Biomedical subjects

Itzhak Fried

Publications and source records attributed to Itzhak Fried.

9 recordsLinked to original sources

PubMed2003

Cellular networks underlying human spatial navigation.

Place cells of the rodent hippocampus constitute one of the most striking examples of a correlation between neuronal activity and complex behaviour in mammals. These cells increase their firing rates when the animal traverses specific regions of its surroundings, providing a context-dependent map of the environment. Neuroimaging studies implicate the hippocampus and the parahippocampal region in human navigation. However, these regions also respond selectively to visual stimuli. It thus remains unclear whether rodent place coding has a homologue in humans or whether human navigation is driven by a different, visually based neural mechanism. We directly recorded from 317 neurons in the human medial temporal and frontal lobes while subjects explored and navigated a virtual town. Here we present evidence for a neural code of human spatial navigation based on cells that respond at specific spatial locations and cells that respond to views of landmarks. The former are present primarily in the hippocampus, and the latter in the parahippocampal region. Cells throughout the frontal and temporal lobes responded to the subjects' navigational goals and to conjunctions of place, goal and view.

Action Potentials↗

PubMed2002

Sleep states differentiate single neuron activity recorded from human epileptic hippocampus, entorhinal cortex, and subiculum.

Animal models of epilepsy have shown that synchronous burst firing is associated with epileptogenesis, yet the evidence from human studies linking neuronal synchrony and burst firing to epileptogenesis remains equivocal. Sleep-wake states have been shown to differentially modulate the generation of epileptiform EEG spikes between brain regions of greater and lesser seizure-generating potential, providing information that helps to identify the primary epileptogenic region. Using these state-dependent mechanisms to assist us in identifying neuronal correlates of human epilepsy, we recorded interictal neuronal activity from mesial temporal lobe (MTL) areas in epileptic patients implanted with depth electrodes required for medical diagnosis during polysomnographically defined sleep-wake states. Results show that single neurons recorded ipsilateral to seizure-initiating MTL ("epileptic") areas had significantly higher firing rates (p = 0.01) and burst propensity (p = 0.01) and greater synchrony of discharges (p = 0.003) compared with neurons recorded from contralateral non-seizure-generating MTL ("non-epileptic") areas. In particular, during episodes of slow wave sleep (SWS) and rapid eye movement (REM) sleep, epileptic hippocampal neurons had significantly higher burst rates compared with non-epileptic hippocampal neurons (both p = 0.01). In contrast, during episodes of wakefulness (Aw), no difference in burst firing between epileptic and non-epileptic hippocampal neurons was observed. Furthermore, synchronous firing was significantly higher between epileptic MTL neurons compared with non-epileptic MTL neurons during SWS (p = 0.04) and REM sleep (p = 0.02), but no difference in neuronal synchrony was found between epileptic and non-epileptic neurons during Aw. These results provide evidence that sleep states differentially modulate abnormal epileptogenic neuronal discharge properties within human MTL and confirm that neuronal burst firing and enhanced neuronal synchrony observed in experimental animal models of epilepsy characterizes human epilepsy as well.

Action Potentials↗

PubMed2002

Single-neuron correlates of subjective vision in the human medial temporal lobe.

Visual information from the environment is transformed into perceptual sensations through several stages of neuronal processing. Flash suppression constitutes a striking example in which the same retinal input can give rise to two different conscious visual percepts. We directly recorded the responses of individual neurons during flash suppression in the human amygdala, entorhinal cortex, hippocampus, and parahippocampal gyrus, allowing us to explore the neuronal responses in untrained subjects at a high spatial and temporal resolution in the medial temporal lobe. Subjects were patients with pharmacologically intractable epilepsy implanted with depth electrodes to localize the seizure onset focus. We observed that the activity of two thirds of all visually selective neurons followed the perceptual alternations rather than the retinal input. None of the selective neurons responded to a perceptually suppressed stimulus. Therefore, the activity of most individual neurons in the medial temporal lobe of naive human subjects directly correlates with the phenomenal visual experience.

Adult↗

PubMed2002

The role of the amygdala in signaling prospective outcome of choice.

Can brain activity reveal a covert choice? Making a choice often evokes distinct emotions that accompany decision processes. Amygdala has been implicated in choice behavior that is guided by a prospective negative outcome. However, its specific involvement in emotional versus cognitive processing of choice behavior has been a subject of controversy. In this study, the human amygdala was monitored by functional magnetic resonance imaging (fMRI) while subjects were playing in a naturalistic choice paradigm against the experimenter. In order to win, players had to occasionally choose to bluff their opponent, risk "getting caught," and suffer a loss. A critical period, when choice has been made but outcome was still unknown, activated the amygdala preferentially following the choice that entailed risk of loss. Thus, the response of the amygdala differentiated between subject's covert choice of either playing fair or foul. These results support a role of the amygdala in choice behavior, both in the appraisal of inherent value of choice and the signaling of prospective negative outcomes.

Adolescent↗

PubMed2002

Interictal high-frequency oscillations (80-500 Hz) in the human epileptic brain: entorhinal cortex.

Unique high-frequency oscillations of 250 to 500 Hz, termed fast ripples, have been identified in seizure-generating limbic areas in rats made epileptic by intrahippocampal injection of kainic acid, and in patients with mesial temporal lobe epilepsy. In the rat, fast ripples clearly are generated by a different neuronal population than normally occurring endogenous ripple oscillations (100-200 Hz), but this distinction has not been previously evaluated in humans. The characteristics of oscillations in the ripple and fast ripple frequency bands were compared in the entorhinal cortex of patients with mesial temporal lobe epilepsy using local field potential and unit recordings from chronically implanted bundles of eight microelectrodes with tips spaced 500 microm apart. The results showed that ripple oscillations possessed different voltage versus depth profiles compared with fast ripple oscillations. Fast ripple oscillations usually demonstrated a reversal of polarity in the middle layers of entorhinal cortex, whereas ripple oscillations rarely showed reversals across entorhinal cortex layers. There was no significant difference in the amplitude distributions of ripple and fast ripple oscillations. Furthermore, multiunit synchronization was significantly increased during fast ripple oscillations compared with ripple oscillations (p < 0.001). These data recorded from the mesial temporal lobe of epileptic patients suggest that the cellular networks underlying fast ripple generation are more localized than those involved in the generation of normally occurring ripple oscillations. Results from this study are consistent with previous studies in the intrahippocampal kainic acid rat model of chronic epilepsy that provide evidence supporting the view that fast ripples in the human brain reflect localized pathological events related to epileptogenesis.

Electrodes, Implanted↗

PubMed2002

Single neuron burst firing in the human hippocampus during sleep.

Although there are numerous non-primate studies of the single neuron correlates of sleep-related hippocampal EEG patterns, very limited hippocampal neuronal data are available for correlation with human sleep. We recorded human hippocampal single neuron activity in subjects implanted with depth electrodes required for medical diagnosis and quantitatively evaluated discharge activity from each neuron during episodes of wakefulness (Aw), combined stage 3 and 4 slow-wave sleep (SWS), and rapid eye movement (REM) sleep. The mean firing rate of the population of single neurons was significantly higher during SWS and Aw compared with REM sleep (p = 0.002; p < 0.0001). In addition, burst firing was significantly greater during SWS compared with Aw (p = 0.001) and REM sleep (p < 0.0001). The synchronized state of SWS and associated high-frequency burst discharge found in human hippocampus may subserve functions similar to those reported in non-primate hippocampus that require burst firing to induce synaptic modifications in hippocampal circuitry and in hippocampal projections to neocortical targets that participate in memory consolidation.

Action Potentials↗

PubMed2002

Regional analyses of CNS microdialysate glucose and lactate in seizure patients.

PURPOSE: To correlate glucose (and lactate) results obtained from microdialysate to recent studies suggesting that glucose transporter activity may be significantly altered in seizures. METHODS: We used a fluorometric technique to quantify glucose and lactate levels in microdialysates collected from two to four depth electrodes implanted per patient in the temporal and frontal lobes of a series of four patients. Hour-by-hour and day-to-day changes in brain glucose and lactate levels at the same site were recorded. Additionally we compared regional variations in lactate/glucose ratios around the predicted epileptogenic region. RESULTS: Lactate/glucose ratios in the range of 1-2:1 were the most commonly seen. When the lactate/glucose ratio was <1:1, we typically observed a relative increase in local glucose concentration (rather than decreased lactate), suggesting increased transport, perhaps without increased glycolysis. In some sites, lactate/glucose ratios of 3:1-15:1 were seen, suggesting that a circumscribed zone of inhibition of tricarboxylic acid cycle activity may have been locally induced. In these dialysates, collected from probes closer to the epileptogenic region, the large increase in lactate/glucose ratios was a result of both increased lactate and reduced glucose levels. CONCLUSIONS: We conclude that regional variations in brain extracellular glucose concentrations may be of greater magnitude than previously believed and become even more accentuated in partial seizure patients. Data from concomitant assays of microdialysate lactate and glucose may aid in understanding cerebral metabolism.

Adult↗

PubMed2002

Inhibitory and excitatory responses of single neurons in the human medial temporal lobe during recognition of faces and objects.

The medial temporal lobe (MTL) plays a critical role in transforming complex stimuli into permanent memory traces, yet little is known on how the activity of neurons in the human brain mediates this process. Recording from single neurons in the human MTL during visual encoding and retrieval of faces and objects, we found that in the hippocampus faces evoked predominantly suppression of neuronal firing below prestimulus baseline ('inhibitory responses'). These responses were also prevalent in the entorhinal cortex but were absent in the amygdala during the first second of stimulus encoding when all responses to faces were 'excitatory' (neuronal firing increased above the prestimulus baseline). Inhibitory responses were more prevalent during recognition than encoding and were also present during processing of objects, albeit less frequently than during processing of faces. Despite the prevalence in the hippocampus of cells with inhibitory responses and their relative specificity to faces, it was mainly the activity of the cells with excitatory responses that was selective for stimulus features such as gender and emotional expression of faces. These findings suggest that a large population of cells with inhibitory responses is engaged in the hippocampal memory network, but primarily cells with excitatory responses process feature-specific information.

Amygdala↗

PubMed2002

Quantitative analysis of high-frequency oscillations (80-500 Hz) recorded in human epileptic hippocampus and entorhinal cortex.

High-frequency oscillations (100-200 Hz), termed ripples, have been identified in hippocampal (Hip) and entorhinal cortical (EC) areas of rodents and humans. In contrast, higher-frequency oscillations (250-500 Hz), termed fast ripples (FR), have been described in seizure-generating limbic areas of rodents made epileptic by intrahippocampal injection of kainic acid and observed in humans ipsilateral to areas of seizure initiation. However, quantitative studies supporting the existence of two spectrally distinct oscillatory events have not been carried out in humans nor has the preferential appearance of FR within seizure generating areas received statistical evaluation based on analysis of a large sample of oscillatory events. Interictal oscillations within the bandwidth of 80-500 Hz were detected in Hip and EC areas of patients with mesial temporal lobe epilepsy using wideband EEG recorded during non-rapid eye-movement sleep from chronically implanted depth electrodes. Power spectral analysis showed that oscillations detected from Hip and EC areas were composed of two spectrally distinct groups. The lower-frequency ripple group was defined by a frequency of 96 +/- 14 Hz (median +/- width), while the higher-frequency FR group had a frequency of 262 +/- 59 Hz. FR oscillations were significantly shorter in duration compared with ripple oscillations (P < 0.0001). In regard to the occurrence of FR and ripples in epileptic Hip and EC, the mean ratio of the number of FR to ripples generated in areas ipsilateral to seizure onset was significantly higher compared with the mean ratio of FR to ripple generation from contralateral areas (P = 0.008). Furthermore, sites ipsilateral to seizure onset with hippocampal atrophy had significantly higher ratios compared with sites contralateral to both seizure onset and hippocampal atrophy (P = 0.001). These data provide compelling quantitative and statistical evidence for the existence of two spectrally distinct groups of limbic oscillations that have frequency and duration characteristics similar to those previously described in epileptic rat and human Hip and EC. The strong association between FR and regions of seizure initiation supports the view that FR reflects pathological hypersynchronous events crucially associated with seizure genesis.

Electrodes, Implanted↗