An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment.

Alzheimer's disease (AD) is characterized by reduced fast brain oscillations in the gamma band (γ, > 30 Hz). Several animal studies show that inducing gamma oscillations through (multi)sensory stimulation at 40 Hz has the potential to impact AD-related cognitive decline and neuropathological processes, including amyloid plaques deposition, neurofibrillary tangles formation, and neuronal and synaptic loss. Therefore Gamma Entrainment Using Sensory stimulation (GENUS) is among the most promising approaches for AD patients' treatment. This review summarizes the evidence on GENUS effectiveness, from animal models to AD patients. Despite the application on human is in its infancy, the available findings suggest its feasibility for the treatment of AD. We discuss such results in light of parameter improvement and possible underlying mechanisms. We finally emphasize the need for further research for its development as a disease-modifying non-pharmacological intervention.

Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia.

Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1-90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63-80 Hz) in occipital regions and upregulated low frequency (5-28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.

Using hypnosis to disrupt face processing: mirrored-self misidentification delusion and different visual media.

Mirrored-self misidentification delusion is the belief that one's reflection in the mirror is not oneself. This experiment used hypnotic suggestion to impair normal face processing in healthy participants and recreate key aspects of the delusion in the laboratory. From a pool of 439 participants, 22 high hypnotisable participants ("highs") and 20 low hypnotisable participants were selected on the basis of their extreme scores on two separately administered measures of hypnotisability. These participants received a hypnotic induction and a suggestion for either impaired (i) self-face recognition or (ii) impaired recognition of all faces. Participants were tested on their ability to recognize themselves in a mirror and other visual media - including a photograph, live video, and handheld mirror - and their ability to recognize other people, including the experimenter and famous faces. Both suggestions produced impaired self-face recognition and recreated key aspects of the delusion in highs. However, only the suggestion for impaired other-face recognition disrupted recognition of other faces, albeit in a minority of highs. The findings confirm that hypnotic suggestion can disrupt face processing and recreate features of mirrored-self misidentification. The variability seen in participants' responses also corresponds to the heterogeneity seen in clinical patients. An important direction for future research will be to examine sources of this variability within both clinical patients and the hypnotic model.

TMS-EEG signatures of GABAergic neurotransmission in the human cortex.

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.