Paired associative stimulation (PAS) combines transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) to induce plastic changes in the corticospinal tract. PAS employing single ...0.2-Hz TMS pulses synchronized with the first pulse of 50-100 Hz PNS trains potentiates motor-evoked potentials (MEPs) in a stable manner in healthy participants and enhances voluntary motor output in spinal cord injury (SCI) patients. We further investigated the impact of settings of this PAS variant on MEP potentiation in healthy subjects. In experiment 1, we compared 0.2-Hz vs 0.4-Hz PAS. In experiment 2, PNS frequencies of 100 Hz, 200 Hz, and 400 Hz were compared. In experiment 3, we added a second TMS pulse. When compared with 0.4-Hz PAS, 0.2-Hz PAS was significantly more effective after 30 minutes (p = 0.05) and 60 minutes (p = 0.014). MEP potentiation by PAS with 100-Hz and 200-Hz PNS did not differ. PAS with 400-Hz PNS was less effective than 100-Hz (p = 0.023) and 200-Hz (p = 0.013) PNS. Adding an extra TMS pulse rendered PAS strongly inhibitory. These negative findings demonstrate that the 0.2-Hz PAS with 100-Hz PNS previously used in clinical studies is optimal and the modifications employed here do not enhance its efficacy.
In recent decades, a multitude of therapeutic approaches has been developed for spinal cord injury (SCI), but few have progressed to regular clinical practice. Novel non‐invasive, cost‐effective, and ...feasible approaches to treat this challenging condition are needed. A novel variant of paired associative stimulation (PAS), high‐PAS, consists of non‐invasive high‐intensity transcranial magnetic stimulation (TMS) and non‐invasive high‐frequency electrical peripheral nerve stimulation (PNS). We observed a therapeutic effect of high‐PAS in 20 patients with incomplete SCI with wide range of injury severity, age, and time since injury. Tetraplegic and paraplegic, traumatic, and neurological SCI patients benefited from upper‐ or lower‐limb high‐PAS. We observed increases in manual motor scores (MMT) of upper and lower limbs, functional hand tests, walking tests, and measures of functional independence. We also optimized PAS settings in several studies in healthy subjects and began elucidating the mechanisms of therapeutic action. The scope of this review is to describe the clinical experience gained with this novel PAS approach. This review is focused on the summary of our results and observations and the methodological considerations for researchers and clinicians interested in adopting and further developing this new method.
High‐PAS is a novel variant of paired associative stimulation (PAS), which consists of non‐invasive high‐intensity transcranial magnetic stimulation (TMS) and non‐invasive high‐frequency electrical peripheral nerve stimulation (PNS). We documented a therapeutic effect of high‐PAS in 20 patients with incomplete SCI and with a wide range of injury severity, age, and time since injury. Tetra‐ and paraplegic, traumatic, and neurological SCI patients benefited from upper or lower limb high‐PAS.
Abstract
BACKGROUND:
Navigated transcranial magnetic stimulation (nTMS) is increasingly used in presurgical brain mapping. Preoperative nTMS results correlate well with direct cortical stimulation ...(DCS) data in the identification of the primary motor cortex. Repetitive nTMS can also be used for mapping of speech-sensitive cortical areas.
OBJECTIVE:
The current cohort study compares the safety and effectiveness of preoperative nTMS with DCS mapping during awake surgery for the identification of language areas in patients with left-sided cerebral lesions.
METHODS:
Twenty patients with tumors in or close to left-sided language eloquent regions were examined by repetitive nTMS before surgery. During awake surgery, language-eloquent cortex was identified by DCS. nTMS results were compared for accuracy and reliability with regard to DCS by projecting both results into the cortical parcellation system.
RESULTS:
Presurgical nTMS maps showed an overall sensitivity of 90.2%, specificity of 23.8%, positive predictive value of 35.6%, and negative predictive value of 83.9% compared with DCS. For the anatomic Broca's area, the corresponding values were a sensitivity of 100%, specificity of 13.0%, positive predictive value of 56.5%, and negative predictive value of 100%, respectively.
CONCLUSION:
Good overall correlation between repetitive nTMS and DCS was observed, particularly with regard to negatively mapped regions. Noninvasive inhibition mapping with nTMS is evolving as a valuable tool for preoperative mapping of language areas. Yet its low specificity in posterior language areas in the current study necessitates further research to refine the methodology.
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► We developed a method that combines navigated TMS (nTMS) and synchronized video recording. ► The setup allows careful monitoring of the effect of nTMS on object naming. ► We present ...speech-related errors induced by nTMS in off-line analysis of the videos. ► This setup is useful for cognitive paradigms and for preoperative surgical planning.
Transcranial magnetic stimulation (TMS) is widely used both in basic research and in clinical practice. TMS has been utilized in studies of functional organization of speech in healthy volunteers. Navigated TMS (nTMS) allows preoperative mapping of the motor cortex for surgical planning. Recording behavioral responses to nTMS in the speech-related cortical network in a manner that allows off-line review of performance might increase utility of nTMS both for scientific and clinical purposes, e.g., for a careful preoperative planning.
Four subjects participated in the study. The subjects named pictures of objects presented every 2-3s on a computer screen. One-second trains of 5 pulses were applied by nTMS 300ms after the presentation of pictures. The nTMS and stimulus presentation screens were cloned. A commercial digital camera was utilized to record the subject's performance and the screen clones. Delays between presentation, audio and video signals were eliminated by carefully tested combination of displays and camera. An experienced neuropsychologist studied the videos and classified the errors evoked by nTMS during the object naming.
Complete anomias, semantic, phonological and performance errors were observed during nTMS of left fronto-parieto-temporal cortical regions. Several errors were detected only in the video classification.
nTMS combined with synchronized video recording provides an accurate monitoring tool of behavioral TMS experiments. This experimental setup can be particularly useful for high-quality cognitive paradigms and for clinical purposes.
Deep brain stimulation (DBS) has proven its clinical efficacy in Parkinson's disease (PD), but its exact mechanisms and cortical effects continue to be unclear. Subthalamic (STN) DBS acutely modifies ...auditory evoked responses, but its long-term effect on auditory cortical processing remains ambiguous. We studied with magnetoencephalography the effect of long-term STN DBS on auditory processing in patients with advanced PD. DBS resulted in significantly increased contra-ipsilateral auditory response latency difference at ~100 ms after stimulus onset compared with preoperative state. The effect is likely due to normalization of neuronal asynchrony in the auditory pathways. The present results indicate that STN DBS in advanced PD patients has long-lasting effects on cortical areas outside those confined to motor processing. Whole-head magnetoencephalography provides a feasible tool to study motor and non-motor neural networks in PD, and to track possible changes related to cortical reorganization or plasticity induced by DBS.
Introduction
Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is ...accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value.
Methods
The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications.
Results
nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here.
Conclusion
At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.
Amplitude or frequency alterations of spontaneous brain oscillations may reveal pathological phenomena in the brain or predict recovery from brain lesions, but the temporal evolution and the ...functional significance of these changes is not well known. We performed follow-up recordings of spontaneous brain oscillations with whole-head MEG in 16 patients with first-ever stroke in the middle cerebral artery territory, affecting upper limb motor function, 1-7 days (T0), 1 month (T1), and 3 months (T2) after stroke, with concomitant clinical examination. Clinical test results improved significantly from T0 to T1 or T2. During recovery (at T1 and T2), the strength of temporo-parietal ≈ 10-Hz oscillations in the affected hemisphere (AH) was increased as compared with the unaffected hemisphere. Abnormal low-frequency magnetic activity (ALFMA) at ≈ 1 Hz in the AH was detected in the perilesional cortex in seven patients at T0. In four of these, ALFMA persisted at T2. In patients with ALFMA, the lesion size was significantly larger than in the rest of the patients, and worse clinical outcome was observed in patients with persisting ALFMA. Our results indicate that temporo-parietal ≈ 10-Hz oscillations are enhanced in the AH during recovery from stroke. Moreover, stroke causes ALFMA, which seems to persist in patients with worse clinical outcome.
: In spinal paired associative stimulation (PAS), orthodromic and antidromic volleys elicited by transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) coincide at ...corticomotoneuronal synapses at the spinal cord. The interstimulus interval (ISI) between TMS and PNS determines whether PAS leads to motor-evoked potential (MEP) potentiation or depression. PAS applied as a long-term treatment for neurological patients might alter conduction of neural fibers over time. Moreover, measurements of motoneuron conductance for determination of ISIs may be challenging in these patients.
: We sought to design a PAS protocol to induce MEP potentiation at wide range of ISIs. We tested PAS consisting of high-intensity (100% stimulator output, SO) TMS and high-frequency (50 Hz) PNS in five subjects at five different ISIs. Our protocol induced potentiation of MEP amplitudes in all subjects at all tested intervals. TMS and PNS alone did not result in MEP potentiation. The variant of PAS protocol described here does not require exact adjustment of ISIs in order to achieve effective potentiation of MEPs.
: This variant of PAS might be feasible as a long-term treatment in rehabilitation of neurological patients.
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