Memory impairment is a disabling condition and one of the most common complaints affecting patients with neurological deficits. Neurological disorders, such as Alzheimer disease (AD), Parkinson disease (PD), traumatic brain injury (TBI), and epilepsy, as well as normal aging, can lead to problems in declarative, working, and episodic memory. These impairments often place significant psychological, social, and financial stresses on patients and their families.
Medical treatments for cognitive deficits are limited and suggest a need for new and innovative therapy. Deep brain stimulation (DBS) is a successful and prevalent treatment for movement disorders, such as PD, tremor, and dystonia; however, its use in treating neuropsychiatric disorders has come to the forefront only in recent years.
In this article, we review the neurobiology and circuitry behind memory as well as current studies involving neuromodulation for memory disorders.
Neuromodulation for memory disorders
DBS is a surgical technique that delivers pulsed electrical impulses to the brain. In addition to its use in treating movement disorders, DBS has been used to manage chronic pain, obsessive-compulsive disorder, and depression. However, the application of DBS for cognitive dysfunction has not been well established.
The Papez circuit is a neural network that is thought to be involved in emotion and episodic memory (Figure). There is evidence that parts of this circuitry may be altered in neurocognitive disorders such as AD, PD, and epilepsy, which suggests potential targets for neuromodulation. The frontal-striatal circuitry has also been implicated in memory processes and cognitive dysfunction. Specifically, deficits in working memory and retrieval often reflect dysfunction in the frontal-striatal systems.
In addition to neural circuitry, specific firing patterns of different brain regions have been associated with mechanisms of learning. For instance, intracranial recordings have demonstrated that high-frequency activity within the prefrontal area, medial temporal lobe, and inferior parietal cortices has been associated with encoding and retrieval states.1,2 In contrast, increased hippocampal low-frequency (theta) activity may be important before memory tasks.3 Preclinical and clinical DBS trials have begun to target these circuits for memory deficits.
Neurodegenerative disorders and memory
Neurodegenerative diseases, such as AD and PD, are characterized by significant deficits in working memory, episodic memory, and semantic memory. MRI findings have demonstrated a reduction in hippocampal and entorhinal cortex volume in the early stages of AD, and decreased metabolism in the frontal lobe, medial temporal lobe, and parietal regions.4 As episodic memory is thought to be mediated by the hippocampus, these findings correlate with deficits in episodic memory and precede widespread cognitive deterioration.5 In contrast, patients with subcortical dementia often have deficits in working memory as opposed to episodic memory.6
Dr. Lee is Stereotactic and Functional Neurosurgery Fellow and William P. Van Wagenen Fellow; Dr. Lozano is Professor, Dan Family Professor and Chairman of Neurosurgery, R. R. Tasker Chair in Functional Neurosurgery, and Canada Research Chair in Neuroscience, Division of Neurosurgery, Toronto Western Hospital, Department of Surgery, University of Toronto. Dr. Lee reports no conflicts of interest concerning the subject matter of this article; Dr. Lozano is a consultant for Medtronic, St Jude, Boston Scientific, and Functional Neuromodulation.
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