Encoding-related brain activity and accelerated forgetting in transient epileptic amnesia.

The accelerated forgetting of newly learned information is common amongst patients with epilepsy and, in particular, in the syndrome of transient epileptic amnesia (TEA). However, the neural mechanisms underlying accelerated forgetting are poorly understood. It has been hypothesised that interictal epileptiform activity during longer retention intervals disrupts normally established memory traces. Here, we tested a distinct hypothesis-that accelerated forgetting relates to the abnormal encoding of memories. We studied a group of 15 patients with TEA together with matched, healthy control subjects. Despite normal performance on standard anterograde memory tasks, patients showed accelerated forgetting of a word list over one week. We used a subsequent memory paradigm to compare encoding-related brain activity in patients and controls. Participants studied a series of visually presented scenes whilst undergoing functional MRI scanning. Recognition memory for these scenes was then probed outside the scanner after delays of 45 min and of 4 days. Patients showed poorer memory for the scenes compared with controls. In the patients but not the controls, subsequently forgotten stimuli were associated with reduced hippocampal activation at encoding. Furthermore, patients demonstrated reduced deactivation of posteromedial cortex regions upon viewing subsequently remembered stimuli as compared to subsequently forgotten ones. These data suggest that abnormal encoding-related activity in key memory areas of the brain contributes to accelerated forgetting in TEA. We propose that abnormally encoded memory traces may be particularly vulnerable to interference from subsequently encountered material and hence be forgotten more rapidly. Our results shed light on the mechanisms underlying memory impairment in epilepsy, and offer support to the proposal that accelerated forgetting may be a useful marker of subtle dysfunction in memory-related brain systems.

Imagining the present: amnesia may impair descriptions of the present as well as of the future and the past.

Recent evidence suggests that in some patients with amnesia the capacity to imagine the future is impaired in parallel with the capacity to remember the past. This paper asks whether descriptions of the present may be similarly affected. We recruited 7 patients with amnesic syndromes of varying aetiologies who were matched for age, sex and education with 7 control participants. Patients showed no deficits on subjective measures of visual imagery. They were impaired by comparison with controls on measures of imagination and future thinking. However there was an even more marked impairment on tasks requiring them to give descriptions of their current experience. Potential explanations include effects of amnesia on narrative construction or on the texture of experience itself, and the confounding influence of cognitive impairments outside the memory domain. We conclude that tasks requiring descriptions of current experience provide a valuable control condition in studies examining the relationship between memory and imagination.

The neural basis of autobiographical memory deficits in transient epileptic amnesia.

Transient epileptic amnesia (TEA) is a recently recognized form of temporal lobe epilepsy which is often associated with persistent interictal impairment of autobiographical memory. We used fMRI to investigate the neural basis of this deficit. Eleven patients with TEA, who had no significant deficits on standard tests of anterograde memory, and 17 age and IQ matched healthy controls retrieved memories from across the lifespan. Both groups engaged the autobiographical memory network, but activation in patients was less extensive than in controls. Direct comparison revealed hypoactivation of regions in the right hemisphere. Specifically, patients showed reduced activation of the posterior parahippocampal gyrus (pPHG), especially for mid-life and recent memories, with decreased engagement of the right temporoparietal junction and the cerebellum. In addition, we found reduced effective connectivity in patients between the right pPHG and the right middle temporal gyrus. Our results are consistent with other evidence that TEA is a syndrome of medial temporal lobe epilepsy and indicate that it affects the function and connectivity of regions within the autobiographical memory network.

Remote memory deficits in transient epileptic amnesia.

Transient epileptic amnesia is a form of temporal lobe epilepsy in which sufferers often complain of irretrievable loss of remote memories. We used a broad range of memory tests to clarify the extent and nature of the remote memory deficits in patients with transient epileptic amnesia. Performance on standard tests of anterograde memory was normal. In contrast, there was a severe impairment of memory for autobiographical events extending across the entire lifespan, providing evidence for the occurrence of 'focal retrograde amnesia' in transient epileptic amnesia. There was a milder impairment of personal semantic memory, most pronounced for midlife years. There were limited deficits of public semantic memory for recent decades. These results may reflect subtle structural pathology in the medial temporal lobes or the effects of the propagation of epileptiform activity through the network of brain regions responsible for long-term memory, or a combination of these two mechanisms.

Loss of imagery phenomenology with intact visuo-spatial task performance: a case of 'blind imagination'.

The capacity for imagery, enabling us to visualise absent items and events, is a ubiquitous feature of our experience. This paper describes the case of a patient, MX, who abruptly lost the ability to generate visual images. He rated himself as experiencing almost no imagery on standard questionnaires, yet performed normally on standard tests of perception, visual imagery and visual memory. These unexpected findings were explored using functional MRI scanning (fMRI). Activation patterns while viewing famous faces were not significantly different between MX and controls, including expected activity in the fusiform gyrus. However, during attempted imagery, activation in MX's brain was significantly reduced in a network of posterior regions while activity in frontal regions was increased compared to controls. These findings are interpreted as suggesting that MX adopted a different cognitive strategy from controls when performing the imagery task. Evidence from experimental tasks thought to rely on mental imagery, such as the Brooks' matrices and mental rotation, support this interpretation. Taken together, these results indicate that successful performance in visual imagery and visual memory tasks can be dissociated from the phenomenal experience of visual imagery.

The syndrome of transient epileptic amnesia.

OBJECTIVE: Transient amnesia can be the principal manifestation of epilepsy. This diagnosis, however, is seldom suspected by clinicians and remains controversial. The amnestic attacks are often associated with persistent memory complaints. This study was designed to provide the first description of transient epileptic amnesia in a substantial series of patients. METHODS: Fifty patients were recruited over 18 months using the following diagnostic criteria: (1) recurrent, witnessed episodes of amnesia; (2) other cognitive functions intact during attacks; and (3) compelling evidence of epilepsy. We assessed clinical features and performed neuropsychological evaluation in cases and 24 matched control subjects. RESULTS: Transient epileptic amnesia develops in later life (mean onset, 62 years). Amnestic episodes are frequent (median, 12/year), brief (median duration, 30-60 minutes), and often occur on waking (37/50 cases). Epilepsy was the initial specialist diagnosis in only 12 of 50 cases. Attacks ceased on anticonvulsant medication in 44 of 47 treated patients. A total of 40 of 50 cases described persistent memory difficulties. Despite normal performance on standard memory tests, patients exhibited accelerated forgetting of verbal and visual material over 3 weeks by comparison with matched control subjects (p < 0.001). They also showed loss of autobiographical memories for events extending back over 40 years (p < 0.05). INTERPRETATION: We propose that transient epileptic amnesia is a distinctive epilepsy syndrome, typically misdiagnosed at presentation and associated with accelerated long-term forgetting and autobiographical amnesia. The syndrome is of clinical and theoretic importance.