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Microstimulation can modulate the activity of individual neurons in order to affect behavior, but the effects of stimulation on neuronal spiking are complex and remain poorly understood. This is especially challenging in the human brain where the response properties of individual neurons are sparse and heterogenous. Here we use micro- electrode array (MEAs) in the human anterior temporal lobe in six participants (3 female) to examine the spiking responses of individual neurons to microstimulation delivered through multiple distinct stimulation sites. We demonstrate that individual neurons can be driven with excitation or inhibition using different stimulation sites, which suggests an approach for providing direct control of spiking activity at the single neuron level. Spiking responses are inhibitory in neurons that are close to the site of stimulation, while excitatory responses are more spatially distributed. Together, our data demonstrate that spiking responses of individual neurons can be reliably identified and manipulated in the human cortex.SIGNIFICANCE STATEMENT:One of the major limitations in our ability to interface directly with the human brain is that the effects of stimulation on the activity of individual neurons remains poorly understood. Here, Youssef et al. examine the spiking responses of neurons in the human temporal cortex in response to pulses of microstimulation. They find that individual neurons can either be excited or inhibited depending on the site of stimulation. These data suggest an approach for modulating the spiking activity of individual neurons in the human brain.

Object repetition commonly leads to long-lasting improvements in identification speed and accuracy, a behavioral facilitation referred to as “repetition priming”. Neuroimaging and non-invasive electromagnetic stimulation studies have most often implicated the involvement of left lateral frontal cortex in repetition priming, although convergent evidence from neuropsychological studies is lacking. In the current study, we examine the impact of surgical resection for the treatment of epilepsy on the magnitude of repetition priming at relatively short-term (30–60 minute delay) and long-term (3 months) delays in 41 patients with varying seizure foci and resection locations. Overall, patients exhibited significant repetition priming at both short-term and long-term delays. However, patients with frontal resections (largely anterior and medial frontal) differed significantly from those with right anterior temporal resections in showing fully intact short-term priming but absent long-term priming. In a comparison set of 10 recovered aphasic patients, patients with left lateral frontal damage exhibited impaired short-term priming relative to other frontal damage locations, suggesting the differential involvement of lateral and anteromedial frontal regions in mediating repetition priming at short-lag and long-lag timescales, respectively.

Human brain activity during memory Animal studies suggest that sequence replay of neuronal activity may underlie memory retrieval and consolidation. However, there is no direct evidence that the replay of spiking activity sequences is important for these processes in the human brain. Vaz et al. simultaneously recorded single-unit spikes, local field potential, and intracranial electroencephalography signals in the brain while participants performed a memory task. Sharp wave ripple oscillations in the temporal lobe cortex reflected bursts of neural spiking, and these bursts of spikes organized into sequences during memory formation. These sequences were replayed during successful memory retrieval. The extent of sequence replay during correct recall was related to the extent to which cortical spiking activity was coupled with ripples in the medial temporal lobe. Science , this issue p. 1131

The sensory cortices of many mammals are often organized into modules in the form of cortical columns, yet whether modular organization at this spatial scale is a general property of the human neocortex is unknown. The strongest evidence for modularity arises when measures of connectivity, structure, and function converge. Here we use microelectrode recordings in humans to examine functional connectivity and neuronal spiking responses in order to assess modularity in submillimeter scale networks. We find that the human temporal lobe consists of temporally persistent spatially compact modules approximately 1.3mm in diameter. Functionally, the information coded by single neurons during an image categorization task is more similar for neurons belonging to the same module than for neurons from different modules. The geometry, connectivity, and spiking responses of these local cortical networks provide converging evidence that the human temporal lobe is organized into functional modules at the micro scale.

Direct brain recordings have provided important insights into how high-frequency activity captured through intracranial EEG (iEEG) supports human memory retrieval. The extent to which such activity is comprised of transient fluctuations that reflect the dynamic coordination of underlying neurons, however, remains unclear. Here, we simultaneously record iEEG, local field potential (LFP), and single unit activity in the human temporal cortex. We demonstrate that fast oscillations within the previously identified 80–120 Hz ripple band contribute to broadband high-frequency activity in the human cortex. These ripple oscillations exhibit a spectrum of amplitudes and durations related to the amount of underlying neuronal spiking. Ripples in the macro-scale iEEG are related to the number and synchrony of ripples in the micro-scale LFP, which in turn are related to the synchrony of neuronal spiking. Our data suggest that neural activity in the human temporal lobe is organized into transient bouts of ripple oscillations that reflect underlying bursts of spiking activity.

Memories of experiences that occur around the same time are linked together by a shared temporal context, represented by shared patterns of neural activity. However, shared temporal context may be problematic for selective retrieval of specific memories. Here, we examine intracranial EEG (iEEG) in the human temporal lobe as participants perform a verbal paired associates memory task that requires the encoding of distinct word pairs in memory. We find that the rate of change in patterns of low frequency (3–12 Hz) power distributed across the temporal lobe is significantly related to memory performance. We also find that exogenous electrical stimulation affects how quickly these neural representations of temporal context change with time, which directly affects the ability to successfully form memories for distinct items. Our results indicate that the ability to retrieve distinct episodic memories is related to how quickly neural representations of temporal context change over time during encoding., Memories formed around the same time are linked together by a shared temporal context. Here, the authors show that the ability to selectively retrieve distinct episodic memories formed close together in time is related to how quickly neural representations of temporal context change over time during encoding.

Direct brain recordings have provided important insights into how persistent oscillatory activity support human memory retrieval, but the extent to which transient fluctuations in intracranial EEG (iEEG) captures the dynamic coordination of underlying neurons involved in memory processing remains unclear. Here, we simultaneously record iEEG, local field potential (LFP), and single unit activity in the human temporal cortex. We demonstrate that cortical ripples contribute to broadband high frequency activity and exhibit a spectrum of amplitudes and durations related to the amount of underlying neuronal spiking. Ripples in the macro-scale iEEG are related to the number and synchrony of ripples in the micro-scale LFP, which in turn are related to the synchrony of neuronal spiking. Our data suggest that neural activity in the human cortex is organized into dynamic, discrete packets of information.

Traveling waves of oscillatory activity are thought to influence neuronal spiking, providing a spatiotemporal frame-work for neural communication. However, no direct link has been established between traveling waves and neuronal spiking in humans. We examined traveling waves in the human lateral temporal lobe by using recordings from intracranial electrodes implanted in twenty participants for seizure monitoring as they performed a paired-associates verbal memory task. We observed ubiquitous low frequency traveling waves across the temporal lobe. While wave occurrence in a broad low frequency range did not differ between successful and unsuccessful memory conditions, in a subset of participants with microelectrode recordings, we found that macro-scale waves co-occurred with micro-scale waves, which in turn were temporally locked to single unit spiking. This temporal coordination between traveling waves at different spatial scales and between waves and neuronal spiking in the human brain suggests a role for traveling waves in neural communication.

Background Direct electrical stimulation of the human brain has been used to successfully treat several neurological disorders, but the precise effects of stimulation on neural activity are poorly understood. Characterizing the neural response to stimulation, however, could allow clinicians and researchers to more accurately predict neural responses, which could in turn lead to more effective stimulation for treatment and to fundamental knowledge regarding neural function. Objective Here we use a linear systems approach in order to characterize the response to electrical stimulation across cortical locations and then to predict the responses to novel inputs. Methods We use intracranial electrodes to directly stimulate the human brain with single pulses of stimulation using amplitudes drawn from a random distribution. Based on the evoked responses, we generate a simple model capturing the characteristic response to stimulation at each cortical site. Results We find that the variable dynamics of the evoked response across cortical locations can be captured using the same simple architecture, a linear time-invariant system that operates separately on positive and negative input pulses of stimulation. We demonstrate that characterizing the response to stimulation using this simple and tractable model of evoked responses enables us to predict the responses to subsequent stimulation with single pulses with novel amplitudes, and the compound response to stimulation with multiple pulses. Conclusion Our data suggest that characterizing the response to stimulation in an approximately linear manner can provide a powerful and principled approach for predicting the response to direct electrical stimulation.

We identify a memory-specific attention mechanism in the human anterior temporal lobe, an area implicated in semantic processing and episodic memory formation. Spiking neuron activity is suppressed and becomes more reliable in preparation for verbal memory formation. Intracranial electroencephalography signals implicate this region as a source of executive control for attentional selection. Consistent with this interpretation, its surgical removal causes significant memory impairment for attended words relative to unattended words.

The rostromedioventral striatum is critical for behavior dependent on evaluating rewards. We asked what contribution tonically active neurons (TANs), the putative striatal cholinergic interneurons, make in coding reward value in this part of the striatum. Two female monkeys were given the option to accept or reject an offered reward in each trial, the value of which was signaled by a visual cue. Forty-five percent of the TANs use temporally modulated activity to encode information about discounted value. These responses were significantly better represented using principal component analysis than by just counting spikes. The temporal coding is straightforward: the spikes are distributed according to a sinusoidal envelope of activity that changes gain, ranging from positive to negative according to discounted value. Our results show that the information about the relative value of an offered reward is temporally encoded in neural spike trains of TANs. This temporal coding may allow well tuned, coordinated behavior to emerge. SIGNIFICANCE STATEMENT Ever since the discovery that neurons use trains of pulses to transmit information, it seemed self-evident that information would be encoded into the pattern of the spikes. However, there is not much evidence that spike patterns encode cognitive information. We find that a set of interneurons, the tonically active neurons (TANs) in monkeys' striatum, use temporal patterns of response to encode information about the discounted value of offered rewards. The code seems straightforward: a sinusoidal envelope that changes gain according to the discounted value of the offer, describes the rate of spiking across time. This temporal modulation may provide a means to synchronize these interneurons and the activity of other neural elements including principal output neurons.

The neural mechanisms underlying human working memory are often inferred from studies using old-world monkeys. Humans use working memory to selectively memorize important information. We recently reported that monkeys do not seem to use selective memorization under experimental conditions that are common in monkey research, but less common in human research. Here we compare the performance of humans and monkeys under the same experimental conditions. Humans selectively remember important images whereas monkeys largely rely on recency information from nonselective memorization. Working memory studies in old-world monkeys must be interpreted cautiously when making inferences about the mechanisms underlying human working memory.

There is an on-going debate over whether area TE, or the anatomically adjacent rhinal cortex, is the final stage of visual object processing. Both regions have been implicated in visual perception, but their involvement in non-perceptual functions, such as short-term memory, hinders clear-cut interpretation. Here, using a two-interval forced choice task without a short-term memory demand, we find that after bilateral removal of area TE, monkeys trained to categorize images based on perceptual similarity (morphs between dogs and cats), are, on the initial viewing, badly impaired when given a new set of images. They improve markedly with a small amount of practice but nonetheless remain moderately impaired indefinitely. The monkeys with bilateral removal of rhinal cortex are, under all conditions, indistinguishable from unoperated controls. We conclude that the final stage of the integration of visual perceptual information into object percepts in the ventral visual stream occurs in area TE.

Intracranial recordings captured from subdural electrodes in patients with drug resistant epilepsy offer clinicians and researchers a powerful tool for examining neural activity in the human brain with high spatial and temporal precision. There are two major challenges, however, to interpreting these signals both within and across individuals. Anatomical distortions following implantation make accurately identifying the electrode locations difficult. In addition, because each implant involves a unique configuration, comparing neural activity across individuals in a standardized manner has been limited to broad anatomical regions such as cortical lobes or gyri. We address these challenges here by introducing a semi-automated method for localizing subdural electrode contacts to the unique surface anatomy of each individual, and by using a surface-based grid of regions of interest (ROIs) to aggregate electrode data from similar anatomical locations across individuals. Our localization algorithm, which uses only a postoperative CT and preoperative MRI, builds upon previous spring-based optimization approaches by introducing manually identified anchor points directly on the brain surface to constrain the final electrode locations. This algorithm yields an accuracy of 2 mm. Our surface-based ROI approach involves choosing a flexible number of ROIs with different spatial resolutions. ROIs are registered across individuals in order to represent identical anatomical locations while accounting for the unique curvature of each brain surface. This ROI based approach therefore enables group level statistical testing from spatially precise anatomical regions.

When we recall an experience, we rely upon the associations that we formed during the experience, such as those among objects, time, and place [1]. These associations are better remembered when they are familiar and draw upon generalized knowledge, suggesting that we use semantic memory in the service of episodic memory [2, 3]. Moreover, converging evidence suggests that episodic memory retrieval involves the reinstatement of neural activity that was present when we first experienced the event. Therefore, we hypothesized that retrieving associations should also reinstate the neural activity responsible for semantic processing. Indeed, previous studies have suggested that verbal memory retrieval leads to the reinstatement of activity across regions of the brain that include the distributed semantic processing network [4-6], but it is unknown whether and how individual neurons in the human cortex participate in the reinstatement of semantic representations. Recent advances using high-density microelectrode arrays (MEAs) have allowed clinicians to record from populations of neurons in the human cortex [7, 8]. Here we used MEAs to record neuronal spiking activity in the human middle temporal gyrus (MTG), a cortical region supporting the semantic representation of words [9-11], as participants performed a verbal paired-associates task. We provide novel evidence that population spiking activity in the MTG forms distinct representations of semantic concepts and that these representations are reinstated during the retrieval of those words.

Seven monkeys performed variants of two short-term memory tasks that others have used to differentiate between selective and nonselective memory mechanisms. The first task was to view a list of sequentially presented images and identify whether a test matched any image from the list, but not a distractor from a preceding list. Performance was best when the test matched the most recently presented image. Response rates depended linearly on recency of repetition whether the test matched a sample from the current list or a distractor from a preceding list, suggesting nonselective memorization of all images viewed instead of just the sample images. The second task was to remember just the first image in a list selectively and ignore subsequent distractors. False alarms occurred frequently when the test matched a distractor presented near the beginning of the sequence. In a pilot experiment, response rates depended linearly on recency of repetition irrespective of whether the test matched the first image or a distractor, again suggesting nonselective memorization of all images instead of just the first image. Modification of the second task improved recognition of the first image, but did not abolish use of recency. Monkeys appear to perform nonspatial visual short-term memory tasks often (or exclusively) using a single, nonselective, memory mechanism that conveys the recency of stimulus repetition.

Recent evidence has suggested that coherent neuronal oscillations may serve as a gating mechanism for flexibly modulating communication between brain regions. For this to occur, such oscillations should be robust and coherent between brain regions that also demonstrate time-locked correlations, with time delays that match the phase delays of the coherent oscillations. Here, by analyzing functional connectivity in both the time and frequency domains, we demonstrate that alpha oscillations satisfy these constraints and are well suited for modulating communication over large spatial scales in the human brain. We examine intracranial EEG in the human temporal lobe and find robust alpha oscillations that are coherent between brain regions with center frequencies that are consistent within each individual participant. Regions demonstrating coherent narrowband oscillations also exhibit time-locked broadband correlations with a consistent time delay, a requirement for an efficient communication channel. The phase delays of the coherent alpha oscillations match the time delays of the correlated components, and importantly, both broadband correlations and neuronal spiking activity are modulated by the phase of the oscillations. These results are specific to the alpha band and build upon emerging evidence suggesting that alpha oscillations may play an active role in cortical function. Our data therefore provide evidence that large scale communication in the human brain may be rhythmically modulated by alpha oscillations.

Phase-amplitude coupling (PAC) is hypothesized to coordinate neural activity, but its role in successful memory formation in the human cortex is unknown. Measures of PAC are difficult to interpret, however. Both increases and decreases in PAC have been linked to memory encoding, and PAC may arise due to different neural mechanisms. Here, we use a waveform analysis to examine PAC in the human cortex as participants with intracranial electrodes performed a paired associates memory task. We found that successful memory formation exhibited significant decreases in left temporal lobe and prefrontal cortical PAC, and these two regions exhibited changes in PAC within different frequency bands. Two underlying neural mechanisms, nested oscillations and sharp waveforms, were responsible for the changes in these regions. Our data therefore suggest that decreases in measured cortical PAC during episodic memory reflect two distinct underlying mechanisms that are anatomically segregated in the human brain.

In the version of this article originally published, the reference citations in the Methods section were misnumbered. This has now been corrected in the HTML and PDF versions of the paper.

Synaptic ribbons are classically associated with mediating indefatigable neurotransmitter release by sensory neurons that encode persistent stimuli. Yet when hair cells lack anchored ribbons, the temporal precision of vesicle fusion and auditory nerve discharges are degraded. A rarified statistical model predicted increasing precision of first-exocytosis latency with the number of readily releasable vesicles. We developed an experimentally constrained biophysical model to test the hypothesis that ribbons enable temporally precise exocytosis by increasing the readily releasable pool size. Simulations of calcium influx, buffered calcium diffusion, and synaptic vesicle exocytosis were stochastic (Monte Carlo) and yielded spatiotemporal distributions of vesicle fusion consistent with experimental measurements of exocytosis magnitude and first-spike latency of nerve fibers. No single vesicle could drive the auditory nerve with requisite precision, indicating a requirement for multiple readily releasable vesicles. However, plasmalemma-docked vesicles alone did not account for the nerve's precision—the synaptic ribbon was required to retain a pool of readily releasable vesicles sufficiently large to statistically ensure first-exocytosis latency was both short and reproducible. The model predicted that at least 16 readily releasable vesicles were necessary to match the nerve's precision and provided insight into interspecies differences in synaptic anatomy and physiology. We confirmed that ribbon-associated vesicles were required in disparate calcium buffer conditions, irrespective of the number of vesicles required to trigger an action potential. We conclude that one of the simplest functions ascribable to the ribbon—the ability to hold docked vesicles at an active zone—accounts for the synapse's temporal precision.

Neural activity preceding an event can influence subsequent memory formation, yet the precise cortical dynamics underlying this activity and the associated cognitive states remain unknown. We investigate these questions here by examining intracranial EEG recordings as 28 participants with electrodes placed for seizure monitoring participated in a verbal paired-associates memory task. We found that, preceding successfully remembered word pairs, an orientation cue triggered a low-frequency 2–4 Hz phase reset in the right temporoparietal junction with concurrent increases in low-frequency power across cortical regions that included the prefrontal cortex and left temporal lobe. Regions that exhibited a significant increase in 2–4 Hz power were functionally bound together through progressive low-frequency 2–4 Hz phase synchrony. Our data suggest that the interaction between power and phase synchrony reflects the engagement of attentional networks that in large part determine the extent to which memories are successfully encoded.SIGNIFICANCE STATEMENTHere we investigate the spatiotemporal cortical dynamics that precede successful memory encoding. Using intracranial EEG, we observed significant changes in oscillatory power, intertrial phase consistency, and pairwise phase synchrony that predict successful encoding. Our data suggest that the interaction between power and phase synchrony reflects the engagement of attentional networks that in large part determine the extent to which memories are successfully encoded.

The projection of neuronal processes is guided by a variety of soluble and insoluble factors, which are sensed by a fiber’s growth cone. It is the differential distribution of such guidance cues that determine the direction in which neurites grow. The growth cone senses these cues on a fine scale, using extensible filopodia that range from a few to tens of µm in length. In order to study the effects of guidance cues on spiral ganglion (SG) neurites, we have used methods for distributing both soluble and insoluble cues on a scale appropriate for sensing by growth filopodia. The scale of these methods are at the micro, rather than nano, level to match the sensing range of the growth cone. Microfluidics and transfected cells were used to spatially localize tropic factors within the fluid environment of extending neurites. Micropatterning was used to present neurites with stripes of insoluble factors. The results indicate that differentially distributed permissive, repulsive and stop signals can control the projection of SG neurites. Implications for future micropatterning studies, for SG development and for the growth of deafferented SG dendrites toward a cochlear implant are discussed.

We present the design of a chamber to evaluate in vitro how species and concentrations of soluble molecules control features of cell growth-potentially including cell proliferation, cell motility, process extension, and process termination. We have created a reusable cell culture plate that integrates a microfluidic media delivery network with standard cell culture environment. The microfluidic network delivers a stream of cell culture media with a step-like concentration gradient down a 50-100 microm wide microchannel called the presentation region. Migrating cells or growing cell processes freely choose between the two distinct chemical environments in the presentation region, but they are forced to exclusively choose either one environment or the other when they grow past a physical barrier acting as a decision point. Our fabrication technique requires little specialized equipment, and can be carried out in approximately 4 days per plate. We demonstrate the effectiveness of our plates as neurites from spiral ganglion explants preferentially grow in media containing neurotrophin-3 (NT-3) as opposed to media without NT-3. Our design could be used without modification to study dissociated cell responses to soluble growth cues, and for behavioral screening of small motile organisms.

A fundamental question in neuroscience is how neurons perform precise operations despite inherent variability. This question also applies to neuromorphic engineering, where low-power microchips emulate the brain using large populations of diverse silicon neurons. Biological neurons in the auditory pathway display precise spike timing, critical for sound localization and interpretation of complex waveforms such as speech, even though they are a heterogeneous population. Silicon neurons are also heterogeneous, due to a key design constraint in neuromorphic engineering: smaller transistors offer lower power consumption and more neurons per unit area of silicon, but also more variability between transistors and thus between silicon neurons. Utilizing this variability in a neuromorphic model of the auditory brain stem with 1,080 silicon neurons, we found that a low-voltage-activated potassium conductance ( gKL) enables precise spike timing via two mechanisms: statically reducing the resting membrane time constant and dynamically suppressing late synaptic inputs. The relative contribution of these two mechanisms is unknown because blocking gKL in vitro eliminates dynamic adaptation but also lengthens the membrane time constant. We replaced gKL with a static leak in silico to recover the short membrane time constant and found that silicon neurons could mimic the spike-time precision of their biological counterparts, but only over a narrow range of stimulus intensities and biophysical parameters. The dynamics of gKL were required for precise spike timing robust to stimulus variation across a heterogeneous population of silicon neurons, thus explaining how neural and neuromorphic systems may perform precise operations despite inherent variability.

The ability to obtain accurate histories for a comparative study of compulsive overeating and alcoholism was severely compromised by the high degree of denial, shame and self-blame present in these two overlapping disease entities. Areas of overlap included similar progression of the disease, familial tendencies, and the presence of protein enzymatic markers for alcoholism within the bariatric population. Since both shame-based diseases tend to run in the same families, four techniques were developed to reduce the amount of shame that obese patients experienced when talking about family histories and their own compulsive, obsessive disease as it progresses through five identifiable stages. These techniques include: the use of specific non-shaming words and gestures; normalization of patients' history and experiences; education about similar biological, genetic, progressive, stress-related diseases to solidify the disease concept of obesity; and a loosely structured interview format which proceeds from the general to the specific and the past to the present, in an orderly, non-shaming fashion.

We present a silicon neuron with a dynamic, active leak that enables precise spike-timing with respect to a time-varying input signal. Our neuron models the mammalian bushy cell, which enhances the phase-locking of its acoustically driven inputs. Our model enhances phase-locking by up to 38% (quantified by vector strength) across a 60 dB range of acoustic intensities, and up to 22% over a passive leak. Its conductance-based log-domain design yields a compact and efficient circuit, fabricated in 0.25 /spl mu/m CMOS, that is an ideal timing-enhancing component for neuromorphic speech recognition systems.

Background The nematode Caenorhabditis elegans is widely used for the genetic analysis of neuronal cell biology, development, and behavior. Because traditional methods for evaluating behavioral phenotypes are qualitative and imprecise, there is a need for tools that allow quantitation and standardization of C. elegans behavioral assays. Results Here we describe a tracking and imaging system for the automated analysis of C. elegans morphology and behavior. Using this system, it is possible to record the behavior of individual nematodes over long time periods and quantify 144 specific phenotypic parameters. Conclusions These tools for phenotypic analysis will provide reliable, comprehensive scoring of a wide range of behavioral abnormalities, and will make it possible to standardize assays such that behavioral data from different labs can readily be compared. In addition, this system will facilitate high-throughput collection of phenotypic data that can ultimately be used to generate a comprehensive database of C. elegans phenotypic information. Availability The hardware configuration and software for the system are available from wschafer@ucsd.edu.

In 3 patients with ischemic coronary disease or primary myocardiopathy who were unresponsive to conventional and experimental antiarrhythmia therapy, surgical treatment of intractable ventricular tachycardia was performed using epicardial, transmural, and endocardial mapping techniques. An experimental canine model of acute and chronic myocardial ischemia with recurrent ventricular tachycardia was developed to refine the mapping technique for clinical use. In patients and animals alike, atrial overdrive pause pacing, premature ventricular pacing, or both were used to bring out a repeatable pattern of tachycardia. Mapping techniques distinguished the irritable focus so that surgical excision of the site of earliest activation could be performed. In addition, the mapping techniques were used in the validation following excision. The limitations of epicardial mapping alone in locating all areas of premature focus are discussed, and the need for mapping in ventricular aneurysm is demonstrated.

Jaundice is rarely encountered in polycystic disease of the liver. In the present case, pressure from tense cysts at the hilus of the liver caused a marked narrowing of the common hepatic duct and slowing of bile flow with the formation of stasis stones. Decompression of the cysts and removal of debris in the intrahepatic ducts resulted in a rapid decrease of the serum bilirubin level.

To determine if subjective improvement correlated with graft patency and completeness of revascularization, we restudied 83 of 115 consecutive patients by angiography, regardless of symptoms, 1 year after operation. A total of 271 grafts were performed, averaging 3.3 per patient. Preoperative and postoperative angiograms were analyzed for completeness of revascularization and graft occlusion. Subjective improvement was assessed from questionnaires sent to patients at 6 month intervals for 2 years. Follow-up was 100% (1 to 3 years). Of patients who were recatheterized, 71% (59/83) were asymptomatic patients, 18% (10/56) for the mildly symptomatic ones (p = NS), and 73% (11115) for the severely symptomatic or not improved at 1 year. Graft occlusion rate was 9% (18/200) in the asymptomatic patients, 18% (10/56) for the mildly symptomatic ones (p = NS), and 73% (11/15) for the severely symptomatic patients (p

Subsequent to the repair of a true aneurysm from the posteromedial-basal aspect of the left ventricle, a 58 year old man developed a draining wound at the site of the sternotomy. Two-dimensional echocardiography revealed recurrence of the aneurysm at the site of the previous aneurysm repair. This aneurysm had a wide neck and looked similar in appearance to the previous true aneurysm. However, at surgery the patient was found to have a ventricular pseudoaneurysm with a car-diocutaneous fistula.

Thirty-eight patients with transposition of the great arteries underwent intraoperative mapping of atrial epicardium and endocardium during various stages of the operative procedure. The purpose was to determine the electrophysiological basis of the postoperative supraventricular arrhythmias associated with this operation. Comparisons were made between atrial activation patterns and times before and after each of the following stages: (1) cannulation, (2) atriotomy, (3) excision of atrial septum and coronary sinus, and (4) placement of intra-atrial baffle. The first stage produced no significant changes in atrial activation times or patterns but did demonstrate a shift of the functional pacemaker to the sulcus terminalis in 8 of 14 patients studied. Longitudinal atriotomy did not significantly lengthen atrial activation. Transverse atriotomy did not alter activation times of the His bundle but did significantly change patterns of epicardial and endocardial activation. Excision of the septum and coronary sinus always produced block in the posterior crista terminalis, and placement of a baffle worsened this block. Four patients developed nodal rhythm on the operating table and had both a posterior crista terminalis block and anterior septal block. Suggestions for modification in the surgical techniques were advanced to help prevent rhythm disturbances in patients undergoing transvenous correction of transposition of the great arteries.

The hemodynamic effect of myocardial revascularization with saphenous vein grafts (mean 3.3 per patient) was analyzed I year after operation in 111 patients. Operations were performed using one continuous period of aortic cross-clamping with hyperkalemic cardioplegia for distal anastomoses in 84% of patients; 16% had arrest with topical and systemic hypothermia for myocardial protection. Group I (N = 18) had normal ventricles (ejection fraction [EF] ≥ 50%; left ventricular end-diastolic pressure [LVEDP] ≤ 12 torr); Group II (N = 64) had ischemic ventricles (EF ≥ 50%, LVEDP > 13 torr); and Group III (N = 30) had abnormal ventricles (EF 13 torr). Hemodynamic measurements were obtained before and 1 year after operation. Fifteen of 18 patients (83%) in Group I did not show significant hemodynamic changes, but in three EF decreased by ≥ 10% and LVEDP increased by ≥ 10% over preoperative levels. In Group II, EF was unchanged or slightly better in 89% (57/64) and worse in seven patients. Improvement in cardiac index (p 35% to

Aortic valvotomy is a satisfactory procedure to relieve significant valvular stenosis in the young child in most instances. Intraoperative measurement to determine the reduction or elimination of a gradient across the valve confirms the adequacy of the orifice achieved by commissurotomy. This paper concerns itself with the occasional patient in whom a bicuspid valve is found for which little can be accomplished by operation because there is minimal or no commissural fusion. The valve orifice is adequate anatomically, but functionally it is severely obstructive. Recent experience with 2 children (aged 7 and 8 years) in whom aortic prosthetic valves were inserted after valvotomy suggests that in those rare circumstances in which life-threatening, severe obstruction cannot be relieved, valve replacement at the time of the initial operation may be appropriate.

Qualitative and quantitative 2-dimensional (2-D) echocardiographic methods were developed to define the anatomic and physiologic significance of valvular calcium in aortic stenosis (AS). Qualitative methods assigned etiologic diagnoses by matching patterns of calcium with anatomic criteria. Quantitative techniques measured echodensities from superimposed short-axis views of calcium. Fifty-five pathologic specimens procured from surgery were photographed and radiographed. Etiologic diagnoses were assigned from gross examination and radiodensities were planimetered. Echocardiographic and anatomic diagnoses were compared. Sensitivities for diagnosing the most common etiologies, congenitally bicuspid and degenerative, were 58% and 100% and specificities were 100% and 76%. Calcium tended to be heaviest in congenitally diseased valves and lightest in those with degenerative disease (p less than 0.2) and showed propensity for the right cusp in all etiologies except for those with degenerative disease. Correlation of echodensities to radiodensities was 0.82. The relation of calcific echodensities to orifice area was curvilinear; beyond a level of calcium, further deposits did not reduce the orifice more. A systematic echocardiographic examination of calcium in stenotic aortic valves can give a correct etiologic diagnosis in most patients and identify the severely narrowed orifice.