Transcranial Magnetic Stimulation

Increased incidence of Alzheimer’s disease (AD) in individuals with Diabetes Type II (DM2) suggests a possible pathophysiologic link. Support for such a link comes from several experimental animal models. Insulin deficiency and resistance are major factors in the pathogenesis of DM2 and appear to be involved in the neurodegenerative processes of AD by altering synaptic brain plasticity. Transcranial magnetic stimulation (TMS) can be used to examine mechanisms of plasticity, and may thus reveal abnormalities in patients with DM2 that might resemble those in patients with AD.Evaluate cortical plasticity mechanisms in subjects with DM2 and compare them with those in patients with AD as assessed by TMS measures. Explore possible similarities in abnormal brain plasticity in order to investigate the link between DM2 and AD.To evaluate cortical brain plasticity we applied intermittent theta burst stimulation (iTBS) at 80% of active motor threshold (aMT) over the left primary motor cortex (M1) in patients with mild to moderate AD, DM2 and in healthy individuals. iTBS consisted of a total of 600 pulses divided into 20 trains, each including bursts of 3 pulses at 50Hz repeated at 5Hz for 2s and with an 8s interval between trains. Motor evoked potentials (MEPs) of the right first dorsal interosseus muscle (FDI) were triggered by neuronavigated single pulse transcranial magnetic stimulation (spTMS) over left M1 at 120% of resting motor threshold (rMT) before and after iTBS. Changes in MEP amplitudes after iTBS were examined as measures of long term potentiation (LTP) like plasticity.Within the first 20min following iTBS baseline corrected MEPs were significantly larger for healthy subjects (1.32 ±0.21mV) compared to patients with AD (0.92 ±0.08mV; p=0.023) and DM2 (0.69±0.15mV; p=0.007) (Fig. 1). There was no significant difference between AD and DM2 (p=0.63). Interestingly, while iTBS had almost no effect on AD patients it tended to have a paradoxically inhibitory effect in patients with DM2.The iTBS-induced modulation of corticospinal excitability is impaired in both AD and DM2. This finding supports the notion of aberrant LTP-like mechanisms of plasticity in DM2 and AD, and suggests a pathophysiologic link between the two diseases. This link may account for the epidemiologically increased risk for patients with DM2 to develop AD. Further studies and longitudinal assessments are needed to explore such a link further, but in this context, TMS-methods appear promising and may become a valuable early biomarker for AD and individuals at risk.The study was sponsored and supported by the Harvard Catalyst, Nexstim, Neuronix Ltd., the National Institutes of Health, and the Berenson-Allen Foundation.

Cognitive decline is one of the core symptoms of Alzheimer's Disease (AD) (Cummings et al., 1998). AD is associated with brain atrophy and connectivity impairments and has a tremendous impact on quality of life (Alzheimer's Association Facts and Figures' Report, 2010). Up to date there is little evidence on beneficial effects from cognitive interventions (Clare et al., 2003), possibly because of abnormal mechanisms of brain plasticity in AD patients. Transcranial magnetic stimulation (TMS) may be used to modulate brain plasticity and thus might prompt the effects of cognitive training (Bashir et al., 2010; Freitas et al., 2010). In this proof-of-principle study we applied NeuroAD using NICE technology (Neuronix Ltd. Israel) and measured its impact on cognitive functions as well as on brain plasticity in patients with mild AD. A recent, open-label study of NeuroAD showed encouraging clinical results (Bentwich et al., 2011).

A wealth of in vitro and in vivo evidence demonstrates alterations in neuroplasticity and impaired synaptic function in Alzheimer's disease (AD). There is a critical need for an assay of neuroplasticity that can act as a surrogate marker of the pathological changes in AD. Theta-burst stimulation (TBS) modulates neuronal responses to TMS, which can be assessed with EEG/EMG. Intermittent (iTBS) or continuous (cTBS) theta-burst stimulation lead to an enhancement or suppression of cortical activity and are considered an index of LTP- and LTD-like induction of synaptic plasticity.

Increased attentional demand has been shown to reduce motor performance, leading to increases in accidents, particularly in elderly populations. While these deficits have been well documented behaviorally, their cortical correlates are lesswell known. Increased attention has been shown to affect activity in prefrontal regions of the cortex. However there have been varying results within past research investigating corticomotor regions, mediating motor performance.This mini-reviewinitially discusses past behavioral research, before moving to studies investigating corticomotor areas in response to changes in attention. Recent dual task studies have revealed a possible decline in the ability of older, but not younger, adults to activate inhibitory processes within the motor cortex, which may be correlated with poor motor performance, and thus accidents. A reduction in cortical inhibition may be caused by neurodegeneration within prefrontal regions of the cortex with age, rendering older adults less able to allocate attention to corticomotor regions.

It has been established that acute (within-session) repetitive transcranial magnetic stimulation (rTMS) improves spatial working memory (SWM). However, questions remain regarding the safety and effectiveness of multiple bouts of rTMS and the optimal cortical area to stimulate. This preliminary study investigated, in healthy participants, multiple bouts of rTMS over the dorsolateral pre-frontal cortex (DLPFC), or posterior parietal cortex (PPC) on SWM. Twenty participants (10m, 10f), all naïve to rTMS, where randomized into a DLPFC or PPC group, receiving six sessions of rTMS (5 Hz at 80% of motor threshold) every second day over two weeks. Prior to and post rTMS bouts, all participants completed testing for SWM measuring individuals’ accuracy, strategy, and speed. Following repeated bouts of rTMS, significant improvements were observed with no contraindications in stimulating PPC but not DLPFC. This preliminary study has demonstrated that repeated rTMS bouts improve SWM safety providing potential for clinical application.

Electroconvulsive therapy (ECT) is the longest standing psychiatric treatment available and has unequivocal benefit in severe depression. However this treatment comes with a number of side effects such as memory impairment. On the other hand, Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new form of treatment which has been shown to be efficacious in patients suffering from a number of psychopathologies, including severe depression, with few reported side effects. Due to its potential therapeutic efficacy and lack of side effects, rTMS has gained traction in the treatment of depression, with a number of authors keen to see it take over from ECT. However, it is not clear whether rTMS represents a therapeutic alternative to ECT. This meta-analysis will therefore compare the “gold standard” treatment for severe depression, with the relatively new but promising rTMS. A literature search will be performed with the intention to include all randomised clinical trials. The null hypothesis is that there is no difference in the antidepressant efficacy between the two types of treatment modalities. Statistical analysis of Hamilton Depression Rating Scale (HDRS) scores will be performed.

The treatment of choice for acute schizophrenia is antipsychotic drug treatment and electroconvulsive therapy (ECT) and should only be considered as an option for treatment-resistant schizophrenia, where treatment with clozapine has already proven ineffective or intolerable. The use of ECT as a maintenance treatment for patients with schizophrenia and comorbid epilepsy is uncommon as scant evidence exists to support this. We describe a patient with a serious case of paranoid schizophrenia and comorbid epilepsy who had not responded to typical and atypical antipsychotic medication, but responded remarkably to acute ECT and required maintenance ECT to sustain a positive therapeutic response.