Despite the success of functional imaging in advancing our understanding of the human brain, our knowledge about physiological processes at the cellular level is largely inferential and based on comparative data from animal models. Fortunately, therapeutic approaches make it possible to carry out invasive recordings in the human brain; for example, in patients with movement disorders such as Parkinson's disease, or in patients with untractable epilepsies where pathological neural activity needs to be localized before the epileptic foci can be surgically removed.
Neurophysiological recordings from human basal ganglia and the motor thalamus produce important insights into the pathophysiological mechanisms of movement disorders. The data are important because none of the available animal models of Parkinson's disease faithfully reproduces all of the symptoms of the human disorder.
Classical models, which account for the key symptoms of Parkinson's disease by assuming enhanced firing rates at the basal ganglia output stages, are now considered limited in their explanatory power. Invasive data support a new pathophysiological model in which dynamic interactions between the basal ganglia, thalamus and cortex in different frequency bands modulate motor functions in a task- and state-dependent way.
In addition to their clinical relevance, recordings in the temporal lobe of patients with epilepsy allow us to address basic questions regarding neural coding and representation. Single-cell recordings are particularly interesting for studying the cellular mechanisms of language-related capacities such as verbal memory, naming and reading. Semichronic recordings of local field potentials with subdural electrodes provide valuable information on the spatiotemporal dynamics of large neural assemblies that underlie language processing and other cognitive functions.
Single-cell recordings from the medial temporal lobes of patients with epilepsy lend support to the role of this structure in declarative memory. Activity of neurons in this region correlates with memory performance, and cells with specific responses to visual stimuli during encoding can be reactivated during visual imagery. Moreover, activity of neurons reflects the conscious perception of stimuli rather than the physical stimulus affecting the sensory surface.
Future applications of invasive techniques will probably include new types of medical intervention, such as the development of demand-controlled pacemakers for deep brain stimulation, devices for real-time seizure prediction, or chronically implantable brain-computer interfaces. In addition to their biomedical relevance, invasive recordings seem indispensable because they provide the only access to the human brain at cellular resolution. By allowing researchers to address the mechanisms of specifically human cognitive functions, invasive recordings might substantially contribute to shaping our understanding of the human mind.
Although non-invasive methods such as functional magnetic resonance imaging, electroencephalograms and magnetoencephalograms provide most of the current data about the human brain, their resolution is insufficient to show physiological processes at the cellular level. Clinical approaches sometimes allow invasive recordings to be taken from the human brain, mainly in patients with epilepsy or with movement disorders, and such recordings can sample neural activity at spatial scales ranging from single cells to distributed cell assemblies. In addition to their clinical relevance, these recordings can provide unique insights into brain functions such as movement control, perception, memory, language and even consciousness.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely moving humans
Nature Neuroscience Open Access 20 February 2023
Intracranial electrophysiological recordings from the human brain during memory tasks with pupillometry
Scientific Data Open Access 13 January 2022
Theta-phase dependent neuronal coding during sequence learning in human single neurons
Nature Communications Open Access 10 August 2021
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Bergman, H., Wichmann, T. & DeLong, M. R. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249, 1436–1438 (1990). A seminal study that indicated that the STN should be a key target in stereotactic neurosurgery for PD.
Pollak, P. et al. Effects of the stimulation of the subthalamic nucleus in Parkinson disease. Rev. Neurol. (Paris) 149, 175–176 (1993).
Eltahawy, H. A., Saint-Cyr, J., Giladi, N., Lang, A. E. & Lozano, A. M. Primary dystonia is more responsive than secondary dystonia to pallidal interventions: outcome after pallidotomy or pallidal deep brain stimulation. Neurosurgery 54, 613–619 (2004).
Papavassiliou, E. et al. Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. Neurosurgery 54, 1120–1129 (2004).
Guridi, J. et al. Targeting the basal ganglia for deep brain stimulation in Parkinson's disease. Neurology 55 (Suppl. 6), S21–S28 (2000).
Benazzouz, A. et al. Intraoperative microrecordings of the subthalamic nucleus in Parkinson's disease. Mov. Disord. 17 (Suppl. 3), S145–S149 (2002).
Hutchison, W. D. et al. Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease. Ann. Neurol. 44, 622–628 (1998).
Rodriguez-Oroz, M. C. et al. The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics. Brain 124, 1777–1790 (2001).
Abosch, A., Hutchison, W. D., Saint-Cyr, J. A., Dostrovsky, J. O. & Lozano, A. M. Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease. J. Neurosurg. 97, 1167–1172 (2002).
Romanelli, P. et al. Microelectrode recording revealing a somatotopic body map in the subthalamic nucleus in humans with Parkinson disease. J. Neurosurg. 100, 611–618 (2004).
Lenz, F. A. et al. Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic tremor cells with the 3–6 Hz component of Parkinsonian tremor. J. Neurosci. 8, 754–764 (1988).
MacMillan, M. L., Dostrovsky, J. O., Lozano, A. M. & Hutchison, W. D. Involvement of human thalamic neurons in internally and externally generated movements. J. Neurophysiol. 91, 1085–1090 (2004).
Lenz, F. A. et al. Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. Brain 117, 531–543 (1994).
Bergman, H. & Deuschl, G. Pathophysiology of Parkinson's disease: from clinical neurology to basic neuroscience and back. Mov. Disord. 17 (Suppl. 3), S28–S40 (2002).
Hurtado, J. M., Gray, C. M., Tamas, L. B. & Sigvardt, K. A. Dynamics of tremor-related oscillations in the human globus pallidus: a single case study. Proc. Natl Acad. Sci. USA 96, 1674–1679 (1999).
Levy, R., Hutchison, W. D., Lozano, A. M. & Dostrovsky, J. O. High-frequency synchronization of neuronal activity in the subthalamic nucleus of Parkinsonian patients with limb tremor. J. Neurosci. 20, 7766–7775 (2000). The first description of synchronized activity in the human STN at the single-cell level.
Magnin, M., Morel, A. & Jeanmonod, D. Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in Parkinsonian patients. Neuroscience 96, 549–564 (2000).
Jeanmonod, D., Magnin, M. & Morel, A. Low-threshold calcium spike bursts in the human thalamus. Common pathophysiology for sensory, motor and limbic positive symptoms. Brain 119, 363–375 (1996).
Paré, D., Curro'Dossi, R. & Steriade, M. Neuronal basis of the Parkinsonian resting tremor: a hypothesis and its implications for treatment. Neuroscience 35, 217–226 (1990).
Obeso, J. A. et al. Pathophysiology of the basal ganglia in Parkinson's disease. Trends Neurosci. 23 (Suppl.), S8–S19 (2000).
Albin, R. L., Young, A. B. & Penney, J. B. The functional anatomy of basal ganglia disorders. Trends Neurosci. 12, 366–375 (1989).
DeLong, M. R. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 13, 281–285 (1990).
Wichmann, T. & DeLong, M. Functional and pathophysiological models of the basal ganglia. Curr. Opin. Neurobiol. 6, 751–758 (1996).
Bergman, H. et al. Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates. Trends Neurosci. 21, 32–38 (1998).
Bar-Gad, I. & Bergman, H. Stepping out of the box: information processing in the neural networks of the basal ganglia. Curr. Opin. Neurobiol. 11, 689–695 (2001).
Nini, A., Feingold, A., Slovin, H. & Bergman, H. Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism. J. Neurophysiol. 74, 1800–1805 (1995).
Raz, A. et al. Activity of pallidal and striatal tonically active neurons is correlated in MPTP-treated monkeys but not in normal monkeys. J. Neurosci. 21, RC 128, 1–5 (2001).
Goldberg, J. A. et al. Enhanced synchrony among primary motor cortex neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine primate model of Parkinson's disease. J. Neurosci. 22, 4639–4653 (2002).
Levy, R., Hutchison, W. D., Lozano, A. M. & Dostrovsky, J. O. Synchronized neuronal discharge in the basal ganglia of Parkinsonian patients is limited to oscillatory activity. J. Neurosci. 22, 2855–2861 (2002).
Levy, R. et al. Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease. Brain 125, 1196–1209 (2002).
Brown, P. et al. Dopamine dependence of oscillations between subthalamic nucleus and pallidum in Parkinson's disease. J. Neurosci. 21, 1033–1038 (2001). The discovery of dopamine-dependent gamma-band activity in the human basal ganglia.
Marsden, J. F., Limousin-Dowsey, P., Ashby, P., Pollak, P. & Brown, P. Subthalamic nucleus, sensorimotor cortex and muscle interrelationships in Parkinson's disease. Brain 124, 378–388 (2001).
Cassidy, M. et al. Movement-related changes in synchronization in the human basal ganglia. Brain 125, 1235–1246 (2002).
Kuhn, A. A. et al. Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance. Brain 127, 735–746 (2004).
Brown, P. & Marsden, C. D. What do the basal ganglia do? Lancet 351, 1801–1804 (1998).
Brown, P. Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson's disease. Mov. Disord. 18, 357–363 (2003).
Limousin, P. et al. Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345, 91–95 (1995).
Graybiel, A. M., Aosaki, T., Flaherty, A. W. & Kimura, M. The basal ganglia and adaptive motor control. Science 265, 1826–1831 (1994).
Vitek, J. Pathophysiology of dystonia: a neuronal model. Mov. Disord. 17 (Suppl. 3), S49–S62 (2002).
Deuschl, G. & Bergman, H. Pathophysiology of nonparkinsonian tremors. Mov. Disord. 17 (Suppl. 3), S41–S48 (2002).
Riehle, A., Gruen, S., Diesmann, M. & Aertsen, A. Spike synchronization and rate modulation differentially involved in motor cortical function. Science 278, 1950–1953 (1997).
Roelfsema, P. R., Engel, A. K., König, P. & Singer, W. Visuomotor integration is associated with zero time-lag synchronization among cortical areas. Nature 385, 157–161 (1997).
Donoghue, J. P., Sanes, J. N., Hatsopoulos, N. G. & Gaal, G. Neural discharge and local field potential oscillations in primate motor cortex during voluntary movements. J. Neurophysiol. 79, 159–173 (1998).
Singer, W. Neuronal synchrony: a versatile code for the definition of relations? Neuron 24, 49–65 (1999).
Engel, A. K., Fries, P. & Singer, W. Dynamic predictions: oscillations and synchrony in top-down processing. Nature Rev. Neurosci. 2, 704–716 (2001).
Herrmann, C. S., Munk, M. H. J. & Engel, A. K. Cognitive functions of gamma-band activity: memory match and utilization. Trends Cogn. Sci. 8, 347–355 (2004).
Ward, A. A. Jr & Thomas, L. B. The electrical activity of single units in the cerebral cortex of man. EEG Clin. Neurophysiol. 7, 135–136 (1955). The first report of successful single-unit recording in the human neocortex.
Ward, A. A. Jr. The epileptic neurones. Epilepsia 2, 70–80 (1961).
Rayport, M. & Waller, H. J. Technique and results of microelectrode recording in human epileptogenic foci. EEG Clin. Neurophysiol. 25 (Suppl.), 143–151 (1967).
Ishijima, B. et al. Neuronal activities in human epileptic foci and surrounding areas. EEG Clin. Neurophysiol. 39, 643–650 (1975).
Wyler, A. R., Ojemann, G. A. & Ward, A. A. Neurons in human epileptic cortex: correlation between unit and EEG activity. Ann. Neurol. 11, 301–308 (1982).
Ojemann, G. A., Ojemann, S. G. & Fried, I. Lessons from the human brain: neuronal activity related to cognition. Neuroscientist 4, 285–300 (1998).
McCormick, D. A. & Contreras, D. On the cellular and network bases of epileptic seizures. Annu. Rev. Physiol. 63, 815–846 (2001).
Avanzini, G. & Franceschetti, S. Cellular biology of epileptogenesis. Lancet Neurol. 2, 33–42 (2003).
Ojemann, G. A. in. Operative Neurosurgical Techniques 3rd edn (eds Schmidek, H. H. & Sweet, W. H.) 1317–1322 (W. B. Saunders Co., Philadelphia, 1995).
Ojemann, G. A., Schoenfield-McNeill, J. & Corina, D. Anatomic subdivisions in human temporal cortical neuronal activity related to recent verbal memory. Nature Neurosci. 5, 64–71 (2002).
Ojemann, G., Ojemann, J., Lettich, E. & Berger, M. Cortical language localization in left, dominant hemisphere: an electrical stimulation mapping investigation in 117 patients. J. Neurosurg. 71, 316–326 (1989).
Ojemann, G. A., Creutzfeldt, O. D., Lettich, E. & Haglund, M. M. Neuronal activity in human lateral temporal cortex related to short-term verbal memory, naming and reading. Brain 111, 1383–1403 (1988). The first controlled study of language-related activity in the human temporal lobe using microelectrode recordings.
Ojemann, G. & Schoenfield-McNeill, J. Activity of neurons in human temporal cortex during identification and memory for names and words. J. Neurosci. 19, 5674–5682 (1999).
Haglund, M. M., Ojemann, G. A., Schwartz, T. W. & Lettich, E. Neuronal activity in human lateral temporal cortex during serial retrieval from short-term verbal memory. J. Neurosci. 14, 1507–1515 (1994).
Schwartz, T., Ojemann, G., Haglund, M. & Lettich, E. Cerebral lateralization of neuronal activity during naming, reading and line-matching. Cogn. Brain Res. 4, 263–273 (1996).
Schwartz, T. H., Haglund, M. M., Lettich, E. & Ojemann, G. A. Asymmetry of neuronal activity during extracellular microelectrode recording from left and right human temporal lobe neocortex during rhyming and line matching. J. Cogn. Neurosci. 12, 803–812 (2000).
Bechtereva, N. P. Abdullaev, Y. G. & Medvedev, S. V. Neuronal activity in frontal speech area 44 of the human cerebral cortex during word recognition. Neurosci. Lett. 124, 61–64 (1991).
Bechtereva, N. P. & Abdullaev, Y. G. Depth electrodes in clinical neurophysiology: neuronal activity and human cognitive function. Int. J. Psychophysiol. 37, 11–29 (2000).
Creutzfeldt, O., Ojemann, G. & Lettich, E. Neuronal activity in the human lateral temporal lobe. I. Responses to speech. Exp. Brain Res. 77, 451–475 (1989).
Creutzfeldt, O., Ojemann, G. & Lettich, E. Neuronal activity in the human lateral temporal lobe. II. Responses to the subjects own voice. Exp. Brain Res. 77, 476–489 (1989).
Lucas, T. H., Schoenfield-McNeill, J., Weber, P. B. & Ojemann, G. A. A direct measure of human lateral temporal lobe neurons responsive to face matching. Cogn. Brain Res. 18, 15–25 (2003).
Perrine, K., Devinsky, O., Uysal, S., Luciano, D. J. & Dogali, M. Left temporal neocortex mediation of verbal memory: evidence from mapping with cortical stimulation. Neurology 44, 1845–1850 (1994).
Kirchhoff, B. A., Wagner, A. D., Maril, A. & Stern, C. E. Prefrontal-temporal circuitry for episodic encoding and subsequent memory. J. Neurosci. 20, 6173–6180 (2000).
Ojemann, G. A., Schoenfield-McNeill, J. & Corina, D. Different neurons in different regions of human temporal lobe distinguish correct from incorrect identification or memory. Neuropsychologia 42, 1383–1393 (2004).
Weber, P. & Ojemann, G. A. Neuronal recordings in human lateral temporal lobe during verbal paired associates learning. Neuroreport 6, 685–689 (1995).
Ojemann, G. A. & Schoenfield-McNeill, J. Neurons in human temporal cortex active with verbal associative learning. Brain Lang. 64, 317–327 (1998).
Wyler, A. R., Ojemann, G. A., Lettich, E. & Ward, A. A. Jr. Subdural strip electrodes for localizing epileptogenic foci. J. Neurosurg. 60, 1195–1200 (1984).
Pfurtscheller, G., Neuper, C. & Kalcher, J. 40-Hz oscillations during motor behavior in man. Neurosci. Lett. 164, 179–182 (1993).
Salenius, S., Salmelin, R., Neuper, C., Pfurtscheller, G. & Hari, R. Human cortical 40 Hz rhythm is closely related to EMG rhythmicity. Neurosci. Lett. 213, 75–78 (1996).
Toro, C. et al. Event-related desynchronization and movement-related cortical potentials on the ECoG and EEG. EEG Clin. Neurophysiol. 93, 380–389 (1994).
Crone, N. E. et al. Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. I. Alpha and beta event-related desynchronization. Brain 121, 2271–2299 (1998).
Crone, N. E., Miglioretti, D. L., Gordon, B. & Lesser, R. P. Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. II. Event-related synchronization in the gamma band. Brain 121, 2301–2315 (1998). The first report of event-related gamma-band synchronization in electrocorticographic recordings.
Aoki, F., Fetz, E. E., Shupe, L., Lettich, E. & Ojemann, G. A. Increased gamma-range activity in human sensorimotor cortex during performance of visuomotor tasks. Clin. Neurophysiol. 110, 524–537 (1999). The demonstration that task-related changes occur in the coherence of electrocorticographic gamma-band activity.
Aoki, F., Fetz, E. E., Shupe, L., Lettich, E. & Ojemann, G. A. Changes in power and coherence of brain activity in human sensorimotor cortex during performance of visuomotor tasks. BioSystems 63, 89–99 (2001).
Pfurtscheller, G., Graimann, B., Huggins, J. E., Levine, S. P. & Schuh, L. A. Spatiotemporal patterns of beta desynchronization and gamma synchronization in corticographic data during self-paced movement. Clin. Neurophysiol. 114, 1226–1236 (2003).
Crone, N. E., Boatman, D., Gordon, B. & Hao, L. Induced electrocorticographic gamma activity during auditory perception. Clin. Neurophys. 112, 565–582 (2001).
Crone, N. E. et al. Electrocorticographic gamma activity during word production in spoken and sign language. Neurology 57, 2045–2053 (2001).
Ulbert, I., Karmos, G., Heit, G. & Halgren, E. Early discrimination of coherent versus incoherent motion by multiunit and synaptic activity in human putative MT+. Hum. Brain Mapp. 13, 226–238 (2001).
Heit, G., Smith, M. E. & Halgren, E. Neural encoding of individual words and faces by the human hippocampus and amygdala. Nature 333, 773–775 (1988).
Heit, G., Smith, M. E. & Halgren, E. Neuronal activity in the human medial temporal lobe during recognition memory. Brain 113, 1093–1112 (1990).
Fried, I. et al. Cerebral microdialysis combined with single-neuron and electroencephalographic recording in neurosurgical patients. Technical note. J. Neurosurg. 91, 697–705 (1999).
Fried, I. et al. Increased dopamine release in the human amygdala during performance of cognitive tasks. Nature Neurosci. 4, 201–206 (2001).
Staba, R. J., Wilson, C. L., Bragin, A., Fried, I. & Engel, J. Jr. Sleep states differentiate single neuron activity recorded from human epileptic hippocampus, entorhinal cortex, and subiculum. J. Neurosci. 22, 5694–5704 (2002).
Elger, C. E. Epilepsy: disease and model to study human brain function. Brain Pathol. 12, 193–198 (2002).
Crick, F., Koch, C., Kreiman, G. & Fried, I. Consciousness and neurosurgery. Neurosurgery 55, 273–282 (2004).
Halgren, E., Babb, T. L. & Crandall, P. H. Activity of human hippocampal formation and amygdala neurons during memory testing. EEG Clin. Neurophysiol. 45, 585–601 (1978).
Squire, L. R. Mechanisms of memory. Science 232, 1612–1619 (1986).
Fried, I., MacDonald, K. A. & Wilson, C. L. Single neuron activity in the human hippocampus and amygdala during recognition of faces and objects. Neuron 18, 753–765 (1997).
Cameron, K. A., Yashar, S., Wilson, C. L. & Fried, I. Human hippocampal neurons predict how well word pairs will be remembered. Neuron 30, 289–298 (2001).
Fried, I., Cameron, K. A., Yashar, S., Fong, R. & Morrow, J. W. Inhibitory and excitatory responses of single neurons in the human medial temporal lobe during recognition of faces and objects. Cereb. Cortex 12, 575–584 (2002).
O'Keefe, J. Do hippocampal pyramidal cells signal non-spatial as well as spatial information? Hippocampus 9, 352–364 (1999).
Ekstrom, A. D. et al. Cellular networks underlying human spatial navigation. Nature 425, 184–187 (2003). The discovery of place cells in the human MTL.
Kreiman, G., Koch, C. & Fried, I. Category-specific visual responses of single neurons in the human medial temporal lobe. Nature Neurosci. 3, 946–953 (2000).
Kreiman, G., Koch, C. & Fried, I. Imagery neurons in the human brain. Nature 408, 357–361 (2000). The first demonstration of imagery neurons in the human MTL.
Kreiman, G., Fried, I. & Koch, C. Single-neuron correlates of subjective vision in the human medial temporal lobe. Proc. Natl Acad. Sci. USA 99, 8378–8383 (2002).
Engel, A. K. & Singer, W. Temporal binding and the neural correlates of sensory awareness. Trends Cogn. Sci. 5, 16–25 (2001).
Rees, G., Kreiman, G. & Koch, C. Neural correlates of consciousness in humans. Nature Rev. Neurosci. 3, 261–270 (2002).
Leopold, D. A. & Logothetis, N. K. Multistable phenomena: changing views in perception. Trends Cogn. Sci. 3, 254–264 (1999).
Donchin, E., Spencer, K. M. & Dien, J. in Brain and Behaviour: Past, Present, and Future (eds van Boxtel, G. J. M. & Bocker, K. B. E.) 67–91 (Tilburg Univ. Press, Tilburg, 1997).
Kranczioch, C., Debener, S. & Engel, A. K. Event-related potential correlates of the attentional blink phenomenon. Cogn. Brain Res. 17, 177–187 (2003).
Halgren, E. et al. Endogenous potentials generated in the human hippocampal formation and amygdala by infrequent events. Science 210, 803–805 (1980).
Halgren, E. et al. Intracerebral potentials to rare target and distractor auditory and visual stimuli. II. Medial, lateral and posterior temporal lobe. EEG Clin. Neurophysiol. 94, 229–250 (1995).
Chatrian, G. E., Bickford, R. G. & Uihlein, A. Depth electrographic study of a fast rhythm evoked from the human calcarine region by steady illumination. EEG Clin. Neurophysiol. 12, 167–176 (1960).
Hirai, N., Uchida, S., Maehara, T., Okubo, Y. & Shimizu, H. Enhanced gamma (30–150Hz) frequency in the human medial temporal lobe. Neuroscience 90, 1149–1155 (1999).
Uchida, S., Maehara, T., Hirai, N., Okubo, Y. & Shimizu, H. Cortical oscillations in human medial temporal lobe during wakefulness and all-night sleep. Brain Res. 891, 7–19 (2001).
Staba, R. J., Wilson, C. L., Bragin, A., Fried, I. & Engel, J. Jr. Quantitative analysis of high-frequency oscillations (80–500Hz) recorded in human epileptic hippocampus and entorhinal cortex. J. Neurophysiol. 88, 1743–1752 (2002).
Bragin, A. et al. Interictal high-frequency oscillations (80–500Hz) in the human epileptic brain: entorhinal cortex. Ann. Neurol. 52, 407–415 (2002).
Chrobak, J. J., Lörincz, A. & Buzsáki, G. Physiological patterns in the hippocampo-entorhinal cortex system. Hippocampus 10, 457–465 (2000).
Fell, J. et al. Human memory formation is accompanied by rhinal–hippocampal coupling and decoupling. Nature Neurosci. 4, 1259–1264 (2001). An important study that showed memory-related changes in gamma-band coherence between the hippocampus and entorhinal cortex.
Fell, J. et al. Rhinal-hippocampal theta coherence during declarative memory formation: interaction with gamma synchronization? Eur. J. Neurosci. 17, 1082–1088 (2003).
Fell, J. et al. Rhinal-hippocampal EEG coherence is reduced during human sleep. Eur. J. Neurosci. 18, 1711–1716 (2003).
Oya, H., Kawasaki, H., Howard, M. A. III & Adolphs, R. Electrophysiological responses in the human amygdala discriminate emotion categories of complex visual stimuli. J. Neurosci. 22, 9502–9512 (2002).
Singer, W. et al. Neuronal assemblies: necessity, signature and detectability. Trends Cogn. Sci. 1, 252–260 (1997).
Normann, R. A., Maynard, E. M., Rousche, P. J. & Warren, D. J. A neural interface for a cortical vision prosthesis. Vision Res. 39, 2577–2587 (1999).
Ulbert, I., Halgren, E., Heit, G. & Karmos, G. Multiple microelectrode recording system for human intracortical applications. J. Neurosci. Meth. 106, 69–79 (2001).
McIntyre, C. C., Savasta, M., Walter, B. L. & Vitek, J. L. How does deep brain stimulation work? Present understanding and future questions. J. Clin. Neurophysiol. 21, 40–50 (2004).
Theodore, W. H. & Fisher, R. S. Brain stimulation for epilepsy. Lancet Neurol. 3, 111–118 (2004).
Tass, P. A. A model of desynchronizing deep brain stimulation with a demand-controlled coordinated reset of neural subpopulations. Biol. Cybern. 89, 81–88 (2003).
Litt, B. & Echauz, J. Prediction of epileptic seizures. Lancet Neurol. 1, 22–30 (2002).
Wolpaw, J. R., Birbaumer, N., McFarland, D. J., Pfurtscheller, G. & Vaughan, T. M. Brain-computer interfaces for communication and control. Clin. Neurophysiol. 113, 767–791 (2002).
Mussa-Ivaldi, F. A. & Miller, L. E. Brain-machine interfaces: computational demands and clinical needs meet basic neuroscience. Trends Neurosci. 26, 329–334 (2003).
Schwartz, A. B. Cortical neural prosthetics. Annu. Rev. Neurosci. 27, 487–507 (2004).
Pfurtscheller, G., Müller, G. R., Pfurtscheller, J., Gerner, H. J. & Rupp, R. 'Thought' — control of functional electrical stimulation to restore hand grasp in a patient with tetraplegia. Neurosci. Lett. 351, 33–36 (2003).
Yoo, S. -S. et al. Brain-computer interface using fMRI: spatial navigation by thoughts. Neuroreport 15, 1591–1595 (2004).
Weiskopf, N. et al. Principles of a brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI). IEEE Trans. Biomed. Eng. 51, 966–970 (2004).
Chapin, J. K., Moxon, K. A., Markowitz, R. S. & Nicolelis, M. A. Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex. Nature Neurosci. 2, 664–667 (1999).
Serruya, M. D., Hatsopoulos, N. G., Paninski, L., Fellows, M. R. & Donoghue, J. P. Instant neural control of a movement signal. Nature 416, 141–142 (2002).
Taylor, D. M., Tillery, S. I. & Schwartz, A. B. Direct cortical control of 3D neuroprosthetic devices. Science 296, 1829–1832 (2002).
Kennedy, P. R. & Bakay, R. A. Restoration of neural output from a paralyzed patient by a direct brain connection. Neuroreport 9, 1707–1711 (1998).
Patil, P. G., Carmena, J. M., Nicolelis, M. A. & Turner, D. A. Ensemble recordings of human subcortical neurons as a source of motor control signals for a brain-machine interface. Neurosurgery 55, 27–38 (2004).
Levine, S. P. et al. Identification of electrocorticogram patterns as the basis for a direct brain interface. J. Clin. Neurophysiol. 16, 439–447 (1999).
Huggins, J. E. et al. Detection of event-related potentials for development of a direct brain interface. J. Clin. Neurophysiol. 16, 448–455 (1999).
Leuthardt, E. C., Schalk, G., Wolpaw, J. R., Ojemann, J. R. & Moran, D. W. A brain-computer interface using electrocorticographic signals in humans. J. Neural Engin. 1, 63–71 (2004). A successful attempt to use event-related synchronization to control a BCI.
Berger, H. Über das Elektrenkephalogramm des Menschen. Arch. Psychiatr. Nervenkr. 87, 527–570 (1929).
Foerster, O. & Altenburger, H. Elektrobiologische Vorgänge an der menschlichen Hirnrinde. Dtsch. Zschr. Nervenheilk. 135, 277–288 (1934).
Jasper, H. H. & Penfield, W. Electrocorticograms in man: effect of voluntary movement upon the electrical activity of the precentral gyrus. Arch. Psychiatr. Nervenkr. 183, 162–174 (1949).
Crandall, P. H., Walter, R. D. & Rand, R. W. Clinical applications of studies on stereotaxically implanted electrodes in temporal lobe epilepsy. J. Neurosurg. 20, 827–840 (1963).
Verzeano, M., Crandall, P. H. & Dymond, A. Neuronal activity of the amygdala in patients with psychomotor epilepsy. Neuropsychologia 9, 331–344 (1971). The first recording of single-unit activity from the human MTL.
Meyers, R. Surgical interruption of the pallidofugal fibres, its effects on the syndrome of paralysis agitans and technical considerations in its application. NY State J. Med. 42, 317–325 (1942).
Jung, R. & Kornmüller, A. E. Eine Methodik der Ableitung lokalisierter Potentialschwankungen aus subcorticalen Hirngebieten. Arch. Psychiatr. 109, 1–30 (1938).
Spiegel, E. A., Wycis, H. T., Marks, M. & Lee, A. J. Stereotaxic apparatus for operations on the human brain. Science 106, 349–350 (1947).
Williams, D. & Parsons-Smith, G. The spontaneous electrical activity of the human thalamus. Brain 72, 450–482 (1949).
Albe-Fessard, D. et al. Identification et délimitation précise de certaines structures sous-corticales de l'homme par l'électrophysiologie. Son intérét dans la chirurgie stéréotaxique des dyskinêsies. CR Acad. Sci. (Paris) 243, 2412–2414 (1961).
Bertrand, G. & Jasper, H. Microelectrode recording of unit activity in the human thalamus. Confin. Neurol. 26, 205–208 (1965).
Umbach, W. & Ehrhardt, K. J. Micro-electrode recording in the basal ganglia during stereotaxic operations. Confin. Neurol. 26, 315–317 (1965).
Struppler, A., Lücking, C. H. & Erbel, F. Neurophysiological findings during stereotactic operation in thalamus and subthalamus. Confin. Neurol. 34, 70–73 (1972).
Benabid, A. L., Pollak, P., Louveau, A., Henry, S. & de Rougemont, J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson's disease. Appl. Neurophysiol. 50, 344–346 (1987). The first study to apply the technique of DBS in humans.
Menne, K. M. L. et al. Online 32-channel signal processing and integrated database improve navigation during cranial stereotactic surgeries. Int. Congr. Ser. 1268, 443–448 (2004).
A.K.E. acknowledges support by grants from the German Federal Ministry of Education and Research (BMBF), the European Commission and the Volkswagen Foundation. C.K.E.M. is supported by the German National Academic Foundation. G.A.O.'s current research is supported by the NIH. The authors thank Hagai Bergman, Peter Brown, Nathan Crone and Tobias Donner for comments on the manuscript.
The authors declare no competing financial interests.
- LOCAL FIELD POTENTIAL
Extracellular voltage fluctuations reflecting the sum of events in the dendrites of a local neuronal population.
- CELL ASSEMBLY
A spatially distributed set of cells that are activated in a coherent fashion and that are part of the same representation.
- IDIOPATHIC DYSTONIA
A movement disorder that leads to involuntary sustained muscle contractions, causing distorted posturing of the foot, leg or arm.
- ESSENTIAL TREMOR
The most common neurological movement disorder. Symptoms include involuntary rhythmic movements of the limbs, head or neck.
- STEREOTACTIC NEUROSURGERY
Microsurgical intervention in deep brain structures for lesion, biopsy or implantation that is based on careful planning using a three-dimensional coordinate system established with the help of neuroimaging.
- DEEP BRAIN STIMULATION
A continuous application of short current pulses that is supposed to lead to functional blockade of basal ganglia nuclei.
- MPTP PRIMATE MODEL
For the study of the pathophysiology of Parkinson's disease, monkeys are exposed to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causing degeneration of dopaminergic neurons in the substantia nigra.
Extracellular recording of muscle fibre activity.
A normalized measure of neural interaction that shows high values when two signals share similar frequencies and adopt a constant phase relationship.
- FOCAL EPILEPSY
A type of seizure with a localized site of onset.
Direct recording of voltage fluctuations from the cortical surface.
A histogram that describes the time relation between two signals, in which a centre peak indicates synchrony and side peaks reflect oscillations.
- WADA TEST
Injection of an anaesthetic (such as amobarbital) into the left or right internal carotid artery, which allows researchers to test the cognitive abilities of one cerebral hemisphere in isolation.
The facilitation of recognition, reproduction or biases in selection of stimuli that have recently been perceived.
- MOVEMENT-RELATED DESYNCHRONIZATION
A decrease or increase in power in a certain frequency band shortly before or during the execution of a movement.
Individual units of speech sound that combine to make words.
- INTERICTAL ACTIVITY
Neural activity in an epileptogenic region in the time between two seizures.
- P3 COMPONENT
A positive electroencephalogram wave that appears 300–500 ms after a salient or novel stimulus that has attracted the subject's attention.
- EVENT-RELATED POTENTIAL
Phase-locked electroencephalogram activity, obtained by averaging data segments recorded after presentation of a stimulus.
- OBSESSIVE-COMPULSIVE DISORDER
A neuropsychiatric disorder that leads to an abnormal degree of disturbing and intrusive thoughts and impulses, as well as compulsive behaviours.
Rights and permissions
About this article
Cite this article
Engel, A., Moll, C., Fried, I. et al. Invasive recordings from the human brain: clinical insights and beyond. Nat Rev Neurosci 6, 35–47 (2005). https://doi.org/10.1038/nrn1585
This article is cited by
A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely moving humans
Nature Neuroscience (2023)
Neural modulation with photothermally active nanomaterials
Nature Reviews Bioengineering (2023)
Treating Chronic Pain with Deep Brain Stimulation
Current Pain and Headache Reports (2023)
Intracranial electrophysiological recordings from the human brain during memory tasks with pupillometry
Scientific Data (2022)
Neurons as will and representation
Nature Reviews Neuroscience (2022)