Biomedical subjects

Hagai Bergman

Publications and source records attributed to Hagai Bergman.

29 records · Page 2Linked to original sources

PubMed2003

Functional correlations between neighboring neurons in the primate globus pallidus are weak or nonexistent.

The anatomical structure of the basal ganglia displays topographical organization and massive funneling of neuronal projections toward the globus pallidus as well as an axonal collateral system within this nucleus. This structure suggests the formation of correlations between the spiking activities of pallidal cells. Nevertheless, previous studies of remote neurons in the pallidum have reported uncorrelated spiking activity. These correlation results may be challenged, because remote pallidal neurons may be located in different pallidal territories. To further test the independence of pallidal activity, we studied the spiking activity of neighboring pairs recorded by the same electrodes. A narrow peak dominated the correlations of all pairs of neurons recorded on the same electrode. This type of peak is classically interpreted as a sign of strong common input. However, recent mathematical analysis shows that such peaks may derive from a technical inability to detect overlapping spikes by spike-sorting techniques. A long-term shallow trough in the correlation of neighboring neurons may also result from the same effect, which we have termed the "shadowing effect." A comparison of the expected shadowing effect with the actual correlations suggests that no real correlations exist between 93.9% of neighboring pallidal pairs. The remaining 6.1% of the pairs display symmetric long-term positive correlations centered on time 0. Thus, functional interactions between neighboring pallidal neurons do not display any significant differences from the interactions between physically remote neurons in this brain area. Moreover, the combination of anatomical data and current physiological results suggests an active decorrelating process performed in the basal ganglia.

Acoustic Stimulation↗

PubMed2003

Information processing, dimensionality reduction and reinforcement learning in the basal ganglia.

Modeling of the basal ganglia has played a major role in our understanding of this elusive group of nuclei. Models of the basal ganglia have undergone evolutionary and revolutionary changes over the last 20 years, as new research in the fields of anatomy, physiology and biochemistry of these nuclei has yielded new information. Early models dealt with a single pathway through the nuclei and focused on the nature of the processing performed within it, convergence of information versus parallel processing of information. Later, the Albin-DeLong "box-and-arrow" model characterized the inter-nuclei interaction as multiple pathways while maintaining a simplistic scalar representation of the nuclei themselves. This model made a breakthrough by providing key insights into the behavior of these nuclei in hypo- and hyper-kinetic movement disorders. The next generation of models elaborated the intra-nuclei interactions and focused on the role of the basal ganglia in action selection and sequence generation which form the most current consensus regarding basal ganglia function in both normal and pathological conditions. However, new findings challenge these models and point to a different neural network approach to information processing in the basal ganglia. Here, we take an in-depth look at the reinforcement driven dimensionality reduction (RDDR) model which postulates that the basal ganglia compress cortical information according to a reinforcement signal using optimal extraction methods. The model provides new insights and experimental predictions on the computational capacity of the basal ganglia and their role in health and disease.

Animals↗

PubMed2003

Abnormal rhythmic motor response in children with attention-deficit-hyperactivity disorder.

Children with attention-deficit-hyperactivity disorder (ADHD) have difficulties with motor control, inhibition of motor responses, motor flexibility, and motor preparedness. We proposed that motor abnormalities in ADHD might result, at least in part, from an abnormal neuronal oscillatory mechanism necessary for motor temporal regulation. The aim of this study was to assess pacing in children with ADHD, by testing for rhythmic abnormalities of motor activity using a tapping test. Twenty-seven children (21 males, six females; aged 6 to 14 years 6 months; mean age 11 years 4 months, SD 2 years 2 months) diagnosed with ADHD according to DSM-IV clinical criteria, and 33 controls (25 males, eight females; aged 6 to 14 years 6 months; mean 11 years 1 month, SD 2 years 2 months), underwent a finger-tapping test requiring rhythmic responses to frequencies from 1 to 6 Hz. All participants who were treated on a daily basis with methylphenidate (n = 22) were medication-free on the day of the test. Most of the children with ADHD responded at a constant rate regardless of stimulus frequency, a phenomenon only seen in a small number of the controls. This specific error pattern, also seen in Parkinson's disease, has been attributed to an abnormal oscillatory mechanism mediated by dopaminergic fronto-striatal circuitry, which might also be pathophysiologically relevant for ADHD.

Adolescent↗

PubMed2003

Preparatory activity in motor cortex reflects learning of local visuomotor skills.

In humans, learning to produce correct visually guided movements to adapt to new sensorimotor conditions requires the formation of an internal model that represents the new transformation between visual input and the required motor command. When the new environment requires adaptation to directional errors, learning generalizes poorly to untrained locations and directions, indicating that such learning is local. Here we replicated these behavioral findings in rhesus monkeys using a visuomotor rotation task and simultaneously recorded neuronal activity. Specific changes in activity were observed only in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation. These changes adhered to the dynamics of behavior during learning and persisted between learning and relearning of the same rotation. These findings suggest a neural mechanism for the locality of newly acquired sensorimotor tasks and provide electrophysiological evidence for their retention in working memory.

Animals↗

PubMed2003

Age-related accelerated tapping response in healthy population.

Different types of rapid tapping responses were described in the finger-tapping test. The "Hastening phenomenon" was described as an abnormal motor response in patients with Parkinson's disease. Accelerated tapping has been shown in a healthy elderly sample. It is not clear whether accelerated tapping relates to the hastening phenomenon or characterizes normal aging. We hypothesized that this sample of 21 healthy elderly people showed increased accelerated tapping but not hastening phenomenon. To assess this hypothesis, 20 healthy young and 21 elderly subjects performed a tapping test, requiring responses from 1 to 6 Hz. The healthy elderly sample showed increased accelerated tapping but not increased "hastening phenomenon." We conclude that Accelerated tapping may represent age-related motor processes unlike the hastening phenomenon characterizing Parkinson's disease.

Adult↗

PubMed2002

Dopamine replacement therapy reverses abnormal synchronization of pallidal neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of parkinsonism.

Previous physiological studies have revealed changes in firing rates and synchronization of pallidal neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. Several primate and human studies have demonstrated that dopamine replacement therapy (DRT) reverses the changes in the pallidal firing rates; however, the effects of DRT on pallidal synchronization have never been explored. To do so, we recorded the simultaneous activity of pallidal neurons of a vervet monkey before and after induction of severe parkinsonism by systemic MPTP treatment. We subsequently recorded the pallidal activity before and after daily administration of oral DRT. We extended the time scale of our correlation studies to +/-5 sec to allow detection of long-duration synchronized neuronal activity. After MPTP treatment, firing rates decreased in the external segment of the globus pallidus (GP(e)) and increased in the internal segment (GP(i)). A reversal of these rate changes occurred during the "on" periods of DRT. The percentage of correlated pairs increased from 16.7% in the normal state to 46.9% after MPTP treatment and was restored to nearly normal values (25% correlated pairs) under the influence of DRT. These changes in rate and correlation were observed at both the population level and at the level of units recorded continuously before, during, and after the clinical transition from "off" to "on" periods. We conclude that changes in both pallidal discharge rates and synchronization are correlated with the clinical manifestations of parkinsonism and its pharmacological treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Enhanced synchrony among primary motor cortex neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease.

Primary motor cortex (MI) neurons discharge vigorously during voluntary movement. A cardinal symptom of Parkinson's disease (PD) is poverty of movement (akinesia). Current models of PD thus hypothesize that increased inhibitory pallidal output reduces firing rates in frontal cortex, including MI, resulting in akinesia and muscle rigidity. We recorded the simultaneous spontaneous discharge of several neurons in the arm-related area of MI of two monkeys and in the globus pallidus (GP) of one of the two. Accelerometers were fastened to the forelimbs to detect movement, and surface electromyograms were recorded from the contralateral arm of one monkey. The recordings were conducted before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rendering the animals severely akinetic and rigid with little or no tremor. The mean spontaneous MI rates during periods of immobility (four to five spikes/sec) did not change after MPTP; however, in this parkinsonian state, MI neurons discharged in long bursts (sometimes >2 sec long). These bursts were synchronized across many cells but failed to elicit detectable movement, indicating that even robust synchronous MI discharge need not result in movement. These synchronized population bursts were absent from the GP and were on a larger timescale than oscillatory synchrony found in the GP of tremulous MPTP primates, suggesting that MI parkinsonian synchrony arises independently of basal ganglia dynamics. After MPTP, MI neurons responded more vigorously and with less specificity to passive limb movement. Abnormal MI firing patterns and synchronization, rather than reduced firing rates, may underlie PD akinesia and persistent muscle rigidity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Pathophysiology of Parkinson's disease: from clinical neurology to basic neuroscience and back.

Parkinson's disease (PD) is characterized by motor and nonmotor (cognitive and limbic) deficits. The motor signs of PD include hypokinetic signs such as akinesia/bradykinesia, rigidity and loss of normal postural reflexes, and hyperkinetic signs such as tremor. Dopamine depletion in the striatum is the hallmark of PD and of its animal models, still the pathophysiology of the parkinsonian symptoms and especially of parkinsonian tremor are under debate. The most extreme hypotheses argue about peripheral versus central nervous system origin, intrinsic cellular oscillator versus network oscillators, and basal ganglia-based pathophysiology versus cerebellar-thalamic based pathophysiology. Recent studies support the view that parkinsonian symptoms are most likely due to abnormal synchronous oscillating neuronal activity within the basal ganglia. Peripheral factors do only play a minor role for the generation, maintenance, and modulation of PD tremor and other signs. The most likely candidates producing these neuronal oscillations are the weakly coupled neural networks of the basal ganglia-thalamo-cortical loops. However, the present evidence supports the view that the basal ganglia loops are influenced by other neuronal structures and systems and that the tuning of these loops by cerebello-thalamic mechanisms and by other modulator neurotransmitter systems entrain the abnormal synchronized oscillations. Neurosurgical procedures, such as lesions or high-frequency stimulation of different parts of the loop, might resume the normal unsynchronized activity of the basal ganglia circuitry, and, therefore, ameliorate the clinical symptoms of Parkinson's disease.

Animals↗

PubMed2002

Pathophysiology of nonparkinsonian tremors.

Patients with nonparkinsonian tremors are the second largest group treated with functional neurosurgery. We summarize the present pathophysiological knowledge of these conditions. Essential tremor (ET) may be due to oscillations within the olivocerebellar circuit. There is experimental evidence from animal models for such a mechanism, and clinical data indicate an abnormal function of the cerebellum in ET. Cerebellar tremor may be closely related to the tremor seen in advanced ET. The malfunction of the cerebellum causes a pathological feed-forward control. Additionally an oscillator within the cerebellum or its input/output pathways may cause cerebellar tremor. Almost nothing is known about the pathophysiology of dystonic tremor. Holmes tremor is based on a nigral and a cerebellar malfunction and presents clinically as the combination of tremor in Parkinson's disease and cerebellar tremor. Neuropathic tremor can be extremely disabling and is thought to be due to an abnormal interaction of the disturbances within the periphery and abnormal cerebellar feedback. Unlike the case of Parkinson's disease, functional neurosurgery of nonparkinsonian tremors is not yet based on a solid pathophysiological background.

Brain↗

PubMed2002

Bilateral overactivation of the sensorimotor cortex in the unilateral rodent model of Parkinson's disease - a functional magnetic resonance imaging study.

Functional magnetic resonance imaging (fMRI) is used to investigate the basal ganglia (BG)-cortex circuit using a rat model of Parkinson's disease (PD). The model involves a unilateral destruction of the right substantia nigra by intranigral injection of the dopaminergic neurotoxin 6-hydroxydopamine. Volume of cortical activity was measured by the blood oxygenation level-dependent contrast method while applying electrical forepaw stimulation. The main findings are the following. (i) Contrary to the predictions of the classic model but in line with recent experimental results (positron emission tomography, fMRI and electrophysiology), an increased cortical activity in the sensorimotor cortex of PD rats compared with sham-operated or normal rats was found. (ii) A diffuse neuronal activity at large cortical areas that were not related directly to the stimulation used, was observed. (iii) No difference was found between the lesion and the nonlesion hemispheres when the left or the right forepaw was stimulated; both cortices show significant overactivation of the sensorimotor cortices in addition to diffuse cortical activation. The last finding could be explained by either corticocortical connections or by bilateral BG-cortex connections. These finding suggest that the mutual influence of the two hemispheres is important in the pathophysiology of the BG-cortex circuit and might be crucial in predicting treatments.

Animals↗

PubMedDate not supplied

Anatomical funneling, sparse connectivity and redundancy reduction in the neural networks of the basal ganglia.

The major anatomical characteristics of the main axis of the basal ganglia are: (1) Numerical reduction in the number of neurons across layers of the feed-forward network, (2) lateral inhibitory connections within the layers, and (3) neuro-modulatory effects of dopamine and acetylcholine, both on the basal ganglia neurons and on the efficacy of information transmission along the basal ganglia axis. We recorded the simultaneous activity of neurons in the output stages of the basal ganglia as well as the activity of dopaminergic and cholinergic neurons during the performance of a probability decision-making task. We found that the functional messages of the cholinergic and dopaminergic neurons differ, and that the cholinergic message is less specific than that of the dopaminergic neurons. The output stage of the basal ganglia showed uncorrelated neuronal activity. We conclude that despite the huge numerical reduction from the cortex to the output nuclei of the basal ganglia, the activity of these nuclei represents an optimally compressed (uncorrelated) version of distinctive features of cortical information.

Animals↗