Temporal association between sleep spindles and ripples in the human anterior and mediodorsal thalamus.

Sleep spindles are major oscillatory components of Non-Rapid Eye Movement (NREM) sleep, reflecting hyperpolarization-rebound sequences of thalamocortical neurons. Reports suggest a link between sleep spindles and several forms of high-frequency oscillations which are considered as expressions of pathological off-line neural plasticity in the central nervous system. Here we investigated the relationship between thalamic sleep spindles and ripples in the anterior and mediodorsal nuclei (ANT and MD) of epilepsy patients. Whole-night LFP from the ANT and MD were co-registered with scalp EEG/polysomnography by using externalized leads in 15 epilepsy patients undergoing a Deep Brain Stimulation protocol. Slow (~12 Hz) and fast (~14 Hz) sleep spindles were present in the human ANT and MD and roughly, 20% of them were associated with ripples. Ripple-associated thalamic sleep spindles were characterized by longer duration and exceeded pure spindles in terms of spindle power as indicated by time-frequency analysis. Furthermore, ripple amplitude was modulated by the phase of sleep spindles within both thalamic nuclei. No signs of pathological processes were correlated with measures of ripple and spindle association, furthermore, the density of ripple-associated sleep spindles in the ANT showed a positive correlation with verbal comprehension. Our findings indicate the involvement of the human thalamus in coalescent spindle-ripple oscillations of NREM sleep.

REM Sleep Microstates in the Human Anterior Thalamus.

Rapid eye movement (REM) sleep is an elusive neural state that is associated with a variety of functions from physiological regulatory mechanisms to complex cognitive processing. REM periods consist of the alternation of phasic and tonic REM microstates that differ in spontaneous and evoked neural activity. Although previous studies indicate, that cortical and thalamocortical activity differs across phasic and tonic microstates, the characterization of neural activity, particularly in subcortical structures that are critical in the initiation and maintenance of REM sleep is still limited in humans. Here, we examined electric activity patterns of the anterior nuclei of the thalamus as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness in a group of epilepsy patients (N = 12, 7 females). Anterothalamic local field potentials (LFPs) showed increased high-α and ß frequency power in tonic compared with phasic REM, emerging as an intermediate state between phasic REM and wakefulness. Moreover, we observed increased thalamocortical synchronization in phasic compared with tonic REM sleep, especially in the slow and fast frequency ranges. Wake-like activity in tonic REM sleep may index the regulation of arousal and vigilance facilitating environmental alertness. On the other hand, increased thalamocortical synchronization may reflect the intrinsic activity of frontolimbic networks supporting emotional and memory processes during phasic REM sleep. In sum, our findings highlight that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested by anterothalamic LFPs and thalamocortical synchronization.SIGNIFICANCE STATEMENT REM sleep is a heterogeneous sleep state that features the alternation of two microstates, phasic and tonic rapid eye movement (REM). These states differ in sensory processing, awakening thresholds, and cortical activity. Nevertheless, the characterization of these microstates, particularly in subcortical structures is still limited in humans. We had the unique opportunity to examine electric activity patterns of the anterior nuclei of the thalamus (ANTs) as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness. Our findings show that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested in the level of the thalamus and thalamocortical networks.

Thalamic activity during scalp slow waves in humans.

Slow waves are major pacemakers of NREM sleep oscillations. While slow waves themselves are mainly generated by cortical neurons, it is not clear what role thalamic activity plays in the generation of some oscillations grouped by slow waves, and to what extent thalamic activity during slow waves is itself driven by corticothalamic inputs. To address this question, we simultaneously recorded both scalp EEG and local field potentials from six thalamic nuclei (bilateral anterior, mediodorsal and ventral anterior) in fifteen epileptic patients (age-range: 17-64 years, 7 females) undergoing Deep Brain Stimulation Protocol and assessed the temporal evolution of thalamic activity relative to scalp slow waves using time-frequency analysis. We found that thalamic activity in all six nuclei during scalp slow waves is highly similar to what is observed on the scalp itself. Slow wave downstates are characterized by delta, theta and alpha activity and followed by beta, high sigma and low sigma activity during subsequent upstates. Gamma activity in the thalamus is not significantly grouped by slow waves. Theta and alpha activity appeared first on the scalp, but sigma activity appeared first in the thalamus. These effects were largely independent from the scalp region in which SWs were detected and the precise identity of thalamic nuclei. Our results suggest that while small thalamocortical neuron assemblies may initiate cortical oscillations, especially in the sleep spindle range, the large-scale neuronal activity in the thalamus which is detected by field potentials is principally driven by global cortical activity, and thus it is highly similar to what is observed on the scalp.

Prolongation of cortical sleep spindles during hippocampal interictal epileptiform discharges in epilepsy patients.

OBJECTIVE: Memory deficits are frequent among patients with epilepsies affecting the temporal lobe. Hippocampal interictal epileptic discharges (hIEDs), the presumed epileptic exaggeration of sharp wave-ripples (SWRs), are known to contribute to memory dysfunction, but the potential underlying mechanism is unknown. The precise temporal coordination between hippocampal SWRs and corticothalamic spindles during sleep is critical for memory consolidation. Moreover, previous investigation indicated that hIEDs induce neocortical spindlelike oscillation. In the present study, we aimed to assess the influence of hIEDs on neocortical spindles. METHODS: We analyzed the spindle characteristics (duration, amplitude, frequency) of 21 epilepsy patients implanted with foramen ovale (FO) electrodes during a whole night sleep. Scalp sleep spindles were categorized based on their temporal relationship to hIEDs detected on the FO electrodes. Three groups were created: (1) spindles coinciding with hIEDs, (2) spindles "induced" by hIEDs, and (3) spindles without hIED co-occurrence. RESULTS: We found that spindles co-occurring with hIEDs had altered characteristics in all measured properties, lasted longer by 126 ± 48 ms (mean ± SD), and had higher amplitude by 3.4 ± 3.2 µV, and their frequency range shifted toward the higher frequencies within the 13-15-Hz range. Also, hIED-induced spindles had identical oscillatory properties to spindles without any temporal relationships with hIEDs. In more than half of our subjects, clear temporal coherence was revealed between hIEDs and spindles, but the direction of the coupling was patient-specific. SIGNIFICANCE: We investigated the effect of hippocampal IEDs on neocortical spindle activity and found spindle alterations in cases of spindle-hIED co-occurrence, but not in cases of hIED-initiated spindles. We propose that this is a marker of a pathologic process, where IEDs may have direct effect on spindle generation. It could mark a potential mechanism whereby IEDs disrupt memory processes, and also provide a potential therapeutic target to treat memory disturbances in epilepsy.

The generation and propagation of the human alpha rhythm.

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

Reorganization of Parvalbumin Immunopositive Perisomatic Innervation of Principal Cells in Focal Cortical Dysplasia Type IIB in Human Epileptic Patients.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. As several studies have revealed, the abnormal functioning of the perisomatic inhibitory system may play a role in the onset of seizures. Therefore, we wanted to investigate whether changes of perisomatic inhibitory inputs are present in FCD. Thus, the input properties of abnormal giant- and control-like principal cells were examined in FCD type IIB patients. Surgical samples were compared to controls from the same cortical regions with short postmortem intervals. For the study, six subjects were selected/each group. The perisomatic inhibitory terminals were quantified in parvalbumin and neuronal nuclei double immunostained sections using a confocal fluorescent microscope. The perisomatic input of giant neurons was extremely abundant, whereas control-like cells of the same samples had sparse inputs. A comparison of pooled data shows that the number of parvalbumin-immunopositive perisomatic terminals contacting principal cells was significantly larger in epileptic cases. The analysis showed some heterogeneity among epileptic samples. However, five out of six cases had significantly increased perisomatic input. Parameters of the control cells were homogenous. The reorganization of the perisomatic inhibitory system may increase the probability of seizure activity and might be a general mechanism of abnormal network activity.

The laminar profile of sleep spindles in humans.

Sleep spindles are functionally important NREM sleep EEG oscillations which are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patterns. We used NREM sleep EEG data recorded from four human epileptic patients undergoing presurgical electrophysiological monitoring with subdural electrocorticographic grids (ECoG) and implanted laminar microelectrodes penetrating the cortex (IME). The position of IMEs within cortical layers was confirmed using postsurgical histological reconstructions. Many spindles detected on the IME occurred only in one layer and were absent from the ECoG, but with increasing amplitude simultaneous detection in other layers and on the ECoG became more likely. ECoG spindles were in contrast usually accompanied by IME spindles. Neither IME nor ECoG spindle cortical profiles were strongly associated with sleep spindle frequency or globality. Multiple-unit and single-unit activity during spindles, however, was heterogeneous across spindle types, but also across layers and patients. Our results indicate that extremely local spindles may occur in any cortical layer, but co-occurrence at other locations becomes likelier with increasing amplitude and the relatively large spindles detected on ECoG channels have a stereotypical laminar profile. We found no compelling evidence that different spindle types are associated with different laminar profiles, suggesting that they are generated in cortical and thalamic circuits with similar cortical innervation patterns. Local neuronal activity is a stronger candidate mechanism for driving functional differences between spindles subtypes.

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus.

We hypothesized that local/regional properties of stimulated structure/circuitry contribute to the effect of deep brain stimulation (DBS). We analyzed intracerebral electroencephalographic (EEG) recordings from externalized DBS electrodes targeted bilaterally in the anterior nuclei of the thalamus (ANT) in 12 patients (six responders, six nonresponders) with more than 1 year of follow-up care. In the bipolar local field potentials of the EEG, spectral power (PW) and power spectral entropy (PSE) were calculated in the passbands 1-4, 4-8, 8-12, 12-20, 20-45, 65-80, 80-200 and 200-500 Hz. The most significant differences between responders and nonresponders were observed in the BRIDGE area (bipolar recordings with one contact within the ANT and the second contact in adjacent tissue). In responders, PW was significantly decreased in the frequency bands of 65-80, 80-200, and 200-500 Hz (p < .05); PSE was significantly increased in all frequency bands (p < .05) except for 200-500 Hz (p = .06). The local EEG characteristics of ANT recorded after implantation may play a significant role in DBS response prediction.

Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex.

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated-in conjunction with the electron microscopy-that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.

Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers.

Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspection, and confirmed with factor analysis. Spindles (10-16 Hz) were largest and most common in upper and middle channels, with limited involvement of deep channels. Many spindles were observed in only upper or only middle channels, but approximately half occurred in both. In spindles involving both middle and upper channels, the spindle envelope onset in middle channels led upper by ∼25-50 ms on average. The phase relationship between spindle waves in upper and middle channels varied dynamically within spindle epochs, and across individuals. Current source density analysis demonstrated that upper and middle channel spindles were both generated by an excitatory supragranular current sink while an additional deep source was present for middle channel spindles only. Only middle channel spindles were accompanied by deep low (25-50 Hz) and high (70-170 Hz) gamma activity. These results suggest that upper channel spindles are generated by supragranular pyramids, and middle channel by infragranular. Possibly, middle channel spindles are generated by core thalamocortical afferents, and upper channel by matrix. The concurrence of these patterns could reflect engagement of cortical circuits in the integration of more focal (core) and distributed (matrix) aspects of memory. These results demonstrate that at least two distinct intracortical systems generate human sleep spindles.SIGNIFICANCE STATEMENT Bursts of ∼14 Hz oscillations, lasting ∼1 s, have been recognized for over 80 years as cardinal features of mammalian sleep. Recent findings suggest that they play a key role in organizing cortical activity during memory consolidation. We used linear microelectrode arrays to study their intracortical organization in humans. We found that spindles could be divided into two types. One mainly engages upper layers of the cortex, which are considered to be specialized for associative activity. The other engages both upper and middle layers, including those devoted to sensory input. The interaction of these two spindle types may help organize the interaction of sensory and associative aspects of memory consolidation.

Presence of synchrony-generating hubs in the human epileptic neocortex.

KEY POINTS: •Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network in both humans and animals. •In the present study, we show that epileptiform interictal-like spikes and seizures emerged in human neocortical slices by blocking GABAA receptors, following the disappearance of the spontaneously occurring synchronous population activity. •Large variability of temporally and spatially simple and complex spikes was generated by tissue from epileptic patients, whereas only simple events appeared in samples from non-epileptic patients. •Physiological population activity was associated with a moderate level of principal cell and interneuron firing, with a slight dominance of excitatory neuronal activity, whereas epileptiform events were mainly initiated by the synchronous and intense discharge of inhibitory cells. •These results help us to understand the role of excitatory and inhibitory neurons in synchrony-generating mechanisms, in both epileptic and non-epileptic conditions. ABSTRACT: Understanding the role of different neuron types in synchrony generation is crucial for developing new therapies aiming to prevent hypersynchronous events such as epileptic seizures. Paroxysmal activity was linked to hyperexcitability and to bursting behaviour of pyramidal cells in animals. Human data suggested a leading role of either principal cells or interneurons, depending on the seizure morphology. In the present study, we aimed to uncover the role of excitatory and inhibitory processes in synchrony generation by analysing the activity of clustered single neurons during physiological and epileptiform synchronies in human neocortical slices. Spontaneous population activity was detected with a 24-channel laminar microelectrode in tissue derived from patients with or without preoperative clinical manifestations of epilepsy. This population activity disappeared by blocking GABAA receptors, and several variations of spatially and temporally simple or complex interictal-like spikes emerged in epileptic tissue, whereas peritumoural slices generated only simple spikes. Around one-half of the clustered neurons participated with an elevated firing rate in physiological synchronies with a slight dominance of excitatory cells. By contrast, more than 90% of the neurons contributed to interictal-like spikes and seizures, and an intense and synchronous discharge of inhibitory neurons was associated with the start of these events. Intrinsically bursting principal cells fired later than other neurons. Our data suggest that a balanced excitation and inhibition characterized physiological synchronies, whereas disinhibition-induced epileptiform events were initiated mainly by non-synaptically synchronized inhibitory neurons. Our results further highlight the differences between humans and animal models, and between in vivo and (pharmacologically manipulated) in vitro conditions.

Hyperexcitability of the network contributes to synchronization processes in the human epileptic neocortex.

KEY POINTS: Hyperexcitability and hypersynchrony of neuronal networks are thought to be linked to the generation of epileptic activity in both humans and animal models. Here we show that human epileptic postoperative neocortical tissue is able to generate two different types of synchronies in vitro. Epileptiform bursts occurred only in slices derived from epileptic patients and were hypersynchronous events characterized by high levels of excitability. Spontaneous population activity emerged in both epileptic and non-epileptic tissue, with a significantly lower degree of excitability and synchrony, and could not be linked to epilepsy. These results help us to understand better the role of excitatory and inhibitory neuronal circuits in the generation of population events, and to define the subtle border between physiological and pathological synchronies. ABSTRACT: Interictal activity is a hallmark of epilepsy diagnostics and is linked to neuronal hypersynchrony. Little is known about perturbations in human epileptic neocortical microcircuits, and their role in generating pathological synchronies. To explore hyperexcitability of the human epileptic network, and its contribution to convulsive activity, we investigated an in vitro model of synchronous burst activity spontaneously occurring in postoperative tissue slices derived from patients with or without preoperative clinical and electrographic manifestations of epileptic activity. Human neocortical slices generated two types of synchronies. Interictal-like discharges (classified as epileptiform events) emerged only in epileptic samples, and were hypersynchronous bursts characterized by considerably elevated levels of excitation. Synchronous population activity was initiated in both epileptic and non-epileptic tissue, with a significantly lower degree of excitability and synchrony, and could not be linked to epilepsy. However, in pharmacoresistant epileptic tissue, a higher percentage of slices exhibited population activity, with higher local field potential gradient amplitudes. More intracellularly recorded neurons received depolarizing synaptic potentials, discharging more reliably during the events. Light and electron microscopic examinations showed slightly lower neuron densities and higher densities of excitatory synapses in the human epileptic neocortex. Our data suggest that human neocortical microcircuits retain their functionality and plasticity in vitro, and can generate two significantly different synchronies. We propose that population bursts might not be pathological events while interictal-like discharges may reflect the epileptogenicity of the human cortex. Our results show that hyperexcitability characterizes the human epileptic neocortical network, and that it is closely related to the emergence of synchronies.

The role of the insula in the parieto-frontomedial epileptic network. Clues from successful surgical treatment.

We present a case of MRI negative SMA seizure with the seizure onset zone in the secondary leg area on the superior bank of the Sylvian fissure, localized with multiscale electro-clinical and neuroradiological examinations. The 34-year-old female patient's intractable epilepsy started at age 14. She had diffuse pain aura in her left leg followed by tonic posturing with fully preserved consciousness suggesting parieto-fronto-medial seizure propagation. Her daily nocturnal SMA seizures became drug-resistant. Multiple 3T MRI images and neuropsychological evaluations were normal. Interictal PET detected a right parietal and insular FDG hypometabolism. The seizure onset zone and the symptomatogenic zone were localized by invasive electrophysiology. The insular deep electrode showed the propagation of ictal activity with an onset in the secondary sensory leg area through the insula to the fronto-medial surface. Eighteen spontaneous seizures, electrical cortical stimulation and cortical mapping confirmed the designated area of the resection, which was later proved macroscopically abnormal during surgery. The histological and immunohistological workup confirmed focal cortical dysplasia (IIb type). Postoperative postprocessing morphometry of the preoperative MRI study confirmed the lesion in the right inferior parietal lobe. The patient remained seizure free after surgery for more than 4 years, and medication free for the last two years. Our results concluded that the insula has a "relay" or "node" function in the parieto-opercular-fronto-medial epileptic network. The insular functional connectivity predisposed frontal propagation of the epileptic activity in the connectome of her epilepsy. The three-way insular structural connectivity has determining function on the seizure propagation.

Case report of a woman with anti amphiphysin positive stiff person syndrome.

Stiff person syndrome is a rare neuroimmunological disease, characterized by severe, involuntary stiffness with superimposed painful muscle spasms, which are worsened by external stimuli. The classical form is associated with high levels of antibodies against glutamic acid decarboxylase. One of the variant forms is associated with antibodies against amphiphysin. This entity is a paraneoplastic syndrome, caused primarily by breast cancer, secondarily by lung cancer. Symptomatic therapy of anti amphiphysin positive stiff person syndrome includes treatment with benzodiazepines and baclofen (including intrathecal baclofen therapy). The effect of immunological therapies is controversial. Treatment of the underlying cancer may be very effective. In this report, we describe a 68 year old female presenting with an unusally rapidly developing anti amphiphysin positive stiff person syndrome, which was associated with breast cancer. Her painful spasms abolished after intrathecal baclofen treatment was initiated. Her condition improved spontaneously and significantly after cancer treatment, which enabled to start her complex rehabilitation and the simultaneous dose reduction of the intrathecal baclofen. The bedridden patient improved to using a rollator walker and the baclofen pump could be removed 18 monthes after breast surgery. This highlights the importance of cancer screening and treatment in anti amphiphysin positive stiff person syndrome cases.

Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report.

We present the case of a 66-year-old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans. At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus. Bilateral stimulation of the subthalamic nucleus also resulted only in transient improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlated with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene, establishing the diagnosis of fragile X-associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. Postural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved.

[Invasive neuromodulation in the treatment of drug-resistant epilepsies]. / Invazív neuromoduláció a gyógyszerrezisztens epilepsziák kezelésében.

Neuromodulation is one of the most developing new disciplines of medical science, which examines how electrical, chemical and mechanical interventions can modulate or change the functioning of the central and peripheral nervous system. Neuromodulation is a reversible form of therapy which uses electrical or mechanical stimulation or centrally-delivered drugs to modulate the abnormal function of the central nervous system in pain, spasticity, epilepsy, movement and psychiatric disorders, and certain cardiac, incontinency, visual and auditory diseases. Neuromodulation therapy has two major branches. Non-invasive neuromodulation includes transcranial magnetic simulation, direct current stimulation and transcutaneous electric nerve stimulation. Invasive neuromodulation includes deep brain stimulation, cortical stimulation, spinal cord stimulation, peripheral nerve stimulation, sacral nerve simulation, and subcutan stimulation. In this article the authors overview the apparently available neural interface technologies in epilepsy surgery.

[Intraoperativ electrophysiological monitoring during neurosurgery on eloquent structures]. / Intraoperatív elektrofiziológia elokvens idegrendszeri struktúrákat erinto idegsebészeti beavatkozások során.

OBJECTIVE: We summarize our experiences on intraoperative electrophysiological monitoring during neurosurgical procedures on eloquent neuronal structures. PATIENTS, METHODS: Sixty patients were enrolled retrospectively in our study with pathologies involving eloquent neuronal structures. They were operated between May 2011. and March 2012. at the University of Debrecen, Department of Neurosurgery and at the National Institute of Neurosciences. Patients underwent standard preoperative examinations due to the primary pathology. In all cases we used intraoperative electrophysiological monitoring. We had 22 cases with cranial nerve monitoring, 10 cases with cauda monitoring, 16 cases with motor system monitoring, six cases with complex spinal cord monitoring, three degenerative spine reconstructions and 3 awake surgeries. RESULTS: We found that with the use of intraoperative electrophysiology we could make these neurosurgical procedures safer, and were able to optimize the extent of resection in the cases of oncological pathologies. CONCLUSIONS: Our experiences as well as the international literature suggests that in certain high risk neurosurgical procedures intraoperative electrophysiology is indispensible for safe and optimally extended operation.

[RADIOSURGERY OF INTRACEREBRAL CAVERNOMAS--CURRENT INTERNATIONAL TRENDS]. / AZ INTRACEREBRALIS CAVERNOMÁK SUGÁRSEBÉSZETE--HOL TART MA A VILÁG?

Although still a controversial management option, radio-surgery of intracranial cavernomas has become increasingly popular world-wide during the last decade. Microsurgery is a safe and effective treatment for symptomatic hemispheric cavernomas. However, the indication for microsurgical resection of deep eloquent cavernomas is relatively limited even in experienced hands. The importance of radiosurgery has recently been appreciated in parallel with increasing positive experiences both in terms of effectiveness and safety, especially for cases high risk for surgical resection, in the brainstem, thalamus and basal ganglia. While radiosurgery was earlier indicated mainly for surgically inaccessible lesions that had bled multiple times, a more proactive policy has recently become more accepted. In our opinion preventive treatment with the low morbidity radiosurgery serves the patients' interest especially for deep eloquent lesions that had bled not more than once, due to the cumulative morbidity of repeated hemorrhages. Despite our increasing knowledge on natural history, there is currently no available treatment algorithm for cavernomas. Arguments for all three treatment modalities (observation, microsurgery and radiosurgery) are established, but their indication criteria are yet to be defined. It is time to organize a prospective population based data collection in Hungary, which appears to be the most realistic way to clarify indication criteria.

Evoked effective connectivity of the human neocortex.

The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico-cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an inverse relationship to distance between sites. Coregistration to Brodmann areas (BA) permitted group analysis. Connections were frequently directional with 43% of early responses and 50% of late responses of connections reflecting relative dominance of incoming or outgoing connections. The most consistent connections were seen as outgoing from motor cortex, BA6-BA9, somatosensory (SS) cortex, anterior cingulate cortex, and Broca's area. Network topology revealed motor, SS, and premotor cortices along with BA9 and BA10 and language areas to serve as hubs for cortical connections. BA20 and BA39 demonstrated the most consistent dominance of outdegree connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated relatively greater indegree. This multicenter, large-scale, directional study of local and long-range cortical connectivity using direct recordings from awake, humans will aid the interpretation of noninvasive functional connectome studies.

[Intra- and perioperative imaging options in neurosurgery]. / Az intra- és perioperatív képalkotás lehetoségei az idegsebészetben.

The treatment of central nervous system tumors is still a major challenge for the oncological and neurosurgical teams. Due to the heterogeneous histological and topological characteristics of these neoplasms, every case requires individual evaluation. In addition to histology and stage, survival is largely determined by the extent of resection, which can be severely limited by the proximity of eloquent brain regions. A key component of current modern neuro-oncological care is the planning and execution of surgical intervention to ensure the longest possible progression-free survival with adequate quality of life. The simultaneous development of several pre- and intra-operative imaging modalities is making optimal therapy more and more accessible and safe. Structural, diffusion and functional MRI offers the possibility to visualize the tumor and the surrounding areas both before and during surgery. For the surgeon, the optimal intra-operative environment, orientation and visual acuity are provided by increasingly sophisticated microscopes, navigation devices, intra-operative imaging equipment, endo- and exoscopes.