Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative and progressive disease related to a gradual decline in cognitive functions such as memory, attention, perceptual-spatial abilities, language, and executive functions. Recent evidence has suggested that interventions promoting neural plasticity can induce significant cognitive gains especially in subjects at risk of or with mild AD. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques that can induce significant and long-lasting changes in focal and non-focal neuroplasticity. In this review, we present initial preliminary evidence that TMS and tDCS can enhance performance in cognitive functions typically impaired in AD. Also, we reviewed the initial six studies on AD that presented early findings showing cognitive gains such as in recognition memory and language associated with TMS and tDCS treatment. In addition, we showed that TMS has also been used to assess neuroplasticity changes in AD supporting the notion that cortical excitability is changed in AD due to the neurodegenerative process. Due to the safe profile, cost of these tools, and initial clinical trials results, further studies are warranted in order to replicate and extend the initial findings of rTMS and tDCS as cognitive enhancers in AD. Further trials should explore different targets of stimulation along with different paradigms of stimulation including combination with behavioural interventions.

Modulation of decision-making in a gambling task in older adults with transcranial direct current stimulation.

Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision-making. Based on our recent findings suggesting that non-invasive brain stimulation can improve decision-making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty-eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high-risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly.

Promoting social plasticity in developmental disorders with non-invasive brain stimulation techniques.

Being socially connected directly impacts our basic needs and survival. People with deficits in social cognition might exhibit abnormal behaviors and face many challenges in our highly social-dependent world. These challenges and limitations are associated with a substantial economical and subjective impact. As many conditions where social cognition is affected are highly prevalent, more treatments have to be developed. Based on recent research, we review studies where non-invasive neuromodulatory techniques have been used to promote Social Plasticity in developmental disorders. We focused on three populations where non-invasive brain stimulation seems to be a promising approach in inducing social plasticity: Schizophrenia, Autism Spectrum Disorder (ASD) and Williams Syndrome (WS). There are still very few studies directly evaluating the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) in the social cognition of these populations. However, when considering the promising preliminary evidences presented in this review and the limited amount of clinical interventions available for treating social cognition deficits in these populations today, it is clear that the social neuroscientist arsenal may profit from non-invasive brain stimulation techniques for rehabilitation and promotion of social plasticity.

Altered semantic integration in autism beyond language: a cross-modal event-related potentials study.

Autism spectrum disorders (ASDs) are characterized by impaired communication, particularly pragmatic and semantic language, resulting in verbal comprehension deficits. Semantic processing in these conditions has been studied extensively, but mostly limited only to linguistic material. Emerging evidence, however, suggests that semantic integration deficits may extend beyond the verbal domain. Here, we explored cross-modal semantic integration using visual targets preceded by musical and linguistic cues. Particularly, we have recorded the event-related potentials to evaluate whether the N400 and late positive potential (LPP) components, two widely studied electrophysiological markers of semantic processing, are differently sensitive to congruence with respect to typically developing children. Seven ASD patients and seven neurotypical participants matched by age, education and intelligence quotient provided usable data. Neuroelectric activity was recorded in response to visual targets that were related or unrelated to a preceding spoken sentence or musical excerpt. The N400 was sensitive to semantic congruence in the controls but not the patients, whereas the LPP showed a complementary pattern. These results suggest that semantic processing in ASD children is also altered in the context of musical and visual stimuli, and point to a functional decoupling between the generators of the N400 and LPP, which may indicate delayed semantic processing. These novel findings underline the importance of exploring semantic integration across multiple modalities in ASDs and provide motivation for further investigation in large clinical samples.

Polarity-dependent transcranial direct current stimulation effects on central auditory processing.

Given the polarity dependent effects of transcranial direct current stimulation (tDCS) in facilitating or inhibiting neuronal processing, and tDCS effects on pitch perception, we tested the effects of tDCS on temporal aspects of auditory processing. We aimed to change baseline activity of the auditory cortex using tDCS as to modulate temporal aspects of auditory processing in healthy subjects without hearing impairment. Eleven subjects received 2mA bilateral anodal, cathodal and sham tDCS over auditory cortex in a randomized and counterbalanced order. Subjects were evaluated by the Random Gap Detection Test (RGDT), a test measuring temporal processing abilities in the auditory domain, before and during the stimulation. Statistical analysis revealed a significant interaction effect of time vs. tDCS condition for 4000 Hz and for clicks. Post-hoc tests showed significant differences according to stimulation polarity on RGDT performance: anodal improved 22.5% and cathodal decreased 54.5% subjects' performance, as compared to baseline. For clicks, anodal also increased performance in 29.4% when compared to baseline. tDCS presented polarity-dependent effects on the activity of the auditory cortex, which results in a positive or negative impact in a temporal resolution task performance. These results encourage further studies exploring tDCS in central auditory processing disorders.

Falsa memória e autismo: qual é a extensão dos déficits semânticos? / False memory and autism: what is the extent of the semantic deficits? / Falsa memoria y autismo: ¿cuál es la magnitud de los déficits semánticos?

Este artigo constitui-se em um estudo de revisão teórica baseado em artigos que abordam o estudo da falsa memória em população com desenvolvimento típico e autismo. Nas últimas décadas, o interesse pela investigação da falsa memória tem se ampliado. No entanto, são observados poucos estudos que investigam os componentes eletrofisiológicos subjacentes envolvidos no reconhecimento verdadeiro e falso, principalmente no que diz respeito a pacientes com autismo. O presente artigo tem como objetivo apresentar os estudos que investigam falsa memória e o processamento semântico em pessoas com desenvolvimento típico por meio do uso da eletroencefalografia, além de apresentar a restrita literatura acerca do tema em pacientes com autismo. Muito se discute sobre déficits semânticos no autismo, mas há ainda poucos estudos nessa área e com resultados contraditórios. Por fim, novas direções para o desenvolvimento e aprimoramento de novos estudos são apresentadas.

In the recent decades, the interest in investigation of false memory has been amplified. However, just a few studies investigate the underlying electrophysiological components involved in true and false recognition, especially with regard to patients with autism. The aim of this article is to present the studies investigating false memory and semantic processing in people with typical development using electroencephalography in addition to (presenting) providing the restricted literature on the subject in patients with autism. There is a debate about semantic deficits in autism, but there are few studies in this area and the results are contradictory. Finally, new directions for the development and improvement of new studies are presented.

En las últimas décadas el interés por la investigación de la falsa memoria se ha ampliado. Sin embargo, se observan pocos estudios que investigan los componentes electrofisiológicos subyacentes implicados en el reconocimiento verdadero y el falso, especialmente con respecto a los pacientes con autismo. Este artículo tiene como objetivo presentar los estudios de investigación de la falsa memoria y procesamiento semántico en las personas con desarrollo típico a través del uso de la electroencefalografía, además de presentar la literatura restringida sobre el tema en los pacientes con autismo. Existe un debate acerca de los déficits semánticos en el autismo, pero hay pocos estudios en esta área y con resultados contradictorios. Por último, se presentan nuevas direcciones para el desarrollo y mejora de nuevos estudios.

An ethical discussion of the use of transcranial direct current stimulation for cognitive enhancement in healthy individuals: a fictional case study

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. Because of its low cost, ease of use, safety, and portability, tDCS has been increasingly investigated for therapeutic purposes in neuropsychiatric disorders and in experimental neuropsychological studies with healthy volunteers. These experiments on healthy cognition have shown significant effects on working memory, decision-making, and language. Such promising results have fomented reflections on studying tDCS to enhance or modify normal cognitive function, a concept described by some as "cosmetic" neurology. As the field evolves, discussing whether the use of tDCS in these situations is appropriate is important, including how bioethical principles may help resolve these challenges. In this article, we present some examples of the effects of tDCS on cognition in healthy participants as a starting point for this ethical debate. We envision a futuristic "Brain Boosting" tDCS clinic that specializes in cosmetic neurology and cognitive enhancement. Using the typical cases of a fictitious Dr. Icarus as a discussion starting point, we raise some issues that are both humorous and provocative about the use of tDCS in healthy people. The importance of this work is to ask relatively new questions regarding cosmetic neurology in the field of neuromodulation and discuss the related ethical conflicts.(AU)

An ethical discussion of the use of transcranial direct current stimulation for cognitive enhancement in healthy individuals: a fictional case study

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. Because of its low cost, ease of use, safety, and portability, tDCS has been increasingly investigated for therapeutic purposes in neuropsychiatric disorders and in experimental neuropsychological studies with healthy volunteers. These experiments on healthy cognition have shown significant effects on working memory, decision-making, and language. Such promising results have fomented reflections on studying tDCS to enhance or modify normal cognitive function, a concept described by some as "cosmetic" neurology. As the field evolves, discussing whether the use of tDCS in these situations is appropriate is important, including how bioethical principles may help resolve these challenges. In this article, we present some examples of the effects of tDCS on cognition in healthy participants as a starting point for this ethical debate. We envision a futuristic "Brain Boosting" tDCS clinic that specializes in cosmetic neurology and cognitive enhancement. Using the typical cases of a fictitious Dr. Icarus as a discussion starting point, we raise some issues that are both humorous and provocative about the use of tDCS in healthy people. The importance of this work is to ask relatively new questions regarding cosmetic neurology in the field of neuromodulation and discuss the related ethical conflicts...

Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories.

A recent study found that false memories were reduced by 36% when low frequency repetitive transcranial magnetic stimulation (rTMS) was applied to the left anterior temporal lobe after the encoding (study) phase. Here we were interested in the consequences on a false memory task of brain stimulation throughout the encoding and retrieval task phases. We used transcranial direct current stimulation (tDCS) because it has been shown to be a useful tool to enhance cognition. Specifically, we examined whether tDCS can induce changes in a task assessing false memories. Based on our preliminary results, three conditions of stimulation were chosen: anodal left/cathodal right anterior temporal lobe (ATL) stimulation ("bilateral stimulation"); anodal left ATL stimulation (with a large contralateral cathodal electrode--referred as "unilateral stimulation") and sham stimulation. Our results showed that false memories were reduced significantly after the two active conditions (unilateral and bilateral stimulation) as compared with sham stimulation. There were no significant changes in veridical memories. Our findings show that false memories are reduced by 73% when anodal tDCS is applied to the anterior temporal lobes throughout the encoding and retrieval stages, suggesting a possible strategy for improving certain aspects of learning.

Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study.

OBJECTIVE: Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation. METHODS: We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS ("tDCS/TENS" group), active tDCS/sham TENS ("tDCS" group), and sham tDCS/sham TENS ("sham" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater. RESULTS: The results showed that there was a significant difference in pain reduction across the conditions of stimulation (P=0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/-10.7), P=0.004] and the tDCS condition [reduction by 15.5% (+/-4.9), P=0.014], but not after sham stimulation (P=0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P=0.02). CONCLUSIONS: The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone.