Sensory Disconnection Research Articles

Consciousness in non-REM-parasomnia episodes.

Sleepwalking and related parasomnias are thought to result from incomplete awakenings out of non-rapid eye movement (non-REM) sleep. Non-REM parasomnia behaviours have been described as unconscious and automatic, or related to vivid, dream-like conscious experiences. Similarly, some observations have suggested that patients are unresponsive during episodes, while others that they can interact with their surroundings. To better grasp and characterise the full spectrum of consciousness and environmental (dis)connection associated with behavioural episodes, 35 adult patients with non-REM sleep parasomnias were interviewed in-depth about their experiences. The level of consciousness during parasomnia episodes was reported to be variable both within and between individuals, ranging from minimal or absent consciousness and largely automatic behaviours (frequently/always present in 36% of patients) to preserved conscious experiences characterised by delusional thinking to varying degrees of specificity (65%), often about impending danger, variably formed, uni- or multisensory hallucinations (53%), impaired insight (77%), negative emotions (75%), and variable, but often pronounced, amnesia (30%). Patients described their experiences as a dream scene during which they felt awake ("awake dreaming"). The surroundings were either realistically perceived, misinterpreted (in the form of perceptual illusions or misidentifications of people), or entirely hallucinated as a function of the prevailing delusion. These observations suggest that the level of consciousness, amnesiaand sensory disconnection during non-REM parasomnia episodes is variable and graded. In their full-fledged expression, non-REM parasomnia experiences feature several core features of dreams. They therefore represent a valuable model for the study of consciousness, sleep-related sensory disconnection and dreaming.

Study protocol: Cerebral characterization of sensory gating in disconnected dreaming states during propofol anesthesia using fMRI.

Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited. To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity. This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness. European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Interactive effects of pain and arousal state on heart rate and cortical activity in the mouse anterior cingulate and somatosensory cortices

Sensory disconnection is a hallmark of sleep, yet the cortex retains some ability to process sensory information. Acute noxious stimulation during sleep increases the heart rate and the likelihood of awakening, indicating that certain mechanisms for pain sensing and processing remain active. However, processing of somatosensory information, including pain, during sleep remains underexplored. To assess somatosensation in natural sleep, we simultaneously recorded heart rate and local field potentials in the anterior cingulate (ACC) and somatosensory (S1) cortices of naïve, adult male mice, while applying noxious and non-noxious stimuli to their hind paws throughout their sleep-wake cycle. Noxious stimuli evoked stronger heart rate increases in both wake and non-rapid eye movement sleep (NREMS), and resulted in larger awakening probability in NREMS, as compared to non-noxious stimulation, suggesting differential processing of noxious and non-noxious information during sleep. Somatosensory information differentially reached S1 and ACC in sleep, eliciting complex transient and sustained responses in the delta, alpha, and gamma frequency bands as well as somatosensory evoked potentials. These dynamics depended on sleep state, the behavioral response to the stimulation and stimulation intensity (non-noxious vs. noxious). Furthermore, we found a correlation of the heart rate with the gamma band in S1 in the absence of a reaction in wake and sleep for noxious stimulation. These findings confirm that somatosensory information, including nociception, is sensed and processed during sleep even in the absence of a behavioral response.

Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection

BackgroundSensory disconnection is a key feature of sleep and anaesthesia. We have proposed that predictive coding offers a framework for understanding the mechanisms of disconnection. Low doses of ketamine that do not induce disconnection should thus diminish predictive coding, but not abolish it. MethodsKetamine was administered to 14 participants up to a blood concentration of 0.3 μg ml−1 Participants were played a series of tones comprising a roving oddball sequence while electroencephalography evoked response potentials were recorded. We fit a Bayesian observer model to the tone sequence, correlating neural activity with the prediction errors generated by the model using linear mixed effects models and cluster-based statistics. ResultsKetamine modulated prediction errors associated with the transition of one tone to the next (transitional probability), but not how often tones changed (environmental volatility), of the system. Transitional probability was reduced when blood concentrations of ketamine were increased to 0.2–0.3 μg ml−1 (96–208 ms, P=0.003); however, correlates of prediction error were still evident in the electroencephalogram (124–168 ms, P=0.003). Prediction errors related to environmental volatility were associated with electroencephalographic activity before ketamine (224–284 ms, P=0.028) and during 0.2–0.3 μg ml−1 ketamine (108–248 ms, P=0.003). At this subanaesthetic dose, ketamine did not exert a dose-dependent modulation of prediction error. ConclusionsSubanaesthetic dosing of ketamine reduced correlates of predictive coding but did not eliminate them. Future studies should evaluate whether states of sensory disconnection, including anaesthetic doses of ketamine, are associated with a complete absence of predictive coding responses. Clinical trial registrationNCT03284307.

Dynamic causal modelling of auditory surprise during disconnected consciousness: The role of feedback connectivity

The neural mechanisms through which individuals lose sensory awareness of their environment during anesthesia remains poorly understood despite being of vital importance to the field. Prior research has not distinguished between sensory awareness of the environment (connectedness) and consciousness itself. In the current study, we investigated the neural correlates of sensory awareness by contrasting neural responses to an auditory roving oddball paradigm during consciousness with sensory awareness (connected consciousness) and consciousness without sensory awareness (disconnected consciousness). These states were captured using a serial awakening paradigm with the sedative alpha2 adrenergic agonist dexmedetomidine, chosen based on our published hypothesis that suppression of noradrenaline signaling is key to induce a state of sensory disconnection. High-density electroencephalography was recorded from 18 human subjects before and after administration of dexmedetomidine. By investigating event-related potentials and taking advantage of advances in Dynamic Causal Modeling (DCM), we assessed alterations in effective connectivity between nodes of a previously established auditory processing network. We found that during disconnected consciousness, the scalp-level response to standard tones produced a P3 response that was absent during connected consciousness. This P3 response resembled the response to oddball tones seen in connected consciousness. DCM showed that disconnection produced increases in standard tone feedback signaling throughout the auditory network. Simulation analyses showed that these changes in connectivity, most notably the increase in feedback from right superior temporal gyrus to right A1, can explain the new P3 response. Together these findings show that during disconnected consciousness there is a disruption of normal predictive coding processes, so that all incoming auditory stimuli become similarly surprising.

Tinnitus: at a crossroad between phantom perception and sleep.

Sensory disconnection from the environment is a hallmark of sleep and is crucial for sleep maintenance. It remains unclear, however, whether internally generated percepts—phantom percepts—may overcome such disconnection and, in turn, how sleep and its effect on sensory processing and brain plasticity may affect the function of the specific neural networks underlying such phenomena. A major hurdle in addressing this relationship is the methodological difficulty to study sensory phantoms, due to their subjective nature and lack of control over the parameters or neural activity underlying that percept. Here, we explore the most prevalent phantom percept, subjective tinnitus—or tinnitus for short—as a model to investigate this. Tinnitus is the permanent perception of a sound with no identifiable corresponding acoustic source. This review offers a novel perspective on the functional interaction between brain activity across the sleep–wake cycle and tinnitus. We discuss characteristic features of brain activity during tinnitus in the awake and the sleeping brain and explore its effect on sleep functions and homeostasis. We ask whether local changes in cortical activity in tinnitus may overcome sensory disconnection and prevent the occurrence of global restorative sleep and, in turn, how accumulating sleep pressure may temporarily alleviate the persistence of a phantom sound. Beyond an acute interaction between sleep and neural activity, we discuss how the effects of sleep on brain plasticity may contribute to aberrant neural circuit activity and promote tinnitus consolidation. Tinnitus represents a unique window into understanding the role of sleep in sensory processing. Clarification of the underlying relationship may offer novel insights into therapeutic interventions in tinnitus management.

Distinct EEG signatures differentiate unconsciousness and disconnection during anaesthesia and sleep

BackgroundHow conscious experience becomes disconnected from the environment, or disappears, across arousal states is unknown. We sought to identify the neural correlates of sensory disconnection and unconsciousness using a novel serial awakening paradigm. MethodsVolunteers were recruited for sedation with dexmedetomidine i.v., propofol i.v., or natural sleep with high-density EEG monitoring and serial awakenings to establish whether subjects were in states of disconnected consciousness or unconsciousness in the preceding 20 s. The primary outcome was classification of conscious states by occipital delta power (0.5–4 Hz). Secondary analyses included derivation (dexmedetomidine) and validation (sleep/propofol) studies of EEG signatures of conscious states. ResultsOccipital delta power differentiated disconnected and unconscious states for dexmedetomidine (area under the curve [AUC] for receiver operating characteristic 0.605 [95% confidence interval {CI}: 0.516; 0.694]) but not for sleep/propofol (AUC 0.512 [95% CI: 0.380; 0.645]). Distinct source localised signatures of sensory disconnection (AUC 0.999 [95% CI: 0.9954; 1.0000]) and unconsciousness (AUC 0.972 [95% CI: 0.9507; 0.9879]) were identified using support vector machine classification of dexmedetomidine data. These findings generalised to sleep/propofol (validation data set: sensory disconnection [AUC 0.743 {95% CI: 0.6784; 0.8050}]) and unconsciousness (AUC 0.622 [95% CI: 0.5176; 0.7238]). We identified that sensory disconnection was associated with broad spatial and spectral changes. In contrast, unconsciousness was associated with focal decreases in activity in anterior and posterior cingulate cortices. ConclusionsThese findings may enable novel monitors of the anaesthetic state that can distinguish sensory disconnection and unconsciousness, and these may provide novel insights into the biology of arousal. Clinical trial registrationNCT03284307.

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.

Cross-participant prediction of vigilance stages through the combined use of wPLI and wSMI EEG functional connectivity metrics.

Functional connectivity (FC) metrics describe brain inter-regional interactions and may complement information provided by common power-based analyses. Here, we investigated whether the FC-metrics weighted Phase Lag Index (wPLI) and weighted Symbolic Mutual Information (wSMI) may unveil functional differences across four stages of vigilance-wakefulness (W), NREM-N2, NREM-N3, and REM sleep-with respect to each other and to power-based features. Moreover, we explored their possible contribution in identifying differences between stages characterized by distinct levels of consciousness (REM+W vs. N2+N3) or sensory disconnection (REM vs. W). Overnight sleep and resting-state wakefulness recordings from 24 healthy participants (27 ± 6 years, 13F) were analyzed to extract power and FC-based features in six classical frequency bands. Cross-validated linear discriminant analyses (LDA) were applied to investigate the ability of extracted features to discriminate (1) the four vigilance stages, (2) W+REM vs. N2+N3, and (3) W vs. REM. For the four-way vigilance stages classification, combining features based on power and both connectivity metrics significantly increased accuracy relative to considering only power, wPLI, or wSMI features. Delta-power and connectivity (0.5-4 Hz) represented the most relevant features for all the tested classifications, in line with a possible involvement of slow waves in consciousness and sensory disconnection. Sigma-FC, but not sigma-power (12-16 Hz), was found to strongly contribute to the differentiation between states characterized by higher (W+REM) and lower (N2+N3) probabilities of conscious experiences. Finally, alpha-FC resulted as the most relevant FC-feature for distinguishing among wakefulness and REM sleep and may thus reflect the level of disconnection from the external environment.

Sleep: The Sensory Disconnection of Dreams

It has been known for some time that the brain can react selectively to meaningful sensory stimuli during sleep. A recent study shows that this ability may be selectively suppressed during rapid eye movements of sleep.

Sleep Differentially Affects Early and Late Neuronal Responses to Sounds in Auditory and Perirhinal Cortices.

A fundamental feature of sleep is reduced behavioral responsiveness to external events, but the extent of processing along sensory pathways remains poorly understood. While responses are comparable across wakefulness and sleep in auditory cortex (AC), neuronal activity in downstream regions remains unknown. Here we recorded spiking activity in 435 neuronal clusters evoked by acoustic stimuli in the perirhinal cortex (PRC) and in AC of freely behaving male rats across wakefulness and sleep. Neuronal responses in AC showed modest (∼10%) differences in response gain across vigilance states, replicating previous studies. By contrast, PRC neuronal responses were robustly attenuated by 47% and 36% during NREM sleep and REM sleep, respectively. Beyond the separation according to cortical region, response latency in each neuronal cluster was correlated with the degree of NREM sleep attenuation, such that late (>40 ms) responses in all monitored regions diminished during NREM sleep. The robust attenuation of late responses prevalent in PRC represents a novel neural correlate of sensory disconnection during sleep, opening new avenues for investigating the mediating mechanisms.SIGNIFICANCE STATEMENT Reduced behavioral responsiveness to sensory stimulation is at the core of sleep's definition, but it is still unclear how the sleeping brain responds differently to sensory stimuli. In the current study, we recorded neuronal spiking responses to sounds along the cortical processing hierarchy of rats during wakefulness and natural sleep. Responses in auditory cortex only showed modest changes during sleep, whereas sleep robustly attenuated the responses of neurons in high-level perirhinal cortex. We also found that, during NREM sleep, the response latency predicts the degree of sleep attenuation in individual neurons above and beyond their anatomical location. These results provide anatomical and temporal signatures of sensory disconnection during sleep and pave the way to understanding the underlying mechanisms.

Cross-participant prediction of vigilance stages through the combined use of wPLI and wSMI EEG functional connectivity metrics

Functional connectivity (FC) metrics describe brain inter-regional interactions and may complement information provided by common power-based analyses. Here, we investigated whether the FC-metrics weighted Phase Lag Index (wPLI) and weighted Symbolic Mutual Information (wSMI) may unveil functional differences across four stages of vigilance-wakefulness (W), NREM-N2, NREM-N3, and REM sleep-with respect to each other and to power-based features. Moreover, we explored their possible contribution in identifying differences between stages characterized by distinct levels of consciousness (REM+W vs. N2+N3) or sensory disconnection (REM vs. W). Overnight sleep and resting-state wakefulness recordings from 24 healthy participants (27 ± 6 years, 13F) were analyzed to extract power and FC-based features in six classical frequency bands. Cross-validated linear discriminant analyses (LDA) were applied to investigate the ability of extracted features to discriminate (1) the four vigilance stages, (2) W+REM vs. N2+N3, and (3) W vs. REM. For the four-way vigilance stages classification, combining features based on power and both connectivity metrics significantly increased accuracy relative to considering only power, wPLI, or wSMI features. Delta-power and connectivity (0.5-4 Hz) represented the most relevant features for all the tested classifications, in line with a possible involvement of slow waves in consciousness and sensory disconnection. Sigma-FC, but not sigma-power (12-16 Hz), was found to strongly contribute to the differentiation between states characterized by higher (W+REM) and lower (N2+N3) probabilities of conscious experiences. Finally, alpha-FC resulted as the most relevant FC-feature for distinguishing among wakefulness and REM sleep and may thus reflect the level of disconnection from the external environment.

Understanding Medjugorje Apparitional Experiences: Medical and Parapsychological Perspectives

Background. The continuing apparitional events at Medjugorje in Bosnia offer an opportunity for sceptics to gain fresh insight into an alleged mystical-cum-paranormal phenomenon. Initially, the apparitional experiences occurred in a collective manner ruling out the possibilities of psychological and spiritual artefacts. Ostensibly, according to the percipients, an active apparition—that has inserted itself harmoniously into our three-dimensional world—is manifesting itself at Medjugorje. In this respect, science is hindered by the lack of both theoretical tools and the vocabulary to handle mystical and paranormal events. Apparitional occurrences involve apparitional experience, the apparition and social events. The apparition is beyond the parameters of science and only apparitional experience can be scientifically studied; social events are more important to social sciences and theology. Aim. To test the postulation that visionary experiences involving RSPK, or RSPK-like activity may be instances of apparitions at the physical site and find the results applying this criterion along with other distinguishable features specific to Marian apparitional experiences. To evaluate the different psychological, parapsychological, psychopathological views usually held against true apparitional experiences. Method. Observational and quantitative studies attempted accepting the limitations. Selective survey of the scientific and journalistic literature including previous reviews has been carried out to collect different interpretations which also help to form a framework for an informed conclusion. Results. The voice extinction and sensory disconnection exhibited by the Medjugorje witnesses could probably be explained as a manifestation of psychokinetic-like activity of the apparition. Unlike other generic apparitional experiences reported in the scientific literature on parapsychology, the percipients and the apparition at Medjugorje partake in back and forth communication for extended periods of time. It is obvious that these are not self-generated. Medical studies indicate that there are dual modes of perception proving an inward cum outward apparitional experience. These apparitional experiences have the same pattern as those the officially authenticated Marian apparitions of the past. Additionally, the terrestrial memories revealed to the percipients prove the identity of the apparition as the Mother of Jesus. Apart from the spiritual and religious implications, Medjugorje is thought to be at the forefront of a revolutionary paradigm shift in the field of consciousness studies that may be unprecedented in scope. Psychiatry is currently founded on medical reduction and will have to make many adjustments according to the paradigmatic shifts in cognitive sciences; mental health professionals should be tuned to these on-going mystical happenings.

Evoked Alpha Power is Reduced in Disconnected Consciousness During Sleep and Anesthesia

Sleep and anesthesia entail alterations in conscious experience. Conscious experience may be absent (unconsciousness) or take the form of dreaming, a state in which sensory stimuli are not incorporated into conscious experience (disconnected consciousness). Recent work has identified features of cortical activity that distinguish conscious from unconscious states; however, less is known about how cortical activity differs between disconnected states and normal wakefulness. We employed transcranial magnetic stimulation–electroencephalography (TMS–EEG) over parietal regions across states of anesthesia and sleep to assess whether evoked oscillatory activity differed in disconnected states. We hypothesized that alpha activity, which may regulate perception of sensory stimuli, is altered in the disconnected states of rapid eye movement (REM) sleep and ketamine anesthesia. Compared to wakefulness, evoked alpha power (8–12 Hz) was decreased during disconnected consciousness. In contrast, in unconscious states of propofol anesthesia and non-REM (NREM) sleep, evoked low-gamma power (30–40 Hz) was decreased compared to wakefulness or states of disconnected consciousness. These findings were confirmed in subjects in which dream reports were obtained following serial awakenings from NREM sleep. By examining signatures of evoked cortical activity across conscious states, we identified novel evidence that suppression of evoked alpha activity may represent a promising marker of sensory disconnection.

Responses in Rat Core Auditory Cortex are Preserved during Sleep Spindle Oscillations.

Sleep is defined as a reversible state of reduction in sensory responsiveness and immobility. A long-standing hypothesis suggests that a high arousal threshold during non-rapid eye movement (NREM) sleep is mediated by sleep spindle oscillations, impairing thalamocortical transmission of incoming sensory stimuli. Here we set out to test this idea directly by examining sensory-evoked neuronal spiking activity during natural sleep. We compared neuronal (n = 269) and multiunit activity (MUA), as well as local field potentials (LFP) in rat core auditory cortex (A1) during NREM sleep, comparing responses to sounds depending on the presence or absence of sleep spindles. We found that sleep spindles robustly modulated the timing of neuronal discharges in A1. However, responses to sounds were nearly identical for all measured signals including isolated neurons, MUA, and LFPs (all differences < 10%). Furthermore, in 10% of trials, auditory stimulation led to an early termination of the sleep spindle oscillation around 150-250 msec following stimulus onset. Finally, active ON states and inactive OFF periods during slow waves in NREM sleep affected the auditory response in opposite ways, depending on stimulus intensity. Responses in core auditory cortex are well preserved regardless of sleep spindles recorded in that area, suggesting that thalamocortical sensory relay remains functional during sleep spindles, and that sensory disconnection in sleep is mediated by other mechanisms.

Auditory responses and stimulus-specific adaptation in rat auditory cortex are preserved across NREM and REM sleep.

Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic "gate," which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences <8% between states). The processing of deviant tones was also compared in sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13-20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas.

Corpus callosum section and other disconnection procedures for medically intractable epilepsy.

Corpus callosum section for carefully selected patients with uncontrolled epilepsy has become more acceptable as operative complications have decreased. From consideration of anatomical pathways utilized in the spread of seizure discharges, section of the corpus callosum is expected to decrease, but not abolish, bilaterally synchronous EEG abnormalities arising from most cerebral locations, perhaps excluding the temporal lobe. Clinical experience confirms this expectation. Persistence of some bilateral synchrony, presumably through subcortical relays, does not usually diminish the effectiveness of corpus callosum section on clinically generalized seizures that are eliminated or markedly decreased in 85% of patients after total corpus callosum section. Generalized seizure types that respond include tonic, atonic, tonic-clonic, and absence seizures. Patients who continue to have generalized seizures usually have low IQ and perhaps extensive bilateral cerebral involvement increases the extent to which subcortical structures participate in generalization. Complex partial seizures may cease, usually in patients with well-circumscribed, often extratemporal seizure foci. Focal seizures intensify in 25% of patients; a predictable consequence of sectioning interhemispheric inhibitory connections. Permanent disconnection syndromes, which are only rarely symptomatic, include sensory disconnection after posterior section, and split-brain syndrome after total section. A small percentage of patients develop impairments in language, motor, or memory functions. Language and motor deficits are predicted by pre-existing unilateral mild or moderate central nervous system damage. Partial section of the corpus callosum produces control of generalized seizures half as frequently as complete section. Neurologic sequelae of partial section occur nearly as frequently but are less severe.