Binding deficits in memory following medial temporal lobe damage in patients with voltage-gated potassium channel complex antibody-associated limbic encephalitis

Abstract

Some prominent studies have claimed that the medial temporal lobe is not involved in retention of information over brief intervals of just a few seconds. However, in the last decade several investigations have reported that patients with medial temporal lobe damage exhibit an abnormally large number of errors when required to remember visual information over brief intervals. But the nature of the deficit and the type of error associated with medial temporal lobe lesions remains to be fully established. Voltage-gated potassium channel complex antibody-associated limbic encephalitis has recently been recognized as a form of treatable autoimmune encephalitis, frequently associated with imaging changes in the medial temporal lobe. Here, we tested a group of these patients using two newly developed visual short-term memory tasks with a sensitive, continuous measure of report. These tests enabled us to study the nature of reporting errors, rather than only their frequency. On both paradigms, voltage-gated potassium channel complex antibody patients exhibited larger errors specifically when several items had to be remembered, but not for a single item. Crucially, their errors were strongly associated with an increased tendency to report the property of the wrong item stored in memory, rather than simple degradation of memory precision. Thus, memory for isolated aspects of items was normal, but patients were impaired at binding together the different properties belonging to an item, e.g. spatial location and object identity, or colour and orientation. This occurred regardless of whether objects were shown simultaneously or sequentially. Binding errors support the view that the medial temporal lobe is involved in linking together different types of information, potentially represented in different parts of the brain, regardless of memory duration. Our novel behavioural measures also have the potential to assist in monitoring response to treatment in patients with memory disorders, such as those with voltage-gated potassium channel complex antibody limbic encephalitis.

Visual short-term memory binding deficits in Alzheimer's disease: a reply to Parra's commentary.

“…relational binding task that we have developed (Pertzov et al, 2013), the number of swap (binding) errors does indeed increase with age.…”

“…In fact, our "What was where?" relational memory task succeeded in showing a binding-specific deficit in both patients with focal medial temporal lobe disease (as a result of voltage-gated potassium channel antibody mediated encephalitis; Pertzov et al 2013) as well as asymptomatic mutation carriers for FAD . In both cases, recognition and localization performance was normal (as assessed by localization of one item and the "nearest item control" analysis for three items) but there was a specific impairment in associating the correct items to their correct locations.…”

“…At present, it would appear that impairments in context-rich, relational binding memory functions such as those probed by the "What was where?" object-location test , Pertzov et al 2013, 2015 can be detected in the asymptomatic stage of AD, and are therefore potentially useful clinical research tools. …”

Exploring Different Stages of Alzheimer's Disease through Topological Analysis of Differentially Expressed Genetic Networks

“…In Tables I, and II [23], GO:0032350(regulation of hormone metabolic process) [24], GO:0006569(tryptophan catabolic process) [25], GO:0046218(indolalkylamine catabolic process) [26], GO:0004718(protein tyrosine kinase activity) [27], GO:0015459(potassium channel regulator activity) [28], GO:0016247(channel regulator activity) [29], GO:0015457(Transport) [30], GO:0008076(voltage-gated potassium channel complex) [31].…”

Correlation between neuronal antibodies and limbic encephalitis in Chinese Han subjects

“…VGKC-ab-associated LE showed good results towards the immunotherapy response (Vincent et al, 2004Barajas et al, 2010). Pertzov et al (2013) tested a group of VGKC-Ab patients using 2 newly developed visual short-term memory tasks with a sensitive and continuous measurements. These tests can be used to examine the nature of reporting errors.…”