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NeuroImage. Clinical Jun 2024The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA)...
OBJECTIVE
The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS.
METHODS
The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses.
RESULTS
FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts.
CONCLUSIONS
Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework.
PubMed: 38889523
DOI: 10.1016/j.nicl.2024.103633 -
CNS Neuroscience & Therapeutics Jun 2024To study the changes in cortical thickness and subcortical gray matter structures in children with complete spinal cord injury (CSCI), reveal the possible causes of...
AIMS
To study the changes in cortical thickness and subcortical gray matter structures in children with complete spinal cord injury (CSCI), reveal the possible causes of dysfunction beyond sensory motor dysfunction after CSCI, and provide a possible neural basis for corresponding functional intervention training.
METHODS
Thirty-seven pediatric CSCI patients and 34 age-, gender-matched healthy children as healthy controls (HCs) were recruited. The 3D high-resolution T1-weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Statistical differences between pediatric CSCI patients and HCs in cortical thickness and volumes of subcortical gray matter structures were evaluated. Then, correlation analyses were performed to analyze the correlation between the imaging indicators and clinical characteristics.
RESULTS
Compared with HCs, pediatric CSCI patients showed decreased cortical thickness in the right precentral gyrus, superior temporal gyrus, and posterior segment of the lateral sulcus, while increased cortical thickness in the right lingual gyrus and inferior occipital gyrus. The volume of the right thalamus in pediatric CSCI patients was significantly smaller than that in HCs. No significant correlation was found between the imaging indicators and the injury duration, sensory scores, and motor scores of pediatric CSCI patients.
CONCLUSIONS
These findings demonstrated that the brain structural reorganizations of pediatric CSCI occurred not only in sensory motor areas but also in cognitive and visual related brain regions, which may suggest that the visual processing, cognitive abnormalities, and related early intervention therapy also deserve greater attention beyond sensory motor rehabilitation training in pediatric CSCI patients.
Topics: Humans; Spinal Cord Injuries; Female; Male; Child; Magnetic Resonance Imaging; Adolescent; Cerebral Cortex; Gray Matter; Organ Size
PubMed: 38887969
DOI: 10.1111/cns.14810 -
EXCLI Journal 2024This case report presents a comprehensive assessment and therapeutic intervention using non-invasive motor cortex neuromodulation for a 70-year-old female patient...
Combined non-invasive neuromodulation using transcranial direct current stimulation, motor imagery and action observation for motor, cognitive and functional recovery in cortico-basal degeneration: a single case study.
This case report presents a comprehensive assessment and therapeutic intervention using non-invasive motor cortex neuromodulation for a 70-year-old female patient diagnosed with corticobasal degeneration (CBD). The study followed the CARE guidelines. The patient meets the criteria for probable CBD, with neuroimaging evidence of exclusively cortical impairment. The patient underwent a non-invasive neuromodulation protocol involving transcranial direct current stimulation (tDCS) and action observation plus motor imagery (AO+MI). The neuromodulation protocol comprised 20 sessions involving tDCS over the primary motor cortex and combined AO+MI. Anodal tDCS was delivered a 2 mA excitatory current for 20 minutes. AO+MI focused on lower limb movements, progressing over four weeks with video observation and gradual execution, both weekly and monthly. The neuromodulation techniques were delivered online (i.e. applied simultaneously in each session). Outcome measures were obtained at baseline, post-intervention and follow-up (1 month later), and included motor (lower limb), cognitive/neuropsychological and functional assessments. Walking speed improvements were not observed, but balance (Berg Balance Scale) and functional strength (Five Times Sit-to-Stand Test) improved post-treatment. Long-term enhancements in attentional set-shifting, inhibitory control, verbal attentional span, and working memory were found. There was neurophysiological evidence of diminished intracortical inhibition. Functional changes included worsening in Cortico Basal Ganglia Functional Scale score. Emotional well-being and general health (SF-36) increased immediately after treatment but were not sustained, while Falls Efficacy Scale International showed only long-term improvement. The findings suggest potential benefits of the presented neuromodulation protocol for CBD patients, highlighting multifaceted outcomes in motor, cognitive, and functional domains.
PubMed: 38887394
DOI: 10.17179/excli2024-7027 -
Acta Neuropathologica Jun 2024Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with average lifespan of 2-5 years after diagnosis. The identification of novel...
Seeding activity of human superoxide dismutase 1 aggregates in familial and sporadic amyotrophic lateral sclerosis postmortem neural tissues by real-time quaking-induced conversion.
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with average lifespan of 2-5 years after diagnosis. The identification of novel prognostic and pharmacodynamic biomarkers are needed to facilitate therapeutic development. Metalloprotein human superoxide dismutase 1 (SOD1) is known to accumulate and form aggregates in patient neural tissue with familial ALS linked to mutations in their SOD1 gene. Aggregates of SOD1 have also been detected in other forms of ALS, including the sporadic form and the most common familial form linked to abnormal hexanucleotide repeat expansions in the Chromosome 9 open reading frame 72 (C9ORF72) gene. Here, we report the development of a real-time quaking-induced conversion (RT-QuIC) seed amplification assay using a recombinant human SOD1 substrate to measure SOD1 seeding activity in postmortem spinal cord and motor cortex tissue from persons with different ALS etiologies. Our SOD1 RT-QuIC assay detected SOD1 seeds in motor cortex and spinal cord dilutions down to 10. Importantly, we detected SOD1 seeding activity in specimens from both sporadic and familial ALS cases, with the latter having mutations in either their SOD1 or C9ORF72 genes. Analyses of RT-QuIC parameters indicated similar lag phases in spinal cords of sporadic and familial ALS patients, but higher ThT fluorescence maxima by SOD1 familial ALS specimens and sporadic ALS thoracic cord specimens. For a subset of sporadic ALS patients, motor cortex and spinal cords were examined, with seeding activity in both anatomical regions. Our results suggest SOD1 seeds are in ALS patient neural tissues not linked to SOD1 mutation, suggesting that SOD1 seeding activity may be a promising biomarker, particularly in sporadic ALS cases for whom genetic testing is uninformative.
Topics: Humans; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Spinal Cord; Motor Cortex; Male; Female; Aged; Middle Aged; C9orf72 Protein; Mutation
PubMed: 38884646
DOI: 10.1007/s00401-024-02752-8 -
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