scholarly journals Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation

2021 ◽  
Vol 7 (33) ◽  
pp. eabd9465
Author(s):  
Shahabeddin Vahdat ◽  
Arjun Vivek Pendharkar ◽  
Terrance Chiang ◽  
Sean Harvey ◽  
Haruto Uchino ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Primary Motor Cortex ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neural Dynamics ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Optogenetic Stimulation ◽  
Important Mediator ◽  
Stimulation Of

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth–associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.

scholarly journals Effects of behavioural activation on the neural circuit related to intrinsic motivation

BJPsych Open ◽  
2018 ◽  
Vol 4 (5) ◽  
pp. 317-323 ◽  
Author(s):  
Asako Mori ◽  
Yasumasa Okamoto ◽  
Go Okada ◽  
Koki Takagaki ◽  
Masahiro Takamura ◽  
...  
Keyword(s):  
Intrinsic Motivation ◽  
Neural Circuit ◽  
Intervention Group ◽  
Behavioural Activation ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Neural Basis ◽  
Efficient Treatment ◽  
The Right ◽  
Magnetic Resonance Imaging Scanning

BackgroundBehavioural activation is an efficient treatment for depression and can improve intrinsic motivation. Previous studies have revealed that the frontostriatal circuit is involved in intrinsic motivation; however, there are no data on how behavioural activation affects the frontostriatal circuit.AimsWe aimed to investigate behavioural activation-related changes in the frontostriatal circuit.MethodFifty-nine individuals with subthreshold depression were randomly assigned to either the intervention or non-intervention group. The intervention group received five weekly behavioural activation sessions. The participants underwent functional magnetic resonance imaging scanning on two separate occasions while performing a stopwatch task based on intrinsic motivation. We investigated changes in neural activity and functional connectivity after behavioural activation.ResultsAfter behavioural activation, the intervention group had increased activation and connectivity in the frontostriatal region compared with the non-intervention group. The increased activation in the right middle frontal gyrus was correlated with an improvement of subjective sensitivity to environmental rewards.ConclusionsBehavioural activation-related changes to the frontostriatal circuit advance our understanding of psychotherapy-induced improvements in the neural basis of intrinsic motivation.Declaration of interestNone.

Striatal dopamine mediates hallucination-like perception in mice

Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. eabf4740
Author(s):  
K. Schmack ◽  
M. Bosc ◽  
T. Ott ◽  
J. F. Sturgill ◽  
A. Kepecs
Keyword(s):  
Psychotic Disorders ◽  
Neural Circuit ◽  
Dopamine Neurons ◽  
Striatal Dopamine ◽  
Model Organisms ◽  
High Confidence ◽  
Optogenetic Stimulation ◽  
The Brain ◽  
Central Symptom ◽  
Stimulation Of

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

scholarly journals Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Arjun Vivek Pendharkar ◽  
Daniel L Smerin ◽  
Lorenzo Gonzales ◽  
Eric Wang ◽  
Sabrina L Levy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Neuronal Nitric Oxide Synthase ◽  
Optogenetic Stimulation ◽  
Oxide Synthase ◽  
Nnos Expression ◽  
Stimulation Of ◽  
Nnos Inhibition

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

Connectivity-Related Roles of Contralesional Brain Regions for Motor Performance Early after Stroke

2020 ◽  
Author(s):  
Lukas Hensel ◽  
Caroline Tscherpel ◽  
Jana Freytag ◽  
Stella Ritter ◽  
Anne K Rehme ◽  
...  
Keyword(s):  
Neural Activity ◽  
Motor Performance ◽  
Primary Motor Cortex ◽  
Effective Connectivity ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Anterior Intraparietal Sulcus

Abstract Hemiparesis after stroke is associated with increased neural activity not only in the lesioned but also in the contralesional hemisphere. While most studies have focused on the role of contralesional primary motor cortex (M1) activity for motor performance, data on other areas within the unaffected hemisphere are scarce, especially early after stroke. We here combined functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to elucidate the contribution of contralesional M1, dorsal premotor cortex (dPMC), and anterior intraparietal sulcus (aIPS) for the stroke-affected hand within the first 10 days after stroke. We used “online” TMS to interfere with neural activity at subject-specific fMRI coordinates while recording 3D movement kinematics. Interfering with aIPS activity improved tapping performance in patients, but not healthy controls, suggesting a maladaptive role of this region early poststroke. Analyzing effective connectivity parameters using a Lasso prediction model revealed that behavioral TMS effects were predicted by the coupling of the stimulated aIPS with dPMC and ipsilesional M1. In conclusion, we found a strong link between patterns of frontoparietal connectivity and TMS effects, indicating a detrimental influence of the contralesional aIPS on motor performance early after stroke.

Neuroanatomical Evidence for Distinct Cognitive and Affective Components of Self

2006 ◽  
Vol 18 (9) ◽  
pp. 1586-1594 ◽  
Author(s):  
J. M. Moran ◽  
C. N. Macrae ◽  
T. F. Heatherton ◽  
C. L. Wyland ◽  
W. M. Kelley
Keyword(s):  
Prefrontal Cortex ◽  
Neural Circuits ◽  
Sense Of Self ◽  
Anterior Cingulate ◽  
Personal Relevance ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Self Reflection ◽  
Emotional Aspects ◽  
Affective Components

This study examines whether the cognitive and affective components of self-reflection can be dissociated using functional magnetic resonance imaging. Using a simple paradigm in which subjects judged the personal relevance of personality characteristics that were either favorable (e.g., “honest”) or unfavorable (e.g., “lazy”, we found that distinct neural circuits in adjacent regions of the prefrontal cortex subserve cognitive and emotional aspects of self-reflection. The medial prefrontal cortex responded only to material that was self-descriptive, and this did not differ as a function of the valence of the trait. When material was judged to be self-relevant, the valence of the material was resolved in an adjacent region of ventral anterior cingulate. The nature of self is one of the most enduring questions in science, and researchers are now beginning to be able to decompose the neural operations that give rise to a unitary sense of self.

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