Jonathan O. Dostrovsky

Bio: Jonathan O. Dostrovsky is an academic researcher from University of Toronto. The author has contributed to research in topics: Deep brain stimulation & Subthalamic nucleus. The author has an hindex of 69, co-authored 202 publications receiving 24848 citations. Previous affiliations of Jonathan O. Dostrovsky include University Health Network & University of Calgary.

Neuropathic pain Redefinition and a grading system for clinical and research purposes

Abstract: Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.

Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease.

Abstract: Local field potentials and pairs of neurones in the subthalamic nucleus (STN) of patients with Parkinson's disease show high-frequency oscillations (HFOs) at 15-30 Hz. This study explores how these HFOs are modulated by voluntary movements and by dopaminergic medication. We examined 15 patients undergoing implantation of bilateral deep brain stimulating electrodes using microelectrode recordings of pairs of STN neurones (eight patients) and macroelectrode recordings of local field potentials from the STN (14 patients). Synchronized HFOs between STN neurones were observed in 28 out of 37 pairs in five patients who had tremor in the operating room and none of 45 pairs in three patients who did not. In two of the three non-tremulous patients, HFOs in the frequency spectra of local field potentials were detected but were weaker than in those patients with tremor. Active movement suppressed synchronized HFOs in three out of five pairs of neurones, independent of changes in firing rate. HFOs observed in the local field potentials in nine out of 14 patients were reduced with voluntary movement in six of the eight patients tested. Dopaminergic medication decreased the incidence of synchronized HFOs in STN neurone pairs, reduced HFO synchrony in a pair of tremor cells concurrent with a reduction in firing rate and limb tremor, and decreased HFOs of local field potentials in the STN. These results demonstrate that HFO synchronization in the STN is reduced by voluntary movements and by exogenous dopaminergic medication. A mechanism for neuronal oscillatory synchronization in basal ganglia is proposed. It is suggested that the firing of STN neurones can be synchronized by 15-30 Hz cortical beta oscillatory activity, particularly when dopamine deficiency results in a higher background firing rate of STN neurones, and that this synchronization contributes to parkinsonian pathophysiology.

Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease

Abstract: Microelectrode recording methods for stereotactic localization of the subthalamic nucleus (STN) and surrounding structures are described. These methods accurately define targets for chronic deep brain stimulation in the treatment of Parkinson's disease. Mean firing rates and a burst index were determined for all recorded neurons, and responses to active and passive limb and orofacial movements were tested. STN neurons had a mean firing rate of 37 ± 17 Hz (n = 248) and an irregular firing pattern (median burst index, 3.3). Movement-related activity and tremor cells were identified in the STN. Ventral to the STN, substantia nigra pars reticulata neurons had a mean rate of 71 ± 23 Hz (n = 56) and a more regular firing pattern (median burst index, 1.7). Short trains (1–2 seconds) of electrical microstimulation of STN could produce tremor arrest but were and found to be useful for localization. Compared with data from normal monkeys our findings suggest that STN neuronal activity is elevated in Parkinson's disease.

Chronic anterior thalamus stimulation for intractable epilepsy.

Abstract: Summary: Purpose: A significant number of patients with epilepsy remain poorly controlled despite antiepileptic medication (AED) treatment and are not eligible for resective surgery. Novel therapeutic methods are required to decrease seizure burden in this population. Several observations have indicated that the anterior thalamic region plays an important role in the maintenance and propagation of seizures. We investigated neuromodulation of the anterior thalamus by using deep-brain stimulation (DBS) in patients with intractable seizures. Methods: Five patients with medically refractory epilepsy underwent stereotactic placement of and received stimulation through bilateral DBS electrodes in the anterior thalamus. Results: Treatment showed a statistically significant decrease in seizure frequency, with a mean reduction of 54% (mean follow-up, 15 months). Two of the patients had a seizure reduction of ≥75%. No adverse effects were observed after DBS electrode insertion or stimulation. Unexpectedly, the observed benefits did not differ between stimulation-on and stimulation-off periods. Conclusions: DBS of the anterior thalamus is a safe procedure and possibly effective in patients with medically resistant seizures.

Place navigation impaired in rats with hippocampal lesions.

Abstract: Electrophysiological studies have shown that single cells in the hippocampus respond during spatial learning and exploration1–4, some firing only when animals enter specific and restricted areas of a familiar environment. Deficits in spatial learning and memory are found after lesions of the hippocampus and its extrinsic fibre connections5,6 following damage to the medial septal nucleus which successfully disrupts the hippocampal theta rhythm7, and in senescent rats which also show a correlated reduction in synaptic enhancement on the perforant path input to the hippocampus8. We now report, using a novel behavioural procedure requiring search for a hidden goal, that, in addition to a spatial discrimination impairment, total hippocampal lesions also cause a profound and lasting placenavigational impairment that can be dissociated from correlated motor, motivational and reinforcement aspects of the procedure.

Précis of The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal System..

Abstract: A model of the neuropsychology of anxiety is proposed. The model is based in the first instance upon an analysis of the behavioural effects of the antianxiety drugs (benzodiazepines, barbiturates, and alcohol) in animals. From such psychopharmacologi-cal experiments the concept of a “behavioural inhibition system” (BIS) has been developed. This system responds to novel stimuli or to those associated with punishment or nonreward by inhibiting ongoing behaviour and increasing arousal and attention to the environment. It is activity in the BIS that constitutes anxiety and that is reduced by antianxiety drugs. The effects of the antianxiety drugs in the brain also suggest hypotheses concerning the neural substrate of anxiety. Although the benzodiazepines and barbiturates facilitate the effects of γ-aminobutyrate, this is insufficient to explain their highly specific behavioural effects. Because of similarities between the behavioural effects of certain lesions and those of the antianxiety drugs, it is proposed that these drugs reduce anxiety by impairing the functioning of a widespread neural system including the septo-hippocampal system (SHS), the Papez circuit, the prefrontal cortex, and ascending monoaminergic and cholinergic pathways which innervate these forebrain structures. Analysis of the functions of this system (based on anatomical, physiological, and behavioural data) suggests that it acts as a comparator: it compares predicted to actual sensory events and activates the outputs of the BIS when there is a mismatch or when the predicted event is aversive. Suggestions are made as to the functions of particular pathways within this overall brain system. The resulting theory is applied to the symptoms and treatment of anxiety in man, its relations to depression, and the personality of individuals who are susceptible to anxiety or depression.

How do you feel? Interoception: the sense of the physiological condition of the body.

Abstract: As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory.

Abstract: Damage to the hippocampal system disrupts recent memory but leaves remote memory intact. The account presented here suggests that memories are first stored via synaptic changes in the hippocampal system, that these changes support reinstatement of recent memories in the neocortex, that neocortical synapses change a little on each reinstatement, and that remote memory is based on accumulated neocortical changes. Models that learn via changes to connections help explain this organization. These models discover the structure in ensembles of items if learning of each item is gradual and interleaved with learning about other items. This suggests that the neocortex learns slowly to discover the structure in ensembles of experiences. The hippocampal system permits rapid learning of new items without disrupting this structure, and reinstatement of new memories interleaves them with others to integrate them into structured neocortical memory systems.