The effect of fornix deep brain stimulation in brain diseases

Liu, Huajie; Temel, Yasin; Boonstra, Jackson; Hescham, Sarah

doi:10.1007/s00018-020-03456-4

Cited by 18 publications

(14 citation statements)

References 97 publications

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“…If the BOLD baseline shift is related to the stimulus-induced altered network "state" then short (consecutive) low frequency pulse stimulations are already sufficient to affect the network "state" of the hippocampus. This is of particular interest as fornix stimulation is also considered as target to treat epilepsy [48,49]. In this context, short low frequency and high-frequency pulse trains would effectively modify the network "state" of the hippocampus but high-frequency pulse trains would also modify brain wide neuronal networks that affect the mPFC, thus low frequency pulse protocols might be better suited to selectively modify hippocampal functions.…”

Section: Frequency-dependent Activation Of Different Neuronal Networkmentioning

confidence: 99%

Frequency-dependent electrical stimulation of fimbria-fornix preferentially affects the mesolimbic dopamine system or prefrontal cortex

Helbing

Angenstein

2020

Brain Stimulation

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Background: The fimbria/fornix fiber system is an essential part of the hippocampal-VTA loop, and therefore activities that are propagated through this fiber system control the activity of the mesolimbic dopamine system. Objectives/hypothesis: We hypothesized that stimulation of the fimbria/fornix with an increasing number of electrical pulses would cause increasing activity of the mesolimbic dopamine system, which coincides with concurrent changes in neuronal activities in target regions of the mesolimbic dopaminergic system. Methods: Right fimbria/fornix fibers were electrically stimulated with different pulse protocols. Stimulus-induced changes in neuronal activities were visualized with BOLD-fMRI, whereas stimulusinduced release of dopamine, as measured for the activity of the mesolimbic dopamine system, was determined in the nucleus accumbens with in vivo fast-scan cyclic voltammetry. Results: Dependent on the protocol, electrical fimbria/fornix stimulation caused BOLD responses in various targets of the mesolimbic dopamine system. Stimulation in the low theta frequency range (5 Hz) triggered significant BOLD responses mainly in the hippocampal formation, infralimbic cortex, and septum. Stimulation in the beta frequency range (20 Hz) caused additional activation in the medial prefrontal cortex (mPFC), nucleus accumbens, striatum, and VTA. Stimulation in the high-gamma frequency range (100 Hz) caused further activation in the hippocampus proper and mPFC. The strong activation in the mPFC during 100 Hz stimulations depended not only on the number of pulses but also on the frequency. Thus, short bursts of 5 or 20 high-frequency pulses caused stronger activation in the mPFC than continuous 5 or 20 Hz pulses. In contrast, high-frequency burst fimbria/fornix stimulation did not further activate the mesolimbic dopamine system when compared to continuous 5 or 20 Hz pulse stimulation. Conclusions: There exists a frequency-dependent dissociation between BOLD responses and activation of the dopaminergic system. Low frequencies were more efficient to activate the mesolimbic dopamine system, whereas high frequencies were more efficient to trigger BOLD responses in target regions of the mesolimbic dopamine system, particularly the mPFC.

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Section: Frequency-dependent Activation Of Different Neuronal Networkmentioning

confidence: 99%

Frequency-dependent electrical stimulation of fimbria-fornix preferentially affects the mesolimbic dopamine system or prefrontal cortex

Helbing

Angenstein

2020

Brain Stimulation

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“…6,10 Pharmacological treatments alleviate symptoms temporarily and have not been effective for all people with AD, leaving many people without effective treatment and hoping for other options. 12 This has led to the investigation of different neuromodulation techniques for the treatment of AD, many of which are currently being used for other neurologic and psychiatric disorders. Given the heterogeneity of the disease, the lack of effective treatments, and the number of people in Canada living with AD, exploring the potential use of neuromodulation techniques has become an evolving field of interest to researchers, caregivers, and patients with AD.…”

Section: Background and Current Practicementioning

confidence: 99%

“…16 Other systematic reviews investigating stimulation of the fornix 2,16 and the nucleus basalis of Meynert 2 with DBS also report promising but inconclusive findings, concluding that DBS appears to be a feasible and safe intervention for patients with AD, but that human research is limited to preliminary results and that different stimulation parameters need to be further investigated because of the heterogenous symptoms associated with AD. 2,12 While preliminary efficacy and safety studies have had positive findings pointing to the potential effectiveness for the treatment of AD, most studies have small sample sizes (fewer than 50 people) consisting of participants with mild AD, with follow-up shortly after DBS and with a lack of long-term evidence of cognitive benefits. 2 After the promising safety results from 1 of the most highly referenced DBS-fornix trials for the treatment of AD -the phase IIb, randomized, double-blind ADvance Study 21 -Functional Neuromodulation's DBS system was approved for the treatment of AD in Europe.…”

Section: Deep Brain Stimulationmentioning

confidence: 99%

Neuromodulation Technologies for the Treatment of Alzheimer Disease

Gunn¹,

Grobelna²

2021

cjht

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There are not very many effective treatment options for Alzheimer disease most of the options have side effects and temporarily reduce symptoms rather than delay disease progression. Effective treatments with minimal side effects that prevent and reduce the severity of Alzheimer disease are needed. Neuromodulation techniques have recently emerged for the treatment of Alzheimer disease, with the hope of filling some of these treatment gaps. Two invasive and 8 noninvasive techniques are described in this Horizon Scan, some with more published evidence than others. Deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation have more published studies involving patients with Alzheimer disease. Technologies at an earlier stage of development and with fewer studies providing an evidence base include vagus nerve stimulation, ultrasound stimulation, electromagnetic stimulation, photobiomodulation, infrared stimulation, and auditory stimulation. The evidence regarding neuromodulation techniques is mostly promising; however, most studies are preliminary or include fewer than 50 participants. Given the heterogeneous nature of Alzheimer disease and the variety of methods in which the different neuromodulation technologies can be used, more research is needed to determine the effectiveness and relative effectiveness of neuromodulation techniques and devices. Limitations in the research include limited evidence on the long-term effects and cost-effectiveness of the techniques in the treatment of Alzheimer disease, as well as the clinical significance of the results in the published studies thus far. Despite the limited evidence, the results emerging from the literature are hopeful for many people living with Alzheimer disease. Importantly, the lack of reported serious side effects is a hopeful start for many who currently experience difficulties with pharmaceuticals. Given the heterogeneous nature of Alzheimer disease, the increased variety in treatment options also offers hope in potentially finding more effective treatments for individuals living with the debilitating disease.

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“…Scopolamine (a muscarinic cholinergic receptor antagonist) impairs memory and learning in animal models (58). DBS of the fornix is able to reverse these behavioural deficits: for instance, DBS of the fornix improves the performance of rats during the acquisition and retention trial of the object location task.…”

Section: Behaviouralmentioning

confidence: 99%

“…While the other potential clinical target of DBS in AD is the fornix that is located in the medial temporal lobe. Forniceal fibers arise from hippocampus and consist from the left and right crura that are united together to form the body of the fornix in which its posterior fibers continue through hypothalamus to mammillary bodies, then to the anterior thalamic nucleus and project to the cingulate cortex (58). The fornix is part of the limbic system that contains a circuit known as the circuit of Papez which is responsible for memory formation (24).…”

mentioning

confidence: 99%

Deep brain stimulation and memory functions

Aldehri¹

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People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website.• The final author version and the galley proof are versions of the publication after peer review.• The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. General introduction 13Chapter 1 MemoryMemory is the brain's ability to encode, store and later retrieve or recall learned knowledge and information (1). Encoding refers to processing recent information (2). Storage refers to the system by which memory is kept and the site where it is kept. Retrieval deals with the process which permits the recall of saved information (1, 2). Learning and memory are important in order to assess how the environment can affect our behavior. Learning can be defined as the ability to obtain and store information from the environment (1, 3, 4).We have both implicit and explicit memories. Implicit memory requires perceptual and motor training and can be unconsciously recalled. Implicit memory has different forms: non-associative and associative. The non-associative learning refers to the replication of one stimulus. In contrast, with associative learning, the relationship is between two stimuli, or the relationship between the stimulus and behaviour (1, 5-7). Explicit memory depends on factual knowledge of people, places or objects that requires a conscious effort to be recalled, and it is represented by the medial temporal lobe. The psychologist Endel Tulving further classified explicit memory (8) as episodic (memory of events and personal experiences, e.g. I remember my first day at school) or semantic (memory of facts, e.g. lead is heavier than wood) (1, 5, 7).The knowledge that has been stored as explicit memory is processed in the polymodal cortices that produce visual, auditory and physical information (prefrontal, limbic and parieto-occcipital temporal cortices). Information is transported afterwards to the parahippocampal and perirhinal cortices, then, to the entorhinal cortex, dentate gyrus, hippocampus, subiculum; and then returns back to the entorhinal cortex. After that the information is conveyed from the entorhinal cortex to the parahippocampal and perirhinal cortices and afterwards to the polymodal area of the neocortex. The entorhinal cortex plays an important role in information processing....

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The effect of fornix deep brain stimulation in brain diseases

Cited by 18 publications

References 97 publications

Frequency-dependent electrical stimulation of fimbria-fornix preferentially affects the mesolimbic dopamine system or prefrontal cortex

Frequency-dependent electrical stimulation of fimbria-fornix preferentially affects the mesolimbic dopamine system or prefrontal cortex

Neuromodulation Technologies for the Treatment of Alzheimer Disease

Deep brain stimulation and memory functions

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