Precision inhibitory stimulation of individual-specific cortical hubs disrupts information processing in humans

ABSTRACTNon-invasive brain stimulation (NIBS) is a promising treatment for psychiatric and neurologic conditions, but outcomes are variable across treated individuals. This variability may be due in part to uncertainty in the selection of the stimulation site – a challenge complicated further by the variable organization of individual human brains. In principle, precise targeting of individual-specific brain areas serving outsized roles in cognition could improve the efficacy of NIBS. Network theory predicts that the importance of a node in network can be inferred from its connections; as such, we hypothesized that targeting individual-specific “hub” brain areas with NIBS would impact cognition more than non-hub brain areas. We first demonstrate that the spatial positioning of hubs is variable across individuals, but highly-reproducible when mapped with sufficient per-individual rsfMRI data. We then tested our hypothesis in healthy individuals using a prospective, within-subject, double-blind design. We found that inhibiting a hub with NIBS disrupted information processing during working-memory to a greater extent than inhibiting a non-hub area of the same gyrus. Furthermore, inhibition of hubs linking specific control networks and sensorimotor systems was retrospectively found to be most impactful. Based on these findings, we propose that precise mapping of individual-specific brain network features could inform future interventions in patients.SIGNIFICANCE STATEMENTThe network organization of every person’s brain is different, but non-invasive brain stimulation (NIBS) interventions do not take this variation into account. Here we demonstrate that the spatial positions of brain areas theoretically serving important roles in cognition, called hubs, differs across individual humans, but are stable within an individual upon repeated neuroimaging. We found that administering NIBS to these individual-specific hub brain areas impacted cognition more than stimulation of non-hub areas. This finding indicates that future NIBS interventions can target individual-specific, but cognitively-relevant features of human brains.

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Precision Inhibitory Stimulation of Individual-Specific Cortical Hubs Disrupts Information Processing in Humans

Cerebral Cortex ◽

10.1093/cercor/bhy270 ◽

2018 ◽

Vol 29 (9) ◽

pp. 3912-3921 ◽

Cited By ~ 11

Author(s):

Charles J Lynch ◽

Andrew L Breeden ◽

Evan M Gordon ◽

Joseph B C Cherry ◽

Peter E Turkeltaub ◽

...

Keyword(s):

Information Processing ◽

Brain Network ◽

Brain Areas ◽

Double Blind ◽

Functional Brain Networks ◽

Promising Treatment ◽

Spatial Positioning ◽

Double Blind Design ◽

The Right

Abstract Noninvasive brain stimulation (NIBS) is a promising treatment for psychiatric and neurologic conditions, but outcomes are variable across treated individuals. In principle, precise targeting of individual-specific features of functional brain networks could improve the efficacy of NIBS interventions. Network theory predicts that the role of a node in a network can be inferred from its connections; as such, we hypothesized that targeting individual-specific “hub” brain areas with NIBS should impact cognition more than nonhub brain areas. Here, we first demonstrate that the spatial positioning of hubs is variable across individuals but reproducible within individuals upon repeated imaging. We then tested our hypothesis in healthy individuals using a prospective, within-subject, double-blind design. Inhibition of a hub with continuous theta burst stimulation disrupted information processing during working-memory more than inhibition of a nonhub area, despite targets being separated by only a few centimeters on the right middle frontal gyrus of each subject. Based upon these findings, we conclude that individual-specific brain network features are functionally relevant and could leveraged as stimulation sites in future NIBS interventions.

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Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology

The Cerebellum ◽

10.1007/s12311-021-01239-6 ◽

2021 ◽

Author(s):

Andrea Pilotto ◽

Maria Cristina Rizzetti ◽

Alberto Lombardi ◽

Clint Hansen ◽

Michele Biggi ◽

...

Keyword(s):

Digital Technology ◽

Repetitive Transcranial Magnetic Stimulation ◽

Health Technology ◽

Controlled Study ◽

Double Blind ◽

Non Invasive ◽

Lower Back ◽

Before And After ◽

Double Blind Design ◽

Theta Burst

AbstractThere are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.

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Individualized non-invasive brain stimulation engages the subgenual anterior cingulate and amygdala

10.1101/503441 ◽

2018 ◽

Cited By ~ 3

Author(s):

Desmond J Oathes ◽

Jared Zimmerman ◽

Romain Duprat ◽

Seda Cavdaroglu ◽

Morgan Scully ◽

...

Keyword(s):

Brain Stimulation ◽

Brain Networks ◽

Brain Network ◽

Anterior Cingulate ◽

Clinical Effects ◽

Brain Response ◽

Subcortical Structures ◽

Non Invasive ◽

Individual Participant ◽

Communication Flow

Brain stimulation is used clinically to treat a variety of neurological and psychiatric conditions. The mechanisms of the clinical effects of these brain-based therapies are presumably dependent on their effects on brain networks. It has been hypothesized that using individualized brain network maps is an optimal strategy for defining network boundaries and topologies. Traditional non-invasive imaging can determine correlations between structural or functional time series. However, they cannot easily establish hierarchies in communication flow as done in non-human animals using invasive methods. In the present study, we interleaved functional MRI recordings with non-invasive transcranial magnetic stimulation in the attempt to map causal communication between the prefrontal cortex and two subcortical structures thought to contribute to affective dysregulation: the subgenual anterior cingulate cortex (sgACC) and the amygdala. In both cases, we found evidence that these brain areas were engaged when TMS was applied to prefrontal sites determined from each participant's previous fMRI scan. Specifically, after transforming individual participant images to within-scan quantiles of evoked TMS response, we modeled the average quantile response within a given region across stimulation sites and individuals to demonstrate that the targets were differentially influenced by TMS. Furthermore, we found that the sgACC distributed brain network, estimated in a separate cohort, was engaged in response to sgACC focused TMS and was partially separable from the proximal default mode network response. The amygdala, but not its distributed network, responded to TMS. Our findings indicate that individual targeting and brain response measurements usefully capture causal circuit mapping to the sgACC and amygdala in humans, setting the stage for approaches to non-invasively modulate subcortical nodes of distributed brain networks in clinical interventions and mechanistic human neuroscience studies.

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BRAIN NETWORK MODULATION WITH NON-INVASIVE BRAIN STIMULATION

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2016-315106.215 ◽

2016 ◽

Vol 87 (12) ◽

pp. e1.130-e1

Author(s):

Lucia Li ◽

Ines Violante ◽

Ewan Ross ◽

Rob Leech ◽

Adam Hampshire ◽

...

Keyword(s):

Brain Stimulation ◽

Brain Network ◽

Non Invasive

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Neuromodulation Special IssueNon-invasive stimulation of the social brain: the methodological challenges

Social Cognitive and Affective Neuroscience ◽

10.1093/scan/nsaa102 ◽

2020 ◽

Author(s):

Tegan Penton ◽

Caroline Catmur ◽

Michael J Banissy ◽

Geoffrey Bird ◽

Vincent Walsh

Keyword(s):

Brain Stimulation ◽

Brain Function ◽

Social Brain ◽

Non Invasive ◽

Social Processing ◽

The Social ◽

Social Difficulties ◽

Lesion Studies ◽

Reliable Interpretation ◽

Stimulation Of

Abstract Use of non-invasive brain stimulation methods (NIBS) has become a common approach to study social processing in addition to behavioural, imaging and lesion studies. However, research using NIBS to investigate social processing faces challenges. Overcoming these is important to allow valid and reliable interpretation of findings in neurotypical cohorts, but also to allow us to tailor NIBS protocols to atypical groups with social difficulties. In this review, we consider the utility of brain stimulation as a technique to study and modulate social processing. We also discuss challenges that face researchers using NIBS to study social processing in neurotypical adults with a view to highlighting potential solutions. Finally, we discuss additional challenges that face researchers using NIBS to study and modulate social processing in atypical groups. These are important to consider given that NIBS protocols are rarely tailored to atypical groups before use. Instead, many rely on protocols designed for neurotypical adults despite differences in brain function that are likely to impact response to NIBS.

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Non-invasive Brain Stimulation of the Posterior Parietal Cortex Alters Postural Adaptation

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2020.00248 ◽

2020 ◽

Vol 14 ◽

Cited By ~ 2

Author(s):

David R. Young ◽

Pranav J. Parikh ◽

Charles S. Layne

Keyword(s):

Parietal Cortex ◽

Brain Stimulation ◽

Posterior Parietal Cortex ◽

Non Invasive ◽

Posterior Parietal ◽

Stimulation Of

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Non-invasive brain stimulation therapies

Revista de Medicina ◽

10.11606/issn.1679-9836.v98i4p279-289 ◽

2019 ◽

Vol 98 (4) ◽

pp. 279-289

Author(s):

Paulo J. C. Suen ◽

Andre R. Brunoni

Keyword(s):

Brain Stimulation ◽

Magnetic Stimulation ◽

Synaptic Activity ◽

Noninvasive Brain Stimulation ◽

Major Depressive ◽

Brain Functioning ◽

Brain Functions ◽

Non Invasive ◽

Activation Level ◽

Stimulation Of

Noninvasive brain stimulation therapies are a promising field for the development of new protocols for the treatment of neuropsychiatric disorders. They are based on the stimulation of neural networks with the intent of modeling their synaptic activity to adequate levels. For this, it is necessary to precisely determine which networks are related to which brain functions, and the normal activation level of each of these networks, so that it is possible to direct the stimulation to the affected networks in order to induce the desired effects. These relationships are under intense investigation by the scientific community, and will contribute to the advancement of treatments by neurostimulation, with the emergence of increasingly accurate and effective protocols for different disorders. Currently, the most used techniques are Transcranial Direct Current Stimulation and Transcranial Magnetic Stimulation, with the most common applications being for treating Major Depressive Disorder. The advancement of research in this field may determine new target networks for stimulation in the treatment of other disorders, extending the application of these techniques and also our knowledge about brain functioning.

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Quality of Life after Deep Brain Stimulation of Pediatric Patients With Dyskinetic Cerebral Palsy: A Prospective, Single‐Arm, Multicenter Study With a Subsequent Randomized Double‐Blind Crossover ( STIM‐CP )

Movement Disorders ◽

10.1002/mds.28898 ◽

2021 ◽

Author(s):

Anne Koy ◽

Andrea A. Kühn ◽

Julius Huebl ◽

Gerd‐Helge Schneider ◽

Anne K. Riesen ◽

...

Keyword(s):

Quality Of Life ◽

Cerebral Palsy ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Multicenter Study ◽

Pediatric Patients ◽

Double Blind ◽

Deep Brain ◽

Stimulation Of

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Deep brain stimulation of the fornix as a therapeutic approach for Alzheimer’s disease: Systematic Review

10.5327/1516-3180.168 ◽

2021 ◽

Author(s):

Paloma Abrantes de Oliveira ◽

Diogo Abrantes de Oliveira ◽

Isabelle Magalhães Guedes Freitas

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Randomized Clinical Trials ◽

Anterior Commissure ◽

Brain Network ◽

Double Blind ◽

Alzheimer Dementia ◽

Deep Brain

INTRODUCTION: Alzheimer’s disease (AD) is a disorder characterized by cognitive impairment. The brain network in DA can be interrupted by deficiencies in glucose metabolismo. Deep brain stimulation (DBS) is used in Parkinson’s disease (PM), once it modulates motor circuits. Considering this potential, the benefits of this approach in DA must be evaluated1,2. OBJECTIVE: To investigate the potential benefit of stimulating the cerebral fornix (CF) through DBS for patients with AD. METHODS: Controlled and randomized clinical trials (ECCR), in English, performed on humans, in the last 5 years, indexed on PubMed, were selected from the keywords “Deep brain Stimulation” and “Alzheimer Dementia”. This review was registered on PROSPERO by protocol 254506 and the PRISMA recommendation was used to improve its organization. RESULTS: Deeb W et al. (2019) conducted an ECCR on 42 patients with AD receiving DBS in CF, anterior commissure, corpus and sub-corpus callosum, demonstrating that in 48% of them, old experiences were reported. Furthermore, the memories became better as the stimulation increased. Lozano AM et al. (2016), in turn, developed an ECCR on 6 patients receiving DBS in CF, showing increases in glucose metabolism in some cerebral areas after 12 months, contrasting to the expected reduction in AD, especially in > 65 years. It’s noteworthy that the multicenter and double-blind ECCR by Ponce FA (2016) showed the safety of DBS in CF as therapy for AD, similar to that verified in the MP. CONCLUSION: The analyzed evidences suggest a potential cognitive benefit of DBS in the therapeutic management of AD.

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