Hierarchical Poincaré analysis for anaesthesia monitoring.

Although the degree of dispersion in Poincaré plots of electroencephalograms (EEG), termed the Poincaré-index, detects the depth of anaesthesia, the Poincaré-index becomes estranged from the bispectral index (BIS) at lighter anaesthesia levels. The present study introduces Poincaré-index20-30 Hz, targeting the 20- to 30-Hz frequency, as the frequency range reported to contain large electromyogram (EMG) portions in frontal EEG. We combined Poincaré-index20-30 Hz with the conventional Poincaré-index0.5-47 Hz using a deep learning technique to adjust to BIS values, and examined whether this layered Poincaré analysis can provide an index of anaesthesia level like BIS. A total of 83,867 datasets of these two Poincaré-indices and BIS-monitor-derived parameters were continuously obtained every 3 s from 30 patients throughout general anaesthesia, and were randomly divided into 75% for a training dataset and 25% for a test dataset. Two Poincaré-indices and two supplemental EEG parameters (EMG70-110 Hz, suppression ratio) in the training dataset were trained in a multi-layer perceptron neural network (MLPNN), with reference to BIS as supervisor. We then evaluated the trained MLPNN model using the test dataset, by comparing the measured BIS (mBIS) with BIS predicted from the model (PredBIS). The relationship between mBIS and PredBIS using the two Poincaré-indices showed a tight linear regression equation: mBIS = 1.00 × PredBIS + 0.15, R = 0.87, p < 0.0001, root mean square error (RMSE) = 7.09, while the relationship between mBIS and PredBIS simply using the original Poincaré-index0.5-47 Hz was weaker (R = 0.82, p < 0.0001, RMSE = 7.32). This suggests the 20- to 30-Hz hierarchical Poincaré analysis has potential to improve on anaesthesia depth monitoring constructed by simple Poincaré analysis.

The fundamental contribution of the electromyogram to a high bispectral index: a postoperative observational study.

The electromyogram (EMG) activity has been reported to falsely increase BIS. Conversely, EMG seems necessary to constitute the high BIS indicative of an awake condition, and may play a fundamental role in calculating BIS, rather than distorting the appropriate BIS. However, exactly how EMG is associated with a high BIS remains unclear. We intended to clarify the respective contributions of EMG and various electroencephalogram (EEG) parameters to high BIS. In 79 courses of anaesthesia, BIS monitor-derived EMG parameters (EMGLOW), and other processed EEG parameters [SEF95 (spectral edge frequency 95%), SynchFastSlow (bispectral parameter), BetaRatio (frequency parameter), total power subtypes in five frequency range], were obtained simultaneously with BIS, every 3 s. These EEG parameters were used for receiver operating characteristic (ROC) analysis of detecting three BIS levels (BIS > 80, BIS > 70, and BIS > 60) to assess their diagnosabilities. A total of 218,418 data points derived from 79 cases were used for analysis. Area under the ROC curve (AUC) was calculated and optimal cut-off (threshold) was determined by Youden index. As the results, for detecting BIS > 80, the AUC of EMGLOW was 0.975 [0.974-0.977] (mean [95% confidence interval]), significantly higher than any other processed EEG parameters such as BetaRatio (0.832 [0.828-0.835]), SEF95 (0.821 [0.817-0.826]) and SynchFastSlow (0.769 [0.764-0.774]) (p < 0.05 each). The threshold of EMGLOW for detecting BIS > 80 was 35.7 dB, with high sensitivity (92.5%) and high specificity (96.5%). Our results suggest EMG contributes considerably to the diagnosis of high BIS, and is particularly essential for determining BIS > 80.

Dopamine D2-receptor Antagonist Droperidol Deepens Sevoflurane Anesthesia.

BACKGROUND: Although midbrain dopaminergic pathways are known to contribute to arousal and emergence from anesthesia, few reports exist regarding the anesthetic effects of dopamine D2 receptor antagonism in humans. This study examined the effect of the D2 receptor antagonist droperidol on sevoflurane anesthesia by examining α and slow wave electroencephalogram oscillations. METHODS: Forty-five patients, age 20 to 60 yr, were enrolled. Frontal electroencephalograms were continuously collected for offline analysis via Bispectral Index monitoring. After induction of anesthesia, end-tidal sevoflurane concentration was deliberately maintained at 1%, and intravenous droperidol (0.05 mg/kg bolus) was administered. Electroencephalogram changes were examined in power spectrum and bicoherence, before and 10 min after droperidol injection, then compared using the Wilcoxon signed-ranks test and/or paired t test. RESULTS: Droperidol significantly augmented the α-bicoherence peak induced by sevoflurane from 30.3% (24.2%, 42.4%) to 50.8% (41.7%, 55.2%) (median [25th, 75th percentiles]; P < 0.0001), Hodges-Lehman median difference, 15.8% (11.3 to 21.4%) (95% CI). The frequency of the α-bicoherence peak was simultaneously shifted to the lower frequency; from 11.5 (11.0, 13.0) to 10.5 (10.0, 11.0) Hz (median [25th, 75th percentiles], P < 0.0001). Averaged bicoherence in the δ-θ area increased conspicuously from 17.2% (15.6 to 18.7%) to 25.1% (23.0 to 27.3%) (mean [95% CI]; P < 0.0001), difference, 8.0% (6.0 to 9.9%). CONCLUSIONS: Droperidol augments both α and δ-θ bicoherences while shifting the α-bicoherence peaks to lower frequencies, and enhances the effect of sevoflurane anesthesia on the electroencephalogram via γ-aminobutyric acid-mediated oscillatory network regulation.

Appetitive and aversive information coding in the primate dorsal raphé nucleus.

Serotonin is known to play a key role in the regulation of emotional behavior. There have been conflicting hypotheses about whether the central serotonergic system is involved in positive or negative emotional information processing. To reveal whether and how such opposing information processing can be achieved by single neurons in the dorsal raphé nucleus (DRN), the major source of serotonin in the forebrain, we recorded the activity of DRN neurons while monkeys were conditioned in a Pavlovian procedure with two distinct contexts: an appetitive block where a reward was available; and an aversive one where an airpuff was delivered. We found that single DRN neurons were involved in several aspects of both appetitive and aversive information processing. First, more than half of the recorded DRN neurons discriminated between appetitive and aversive contexts by tonic changes in their activity. In the appetitive context, they then kept track of the expected reward value indicated by the conditioned stimuli. Some of them also encoded an error between the obtained and expected values. In the aversive context, the same neurons maintained tonic modulation in their activity throughout the block. However, modulation of their responses to aversive task events depending on airpuff probability was less common. Together, these results indicate that single DRN neurons encode both appetitive and aversive information, but over differing time scales: relatively shorter for appetitive, and longer for aversive. Such temporally distinct processes of value coding in the DRN may provide the neural basis of emotional information processing in different contexts.

Effect-site concentrations of remifentanil causing bradycardia in hypnotic and non-hypnotic patients.

Although the induction of anaesthesia with remifentanil often causes bradycardia, the relationship between the effect-site concentration (Ce) of remifentanil and instantaneous heart rate (HR) has remained unclear. The present study examined the relationship between instantaneous HR and remifentanil Ce at the induction of anaesthesia with and without propofol hypnosis, to facilitate safe management of anaesthesia induction with remifentanil. Instantaneous HR was calculated every 5 s using an electrocardiographic real-time analysis system (MemCalc/Makin2; GMS, Tokyo, Japan). At the beginning of anaesthesia induction, continuous infusion of remifentanil (1 µg min-1 kg-1) preceded hypnosis with propofol in 13 patients [non-hypnosis group; mean age, 67.8 (17.5) years], while propofol bolus (30-50 mg) was injected together with continuous remifentanil medication in 18 patients [hypnosis group; mean age, 62.9 (16.5) years]. Remifentanil Ce was estimated every 5 s using the three-compartment model proposed by Minto et al. and the relationship between estimated remifentanil Ce and instantaneous HR was examined. In the hypnosis group, HR was significantly lower than basal HR when remifentanil Ce was increased to 3.5 ng ml-1 (p < 0.05), whereas no significant HR reduction was found in the non-hypnosis group until remifentanil Ce reached >5 ng ml-1 (p < 0.05). The induction of anaesthesia using remifentanil with propofol hypnotics significantly reduces HR even in a low remifentanil Ce insufficient to suppress the cardiovascular response at tracheal intubation. Preparations to treat bradycardia are recommended for the safe management of anaesthesia induction when remifentanil is combined with hypnotics.

[Serious Coagulation Dysfunction in a Patient with Gallstone-related Cholecystitis Successfully Treated with Vitamin K].

An 85-year-old woman with a diagnosis of choledocholithiasis due to common duct stones gradually developed severe coagulation dysfunction over the course of 27 days after hospitalization. Initial clinical findings were fever, general malaise, and obstructive jaundice. She was treated with fasting, and received cephem antibiotics containing N-methyl-thio-tetrazole. Because the common duct stones were not removed endoscopically, cholecystectomy was scheduled. Coagulation on admission was normal, but gradually became impaired. On the scheduled day of the operation, 27 days after hospitalization, coagulation [both prothrombin time (PT) and activated partial thromboplastin time (APTT)] were severely impaired PT, < 10%; PT-international normalized ratio, 6.29; and APTT, 71.6 s. No other abnormalities were identified. Surgery was postponed and antibiotics were discontinued. Simultaneously, administration of vitamin K was initiated. Six days after starting vitamin K, coagulation dysfunction had resolved and the surgery was safely performed under general anesthesia combined with thoracic epidural anesthesia. Care is warranted regarding coagulation dysfunction due to vitamin K deficiency in patients with hepatobiliary disease treated by fasting and antibiotics.

[Use and Safety of Preoperative Oral Rehydration Therapy Using a Jelly Type Oral Rehydration Solution].

BACKGROUND: Traditionally, perioperative nutritional management centered on fluid therapy, but in recent years, with the spread of enhanced recovery after surgery (ERAS) protocols, the utility of oral rehydration therapy (ORT) has been reported. There are few reports, however, on the safety of using jelly type oral rehydration solutions for ORT. We examined the effects of OS-1 jelly on gastric fluid and investigated its safety. METHODS: A total of 147 patients (age range, 4-91 years), scheduled for elective surgery at our institution for whom ORT was indicated, were enrolled in this study. If the surgery was scheduled for the morning, patients were given two bottles of 200 g OS-1 jelly during the previous evening meal. If surgery was scheduled for the afternoon, two additional 200 g bottles were given to the patient with the morning meal on the day of surgery. Patients were allowed to drink water until two hours before the surgery. Gastric fluid was aspirated with a gastric tube after anesthesia induction, after which, volume and pH were measured. RESULTS: In all cases, gastric content was aspirated as a liquid, not a jelly. The volume and pH were 11.4 ± 14.6 ml and 2.8 ± 2.2, respectively. No major difference was seen in comparison with the data for OS-1 liquid. No postoperative aspiration pneumonia or reflux of gastric contents at the time of anesthesia induction was seen in any of the patients. CONCLUSIONS: From the present findings, if the time of water intake is strictly controlled, preoperative rehydration therapy using jelly-type oral rehydration solution is thought to be safe and comparable to liquid solution regarding its effects on gastric fluid.

Chaotic nature of the electroencephalogram during shallow and deep anesthesia: From analysis of the Lyapunov exponent.

In conscious states, the electrodynamics of the cortex are reported to work near a critical point or phase transition of chaotic dynamics, known as the edge-of-chaos, representing a boundary between stability and chaos. Transitions away from this boundary disrupt cortical information processing and induce a loss of consciousness. The entropy of the electroencephalogram (EEG) is known to decrease as the level of anesthesia deepens. However, whether the chaotic dynamics of electroencephalographic activity shift from this boundary to the side of stability or the side of chaotic enhancement during anesthesia-induced loss of consciousness remains poorly understood. We investigated the chaotic properties of EEGs at two different depths of clinical anesthesia using the maximum Lyapunov exponent, which is mathematically regarded as a formal measure of chaotic nature, using the Rosenstein algorithm. In 14 adult patients, 12 s of electroencephalographic signals were selected during two depths of clinical anesthesia (sevoflurane concentration 2% as relatively deep anesthesia, sevoflurane concentration 0.6% as relatively shallow anesthesia). Lyapunov exponents, correlation dimensions and approximate entropy were calculated from these electroencephalographic signals. As a result, maximum Lyapunov exponent was generally positive during sevoflurane anesthesia, and both maximum Lyapunov exponents and correlation dimensions were significantly greater during deep anesthesia than during shallow anesthesia despite reductions in approximate entropy. The chaotic nature of the EEG might be increased at clinically deeper inhalational anesthesia, despite the decrease in randomness as reflected in the decreased entropy, suggesting a shift to the side of chaotic enhancement under anesthesia.

Transplantation of human pluripotent stem cell-derived retinal sheet in a primate model of macular hole.

Macular hole (MH) is a retinal break involving the fovea that causes impaired vision. Although advances in vitreoretinal surgical techniques achieve >90% MH closure rate, refractory cases still exist. For such cases, autologous retinal transplantation is an optional therapy showing good anatomic success, but visual improvement is limited and peripheral visual field defects are inevitable after graft harvesting. Here, using a non-human primate model, we evaluated whether human embryonic stem cell-derived retinal organoid (RO) sheet transplantation can be an effective option for treating MH. After transplantation, MH was successfully closed by continuous filling of the MH space with the RO sheet, resulting in improved visual function, although no host-graft synaptic connections were confirmed. Mild xeno-transplantation rejection was controlled by additional focal steroid injections and rod/cone photoreceptors developed in the graft. Overall, our findings suggest pluripotent stem cell-derived RO sheet transplantation as a practical option for refractory MH treatment.

Neural correlates of category learning in monkey inferior temporal cortex.

We trained two monkeys implanted with multi-electrode arrays to categorize natural images of cats and dogs, in order to observe changes in neural activity related to category learning. We recorded neural activity from area TE, which is required for normal learning of visual categories based on perceptual similarity. Neural activity during a passive viewing task was compared pre- and post-training. After the category training, the accuracy of abstract category decoding improved. Specifically, the proportion of single units with category selectivity increased, and units sustained their category-specific responses for longer. Visual category learning thus appears to enhance category separability in area TE by driving changes in the stimulus selectivity of individual neurons and by recruiting more units to the active network.

The histamine H1 receptor antagonist hydroxyzine enhances sevoflurane and propofol anesthesia: A quantitative EEG study.

OBJECTIVE: The aim of this study was to determine the anesthesia-promoting effects of hydroxyzine on electroencephalograms during sevoflurane anesthesia and during propofol anesthesia. METHODS: We analyzed 40 patients scheduled for elective surgery under sevoflurane anesthesia (n = 20) or propofol anesthesia (n = 20). Anesthesia was adjusted at a bispectral index value of 50-60, and then 0.5 mg/kg of hydroxyzine was administered intravenously. We analyzed frontal electroencephalograms before and after hydroxyzine injection with power spectral and bicoherence analyses, which are suitable for assessing the anesthetic depth induced by γ-aminobutyric acid (GABA)ergic anesthetics. RESULTS: Hydroxyzine increased the α bicoherence peaks in both sevoflurane anesthesia (mean difference, 11.2%; 95% confidence interval (CI), 7.6 to 14.8; P < 0.001) and propofol anesthesia (mean difference, 5.6%; 95% CI, 1.7 to 9.4; P = 0.008). Hydroxyzine increased the averaged δ bicoherence values in both sevoflurane anesthesia (mean difference, 5.5%; 95% CI, 2.1 to 8.8; P = 0.003) and propofol anesthesia (mean difference, 3.9%; 95% CI, 1.0 to 6.8; P = 0.011). CONCLUSIONS: Hydroxyzine enhances both sevoflurane anesthesia and propofol anesthesia probably by facilitation of GABAergic neural circuit mechanisms. SIGNIFICANCE: The findings provide a new insight into the role of histaminergic neurons during general anesthesia in humans.

A convolutional neural network for estimating synaptic connectivity from spike trains.

The recent increase in reliable, simultaneous high channel count extracellular recordings is exciting for physiologists and theoreticians because it offers the possibility of reconstructing the underlying neuronal circuits. We recently presented a method of inferring this circuit connectivity from neuronal spike trains by applying the generalized linear model to cross-correlograms. Although the algorithm can do a good job of circuit reconstruction, the parameters need to be carefully tuned for each individual dataset. Here we present another method using a Convolutional Neural Network for Estimating synaptic Connectivity from spike trains. After adaptation to huge amounts of simulated data, this method robustly captures the specific feature of monosynaptic impact in a noisy cross-correlogram. There are no user-adjustable parameters. With this new method, we have constructed diagrams of neuronal circuits recorded in several cortical areas of monkeys.

Cerebromalacia with epilepsy and cortical blindness in a laboratory Japanese macaque (Macaca fuscata).

The authors performed a pathological examination of a 5-year-old female laboratory Japanese monkey who developed cortical blindness and epileptic seizures. Generalized, tonic-clonic seizures started to occur during behavioral training to get the animal to enter a carrying cage for future psychological experiments. Blindness was suspected because of a lack of approaching behavior toward foods such as fruits. Although the monkey was extensively treated with anticonvulsants, the clinical signs did not improve. An increased serum creatine phosphokinase (CPK) level and bilateral occipital brain atrophy were detected. Histopathologically, a severe degree of cerebromalacia was detected bilaterally in the occipital lobe, and necrosis and gliosis were seen mainly in the temporal lobe. Focal inflammation was found in the meninges. No other changes were observed in other nervous tissues or organs, and no signs of a parasitic or viral infection were found in the systemic organs. Spontaneously occurring lesions in the central nervous system have been rarely reported in laboratory monkeys. In the present case, the cause of cerebromalacia could not be confirmed, but the relationship between symptoms such as abnormal vision and the presence of brain lesions was distinct. The authors believe that this case is a valuable historical control case for the laboratory Japanese macaque.

Anesthesia depth-dependent features of electroencephalographic bicoherence spectrum during sevoflurane anesthesia.

BACKGROUND: Growth pattern in the electroencephalographic bicoherence spectrum has recently been found to relate to anesthetic depth, and bicoherence analysis can reflect behavior of the thalamocortical reverberating network. Because the thalamocortical network is known to represent a key factor in sleep by anesthesia, systematic and qualitative bicoherence studies of different anesthetic depths is necessary throughout all pairs of frequencies. METHODS: Sixteen patients were anesthetized using sevoflurane (1, 2, or 3%) combined with remifentanil (0.4 microg x kg x min). Raw electroencephalographic signals were collected, and bicoherence was estimated in all pairs of frequencies, between 0.5 and 40 Hz at 0.5-Hz intervals. RESULTS: Sevoflurane (1%) caused two main peaks, spindle frequencies (11.0 +/- 1.2 Hz, 44.7 +/- 12.3% [bicoherence growth]) and delta-theta frequencies (5.4 +/- 0.5 Hz, 33.0 +/- 8.4%), in the diagonal line of biphasic bicoherence plots. High concentrations of sevoflurane (2% and 3%) shifted these peaks to 9.8 +/- 1.1 Hz, 46.2 +/- 12.7%; 8.7 +/- 1.3 Hz, 37.2 +/- 13.7% and 4.9 +/- 0.5 Hz, 44.6 +/- 7.0%; 4.3 +/- 0.8 Hz, 45.2 +/- 10.6%, respectively. Sevoflurane caused a third bicoherence peak to appear in another heterogeneous pair frequency (pair of alpha basal frequency and its double frequency), outside the diagonal line, which also inherited the behavior of alpha bicoherence peaks at different anesthetic depths. CONCLUSIONS: Sevoflurane anesthesia caused bicoherence peaks in alpha and delta-theta areas and also formed secondary third peaks. Deeper sevoflurane anesthesia shifted all bicoherence peaks to lower frequencies and caused increased bicoherence growth in the delta-theta area. The obtained features are consistent with characteristics of the thalamocortical reverberating network and suggest the importance of bicoherence analysis for the thalamic system.

Proteomic identification of haptoglobin as a stroke plasma biomarker in spontaneously hypertensive stroke-prone rats.

AIMS: We investigated changes in the expression of plasma proteins in spontaneously hypertensive stroke-prone rats (SHRSP) to identify stroke biomarkers. MAIN METHODS AND KEY FINDINGS: The present analysis using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) demonstrated that three peaks at mass/charge ratios (m/z) of 9330, 9480 and 9700 decreased in intensity during the development and progression of hypertensive stroke in SHRSPs, but not in age-matched control SHR and Wistar rats. Administration of verapamil, an L-type calcium channel blocker which was effective for hypertension in SHRSP rats, prevented the decrease in plasma protein expression. A candidate biomarker protein (m/z 9330) was identified using LC-MS/MS as haptoglobin (Hp). Immunoblotting with anti-Hp antibody demonstrated the decreased expression of both Hpalpha and Hpbeta chains in SHRSP. In contrast, haptoglobin mRNA expression in the liver of SHRSPs slightly increased as compared with control rats. SIGNIFICANCE: These findings suggest that Hp is a biomarker candidate for discriminating pathogenic alterations of stroke.

Involvement of hippocampal metabotropic glutamate receptors in radial maze performance.

We investigated the role of hippocampal metabotropic glutamate receptors in spatial learning and memory, using an eight-arm radial maze task. (S)-4-Carboxyphenylglycine, a group I metabotropic glutamate receptor antagonist, or trans-(+/-)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid, a broad-spectrum metabotropic glutamate receptor agonist, was administered into the dorsal hippocampus after rats had acquired the task. Both of these agents significantly impaired radial maze performance, suggesting a functional importance of hippocampal metabotropic glutamate receptors in spatial working memory.

Pure word deafness due to left subcortical lesion: neurophysiological studies of two patients.

OBJECTIVE: This study investigated the auditory processing in two patients with pure word deafness (PWD) using neurophysiological experimental methods. METHODS: We recorded the auditory brainstem response (ABR), the middle latency auditory-evoked response (MLR) and the auditory-evoked event-related potentials (ERPs) in two patients with PWD after subcortical hemorrhage in the left temporal lobe. RESULTS: Both patients showed normal response in ABR and abnormality in MLR. The latency of P300 evoked by right-ear stimulation was 51 ms longer in one patient and 26 ms longer in the other patient than that evoked by left-ear stimulation. CONCLUSIONS: Our results suggested that the prolongation of P300 latency could be caused by the deterioration of auditory stimulus processing and supported the hypothesis that the defect in auditory temporal resolution was an important factor in the development of PWD. SIGNIFICANCE: This study demonstrated that recordings of ERP with auditory-evoked response such as ABR and MLR are useful to elucidate the deterioration of auditory stimulus processing in patients with PWD.

Electroencephalographic monitoring during sevoflurane anaesthesia in an amyotrophic lateral sclerosis patient with locked-in state.

Recently, the cognitive abilities of patients with amyotrophic lateral sclerosis (ALS) have been found to be impaired along with the neurodegeneration of motor neurons. Electroencephalography (EEG) of end-stage ALS patients has reportedly shown specific features based on neuronal network modulations, differing from EEG of other patients with cognitive failure and dementia. However, EEG of end-stage ALS patients during anaesthesia has not yet been reported. A 64-year-old male ALS patient with locked-in state (LIS), supported by tracheostomy positive-pressure ventilation (TPPV) and enteral nourishment for 9years, underwent scheduled general anaesthesia for repair of a fractured mandible. He could blink and open his eyes, but seldom opened or closed his eyes on instruction. Sevoflurane anaesthesia was induced under continuous EEG monitoring with bispectral index (BIS), which is commonly used to examine the level of anaesthesia. Prominent alpha oscillations with lower peak frequency and high amplitude appeared during anaesthesia, differing from the characteristics of EEG seen in patients with general cognitive failure. Conversely, BIS reflected the sevoflurane concentration in this ALS patient, similar to healthy individuals, and BIS monitoring was useful for estimating the depth of anaesthesia. The prominent alpha oscillation revealed in this rare case report may suggest modulation of the functional neuronal network system during anaesthesia in patients with progressive ALS, in a manner quite different from typical dementia patients. EEG abnormalities in the present ALS patient did not influence the availability of BIS monitoring.

Approaches to subjective midpoint of horizontal lines in unilateral spatial neglect.

Patients with unilateral spatial neglect usually bisect longer lines with greater rightward errors, while they sometimes err leftward for very short lines (e.g., 25 mm). We analysed movements of eye fixation from the time before line presentation to elucidate whether patients with neglect approach the subjective midpoint differently for lines of various lengths. Four patients with left neglect bisected 200 mm, 100 mm, and 25 mm lines that appeared across the centre of a liquid crystal display (LCD) monitor. The fixation immediately before line presentation was located on average near the centre of the lines. Three of the patients approached the subjective midpoint point directly from the left side in more than 70% of the 200 mm and 100 mm trials. The subjective midpoint frequently deviated leftward on the "attended" segment between the leftmost point of fixation and the right endpoint, while it was displaced rightward on the total extent. The three patients initially explored the 25 mm lines searching for the left endpoint. They thereafter bisected the same lines with leftward errors approaching the subjective midpoint from the left side. The remaining patient searched beyond the right endpoint and in turn approached the subjective midpoint from the right side in about half of the trials and independently of line length. In the 200 mm and 100 mm trials, the subjective midpoint divided the attended right segment nearer to the right endpoint. On the attended right extent of a line, patients with neglect may place the subjective midpoint toward the side from which they approached that point. In the bisection of very short lines, approaches from the left endpoint may cause leftward errors of the subjective midpoint. For longer lines, however, approaches from the left side may result in rightward error of bisection for the total length, as the leftward extent from the fixation immediately before line presentation is hardly explored.