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  • Review Article
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Invasive recordings from the human brain: clinical insights and beyond

Nature Reviews Neuroscience volume 6, pages 35–47 (2005)Cite this article

Key Points

  • 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.

Abstract

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.

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Figure 1: Multisite recordings help to elucidate the pathophysiology of basal ganglia disorders.
Figure 2: Single-unit recordings in the lateral temporal lobe probe language-related capacities.
Figure 3: Invasive recordings reveal assembly dynamics in the human brain.
Figure 4: Recordings in the medial temporal lobe (MTL) yield insights into perceptual and memory functions.

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Acknowledgements

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.

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Authors and Affiliations

  1. Institute of Neurophysiology and Pathophysiology, Center of Experimental Medicine, University Hospital Eppendorf, Martinistrasse 52, Hamburg, 20246, Germany

    Andreas K. Engel & Christian K. E. Moll

  2. Division of Neurosurgery, UCLA Medical Center, PO Box 957039, Los Angeles, 90095-7039, California, USA

    Itzhak Fried

  3. Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Itzhak Fried

  4. Department of Neurological Surgery, University of Washington, PO Box 356470, Seattle, 98195, Washington, USA

    George A. Ojemann

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Correspondence to Andreas K. Engel.

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DATABASES

OMIM

Parkinson's disease

FURTHER INFORMATION

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Glossary

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.

ELECTROMYOGRAM

Extracellular recording of muscle fibre activity.

COHERENCE

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.

ELECTROCORTICOGRAM

Direct recording of voltage fluctuations from the cortical surface.

CROSS-CORRELOGRAM

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.

PRIMING

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.

PHONEMES

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.

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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

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