The current drug treatment for Alzheimer's disease (AD) is only partially and temporary effective. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current inducing modulation in cortical excitability. In addition, cognitive training (COG) may improve cognitive functions in AD. Our aim was to treat AD patients combining high-frequency repetitive TMS interlaced with COG (rTMS-COG). Eight patients with probable AD, treated for more than 2 months with cholinesterase inhibitors, were subjected to daily rTMS-COG sessions (5/week) for 6 weeks, followed by maintenance sessions (2/week) for an additional 3 months. Six brain regions, located individually by MRI, were stimulated. COG tasks were developed to fit these regions. Primary objectives were average improvement of Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) and Clinical Global Impression of Change (CGIC) (after 6 weeks and 4.5 months, compared to baseline). Secondary objectives were average improvement of MMSE, ADAS-ADL, Hamilton Depression Scale (HAMILTON) and Neuropsychiatric Inventory (NPI). One patient abandoned the study after 2 months (severe urinary sepsis). ADAS-cog (average) improved by approximately 4 points after both 6 weeks and 4.5 months of treatment (P < 0.01 and P < 0.05) and CGIC by 1.0 and 1.6 points, respectively. MMSE, ADAS-ADL and HAMILTON improved, but without statistical significance. NPI did not change. No side effects were recorded. In this study, rTMS-COG (provided by Neuronix Ltd., Yokneam, Israel) seems a promising effective and safe modality for AD treatment, possibly as good as cholinesterase inhibitors. A European double blind study is underway.

A key working hypothesis in neuroscience is 'materialistic reductionism', i.e., the assumption whereby all physiological, behavioral or cognitive phenomena is produced by localized neurochemical brain activation (but not vice versa). However, analysis of sub-threshold Weber's psychophysical stimulation indicates its computational irreducibility to the direct interaction between psychophysical stimulation and any neuron/s. This is because the materialistic-reductionistic working hypothesis assumes that the determination of the existence or non-existence of any psychophysical stimulation [s] may only be determined through its direct interaction [di1] with a given neuron/s [N] that together forms the 'neural registry' computational level [NR/di1]. But, this implies that in cases of (initial) sub-threshold (sensory-specific) psychophysical stimulation which is increased above the sensory-specific threshold but below Weber's psychophysical 'dv'-the psychophysical computational processing [PCP] produces an apparently 'computationally indeterminate' output. This is because materialistic reductionism asserts the contingency of PCP upon the existence of a direct interaction between 's' and 'N' within the NR/di1 level, but in the special case of Weber's sub-threshold psychophysical stimulation the same PCP/di1 also asserts the non-existence of 's' (as demanded by Weber's psychophysical law). However, given robust empirical evidence indicating the capability of PCP to determine whether (or not) 's' exists, we must conclude that PCP may not be carried out from within NR's direct interaction between a particular psychophysical stimulation and any set of neuron/s in the brain. Hence, the Duality Principle asserts the conceptual irreducibility of sub-threshold psychophysical stimulation to any direct NR/di1: s-N interaction, thereby challenging the current materialistic-reductionistic assumption.

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