Stimulation-induced side effects after deep brain stimulation – a systematic review

Zarzycki, Marcin Zygmunt; Domitrz, Izabela

doi:10.1017/neu.2019.35

Cited by 59 publications

(42 citation statements)

References 46 publications

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“…Here we show that the effects of neural stimulation are not simply localized but spread out over a large network, and persist following stimulation. These observations could provide a mechanism for the yet unexplained side effects of real-time interventions such as DBS, which include mania, psychosis, and depression [43]. Fortunately, we show that the secondary effects of network-level and persisting FCC can be predicted by taking into account characteristics of the underlying cortical network.…”

Section: Discussionmentioning

confidence: 66%

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Cortical network structure mediates response to stimulation: an optogenetic study in non-human primates

Bloch

Greaves-Tunnell

Shea‐Brown

et al. 2021

Preprint

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Brain stimulation interventions are used for the treatment of neurological disorders such as Parkinson's and depression. Despite some success, the effects of stimulation are poorly understood, as evidenced by unknown mechanisms governing therapeutic outcomes, widespread side-effects, and inconsistent results in clinical translation. This incomplete understanding may originate from incomplete treatment of the effects of stimulation, as most studies limit their scale and subject of analysis to local effects of various stimulation protocols. Indeed, in a recent paper we demonstrated that neural stimulation impacts the brain at the network scale; here, we leverage advances in neural interfaces and interpretable machine learning to reveal that the cortical network is the primary controlling factor of the response to stimulation. Using optogenetic stimulation and micro-electrocorticography (μECoG) recording in two awake rhesus macaques, we induce and record widespread functional connectivity changes over large-scale sensorimotor cortical networks. We then use a novel nonparametric modeling framework to predict these changes from the stimulation protocol and from characteristics of the underlying cortical network. We observe that the stimulation protocol only explains a small portion of the network response to stimulation while the network structure characteristics explain much more of the response, implicating the underlying network as the primary mediator of the response to stimulation. We extract the relationships linking the stimulation and network characteristics to the functional connectivity changes and observe that the mappings diverge over frequency bands and successive stimulations. Finally, we uncover shared processes governing real-time and longer-term effects of stimulation, demonstrating that all neural stimulation interventions must consider both timescales for their effects to be fully understood. The insights and developments generated in this work represent a paradigm shift for the field of neural stimulation.

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Section: Discussionmentioning

confidence: 66%

“…However, these interventions cause many reported side effects [43], and the mechanisms underlying the side affects and governing their therapeutic outcomes are not understood.…”

Section: The Influence Of the Stimulation Protocolmentioning

confidence: 99%

Cortical network structure mediates response to stimulation: an optogenetic study in non-human primates

Bloch

Greaves-Tunnell

Shea‐Brown

et al. 2021

Preprint

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“…In the bioethics literature, it is common that the side effects of DBS are portrayed as a threat to patients’ personality, identity, agency, and self-perception [ 32 , 78 , 79 , 80 ]. Although many of these articles are not based on firsthand studies, there are studies showing some post-operative changes that could negatively affect personality, behavior, or mood (e.g., impulsive behavior, depression, mania) [ 35 , 81 , 82 , 83 , 84 , 85 ]. While these may occur, it should not be forgotten that PD often presents with psychological and psychiatric manifestations (e.g., depression, anxiety, hallucination, apathy) [ 86 ] and dopaminergic medication like dopamine agonists can also lead to impulsive behavior such as compulsive buying, hyperactivity, or sexual behavior [ 87 , 88 , 89 , 90 ].…”

Section: Discussionmentioning

confidence: 99%

Parkinson’s Disease and Deep Brain Stimulation Have an Impact on My Life: A Multimodal Study on the Experiences of Patients and Family Caregivers

Gámez

Brugger

Biller‐Andorno

2021

IJERPH

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Parkinson’s disease (PD) has a large impact on patients’ physical and mental health, which also greatly affects their family caregivers. Deep brain stimulation (DBS) has emerged as an effective treatment for PD, but different authors have expressed their concerns about the potential impact of DBS on personality and identity. Our study aims at better understanding how patients and family caregivers experience life with PD and DBS, the impact of both on their personal and social lives, and their perception of the changes that have occurred as a result of the disease and the treatment. Our study applies a multimodal approach by means of narrative semi-structured interviews and drawings. Seven principal themes have been identified: “everyone’s Parkinson’s is different”, “changing as a person during the disease”, “going through Parkinson’s together”, “DBS improved my life”, “I am treated with DBS but I have Parkinson’s still”, “DBS is not perfect”, and “being different after DBS”. PD is perceived as an unpredictable and heterogeneous disease that changes from person to person, as does the effect of DBS. While DBS side-effects may have an impact on patients’ personality, behavior, and self-perception, PD symptoms and drug side-effects also have a great impact on these aspects.

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“…Sensory side effects are often considered susceptible to habituation over time and less prone to impede the treatment results ( 37 ). Paresthesia can be overcome with programming adjustments ( 38 ). Paresthesia can be diminished by decreasing the amplitude of stimulation since it is voltage dependent.…”

Section: Discussionmentioning

confidence: 99%

Stimulation-Induced Side Effects of Deep Brain Stimulation in the Ventralis Intermedius and Posterior Subthalamic Area for Essential Tremor

et al. 2021

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Deep brain stimulation (DBS) targeting the ventralis intermedius (VIM) nucleus of the thalamus and the posterior subthalamic area (PSA) has been shown to be an effective treatment for essential tremor (ET). The aim of this study was to compare the stimulation-induced side effects of DBS targeting the VIM and PSA using a single electrode. Patients with medication-refractory ET who underwent DBS electrode implantation between July 2011 and October 2020 using a surgical technique that simultaneously targets the VIM and PSA with a single electrode were enrolled in this study. A total of 93 patients with ET who had 115 implanted DBS electrodes (71 unilateral and 22 bilateral) were enrolled. The Clinical Rating Scale for Tremor (CRST) subscores improved from 20.0 preoperatively to 4.3 (78.5% reduction) at 6 months, 6.3 (68.5% reduction) at 1 year, and 6.5 (67.5% reduction) at 2 years postoperation. The best clinical effect was achieved in the PSA at significantly lower stimulation amplitudes. Gait disturbance and clumsiness in the leg was found in 13 patients (14.0%) upon stimulation of the PSA and in significantly few patients upon stimulation of the VIM (p = 0.0002). Fourteen patients (15.1%) experienced dysarthria when the VIM was stimulated; this number was significantly more than that with PSA stimulation (p = 0.0233). Transient paresthesia occurred in 13 patients (14.0%) after PSA stimulation and in six patients (6.5%) after VIM stimulation. Gait disturbance and dysarthria were significantly more prevalent in patients undergoing bilateral DBS than in those undergoing unilateral DBS (p = 0.00112 and p = 0.0011, respectively). Paresthesia resolved either after reducing the amplitude or switching to bipolar stimulation. However, to control gait disturbance and dysarthria, some loss of optimal tremor control was necessary at that particular electrode contact. In the present study, the most common stimulation-induced side effect associated with VIM DBS was dysarthria, while that associated with PSA DBS was gait disturbance. Significantly, more side effects were associated with bilateral DBS than with unilateral DBS. Therefore, changing active DBS contacts to simultaneous targeting of the VIM and PSA may be especially helpful for ameliorating stimulation-induced side effects.

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Stimulation-induced side effects after deep brain stimulation – a systematic review

Cited by 59 publications

References 46 publications

Cortical network structure mediates response to stimulation: an optogenetic study in non-human primates

Cortical network structure mediates response to stimulation: an optogenetic study in non-human primates

Parkinson’s Disease and Deep Brain Stimulation Have an Impact on My Life: A Multimodal Study on the Experiences of Patients and Family Caregivers

Stimulation-Induced Side Effects of Deep Brain Stimulation in the Ventralis Intermedius and Posterior Subthalamic Area for Essential Tremor

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