Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer’s dementia

Kuhn, Jens; Hardenacke, K.; Lenartz, Doris; Gruendler, Theo O.J.; Ullsperger, Markus; Bartsch, Christina; K, J; Zilles, Karl; Bauer, Andreas; Matusch, Andreas; Rj, Schulz; Noreik, Michaela; Bührle, Christian; Maintz, David; Woopen, Christiane; Häussermann, Peter; Hellmich, Martin; Klosterkötter, Joachim; Wiltfang, Jens; Maarouf, Mohammad; Freund, H. J.; Sturm, Volker

doi:10.1038/mp.2014.32

Cited by 225 publications

(228 citation statements)

References 34 publications

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“…Deep brain stimulation (DBS) is a surgical technique that involves the delivery of electrical current to the brain parenchyma through implanted electrodes. In psychiatry, DBS has been approved for treatment-resistant obsessivecompulsive disorders (Hamani et al, 2014b) and is currently being investigated for depression (Holtzheimer et al, 2012;Lozano et al, 2008;Malone et al, 2009;Mayberg et al, 2005), anorexia (Lipsman et al, 2013), Alzheimer's disease (Kuhn et al, 2015;Laxton et al, 2010) and drug addiction Stelten et al, 2008;Voges et al, 2013). So far, though different targets have been proposed (Ewing and Winter, 2013;Mikell et al, 2009), no clinical trials have been reported on the use of DBS in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia

Bikovsky

Hadar

Soto-Montenegro

et al. 2016

Experimental Neurology

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Schizophrenia is a debilitating psychiatric disorder with a significant number of patients not adequately responding to treatment. Deep brain stimulation (DBS) is a surgical technique currently investigated for medically-refractory psychiatric disorders. Here, we use the poly I:C rat model of schizophrenia to study the effects of medial prefrontal cortex (mPFC) and nucleus accumbens (Nacc) DBS on two behavioral schizophrenia-like deficits, i.e. sensorimotor gating, as reflected by disrupted prepulse inhibition (PPI), and attentional selectivity, as reflected by disrupted latent inhibition (LI). In addition, the neurocircuitry influenced by DBS was studied using FDG PET. We found that mPFC-and Nacc-DBS alleviated PPI and LI abnormalities in poly I:C offspring, whereas Nacc-but not mPFC-DBS disrupted PPI and LI in saline offspring. In saline offspring, mPFC-DBS increased metabolism in the parietal cortex, striatum, ventral hippocampus and Nacc, while reducing it in the brainstem, cerebellum, hypothalamus and periaqueductal gray. Nacc-DBS, on the other hand, increased activity in the ventral hippocampus CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscriptand olfactory bulb and reduced it in the septal area, brainstem, periaqueductal gray and hypothalamus. In poly I:C offspring changes in metabolism following mPFC-DBS were similar to those recorded in saline offspring, except for a reduced activity in the brainstem and hypothalamus. In contrast, Nacc-DBS did not induce any statistical changes in brain metabolism in poly I:C offspring. Our study shows that mPFC-or Nacc-DBS delivered to the adult progeny of poly I:C treated dams improves deficits in PPI and LI. Despite common behavioral responses, stimulation in the two targets induced different metabolic effects.

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Section: Introductionmentioning

confidence: 99%

Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia

Bikovsky

Hadar

Soto-Montenegro

et al. 2016

Experimental Neurology

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“…With NBM DBS off, the patient returned to his baseline poor cognitive state; with the NBM DBS on, the patient regained his cognitive improvement as before. These promising results led these authors to initiate a phase I trial of NBM DBS in six patients with mild to moderate AD, which has recently been completed and published (Kuhn et al 2015).…”

Section: Electrical Neural Stimulation For Alzheimer's Diseasementioning

confidence: 96%

The rationale for deep brain stimulation in Alzheimer’s disease

2015

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Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials.

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“…Stimulation of the nucleus basalis of Meynert (NBM) has been used in PD dementia reported in a single case [90] and there is also a phase I trial of NBM stimulation in Alzheimer's dementia [91]. Despite the mostly advanced age of these patients, a recent analysis has shown that clinical and economic thresholds required for DBS to be cost-effective for dementia are relatively low [92].…”

Section: Lewy Body Dementiasmentioning

confidence: 98%

Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments

2015

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Modern deep brain stimulation (DBS) has become a routine therapy for patients with movement disorders such as Parkinson's disease, generalized or segmental dystonia and for multiple forms of tremor. Growing numbers of publications also report beneficial effects in other movement disorders such as Tourette's syndrome, various forms of chorea and DBS is even being studied for Parkinson's-related dementia. While exerting remarkable effects on many motor symptoms, DBS does not restore normal neurophysiology and therefore may also have undesirable side effects including speech and gait deterioration. Furthermore, its efficacy might be compromised in the long term, due to progression of the underlying disease. Various programming strategies have been studied to try and address these issues, e.g., the use of low-frequency rather than high-frequency stimulation or the targeting of alternative brain structures such as the pedunculopontine nucleus. In addition, further technical developments will soon provide clinicians with an expanded choice of hardware such as segmented electrodes allowing for a steering of the current to optimize beneficial effects and reduce side effects as well as the possibility of adaptive stimulation systems based on closed-loop concepts with or without accompanying advances in programming and imaging software. In the present article, we will provide an update on the most recent achievements and discoveries relevant to the application of DBS in the treatment of movement disorder patients and give an outlook on future clinical and technical developments.

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Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer’s dementia

Cited by 225 publications

References 34 publications

Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia

Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia

The rationale for deep brain stimulation in Alzheimer’s disease

Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments

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