Search Results (12)

Background: Perinatal brain injury is a leading cause of developmental disabilities, including cerebral palsy. However, further work is needed to understand early brain development in the presence of brain injury. In this case report, we examine the longitudinal neuromotor development of a term infant following a significant loss of right-hemispheric brain tissue due to a unilateral ischemic stroke. Our analysis focuses on the integrity and development of the corticospinal tract (CST) from the lesioned hemisphere. This case provides a unique opportunity to evaluate CST development after loss of the majority of the motor cortex. Methods: Evaluations were conducted when the infant was 4 (Visit-1), 18 (Visit 2), and 25 (Visit 3) months old. Assessments included magnetic resonance imaging (MRI) to characterize the lesion and quantify CST structural integrity, single-pulse transcranial magnetic stimulation (spTMS) to evaluate CST functional circuitry, and neuromotor assessments. Results: At Visit 1, bilateral CSTs were identified through diffusion-weighted MRI (dMRI) despite an estimated loss of 92.7% (7.3% retained) of age-typical motor cortex from the right hemisphere. Both hemispheres exhibited bilateral motor-evoked potential in response to stimulation with spTMS, which remained when reassessed at Visits 2 and 3. Longitudinal MRI showed distinct developmental trajectories of CST integrity in each hemisphere, with the lesioned hemisphere exhibiting initial increases in integrity between Visits 1 and 2 followed by a decrease in integrity between Visits 2 and 3. The non-lesioned hemisphere showed increased integrity from Visit 1 to Visit 2, which remained stable at Visit 3. Motor assessments at all visits indicated a high risk of cerebral palsy. Conclusions: This report highlights the utility of MRI and spTMS in studying neuromotor development. The findings reveal preserved functional bilateral CST circuitry despite majority loss of the right-hemispheric motor cortex as well as distinct developmental trajectories in CST integrity between hemispheres. These results underscore the potential for neural plasticity after perinatal brain injury. Clinical Trials Registration: NCT05013736. Full article

Objective: Navigated transcranial magnetic stimulation (nTMS) has seldom been used to study visuospatial (VS) circuits so far. Our work studied (I) VS functions in neurosurgical oncological patients by using repetitive nTMS (rnTMS), (II) the possible subcortical circuits underneath, and (III) the correspondence between nTMS and direct cortical stimulation (DCS) during awake procedures. Methods: We designed a monocentric prospective study, adopting a protocol to use rnTMS for preoperative planning, including VS functions for lesions potentially involving the VS network, including neurosurgical awake and asleep procedures. nTMS-based-DTI tractography allowed the visualization of subcortical circuits. Statistical analyses on nTMS/DCS points were performed. Clinical results were collected pre- and postoperatively. Results: Finally, 27 patients with primitive intra-axial brain lesions were enrolled between April 2023 and March 2024. Specific tests and an experimental integrated VS test (VISA) were used. The clinical evaluation (at 5 ± 7, 30 ± 10, 90 ± 10 days after surgery) documented 33% of patients with neglect in the left hemisphere four days after surgery and, during the 3-month follow-up, preservation of visuospatial function/clinical recovery (90.62% in MMSE, 98.86% in the bell test, 80% in the clock test, and 98% in the OCS test). The surgical strategy was modulated according to the nTMS map. Subcortical bundles were traced to identify those most involved in these functions: SFLII > SLFII > SLFI. A comparison of the nTMS and DCS points in awake surgery (n = 10 patients) documented a sensitivity (Se) of 12%, a specificity (Sp) of 91.21%, a positive predictive value (PPV) of 42%, a negative predictive value (NPV) of 66%, and an accuracy of ~63.7%. Conclusions: Based on our preliminary results, nTMS is advantageous for studying cognitive functions, minimising neurological impairment. Further analyses are needed to validate our data. Full article

Background: Major depressive disorder (MDD) is frequently chronic and relapsing. The use of maintenance or continuation transcranial magnetic stimulation (TMS) has received clinical and some research support. Objective: To conduct a case series study to report the outcomes of once-weekly (OW) or once-fortnightly (OF) continuation TMS in a real-life setting. Methods: We offered OW or OF TMS sessions to patients with MDD in remission or partial remission/relapse. Results: Ten patients received OW TMS and four received OF TMS, for 8 to 46 weeks. No patients in either group who were in remission or partial remission at baseline experienced a relapse. Improvements in HAMD6 and CGI-S scores were statistically significant or of borderline significance for the total sample and the OW group. Conclusions: This naturalistic, open-label observational study indicates that OW TMS is effective as maintenance therapy in MDD, while also offering some support for OF TMS maintenance in preventing relapse. Full article

Approaches to preserve corticomotor excitability (CE) are attracting interest as a treatment for pain-induced changes in neural plasticity. We determined the effects of mirror therapy (MT) on skeletal muscle pain. Fifteen healthy adults who received hypertonic saline injections (5.8% NaCl, 0.2 mL) into the first dorsal interosseous (FDI) muscle of the right hand to induce experimental skeletal muscle pain were assigned to either the “MT and injection” or “injection only” group. Post-injection, the “MT and injection” group observed their left index finger abducting and adducting for 4 min, creating the illusion that the right index finger was moving. The “injection only” group remained at rest. CE and pain were assessed by measuring motor-evoked potentials (MEPs) of the right FDI triggered by transcranial magnetic stimulation and the numerical rating scale (NRS), respectively. MEP amplitudes were significantly higher in the “MT and injection” group, a trend that persisted post-MT intervention (MT intervention; p < 0.01, post-1; p < 0.05). The time for the NRS score to reach 0 was notably shorter in the “MT and injection” group (p < 0.05). Our preliminary results suggested that MT decreases CE and pain in skeletal muscles, potentially preventing neural plasticity changes associated with skeletal muscle pain and providing early pain relief. Full article

Background: Resection of brain metastases (BM) close to motor structures is challenging for treatment. Navigated transcranial magnetic stimulation (nTMS) motor mapping, combined with diffusion tensor imaging (DTI)-based fiber tracking (DTI-FT_mot.TMS), is a valuable tool in neurosurgery to preserve motor function. This study aimed to assess the practicability of DTI-FT_mot.TMS for local adjuvant radiotherapy (RT) planning of BM. Methods: Presurgically generated DTI-FT_mot.TMS-based corticospinal tract (CST) reconstructions (FT_mot.TMS) of 24 patients with 25 BM resected during later surgery were incorporated into the RT planning system. Completed fractionated stereotactic intensity-modulated RT (IMRT) plans were retrospectively analyzed and adapted to preserve FT_mot.TMS. Results: In regular plans, mean dose (D_mean) of complete FT_mot.TMS was 5.2 ± 2.4 Gy. Regarding planning risk volume (PRV-FT_TMS) portions outside of the planning target volume (PTV) within the 17.5 Gy (50%) isodose line, the DTI-FT_mot.TMS D_mean was significantly reduced by 33.0% (range, 5.9–57.6%) from 23.4 ± 3.3 Gy to 15.9 ± 4.7 Gy (p < 0.001). There was no significant decline in the effective treatment dose, with PTV D_mean 35.6 ± 0.9 Gy vs. 36.0 ± 1.2 Gy (p = 0.063) after adaption. Conclusions: The DTI-FT_mot.TMS-based CST reconstructions could be implemented in adjuvant IMRT planning of BM. A significant dose reduction regarding motor structures within critical dose levels seems possible. Full article

Dopamine is crucial for neuroplasticity, which is considered to be the neurophysiological foundation of learning and memory. The specific effect of dopamine on plasticity such as long-term potentiation (LTP) and long-term depression (LTD) is determined by receptor subtype specificity, concentration level, and the kind of plasticity induction technique. In healthy human subjects, the dopamine precursor levodopa (L-DOPA) exerts a dosage-dependent non-linear effect on motor cortex plasticity. Low and high dosage L-DOPA impaired or abolished plasticity, while medium-dose preserved and reversed plasticity in previous studies. Similar dosage-dependent effects were also observed for selective D1-like and D2-like receptor activation that favor excitatory and inhibitory plasticity, respectively. However, such a dosage-dependent effect has not been explored for a nonselective dopamine agonist such as apomorphine in humans. To this aim, nonfocal and focal motor cortex plasticity induction using paired associative stimulation (PAS) and transcranial direct current stimulation (tDCS) were performed respectively in healthy participants under 0.1, 0.2, 0.3 mg apomorphine or placebo drug. Transcranial magnetic stimulation-elicited motor-evoked potentials were used to monitor motor cortical excitability alterations. We hypothesized that, similar to L-DOPA, apomorphine will affect motor cortex plasticity. The results showed that apomorphine with the applied dosages has an inhibitory effect for focal and nonfocal LTP-like and LTD-like plasticity, which was either abolished, diminished or reversed. The detrimental effect on plasticity induction under all dosages of apomorphine suggests a predominantly presynaptic mechanism of action of these dosages. Full article

Awake surgery and intraoperative neuromonitoring represent the gold standard for surgery of lesion located in language-eloquent areas of the dominant hemisphere, enabling the maximal safe resection while preserving language function. Nevertheless, this functional mapping is invasive; it can be executed only during surgery and in selected patients. Moreover, the number of neuro-oncological bilingual patients is constantly growing, and performing awake surgery in this group of patients can be difficult. In this scenario, the application of accurate, repeatable and non-invasive preoperative mapping procedures is needed, in order to define the anatomical distribution of both languages. Repetitive navigated transcranial magnetic stimulation (rnTMS) associated with functional subcortical fiber tracking (nTMS-based DTI-FT) represents a promising and comprehensive mapping tool to display language pathway and function reorganization in neurosurgical patients. Herein we report a case of a bilingual patient affected by brain tumor in the left temporal lobe, who underwent rnTMS mapping for both languages (Romanian and Italian), disclosing the true eloquence of the anterior part of the lesion in both tests. After surgery, language abilities were intact at follow-up in both languages. This case represents a preliminary application of nTMS-based DTI-FT in neurosurgery for brain tumor in eloquent areas in a bilingual patient. Full article

In the human brain, aging is characterized by progressive neuronal loss, leading to disruption of synapses and to a degree of failure in neurotransmission. However, there is increasing evidence to support the notion that the aged brain has a remarkable ability to reorganize itself, with the aim of preserving its physiological activity. It is important to develop objective markers able to characterize the biological processes underlying brain aging in the intact human, and to distinguish them from brain degeneration associated with many neurological diseases. Transcranial magnetic stimulation (TMS), coupled with electromyography or electroencephalography (EEG), is particularly suited to this aim, due to the functional nature of the information provided, and thanks to the ease with which it can be integrated with behavioral manipulation. In this review, we aimed to provide up to date information about the role of TMS and TMS-EEG in the investigation of brain aging. In particular, we focused on data about cortical excitability, connectivity and plasticity, obtained by using readouts such as motor evoked potentials and transcranial evoked potentials. Overall, findings in the literature support an important potential contribution of TMS to the understanding of the mechanisms underlying normal brain aging. Further studies are needed to expand the current body of information and to assess the applicability of TMS findings in the clinical setting. Full article

Intraoperative direct electrostimulation mapping (DEM) is currently the gold-standard for glioma surgery, since functional-based resection allows an optimization of the onco-functional balance (increased resection with preserved quality of life). Besides intrasurgical awake mapping of conation, cognition, and behavior, preoperative mapping by means of functional neuroimaging (FNI) and transcranial magnetic stimulation (TMS) has increasingly been utilized for surgical selection and planning. However, because these techniques suffer from several limitations, particularly for direct functional mapping of subcortical white matter pathways, DEM remains crucial to map neural connectivity. On the other hand, non-invasive FNI and TMS can be repeated before and after surgical resection(s), enabling longitudinal investigation of brain reorganization, especially in slow-growing tumors like low-grade gliomas. Indeed, these neoplasms generate neuroplastic phenomena in patients with usually no or only slight neurological deficits at diagnosis, despite gliomas involving the so-called “eloquent” structures. Here, data gained from perioperative FNI/TMS mapping methods are reviewed, in order to decipher mechanisms underpinning functional cerebral reshaping induced by the tumor and its possible relapse, (re)operation(s), and postoperative rehabilitation. Heterogeneous spatiotemporal patterns of rearrangement across patients and in a single patient over time have been evidenced, with structural changes as well as modifications of intra-hemispheric (in the ipsi-lesional and/or contra-lesional hemisphere) and inter-hemispheric functional connectivity. Such various fingerprints of neural reconfiguration were correlated to different levels of cognitive compensation. Serial multimodal studies exploring neuroplasticity might lead to new management strategies based upon multistage therapeutic approaches adapted to the individual profile of functional reallocation. Full article

We report on a patient with mild traumatic brain injury (TBI) who was diagnosed with conversion disorder for severe weakness of an arm, which was demonstrated using diffusion tensor tractography (DTT) and transcranial magnetic stimulation (TMS). A 23-year-old right-handed female suffered from head trauma resulting from a pedestrian car accident. She underwent rehabilitative management for memory impairment and central pain. At 14 months after onset, she complained of severe weakness of her right arm, which was detected in the morning after sleeping (right shoulder abductor: 3/5, elbow flexor: 3/5, wrist extensor: 1/5, finger flexor: 1/5, and finger extensor: 1/5). Electromyography study for peripheral neuropathy performed at 2 weeks after onset of weakness showed no abnormality. On a 14-month DTT configuration, the integrities of the left corticospinal tract (CST), supplementary motor area-corticofugal tract (SMA-CFT), and dorsal premotor cortex (dPMC)-CFT were well-preserved. Significant differences were not observed for the fractional anisotropy (FA), mean diffusivity (MD), and tract volume (TV) values of the CST, SMA-CFT, and dPMC-CFT in both hemispheres between the patient and ten right-handed age- and sex-matched normal subjects (p > 0.05). On a 14-month TMS study, MEPs obtained at the right abductor pollicis brevis muscle showed no abnormality. Using DTT and TMS, conversion disorder was demonstrated in a patient with mild TBI, who showed severe weakness of an arm. Our results suggest the usefulness of an evaluation of the CST and CFTs from the secondary motor areas using DTT, and the CST using TMS for patients who complain of motor weakness due to conversion disorder. Full article

Differentiating Mild Cognitive Impairment (MCI) from dementia and estimating the risk of MCI-to-dementia conversion (MDC) are challenging tasks. Thus, objective tools are mandatory to get early diagnosis and prognosis. About that, there is a growing interest on the role of cerebellum-cerebrum connectivity (CCC). The aim of this study was to differentiate patients with an early diagnosis of dementia and MCI depending on the effects of a transcranial magnetic stimulation protocol (intermittent theta-burst stimulation -iTBS) delivered on the cerebellum able to modify cortico-cortical connectivity. Indeed, the risk of MDC is related to the response to iTBS, being higher in non-responder individuals. All patients with MCI, but eight (labelled as MCI-), showed preserved iTBS aftereffect. Contrariwise, none of the patients with dementia showed iTBS aftereffects. None of the patients showed EEG aftereffects following a sham TBS protocol. Five among the MCI- patients converted to dementia at 6-month follow-up. Our data suggest that cerebellar stimulation by means of iTBS may support the differential diagnosis between MCI and dementia and potentially identify the individuals with MCI who may be at risk of MDC. These findings may help clinicians to adopt a better prevention/follow-up strategy in such patients. Full article

(1) Background: The primary motor cortex (M1) experiences reorganization following spinal cord injury (SCI). However, there is a paucity of research comparing bilateral M1 organization in SCI and questions remain to be answered. We explored the presence of somatotopy within the M1 representation of arm muscles, and determined whether anatomical shifts in these representations occur, and investigated the symmetry in organization between the two hemispheres.; (2) Methods: Transcranial magnetic stimulation (TMS) was used to map the representation of the biceps, flexor carpi radialis and abductor pollicis brevis (APB) bilaterally in nine individuals with chronic incomplete cervical spinal cord injury and nine aged- and handed-matched uninjured controls. TMS was delivered over a 6 × 5 point grid that encompassed M1 using an intensity specific to the resting motor threshold for each muscle tested.; (3) Results: Results indicate that, compared to controls, muscle representations in SCI are shifted medially but preserve a general somatotopic arrangement, and that territory dedicated to the APB muscle is greater.; (4) Conclusions: These findings demonstrate differences in the organization of M1 between able-bodied controls and those with incomplete cervical SCI. This altered organization may have future implications in understanding the functional deficits observed in SCI and rehabilitation techniques aimed at restoring function. Full article