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MedRxiv : the Preprint Server For... Jun 2024Neuropsychiatric symptoms are common and disabling in Parkinson's disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD...
BACKGROUND
Neuropsychiatric symptoms are common and disabling in Parkinson's disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD is challenging, hampered by insufficient insight into underlying mechanisms, lack of objective anxiety measurements, and largely ineffective treatments.In this study, we assessed the intracranial neurophysiological correlates of anxiety in PD patients treated with deep brain stimulation (DBS) in the laboratory and at home. We hypothesized that low-frequency (theta-alpha) activity would be associated with anxiety.
METHODS
We recorded local field potentials (LFP) from the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi) DBS implants in three PD cohorts: 1) patients with recordings (STN) performed in hospital at rest via perioperatively externalized leads, without active stimulation, both ON or OFF dopaminergic medication; 2) patients with recordings (STN or GPi) performed at home while resting, via a chronically implanted commercially available sensing-enabled neurostimulator (Medtronic Percept device), ON dopaminergic medication, with stimulation both ON or OFF; 3) patients with recordings performed at home while engaging in a behavioral task via STN and GPi leads and electrocorticography paddles (ECoG) over premotor cortex connected to an investigational sensing-enabled neurostimulator, ON dopaminergic medication, with stimulation both ON or OFF. Trait anxiety was measured with validated clinical scales in all participants, and state anxiety was measured with momentary assessment scales at multiple time points in the two at-home cohorts. Power in theta (4-8 Hz) and alpha (8-12 Hz) ranges were extracted from the LFP recordings, and their relation with anxiety ratings was assessed using linear mixed-effects models.
RESULTS
In total, 33 PD patients (59 hemispheres) were included. Across three independent cohorts, with stimulation OFF, basal ganglia theta power was positively related to trait anxiety (all p<0.05). Also in a naturalistic setting, with individuals at home at rest with stimulation and medication ON, basal ganglia theta power was positively related to trait anxiety (p<0.05). This relationship held regardless of the hemisphere and DBS target. There was no correlation between trait anxiety and premotor cortical theta-alpha power. There was no within-patient association between basal ganglia theta-alpha power and state anxiety.
CONCLUSION
We showed that basal ganglia theta activity indexes trait anxiety in PD. Our data suggest that theta could be a possible physiomarker of neuropsychiatric symptoms and specifically of anxiety in PD, potentially suitable for guiding advanced DBS treatment tailored to the individual patient's needs, including non-motor symptoms.
PubMed: 38883720
DOI: 10.1101/2024.06.04.24308449 -
Nature Communications Jun 2024Motor learning relies on experience-dependent plasticity in relevant neural circuits. In four experiments, we provide initial evidence and a double-blinded,...
Motor learning relies on experience-dependent plasticity in relevant neural circuits. In four experiments, we provide initial evidence and a double-blinded, sham-controlled replication (Experiment I-II) demonstrating that motor learning involving ballistic index finger movements is improved by preceding paired corticospinal-motoneuronal stimulation (PCMS), a human model for exogenous induction of spike-timing-dependent plasticity. Behavioral effects of PCMS targeting corticomotoneuronal (CM) synapses are order- and timing-specific and partially bidirectional (Experiment III). PCMS with a 2 ms inter-arrival interval at CM-synapses enhances learning and increases corticospinal excitability compared to control protocols. Unpaired stimulations did not increase corticospinal excitability (Experiment IV). Our findings demonstrate that non-invasively induced plasticity interacts positively with experience-dependent plasticity to promote motor learning. The effects of PCMS on motor learning approximate Hebbian learning rules, while the effects on corticospinal excitability demonstrate timing-specificity but not bidirectionality. These findings offer a mechanistic rationale to enhance motor practice effects by priming sensorimotor training with individualized PCMS.
Topics: Humans; Male; Learning; Female; Adult; Neuronal Plasticity; Young Adult; Motor Neurons; Transcranial Magnetic Stimulation; Pyramidal Tracts; Evoked Potentials, Motor; Double-Blind Method; Motor Cortex; Fingers; Motor Skills; Synapses
PubMed: 38879614
DOI: 10.1038/s41467-024-49478-5 -
Neuromodulation : Journal of the... Jun 2024Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates...
BACKGROUND
Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability.
MATERIALS AND METHODS
In a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS.
RESULTS
A significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions.
CONCLUSIONS
The significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.
PubMed: 38878056
DOI: 10.1016/j.neurom.2024.05.002 -
Cortex; a Journal Devoted To the Study... Jun 2024The ability to inhibit movements is an essential component of a healthy executive control system. Two distinct but commonly used tasks to assess motor inhibition are the...
The ability to inhibit movements is an essential component of a healthy executive control system. Two distinct but commonly used tasks to assess motor inhibition are the stop signal task (SST) and the anticipated response inhibition (ARI) task. The SST and ARI tasks are similar in that they both require cancelation of a prepotent movement; however, the SST involves cancelation of a speeded reaction to a temporally unpredictable signal, while the ARI task involves cancelation of an anticipated response that the participant has prepared to enact at a wholly predictable time. 33 participants (mean age = 33.3 years, range = 18-55 years) completed variants of the SST and ARI task. In each task, the majority of trials required bimanual button presses, while on a subset of trials a stop signal indicated that one of the presses should be cancelled (i.e., motor selective inhibition). Additional variants of the tasks also included trials featuring signals which were to be ignored, allowing for insights into the attentional component of the inhibitory response. Electromyographic (EMG) recordings allowed detailed comparison of the characteristics of voluntary action and cancellation. The speed of the inhibitory process was not influenced by whether the enacted movement was reactive (SST) or anticipated (ARI task). However, the ongoing (non-cancelled) component of anticipated movements was more efficient than reactive movements, as a result of faster action reprogramming (i.e., faster ongoing actions following successful motor selective inhibition). Older age was associated with both slower inhibition and slower action reprogramming across all reactive and anticipated tasks.
PubMed: 38875737
DOI: 10.1016/j.cortex.2024.05.010 -
Cortex; a Journal Devoted To the Study... May 2024The sense of a bodily self is thought to depend on adaptive weighting and integration of bodily afferents and prior beliefs. While the physical body changes in shape,...
The sense of a bodily self is thought to depend on adaptive weighting and integration of bodily afferents and prior beliefs. While the physical body changes in shape, size, and functionality across the lifespan, the sense of body ownership remains relatively stable. Yet, little is known about how multimodal integration underlying such sense of ownership is altered in ontogenetic periods of substantial physical changes. We aimed to study this link for the motor and the tactile domain in a mixed-realty paradigm where participants ranging from 7 to 80 years old saw their own body with temporally mismatching multimodal signals. Participants were either stroked on their hand or moved it, while they saw it in multiple trials with different visual delays. For each trial, they judged the visuo-motor/tactile synchrony and rated the sense of ownership for the seen hand. Visual dependence and proprioceptive acuity were additionally assessed. The results show that across the lifespan body ownership decreases with increasing temporal multisensory mismatch, both in the tactile and the motor domain. We found an increased sense of ownership with increasing age independent of delay and modality. Delay sensitivity during multisensory conflicts was not consistently related to age. No effects of age were found on visual dependence or proprioceptive accuracy. The results are at least partly in line with an enhanced weighting of top-down and a reduced weighting of bottom-up signals for the momentary sense of bodily self with increasing age.
PubMed: 38875735
DOI: 10.1016/j.cortex.2024.05.013 -
Journal of Neuroengineering and... Jun 2024In post-stroke rehabilitation, functional connectivity (FC), motor-related cortical potential (MRCP), and gait activities are common measures related to recovery...
BACKGROUND
In post-stroke rehabilitation, functional connectivity (FC), motor-related cortical potential (MRCP), and gait activities are common measures related to recovery outcomes. However, the interrelationship between FC, MRCP, gait activities, and bipedal distinguishability have yet to be investigated.
METHODS
Ten participants were equipped with EEG devices and inertial measurement units (IMUs) while performing lower limb motor preparation (MP) and motor execution (ME) tasks. MRCP, FCs, and bipedal distinguishability were extracted from the EEG signals, while the change in knee degree during the ME phase was calculated from the gait data. FCs were analyzed with pairwise Pearson's correlation, and the brain-wide FC was fed into support vector machine (SVM) for bipedal classification.
RESULTS
Parietal-frontocentral connectivity (PFCC) dysconnection and MRCP desynchronization were related to the MP and ME phases, respectively. Hemiplegic limb movement exhibited higher PFCC strength than nonhemiplegic limb movement. Bipedal classification had a short-lived peak of 75.1% in the pre-movement phase. These results contribute to a better understanding of the neurophysiological functions during motor tasks, with respect to localized MRCP and nonlocalized FC activities. The difference in PFCCs between both limbs could be a marker to understand the motor function of the brain of post-stroke patients.
CONCLUSIONS
In this study, we discovered that PFCCs are temporally dependent on lower limb gait movement and MRCP. The PFCCs are also related to the lower limb motor performance of post-stroke patients. The detection of motor intentions allows the development of bipedal brain-controlled exoskeletons for lower limb active rehabilitation.
Topics: Humans; Male; Stroke; Stroke Rehabilitation; Female; Middle Aged; Gait; Electroencephalography; Parietal Lobe; Evoked Potentials, Motor; Frontal Lobe; Aged; Adult; Motor Cortex; Support Vector Machine
PubMed: 38872209
DOI: 10.1186/s12984-024-01330-z -
NeuroImage Jun 2024Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been...
Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been suggested to play a key role in the control of attention, by regulating the flow of information to different brain regions such as the ascending reticular system, basal ganglia, and cortex. While the neurophysiology of attention in visual and auditory systems has been studied in animal models, combined single unit and LFP recordings in human have not, to our knowledge, been reported. Here, we recorded neuronal activity in the CM nucleus in 11 patients prior to insertion of deep brain stimulation electrodes for the treatment of epilepsy while subjects performed an auditory attention task. Patients were requested to attend and count the infrequent (p = 0.2) odd or "deviant" tones, ignore the frequent standard tones and report the total number of deviant tones at trial completion. Spikes were discriminated, and LFPs were band pass filtered (5-45 Hz). Average peri‑stimulus time histograms and spectra were constructed by aligning on tone onsets and statistically compared. The firing rate of CM neurons showed selective, multi-phasic responses to deviant tones in 81% of the tested neurons. Local field potential analysis showed selective beta and low gamma (13-45 Hz) modulations in response to deviant tones, also in a multi-phasic pattern. The current study demonstrates that CM neurons are under top-down control and participate in the selective processing during auditory attention and working memory. These results, taken together, implicate the CM in selective auditory attention and working memory and support a role of beta and low gamma oscillatory activity in cognitive processes. It also has potential implications for DBS therapy for epilepsy and non-motor symptoms of PD, such as apathy and other disorders of attention.
PubMed: 38871037
DOI: 10.1016/j.neuroimage.2024.120686 -
Developmental Cognitive Neuroscience Jun 2024The human brain undergoes structural development from childhood to adolescence, with specific regions in the sensorimotor, social, and affective networks continuing to...
Genetic and environmental influences on structural brain development from childhood to adolescence: A longitudinal twin study on cortical thickness, surface area, and subcortical volume.
The human brain undergoes structural development from childhood to adolescence, with specific regions in the sensorimotor, social, and affective networks continuing to grow into adulthood. While genetic and environmental factors contribute to individual differences in these brain trajectories, the extent remains understudied. Our longitudinal study, utilizing up to three biennial MRI scans (n=485), aimed to assess the genetic and environmental effects on brain structure (age 7) and development (ages 7-14) in these regions. Heritability estimates varied across brain regions, with all regions showing genetic influence (ranging from 18 % to 59 %) with additional shared environmental factors affecting the primary motor cortex (30 %), somatosensory cortex (35 %), DLPFC (5 %), TPJ (17 %), STS (17 %), precuneus (10 %), hippocampus (22 %), amygdala (5 %), and nucleus accumbens (10 %). Surface area was more genetically driven (38 %) than cortical thickness (14 %). Longitudinal brain changes were primarily driven by genetics (ranging from 1 % to 29 %), though shared environment factors (additionally) influenced the somatosensory cortex (11 %), DLPFC (7 %), cerebellum (28 %), TPJ (16 %), STS (20 %), and hippocampus (17 %). These findings highlight the importance of further investigating brain-behavior associations and the influence of enriched and deprived environments from childhood to adolescence. Ultimately, our study can provide insights for interventions aimed at supporting children's development.
PubMed: 38870602
DOI: 10.1016/j.dcn.2024.101407 -
PloS One 2024Transcranial direct current stimulation (tDCS) has been shown to modify excitability of the primary motor cortex (M1) and influence online motor learning. However,... (Randomized Controlled Trial)
Randomized Controlled Trial
Transcranial direct current stimulation (tDCS) has been shown to modify excitability of the primary motor cortex (M1) and influence online motor learning. However, research on the effects of tDCS on motor learning has focused predominantly on simplified motor tasks. The purpose of the present study was to investigate whether anodal stimulation of M1 over a single session of practice influences online learning of a relatively complex rhythmic timing video game. Fifty-eight healthy young adults were randomized to either a-tDCS or SHAM conditions and performed 2 familiarization blocks, a 20-minute 5 block practice period while receiving their assigned stimulation, and a post-test block with their non-dominant hand. To assess performance, a performance index was calculated that incorporated timing accuracy elements and incorrect key inputs. The results showed that M1 a-tDCS enhanced the learning of the video game based skill more than SHAM stimulation during practice, as well as overall learning at the post-test. These results provide evidence that M1 a-tDCS can enhance acquisition of skills where quality or success of performance depends on optimized timing between component motions of the skill, which could have implications for the application of tDCS in many real-world contexts.
Topics: Humans; Transcranial Direct Current Stimulation; Male; Video Games; Female; Learning; Young Adult; Motor Cortex; Adult; Motor Skills
PubMed: 38870202
DOI: 10.1371/journal.pone.0295373 -
Functional specialization of medial and lateral orbitofrontal cortex in inferential decision-making.IScience Jun 2024Inferring prospective outcomes and updating behavior are prerequisites for making flexible decisions in the changing world. These abilities are highly associated with...
Inferring prospective outcomes and updating behavior are prerequisites for making flexible decisions in the changing world. These abilities are highly associated with the functions of the orbitofrontal cortex (OFC) in humans and animals. The functional specialization of OFC subregions in decision-making has been established in animals. However, the understanding of how human OFC contributes to decision-making remains limited. Therefore, we studied this issue by examining the information representation and functional interactions of human OFC subregions during inference-based decision-making. We found that the medial OFC (mOFC) and lateral OFC (lOFC) collectively represented the inferred outcomes which, however, were context-general coding in the mOFC and context-specific in the lOFC. Furthermore, the mOFC-motor and lOFC-frontoparietal functional connectivity may indicate the motor execution of mOFC and the cognitive control of lOFC during behavioral updating. In conclusion, our findings support the dissociable functional roles of OFC subregions in decision-making.
PubMed: 38868183
DOI: 10.1016/j.isci.2024.110007