The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer's disease.

Evidence suggests that Alzheimer's disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to healthy elderly who presented both. At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal locations. Our study provides empirical evidence for the possibility to adopt aMMN as an index for assessing cognitive decline in pathological ageing.

Bursts of transcranial electrical stimulation increase arousal in a continuous performance test.

Arousal reflects a state of generalised physiological activation, and its key role in cognition and behaviour has been extensively described. The regulation of arousal is controlled by specific nuclei located in the brainstem that contain widely distributed projections to the cortex and form the arousal systems. In humans, arousal has been commonly studied and modulated through behavioural paradigms, whereas in animals, direct electrical stimulation has been used to confirm the important role of these widely distributed structures. Recent evidence suggests that it might be possible to use transcranial electrical stimulation (tES) to non-invasively induce currents in the brainstem regions of the brain. Therefore, we hypothesise that, using a specific electrode arrangement, it might be possible to employ tES to stimulate subcortical-cortical neuromodulatory networks, inducing modulation of general arousal. The aim of the present study was to determine if it is possible to increase arousal during a discriminative reaction times (RTs) task, through the application of tES, to improve the subjects' performance. We developed 3 experiments: Experiment 1 validated the behavioural task, which was an adapted version of the continuous performance test. Experiment 2 aimed to show the task sensitivity to the level of activation. The results confirmed that the task was sensitive enough to reveal modulations of arousal. In Experiment 3, we applied bursts of tES concurrent with the onset of the relevant stimuli of the task to increase the physiological phasic activation of arousal. The skin conductance response was recorded during the experiment in addition to the RTs. The results showed a reduction of RTs and a concurrent increase in skin conductance during the real stimulation condition, which is consistent with a general increase in arousal. In all, these data support the effectiveness of bursts of tES in modulating arousal.

The functional importance of rhythmic activity in the brain.

Oscillations in brain activity have long been known, but many fundamental aspects of such brain rhythms, particularly their functional importance, have been unclear. As we review here, new insights into these issues are emerging from the application of intervention approaches. In these approaches, the timing of brain oscillations is manipulated by non-invasive brain stimulation, either through sensory input or transcranially, and the behavioural consequence then monitored. Notably, such manipulations have led to rapid, periodic fluctuations in behavioural performance, which co-cycle with underlying brain oscillations. Such findings establish a causal relationship between brain oscillations and behaviour, and are allowing novel tests of longstanding models about the functions of brain oscillations.

Transcranial brain stimulation studies of episodic memory in young adults, elderly adults and individuals with memory dysfunction: a review.

Transcranial magnetic and electric stimulation studies examining episodic memory in young participants have established the role of the left prefrontal cortex during encoding and the right prefrontal cortex during episodic retrieval. Furthermore, these techniques have been used to verify the reduction in functional asymmetry in the prefrontal cortex that occurs with ageing, at least during encoding, suggesting the existence of compensatory adjustments for the structural and neurotransmitter loss that occurs with physiological ageing. Nevertheless, it has been shown that several factors can modulate performance based on the type of material or strategy used. It is important to note that although numerous studies have addressed the role of the prefrontal cortex in episodic memory, a number of studies have also demonstrated the involvement of a more distributed neural network sustaining this function involving the temporal lobes and parietal cortices. Finally, it is evident that the use of transcranial stimulation techniques might represent a powerful tool not only for investigating the involvement of cerebral areas in a specific cognitive task but also for designing interventional therapies for individuals with memory impairment.

Random noise stimulation improves neuroplasticity in perceptual learning.

Perceptual learning is considered a manifestation of neural plasticity in the human brain. We investigated brain plasticity mechanisms in a learning task using noninvasive transcranial electrical stimulation (tES). We hypothesized that different types of tES would have varying actions on the nervous system, which would result in different efficacies of neural plasticity modulation. Thus, the principal goal of the present study was to verify the possibility of inducing differential plasticity effects using two tES approaches [i.e., direct current stimulation (tDCS) and random noise stimulation (tRNS)] during the execution of a visual perceptual learning task.

Anomia training and brain stimulation in chronic aphasia.

Recent studies have reported enhanced performance on language tasks induced by non-invasive brain stimulation, i.e., repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), in patients with aphasia due to stroke or Alzheimer's disease (AD). The first part of this article reviews brain stimulation studies related to language recovery in aphasic patients. The second part reports results from a pilot study with three chronic stroke patients who had non-fluent aphasia, where real or placebo rTMS was immediately followed by 25 minutes of individualised speech therapy. Real rTMS consisted of high-frequency rTMS over the left dorsolateral prefrontal cortex (BA 8/9) for 25 minutes. Each patient underwent a total of four weeks of intervention. P1 underwent four weeks of real rTMS (5 days/week) where individualised speech therapy was provided for 25 minutes immediately following each rTMS session. P2 and P3 each underwent two weeks of placebo rTMS, followed immediately by individualised speech therapy; then two weeks of real rTMS, followed immediately by individualised speech therapy. Assessments took place at 2, 4, 12, 24 and 48 weeks post-entry/baseline testing. Relative to entry/baseline testing, a significant improvement in object naming was observed at all testing times, from two weeks post-intervention in real rTMS plus speech therapy, or placebo rTMS plus speech therapy. Our findings suggest beneficial effects of targeted behavioural training in combination with brain stimulation in chronic aphasic patients. However, further work is required in order to verify whether optimal combination parameters (rTMS alone or speech therapy alone) and length of rTMS treatment may be found.

Efficacy of repetitive transcranial magnetic stimulation/transcranial direct current stimulation in cognitive neurorehabilitation.

Cognitive deficits are a common consequence of neurologic disease, in particular, of traumatic brain injury, stroke, and neurodegenerative disorders, and there is evidence that specific cognitive training may be effective in cognitive rehabilitation. Several investigations emphasize the fact that interacting with cortical activity, by means of cortical stimulation, can positively affect the short-term cognitive performance and improve the rehabilitation potential of neurologic patients. In this respect, preliminary evidence suggests that cortical stimulation may play a role in treating aphasia, unilateral neglect, and other cognitive disorders. Several possible mechanisms can account for the effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) on cognitive performance. They all reflect the potential of these methods to improve the subject's ability to relearn or to acquire new strategies for carrying out behavioral tasks. The responsible mechanisms remain unclear but they are most likely related to the activation of impeded pathways or inhibition of maladaptive responses. Modifications of the brain activity may assist relearning by facilitating local activity or by suppressing interfering activity from other brain areas. Notwithstanding the promise of these preliminary findings, to date no systematic application of these methods to neurorehabilitation research has been reported. Considering the potential benefit of these interventions, further studies taking into consideration large patient populations, long treatment periods, or the combination of different rehabilitation strategies are needed. Brain stimulation is indeed an exciting opportunity in the field of cognitive neurorehabilitation, which is clearly in need of further research.