showed little Class II skeletal correction with no headgear-type restraining effect on the maxilla or mandibular growth stimulation noted. Significant amounts of maxillary incisor retraction and mandibular incisor proclination were observed. The maxillary intermolar width along with the mandibular intercanine and intermolar widths were significantly increased during treatment. No significant changes in condylar position were found during Fränkel therapy and only a small increase in mandibular plane angle was noted.

Survival improvement in coccidioidal meningitis by high-dose intrathecal amphotericin B.

Eleven patients with coccidioidal meningitis were treated with high individual doses (1.0 to 1.5 mg) of intrathecal amphotericin B mixed with 25 to 50 mg of hydrocortisone in an attempt to reach a dose of 12 mg per month for at least two consecutive months. Patients received a mean intrathecal dose of amphotericin B of 82 mg (range, 40 to 157 mg) and 2.4 g intravenously (range, 1.0 to 3.5 g). No deaths related to disease or treatment occurred, and overall survival was 91% during an average follow-up period of 75 months (range, 30 to 137 months). Comparative analysis with eight well-known series in the literature reveals that our survival rate and follow-up time are significantly greater than the more recent series (1977-1981). Rank correlation and linear regression showed that the mean intrathecal dose of amphotericin B used in all series corresponds well with mean survival time. Our clinical results and analysis of the literature suggest that intrathecal amphotericin B administered at a high dose rate of 0.75 mg (or greater) three times per week promptly reaching 20 mg and a total surpassing 40 mg is associated with significantly enhanced survival rates.

Nature and Amount of Auxin in Algae : IAA from Extracts of Caulerpa paspaloides (Siphonales).

Evidence for the occurrence of indole 3-acetic acid in Caulerpa paspaloides extracts was obtained by bioassay, by high-performance liquid chromatography with an electrochemical detector, and by capillary gas chromatography combined with mass spectrometry. The amount of indole 3-acetic acid present was estimated to be about 1 milligram per kilogram fresh weight, with an error limit of one order of magnitude. This is in the range reported from angiosperms.

Effects of gibberellic Acid on endogenous indole-3-acetic Acid and indoleacetyl aspartic Acid levels in a dwarf pea.

Two-week-old dwarf peas (Pisum sativum cv Little Marvel) were sprayed with gibberellic acid (GA(3)), and after 3 or 4 days the upper stem and young leaf samples were analyzed for indole-3-acetic acid (IAA) and indole-3-acetyl aspartic acid by an isotope dilution high performance liquid chromatography method. GA(3) increased IAA levels as much as 8-fold and decreased indole-3-acetyl aspartic acid levels.

Evidence for compartmentalization of conjugates of 2,4-dichlorophenoxyacetic Acid in soybean callus tissue.

Soybean Glycine max L. Merrill var. Amsoy 71 root callus tissue labeled with [1-(14)C]2,4-dichlorophenoxyacetic acid (2,4-D) which was subsequently incubated for 24 hours in the absence of 2,4-D, released considerable amounts of label into the media. These results led to an examination of the efflux of 2,4-D and 2,4-D metabolites during a 6-hour time period. Fifty% of the free 2,4-D was lost in 15 minutes and 99% in 6 hours. After 6 hours, only about 48% of the ether-soluble fraction (mainly the glutamic and aspartic conjugates) and about 33% of the aqueous-soluble fraction (mainly hydroxylated glycosides) effluxed from the tissue. Neutral red efflux from stained callus tissue was enhanced only 5% above the control by treatment with 7.5% dimethylsulfoxide (DMSO) and 50% with 20% DMSO. Similar soybean callus tissue preincubated with [1-(14)C]2,4-D and subsequently incubated with H(2)O, 7.5% DMSO, and 20% DMSO was examined for efflux of (14)C label. DMSO similarly enhanced the efflux of the ether and aqueous soluble conjugates.DMSO concentrations of less than 10% did not damage the vacuolar membranes which also has been reported with cultured tobacco cells (Delmer 1979 Plant Physiol 64: 623-629). From these data, it seems that the 2,4-D metabolites are located in a compartment of the cell and presumably the vacuole.

Biological Properties of d-Amino Acid Conjugates of 2,4-D.

Some d-amino acid (glutamic acid, valine, or leucine) conjugates of 2,4-dichlorophenoxyacetic acid (2,4-D) at 10(-5) molar, stimulated elongation of Avena sativa L. var Mariner coleoptile sections and growth of soybean (Glycine max. L. var Amsoy) tissue as much as did the l-amino acid conjugates at 10(-6) molar. The d-methionine conjugate did not stimulate growth of soybean root callus tissue but did stimulate Avena elongation. The d-aspartic acid conjugate did not stimulate elongation of Avena coleoptiles but did stimulate growth of root callus tissue.Pretreatment of root callus tissue with 100 micromolar 2,4-D-(d) -or (l) glutamic acid for 18 hours prior to incubation for 6 hours in [1-(14)C]2,4-D resulted in a greater uptake of [1-(14)C]2,4-D than did pretreatment with 2,4-d. Qualitatively the metabolites were similar in all preincubation treatments. Preincubation with 2,4-D-(d)-glutamic acid also resulted in larger free [(14)C]2,4-D pool and a significant increase in water-soluble conjugates when compared with 2,4-D, or 2,4-D-(l)-glutamic acid preincubations.

Advances in pesticide metabolite identification through the use of plant tissue cultures.

Plant tissue cultures are powerful tools for metabolism studies. Culture conditions can be selected which mimic conditions of whole plants or conditions can be employed to mass-produce selected metabolites such as aglycons or conjugates. Culture variables that affect metabolism are medium composition, age of tissue cultures, concentration of test chemical, and the source of plant tissue. The type of culture, such as suspension cultures, callus tissue cultures, differentiated tissue or organ cultures will also influence the type of metabolites obtained. Ease of standardizing conditions makes tissue culture suitable to comparatively examine metabolism in different plant species and strains and in different plant parts such as tissues derived from leaves and roots. Recent advances with plant tissue cultures involve studies of the mechanism of action or selectivity of growth regulators and herbicides, and the use of resistant strains to investigate mechanisms of biological detoxification.

Metabolism of 2,4-dichlorophenoxyacetic Acid in 2,4-dichlorophenoxyacetic Acid-resistant soybean callus tissue.

Three 2,4-dichlorophenoxyacetic acid (2,4-D) -resistant root callus tissue lines of Glycine max L. Merrill var. Acme were derived by culturing callus tissue 2 to 6 months on 40 milligrams per liter 2,4-D and designated 40R, 40B, and 40C. Tissue line 40R had a lower level of 2,4-D uptake in 2-week-old tissue which disappeared in 3.5-week-old tissue and less free 2,4-D following incubation for 24 hours with [1-(14)C]2,4-D. This tissue line accumulated more hydroxylated glycosides of 2,4-D than did nonresistant tissue. Tissue line 40B showed no difference in uptake of 2,4-D when compared to nonresistant tissue but it did contain less free 2,4-D and more hydroxylated glycosides. The metabolism of 2,4-D in the 40C tissue line did not differ significantly from nonresistant tissue although uptake was less. The 40R line reverted to the same 2,4-D sensitivity as Acme root callus following six transfers on 10 micromolar naphthaleneacetic acid medium. The altered 2,4-D uptake and metabolism characteristic of 40R were also lost. The levels of amino acid conjugates of 2,4-D in the resistant root callus tissue lines were either lower or not significantly different from the Acme tissue lines. Therefore, variations in uptake and metabolism of 2,4-D do not wholly explain the resistance of the derived tissue lines, and perhaps modification of the active site or compartmentation is involved.