Article

Deep Brain Stimulation for the Treatment of Alzheimer Disease and Dementias

Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
World Neurosurgery (Impact Factor: 2.88). 06/2012; 80(3-4). DOI: 10.1016/j.wneu.2012.06.028
Source: PubMed

ABSTRACT

Objective:
To review the use of deep brain stimulation (DBS) for treatment of dementia.

Methods:
A PubMed literature search was conducted to identify all studies that have investigated the use of DBS for treatment of dementia.

Results:
Three studies examined the use of DBS for dementia. One study involved fornix DBS for Alzheimer disease (AD), and two studies involved DBS of the nucleus basalis of Meynert, one to treat AD and one to treat Parkinson disease dementia.

Conclusions:
Evidence for the use of DBS to treat dementia is preliminary and limited. Fornix and nucleus basalis of Meynert DBS can influence activity in the pathologic neural circuits that underlie AD and Parkinson disease dementia. Further investigation into the potential clinical effects of DBS for dementia is warranted.

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Available from: Adrian W. Laxton, Aug 01, 2014
    • "This circuit includes the hippocampus (HP), fornix, mammillary body, anterior nucleus of the thalamus, cingulate cortex, parahippocampal gyrus, and entorhinal cortex (Mesulam, 2000). Within this circuit, the fornix is a major candidate brain target for DBS to treat memory impairment (Hescham et al., 2013;Laxton and Lozano, 2013). Specifically, in Alzheimer's disease (AD), it is proposed that fornix DBS influences memory recall by enhancing activity across distinct nodes involved in memory retrievalNeuroImage "
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    ABSTRACT: Introduction: Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. Methods: A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Results: Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. Conclusions: The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop.
    No preview · Article · Jan 2016 · NeuroImage
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    • "Evidence that MTL activity exerts a driving influence on PCC activity comes from a recent report on deep brain stimulation for Alzheimer's disease. Chronic stimulation of the fornix, an important component of hippocampal circuitry, was associated with significantly increased glucose metabolism in the PCC (Laxton et al., 2012). "
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    ABSTRACT: Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neural dynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of ‘primary states’ is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. It is noted that elevated entropy in this sense, is a characteristic of systems exhibiting ‘self-organised criticality’, i.e., a property of systems that gravitate towards a ‘critical’ point in a transition zone between order and disorder in which certain phenomena such as power-law scaling appear. This implies that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organised activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as REM sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetised state.
    Full-text · Article · Feb 2014 · Frontiers in Human Neuroscience
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    • "By comparison to this pharmacological work, there are relatively few studies examining how cortical processing is affected by electrical BF stimulation, which evokes endogenous Acetylcholine (ACh) release in the cortex [32-34]. This is somewhat surprising given that BF stimulation is currently being tested for clinical use in patients suffering from brain disorders linked to cholinergic dysfunction such as Alzheimer’s disease and Lewy body dementia [35,36]. We therefore aimed to investigate the effects of BF stimulation on sensory processing in the visual cortex, and link the observed effects to our previous results of selective nAChR and mAChR stimulation [37]. "
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    ABSTRACT: Background The basal forebrain (BF) regulates cortical activity by the action of cholinergic projections to the cortex. At the same time, it also sends substantial GABAergic projections to both cortex and thalamus, whose functional role has received far less attention. We used deep brain stimulation (DBS) in the BF, which is thought to activate both types of projections, to investigate the impact of BF activation on V1 neural activity. Results BF stimulation robustly increased V1 single and multi-unit activity, led to moderate decreases in orientation selectivity and a remarkable increase in contrast sensitivity as demonstrated by a reduced semi-saturation contrast. The spontaneous V1 local field potential often exhibited spectral peaks centered at 40 and 70 Hz as well as reliably showed a broad γ-band (30-90 Hz) increase following BF stimulation, whereas effects in a low frequency band (1-10 Hz) were less consistent. The broad γ-band, rather than low frequency activity or spectral peaks was the best predictor of both the firing rate increase and contrast sensitivity increase of V1 unit activity. Conclusions We conclude that BF activation has a strong influence on contrast sensitivity in V1. We suggest that, in addition to cholinergic modulation, the BF GABAergic projections play a crucial role in the impact of BF DBS on cortical activity.
    Full-text · Article · May 2013 · BMC Neuroscience
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