Dataset Information

Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex.

ABSTRACT: Previous studies that focused on treating major depressive disorder with conventional deep brain stimulation (DBS) paradigms produced inconsistent results. In this proof-of-concept preclinical study in rats (n = 8), we used novel paradigms of orientation selective DBS for stimulating the complex circuitry crossing the infralimbic cortex, an area considered analogous to human subgenual cingulate cortex. Using functional MRI at 9.4 T, we monitored whole brain responses to varying the electrical field orientation of DBS within the infralimbic cortex. Substantial alterations of functional MRI responses in the amygdala, a major node connected to the infralimbic cortex implicated in the pathophysiology of depression, were observed. As expected, the activation cluster near the electrode was insensitive to the changes of the stimulation orientation. Hence, our findings substantiate the ability of orientation selective stimulation (OSS) to recruit neuronal pathways of distinct orientations relative to the position of the electrode, even in complex circuits such as those involved in major depressive disorder. We conclude that OSS is a promising approach for stimulating brain areas that inherently require individualisation of the treatment approach.

SUBMITTER: Lehto LJ

PROVIDER: S-EPMC6300504 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex.

Lehto Lauri J LJ Filip Pavel P Laakso Hanne H Sierra Alejandra A Slopsema Julia P JP Johnson Matthew D MD Eberly Lynn E LE Low Walter C WC Gröhn Olli O Tanila Heikki H Mangia Silvia S Michaeli Shalom S

Frontiers in neuroscience 20181213

Previous studies that focused on treating major depressive disorder with conventional deep brain stimulation (DBS) paradigms produced inconsistent results. In this proof-of-concept preclinical study in rats (<i>n</i> = 8), we used novel paradigms of orientation selective DBS for stimulating the complex circuitry crossing the infralimbic cortex, an area considered analogous to human subgenual cingulate cortex. Using functional MRI at 9.4 T, we monitored whole brain responses to varying the electr ...[more]

PMID: 30618544

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Project description:The medial frontal cortex remains functionally ill-understood; this is reflected by the heterogeneity of behavioural outcomes following damage to the region. We aim to use the rich information provided by extraoperative direct electrical cortical stimulation to enhance our understanding of its functional anatomy. Examining a cohort of 38 epilepsy patients undergoing direct electrical cortical stimulation in the context of presurgical evaluation, we reviewed stimulation findings and classified them in a behavioural framework (positive motor, negative motor, somatosensory, speech disturbances, and "other"). The spatially discrete cortical stimulation-derived data points were then transformed into continuous probabilistic maps, thereby enabling the voxel-wise spatial inference widely used in the analysis of functional and structural imaging data. A functional map of stimulation findings of the medial wall emerged. Positive motor responses occurred in 141 stimulations (31.2%), anatomically located on the paracentral lobule (threshold at p<.05), extending no further than the vertical anterior commissure (VCA) line. Thirty negative motor responses were observed (6.6%), localised to the VCA line (at p < .001 uncorrected). In 43 stimulations (9.5%) a somatosensory response localised to the caudal cingulate zone (at p < .001 uncorrected), with a second region posterior to central sulcus. Speech disturbances were elicited in 38 stimulations (8.4%), more commonly but not exclusively from the language fMRI dominant side, just anterior to VCA (p < .001 uncorrected). In only 2 stimulations, the patient experienced a subjective "urge" to move in the absence of overt movement. Classifying motor behaviour along the dimensions of effector, and movement vs arrest, we derive a wholly data-driven stimulation map of the medial wall, powered by the largest number of stimulations of the region reported (n = 452) in patients imaged with MRI. This model and the underlying data provide a robust framework for understanding the architecture of the region through the joint analysis of disruptive and correlative anatomical maps.

Dataset Information

Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex.

Publications

Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex.

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