Episodic memory effects of gamma frequency precuneus transcranial magnetic stimulation in Alzheimer's disease: A randomized multiple baseline study

Episodic memory decline is the prominent neuropsychological feature of typical Alzheimer's Disease (AD), for which current treatments have a limited clinical response. Recently, gamma entrainment therapy has been used as a non-invasive treatment in AD, providing evidence that it may have the potential to alleviate brain pathology and improve cognitive function in AD patients. At the same time, the precuneus (PC) has been recognized as a key area involved in AD related memory deficits and as a key node of the Default Mode Network. This study aimed to investigate the effectiveness of a 40 Hz Transcranial Magnetic Stimulation (TMS) intervention, delivered bilaterally to the precuneus for 10 days, in improving the patients' episodic memory performance. Secondary outcome variables investigated included general cognitive function, semantic and spatial memory, as well as attention and executive function. A concurrent multiple baseline design across five cases was employed. Four patients completed the study. Visual analysis combined with effect size indices were used to evaluate changes across phases. An increase in the average level of immediate recalled words was observed in three out of four patients. Effect size indices indicated significant improvement of attention skills in two patients. No treatment effect was observed for semantic and visual memory, or for executive function. An immediate treatment effect was observed in all patients' general cognitive function as assessed with the Alzheimer's Disease Assessment Scale (mean reduction of 5 points), which was maintained and improved further three months post-treatment. The neuropsychological evaluations indicated improved performance three months post-treatment in immediate and delayed recall, attention, phonological verbal fluency, anxiety, and neuropsychiatric symptoms. This study provides preliminary evidence for the efficacy of a novel non-pharmacological treatment using gamma-band TMS in addressing cognitive dysfunction in AD.     

中国传统情绪疗法及其应用

系统地探讨了中国传统情绪疗法：情志相胜疗法,相反情绪疗法,激情刺激疗法,与感觉刺激有关的情绪疗法,与别人有关的情绪疗法,顺情从欲疗法,抑情顺理疗法,移情易性疗法,情志导引疗法,七情合参疗法。这些中国传统心理疗法在现代仍有实用价值。     

Effect of delay-interval stimuli on delayed symbolic matching to sample in the pigeon

In Experiment 1, food-deprived pigeons received delayed symbolic matching to sample training in a darkened Skinner box. Trials began with the illumination of the grain feeder lamp (no food sample), or illumination of this lamp, accompanied by the raising of the feeder tray (food sample). After a delay of a few seconds, the two side response keys were illuminated, one with red and one with green light, with positions counterbalanced over trials. Pecking the red (green) comparison produced grain reinforcement if the trial had started with food (no food); pecking red after a no-food sample or green after a food sample was not reinforced. Once matching performance was stable, four stimuli were presented during the delay interval, and their effects on matching accuracy were evaluated. Both illumination of the houselight and the center key with white geometric forms decreased matching accuracy, whereas presentation of a tone and vibration of the test chamber did not. In Experiment 2, pecking the red center key was reinforced with food according to a variable interval schedule. The effects of occasional brief presentations of the four stimuli used in the first experiment on ongoing pecking were assessed. The houselight and form disturbed key pecking, but the tone and vibration did not. Thus, stimuli that interfered with delayed matching also interfered with simple operant behavior. Implications of these results for theories of remembering are discussed.     

Economic substitutability of electrical brain stimulation, food, and water.

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other.     

Stimulation cognitive chez les personnes âgées : effets d’une méthode de stimulation cognitive par les jeux sur les fonctions cognitives et l’estime de soi

The purpose of this study was to examine the effects of a cognitive stimulation program with games on scores to cognitive tests (processing speed, mental flexibility, working memory, inhibition) and how this program can benefit to a psycho-affective measure, self-esteem in older adults. Forty-eight participants over 60 years old took part in the experiment. They were divided into two groups: 1 group followed a program of cognitive stimulation using leisure activities with games and 1 control group in which people gathered every week. There were 8 sessions of cognitive stimulation using leisure activities like games, one-hour session a week. Measures have focused on speed of processing and executive functions (shifting, updating and inhibition). They have been evaluated before and after the training program. Results show that the cognitive stimulation program using leisure activities with games is effective on speed of processing, memory span, inhibition and self-esteem but shows no benefits on shifting and updating. These results indicate that it seems to be possible to enhance cognitive resources, inhibition and self-esteem using leisure activities with games as a tool for cognitive stimulation.     

背外侧前额叶对主动遗忘负性社会反馈的作用：针对抑郁症的TMS研究

抑郁症患者的负性心境可能源于其抑制功能障碍。患者在主动遗忘负性材料时无法有效调用背外侧前额叶(the dorsolateral prefrontal cortex, DLPFC)等负责抑制控制的额叶脑网络。同时, 患者对社会信息的加工比对非社会信息的加工存在更明显的认知神经障碍, 很难主动遗忘对自己不利的社会反馈信息。为了提高抑郁症患者对负性社会反馈的主动遗忘能力, 本研究采用经颅磁刺激技术(transcranial magnetic stimulation, TMS), 考察抑郁症患者在左侧(n = 32)或右侧DLPFC (n = 30)被激活后其记忆控制能力的改变。结果表明, 当患者的DLPFC被TMS激活时, 他们对社会拒绝的回忆正确率与健康对照组(n = 31)无差异, 且TMS激活右侧DLPFC还改善了患者对他人的社会态度。本研究是采用TMS提高抑郁症患者主动遗忘能力的首次尝试, 研究结果不但支持了DLPFC与记忆控制功能的因果关系, 还为临床治疗抑郁症、创伤后应激障碍、药物成瘾等患者的记忆控制缺陷提供了明确的神经靶点。     

Evidence for a motor mechanism of pain-induced aggression instigation in humans

The automatic skeletal motor responses of 20 male and 20 female student subjects (aged 20–36) receiving a painful stimulation (electric shock) were studied by examining voluntary concomitant extensions and flexions of the arm. These movements were either of long duration, allowing for an on-line control of their execution or, of short duration, requiring extensive pre-programming. Subjects were instructed either to push or to pull a lever upon receipt of an acoustic signal, which was paired or unpaired with an electric shock. Latencies for long duration movements (regardless of direction) were reduced by reception of painful stimulation. Latencies of short duration extensions and flexions were respectively reduced and increased by painful stimulation. Latencies of short duration movements were larger for females than males, regardless of movement direction. These data suggest that painful stimulation elicits automatic movements which affect programming of the termination of simultaneous voluntary movements. Implications of these findings for the study of aggressive behavior are discussed. © 1994 Wiley-Liss, Inc.     

Bilateral Transcranial Direct Stimulation Over the Primary Motor Cortex Alters Motor Modularity of Multiple Muscles

Abstract

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been demonstrated to modulate the motor performance of both healthy individuals and patients with neuromuscular disorders. However, the effect of tDCS on motor control of multiple muscles, which is a prerequisite to change in motor performance, is currently unknown. Using dimensionality reduction analysis, we investigated whether bilateral tDCS over M1 modulates the coordinated activity of 12 muscles. Fifteen healthy men participated in this randomized, double-blind crossover study. Each participant received a 20-min sham and 2-mA stimulation bilaterally over M1 (anode on the right M1 and cathode on the left M1), with a minimum washout period of 4?days. Muscle activation and end-point kinematics were evaluated during a task where participants reached out to a marked target with non-dominant hand as fast as possible, before and immediately after tDCS application. We found decreased similarity in motor modularity and significant changes in muscle activation in a specific motor module, particularly when reaching out to a target placed within arm’s length and improved smoothness index of movement only following 2-mA stimulation. These findings indicate that clinicians and researchers need to consider the simultaneous effect of bilateral tDCS over M1 on multiple muscles when they establish tDCS protocol to change in motor performance of patients with neuromuscular deficits.     

The neural pathways mediating quiet-biting attack behavior from the hypothalamus in the cat: A functional autoradiographic study

Electrical stimulation of the region of the lateral hypothalamus produced a consistent form of quiet-biting attack behavior in cats. In one series of experiments, cats, implanted with electrodes from which attack had been elicited, were anesthetized and then were injected with a bolus of ¹⁴C-2-deoxyglucose at the same time as electrical stimulation was delivered through the attack electrodes. Brains prepared for X-ray autoradiography revealed that lateral hypothalamic stimulation activated the classical medial forebrain bundle pathway supplying the septal region, diagonal band, lateral preoptic area, and ventral tegmental region. Stimulation of quiet-attack sites in perifornical hypothalamus resulted in the activation of a much more extensive projection system which included the central and lateral tegmental fields of the midbrain and pons, and central gray region, as well as the structures described above. In a second series of experiments, ³H-leucine was placed into the region of the electrode tip from which attack was elicited in order to identify more precisely the pathways arising from that site. In general, tritiated amino acid radioautography replicated the ¹⁴C-2-deoxyglucose findings. In addition, the amino acid radioautographic data revealed the presence of extensive projections from perifornical hypothalamus to such pontine structures as the nucleus locus coeruleus, motor nucleus of NV , and the lateral pontine tegmental field. The functional connections between the lateral hypothalamic “attack region” and lateral preoptic zone were also confirmed by electrophysiological methods.