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Transcranial static magnetic field stimulation (tSMS) was recently introduced as a promising tool to modulate human cerebral excitability in a noninvasive and portable way. However, a demonstration that static magnetic fields can influence human brain activity and behavior is currently lacking, despite evidence that static magnetic fields interfere with neuronal function in animals. Here we show that transcranial application of a static magnetic field (120 -200 mT at 2-3 cm from the magnet surface) over the human occiput produces a focal increase in the power of alpha oscillations in underlying cortex. Critically, this neurophysiological effect of tSMS is paralleled by slowed performance in a visual search task, selectively for the most difficult target detection trials. The typical relationship between prestimulus alpha power over posterior cortical areas and reaction time (RT) to targets during tSMS is altered such that tSMS-dependent increases in alpha power are associated with longer RTs for difficult, but not easy, target detection trials. Our results directly demonstrate that a powerful magnet placed on the scalp modulates normal brain activity and induces behavioral changes in humans. [ABSTRACT FROM AUTHOR]

Due to the lack of a specific diagnostic tool for neuropathic pain, a grading system to categorize pain as 'definite', 'probable', 'possible' and 'unlikely' neuropathic was proposed. Somatosensory abnormalities are common in neuropathic pain and it has been suggested that a greater number of abnormalities would be present in patients with 'probable' and 'definite' grades. To test this hypothesis, we investigated the presence of somatosensory abnormalities by means of Quantitative Sensory Testing (QST) in patients with a clinical diagnosis of neuropathic pain and correlated the number of sensory abnormalities and sensory profiles to the different grades. Of patients who were clinically diagnosed with neuropathic pain, only 60% were graded as 'definite' or 'probable', while 40% were graded as 'possible' or 'unlikely' neuropathic pain. Apparently, there is a mismatch between a clinical neuropathic pain diagnosis and neuropathic pain grading. Contrary to the expectation, patients with 'probable' and 'definite' grades did not have a greater number of abnormalities. Instead, similar numbers of somatosensory abnormalities were identified for each grade. The profiles of sensory signs in 'definite' and 'probable' neuropathic pain were not significantly different, but different from the 'unlikely' grade. This latter difference could be attributed to differences in the prevalence of patients with a mixture of sensory gain and loss and with sensory loss only. The grading system allows a separation of neuropathic and non-neuropathic pain based on profiles but not on the total number of sensory abnormalities. Our findings indicate that patient selection based on grading of neuropathic pain may provide advantages in selecting homogenous groups for clinical research. [ABSTRACT FROM AUTHOR]

Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the hypothesis that the significance of spike timing in somatosensory processing is not a specific feature of the whisker cortex but a more general characteristic of the primary somatosensory cortex. We recorded ensembles of neurons using microwire arrays implanted in the deep layers of the forelimb region of the rat primary somatosensory cortex in response to step stimuli delivered to the cutaneous surface of the contralateral body. We used a recently developed peristimulus time histogram (PSTH)-based classification method to investigate the temporal precision of the code by evaluating how changing the bin size (from 40 to 1 msec) would affect the ability of the ensemble responses to discriminate stimulus location on a single-trial basis. The information related to the discrimination was redundantly distributed within the ensembles, and the ability to discriminate stimulus location increased when decreasing the bin size, reaching a maximum at 4 msec. In our experiment, at 4 msec bin size the first spike per neuron after the stimulus conveyed almost as much information as the entire responses, so the temporal precision of the code was preserved in the first spikes. Subsequent spikes were less frequent but conveyed more information per spike. Finally, not only the trials correctly classified but also the trials incorrectly classified conveyed information about stimulus location with a similar temporal precision. We conclude that the role of spike timing in cortical somatosensory processing is not an exclusive feature of the highly specialized rat trigeminal system, but a more general property of the rat primary somatosensory cortex. [ABSTRACT FROM AUTHOR]

Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network. [ABSTRACT FROM AUTHOR]

Background Transcranial static magnetic field stimulation (tSMS) reduces cortical excitability in humans. Methods The objective of this study was to determine whether tSMS over the occipital cortex is effective in reducing experimental photophobia. In a sham-controlled double-blind crossover study, tSMS (or sham) was applied for 10 minutes with a cylindrical magnet on the occiput of 20 healthy subjects. We assessed subjective discomfort induced by low-intensity and high-intensity visual stimuli presented in a dark room before, during and after tSMS (or sham). Results Compared to sham, tSMS significantly reduced the discomfort induced by high-intensity light stimuli. Conclusions The visual cortex may contribute to visual discomfort in experimental photophobia, providing a rationale for investigating tSMS as a possible treatment for photophobia in migraine. [ABSTRACT FROM AUTHOR]

Background: Ablative neurosurgery has been used to treat Parkinson's disease for many decades. MRI-guided focused ultrasound allows focal lesions to be made in deep brain structures without skull incision. We investigated the safety and preliminary efficacy of unilateral subthalamotomy by focused ultrasound in Parkinson's disease.Methods: This prospective, open-label pilot study was done at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric disease, or a skull density ratio of 0·3 or less were excluded. Enrolled patients underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus was targeted by means of brain images acquired with a 3-Tesla MRI apparatus. Several sonications above the definitive ablation temperature of 55°C were delivered and adjusted according to clinical response. The primary outcomes were safety and a change in the motor status of the treated hemibody as assessed with part III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6 months. Adverse events were monitored up to 48 h after treatment and at scheduled clinic visits at 1, 3, and 6 months after treatment. The study is registered with ClinicalTrials.gov, number NCT02912871.Findings: Between April 26 and June 14, 2016, ten patients with markedly asymmetric parkinsonism that was poorly controlled pharmacologically were enrolled for focused ultrasound unilateral subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been recorded, none of which were serious or severe. Seven adverse events were present at 6 months. Three of these adverse events were directly related to subthalamotomy: off-medication dyskinesia in the treated arm (one patient, almost resolved by 6 months); on-medication dyskinesia in the treated arm (one patient, resolved after levodopa dose reduction); and subjective speech disturbance (one patient). Four of the adverse events present at 6 months were related to medical management (anxiety and fatigue [one patient each] and weight gain [two patients]). The most frequent adverse events were transient gait ataxia (related to subthalamotomy, six patients), transient pin-site head pain (related to the head frame, six patients), and transient high blood pressure (during the procedure, five patients). Transient facial asymmetry (one patient) and moderate impulsivity (two patients) were also recorded. The mean MDS-UPDRS III score in the treated hemibody improved by 53% from baseline to 6 months in the off-medication state (16·6 [SD 2·9] vs 7·5 [3·9]) and by 47% in the on-medication state (11·9 [3·1] vs 5·8 [3·5]).Interpretation: MRI-guided focused ultrasound unilateral subthalamotomy was well tolerated and seemed to improve motor features of Parkinson's disease in patients with noticeably asymmetric parkinsonism. Large randomised controlled trials are necessary to corroborate these preliminary findings and to assess the potential of such an approach to treat Parkinson's disease.Funding: Fundación de investigación HM Hospitales and Insightec. [ABSTRACT FROM AUTHOR]

The clinical applications of neurotechnology are rapidly expanding, and the combination of different approaches could be more effective and precise to treat brain disorders. This Perspective discusses the potential and challenges of "multimodal neuromodulation," which combines modalities such as electrical, magnetic, and ultrasound stimulation., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: GF is co-founder and shareholder of Neuronika S.p.A. (Italy), which develops and commercializes products for deep brain stimulation and transcranial direct current stimulation, and of Neurek SL (Spain), which develops and commercializes products for transcranial static magnetic field stimulation. SM is co-founder and shareholder of Sensars Neurotechnology, which develops neuromodulation devices for pain management and of Action Potential Neurotechnology, which develops neuromodulation devices for sensory and motor function restoration., (Copyright: © 2024 Micera, Foffani. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Consciousness, defined as being aware of and responsive to one's surroundings, is characteristic of normal waking life and typically is lost during sleep and general anaesthesia. The traditional view of consciousness as a global brain state has evolved toward a more sophisticated interplay between global and local states, with the presence of local sleep in the awake brain and local wakefulness in the sleeping brain. However, this interplay is not clear for general anaesthesia, where loss of consciousness was recently suggested to be associated with a global state of brain-wide synchrony that selectively involves layer 5 cortical pyramidal neurons across sensory, motor and associative areas. According to this global view, local wakefulness of layer 5 cortex should be incompatible with deep anaesthesia, a hypothesis that deserves to be scrutinised with causal manipulations. Here, we show that unilateral chemogenetic activation of layer 5 pyramidal neurons in the sensorimotor cortex of isoflurane-anaesthetised mice induces a local state transition from slow-wave activity to tonic firing in the transfected hemisphere. This wakefulness-like activity dramatically disrupts layer 5 interhemispheric synchrony with mirror-image locations in the contralateral hemisphere, but does not reduce the level of unconsciousness under deep anaesthesia, nor in the transitions to/from anaesthesia. Global layer 5 synchrony may thus be a sufficient condition for anaesthesia-induced unconsciousness, but is not a necessary one, at least under isoflurane anaesthesia. Local wakefulness-like activity of layer 5 cortex can be induced and maintained under deep anaesthesia, encouraging further investigation into the local vs. global aspects of anaesthesia-induced unconsciousness. KEY POINTS: The neural correlates of consciousness have evolved from global brain states to a nuanced interplay between global and local states, evident in terms of local sleep in awake brains and local wakefulness in sleeping brains. The concept of local wakefulness remains unclear for general anaesthesia, where the loss of consciousness has been recently suggested to involve brain-wide synchrony of layer 5 cortical neurons. We found that local wakefulness-like activity of layer 5 cortical can be chemogenetically induced in anaesthetised mice without affecting the depth of anaesthesia or the transitions to and from unconsciousness. Global layer 5 synchrony may thus be a sufficient but not necessary feature for the unconsciousness induced by general anaesthesia. Local wakefulness-like activity of layer 5 neurons is compatible with general anaesthesia, thus promoting further investigation into the local vs. global aspects of anaesthesia-induced unconsciousness., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Social cognition (SC) encompasses a set of cognitive functions that enable individuals to understand and respond appropriately to social interactions. Although focused ultrasound subthalamotomy (FUS-STN) effectively treats Parkinson's disease (PD) clinical motor features, its impact and safety on cognitive-behavioral interactions/interpersonal awareness are unknown. This study investigated the effects of unilateral FUS-STN on facial emotion recognition (FER) and affective and cognitive theory of mind (ToM) in PD patients from a randomized sham-controlled trial (NCT03454425). Subjects performed SC evaluation before and 4 months after the procedure while still under blind assessment conditions. The SC assessment included the Karolinska Directed Emotional Faces task for FER, the Reading the Mind in the Eyes (RME) test for affective ToM, and The Theory of Mind Picture Stories Task (ToM PST) (order, questions, and total score) for cognitive ToM. The active treatment group showed anecdotal-to-moderate evidence of no worsening in SC after FUS-STN. Anecdotal evidence for an improvement was recognized in the SC score changes, from baseline to post-treatment, for the active treatment group compared with sham for the RME, ToM PST order, ToM PST total, FER total, and recognition of fear, disgust, and anger. This study provides the first evidence that unilateral FUS-STN does not impair social cognitive abilities, indicating that it can be considered a safe treatment approach for this domain in PD patients. Furthermore, the results suggest FUS-STN may even lead to some improvement in social cognitive outcomes, which should be considered as a preliminary finding requiring further investigation with larger samples sizes. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation technique that is portable and easy to use. Long-term, home-based treatments with tSMS of the supplementary motor area (SMA) are promising for movement disorders and other brain diseases. The aim of the present work was to investigate the potential of SMA-tSMS for reducing corticospinal excitability. We completed an open pilot study in which twenty right-handed healthy subjects (8 females; age: 31.3 ± 5.4 years) completed two 30-min sessions (at least one week apart) of SMA-tSMS. We assessed corticospinal excitability by applying transcranial magnetic stimulation (TMS) over the primary motor cortex, recording 30 motor evoked potentials (MEPs) from either the left or right first dorsal interosseous (FDI, 'hotspot' muscle) and extensor carpi radialis (ECR, 'offspot' muscle) in each session before and after (up to 30 min) tSMS. We observed moderate-to-extreme level of Bayesian evidence for a reduction of MEP amplitude after 30 min of tSMS over SMA compared to baseline. Thus, tSMS applied over SMA may reduce corticospinal excitability. These findings, if confirmed with double-blind, placebo-controlled experiments, support the potential of targeting the SMA for neuromodulating a large motor network in future therapeutic applications of tSMS., (© 2024. The Author(s).)

Brain states in health and disease are classically defined by the power or the spontaneous amplitude modulation (AM) of neuronal oscillations in specific frequency bands. Conversely, the possible role of the spontaneous frequency modulation (FM) in defining pathophysiological brain states remains unclear. As a paradigmatic example of pathophysiological resting states, here we assessed the spontaneous AM and FM dynamics of subthalamic beta oscillations recorded in patients with Parkinson's disease before and after levodopa administration. Even though AM and FM are mathematically independent, they displayed negatively correlated dynamics. First, AM decreased while FM increased with levodopa. Second, instantaneous amplitude and instantaneous frequency were negatively cross-correlated within dopaminergic states, with FM following AM by approximately one beta cycle. Third, AM and FM changes were also negatively correlated between dopaminergic states. Both the slow component of the FM and the fast component (i.e. the phase slips) increased after levodopa, but they differently contributed to the AM-FM correlations within and between states. Finally, AM and FM provided information about whether the patients were OFF vs. ON levodopa, with partial redundancy and with FM being more informative than AM. AM and FM of spontaneous beta oscillations can thus both separately and jointly encode the dopaminergic state in patients with Parkinson's disease. These results suggest that resting brain states are defined not only by AM dynamics but also, and possibly more prominently, by FM dynamics of neuronal oscillations., (© 2022. The Author(s).)

For the last two decades, pathogenic concepts in Parkinson disease (PD) have revolved around the toxicity and spread of α-synuclein. Thus, α-synuclein would follow caudo-rostral propagation from the periphery to the central nervous system, first producing non-motor manifestations (such as constipation, sleep disorders and hyposmia), and subsequently impinging upon the mesencephalon to account for the cardinal motor features before reaching the neocortex as the disease evolves towards dementia. This model is the prevailing theory of the principal neurobiological mechanism of disease. Here, we scrutinize the temporal evolution of motor and non-motor manifestations in PD and suggest that, even though the postulated bottom-up mechanisms are likely to be involved, early involvement of the nigrostriatal system is a key and prominent pathophysiological mechanism. Upcoming studies of detailed clinical manifestations with newer neuroimaging techniques will allow us to more closely define, in vivo, the role of α-synuclein aggregates with respect to neuronal loss during the onset and progression of PD., (© 2021. Springer Nature Limited.)

Brain oscillations have been associated with Parkinson's disease (PD) for a long time mainly due to the fundamental oscillatory nature of parkinsonian rest tremor. Over the years, this association has been extended to frequencies well above that of tremor, largely owing to the opportunities offered by deep brain stimulation (DBS) to record electrical activity directly from the patients' basal ganglia. This chapter reviews the results of research on brain oscillations in PD focusing on theta (4-7Hz), beta (13-35Hz), gamma (70-80Hz) and high-frequency oscillations (200-400Hz). For each of these oscillations, we describe localization and interaction with brain structures and between frequencies, changes due to dopamine intake, task-related modulation, and clinical relevance. The study of brain oscillations will also help to dissect the mechanisms of action of DBS. Overall, the chapter tentatively depicts PD in terms of "oscillopathy.", (Copyright © 2022 Elsevier B.V. All rights reserved.)

Adaptation of neural responses due to the history of sensory input has been observed across all sensory modalities. However, the computational role of adaptation is not fully understood, especially when one considers neural coding problems in which adaptation increases the ambiguity of the neural responses to simple stimuli. To address this, we quantified the impact of adaptation on the information conveyed by thalamic neurons about paired whisker stimuli in male rat. At the single neuron level, although paired-pulse adaptation reduces the information about the present stimulus, the information per spike increases. Moreover, the adapted response can convey significant amounts of information about whether, when and where a previous stimulus occurred. At the population level, ambiguity of the adapted responses about the present stimulus can be compensated for by large numbers of neurons. Therefore, paired-pulse adaptation does not reduce the discriminability of simple stimuli. It provides information about the spatiotemporal context of stimulus history. SIGNIFICANCE STATEMENT The present work provides a computational framework that demonstrates how adaptation allows neurons to encode spatiotemporal dynamics of stimulus history., (Copyright © 2017 the authors 0270-6474/17/3710012-10$15.00/0.)

Local field potentials (LFPs) recorded from implanted deep brain electrodes demonstrated the oscillatory nature of human basal ganglia. LFP rhythms were mainly characterized by means od power spectral analysis, thus loosing information related to rhythm phase synchronization and to event related phase modulations. Because the application of higher-order spectral analysis methodology can overcome such limitation, here we review the present applications of bispectral and cross-bispectral analysis to LFP recordings. The results obtained up to now showed that higher-order spectral analysis was able to clarify detect different rhythm synchronizations and interactions characterizing different pathologies and patient's states.

Fast ripples are a type of transient high-frequency oscillations recorded from the epileptogenic regions of the hippocampus and the temporal cortex of epileptic humans and rodents. These events presumably reflect hypersynchronous bursting of pyramidal cells. However, the oscillatory spectral content of fast ripples varies from 250 to 800 Hz, well above the maximal firing frequency of most hippocampal pyramidal neurons. How such high-frequency oscillations are generated is therefore unclear. Here, we combine computational simulations of fast ripples with multisite and juxtacellular recordings in vivo to examine the underlying mechanisms in the hippocampus of epileptic rats. We show that populations of bursting cells firing individually at 100-400 Hz can create fast ripples according to two main firing regimes: (1) in-phase synchronous firing resulting in "pure" fast ripples characterized by single spectral peaks that reflect single-cell behavior and (2) out-of-phase firing that results in "emergent" fast ripples. Using simulations, we found that fast ripples generated under these two different regimes can be quantitatively separated by their spectral characteristics, and we took advantage of this separability to examine their dynamics in vivo. We found that in-phase firing can reach frequencies up to 300 Hz in the CA1 and up to 400 Hz in the dentate gyrus. The organization of out-of-phase firing is determined by firing delays between cells discharging at low frequencies. The two firing regimes compete dynamically, alternating randomly from one fast ripple event to the next, and they reflect the functional dynamic organization of the different regions of the hippocampus.