CLINICAL EEG and NEUROSCIENCE - Dynamic Memory Lab

CLINICAL EEG and NEUROSCIENCE ©2007 VOL. 38 NO. 1For example, Auchterlonie and colleagues 3 investigatedwhether anomia in AD was attributable to degradation ofthe semantic store or to an independent word-findingdeficit. In that study, the N400 component-sensitive tosemantic processing load, was equally diminished inresponse to named and unnamed pictures, suggesting thatanomia and semantic deficits are independent in AD.As sensitive measures of cognitive processes and theirdisruption due to neuropathology, ERPs have much potentialclinical utility. For example, ERPs may aid in the earlydiagnosis of neurodegenerative disorders such as AD. Wi t hcareful study design, ERPs may be used to isolate relevantcognitive processes and to facilitate differential diagnosis. A sdirect measures of synaptic function, ERPs are also potentiallyuseful in the evaluation of pharmacological treatments.The present work is a selective review of cognitive-ERP studies of memory and language impairments inamnesia and AD. The amnestic syndrome, typically causedby bilateral lesions of the MTL, is characterized by theinability to encode and retrieve episodic memories beyondthe brief duration of working memory. The neuropathologyof AD includes MTL structures early in the course of thedisease, and a deficit of episodic memory is one of theearly behavioral hallmarks of the disease. However, neocorticalassociation areas are also affected early in AD, andpatients may present with semantic memory and wordfindingdeficits. Therefore, ERP effects that are dependentupon successful encoding and retrieval from episodicmemory are expected to be absent or diminished in bothamnesia and AD, whereas ERP effects that index semanticprocessing or other higher cognitive functions (e.g.,attention, response selection) may be selectively diminishedin AD. Intracranial EEG/ERP studies of pre-surgicaltemporal lobe epilepsy patients provide clues to the neuralgenerators of scalp-recorded ERP components, and someof these studies are discussed here. ERP studies of individualswith mild cognitive impairment (MCI), memorydeficits in the absence of functional decline and thereforenot meeting the diagnostic criteria for probable AD, arealso discussed, as they may reveal neurophysiologicalchanges that precede clinical deficits. These studies holdgreat potential for the early detection and diagnosis of AD.Through this review, we hope to illustrate several keydifferences in the ERP abnormalities in well-circumscribedamnesia compared to dementias such as AD. To anticipate,while well-circumscribed lesions of the MTL or diencephalonappear to produce altered plasticity of the latepositive P600 component, the P300 and N400 are usuallyspared. However, with the widespread neuropathologicalchanges in AD, all three of these components commonlyshow abnormalities.P300: OverviewThe P300 (or “P3b”) component is a scalp positivityelicited by low-probability stimuli during stimulus classificationtasks which peaks ~300 ms post-stimulus, maximal overmidline centroparietal sites. In the canonical P300 experiment,the “auditory oddball” task, participants detect a lowprobability“target” (e.g., high-pitched) tone in a stream of“standard” (e.g., low-pitched) tones, and the typical result isa clear P300 for targets with a relatively flat ERP r e s p o n s ein the same latency range for standards. The P300 has beenextensively studied and well characterized in both normaland neurologically impaired populations. P300 latency isvariable and generally proportional to the complexity of thestimulus evaluation and decisional processes demanded bythe task. It has been suggested that the P300 reflectsprocesses involved in updating working memory, 4 or theprocesses of stimulus discrimination and response selecti o n . 5 H o w e v e r, P300 amplitude and latency are modulatedby a variety of factors — subjective probability, stimuluss a l i e n c y, availability of attentional resources 6 — and itappears to be generated by a distributed network of neuralregions — inferotemporal, perirhinal, prefrontal, cingulate,superior temporal and parietal cortices, as well as the hippo c a m p u s 7 , 8 — suggesting that P300 likely indexes a heterogeneousset of cognitive processes. On the other hand,studies of patients with damage to the temporo-parietal junctionhave found that the auditory P300 response is eliminated , 9 suggesting that this neocortical region may be critical ingeneration or propagation of the scalp P300.P300 in amnesiaGiven that working memory and response selectionprocesses are not typically disturbed in circumscribed medial-temporalamnesia, one might expect the P300 responseto low-probability stimuli to be intact in this population.H o w e v e r, as noted above, intracranial recordings haveshown that the hippocampus and paralimbic cortices areamong the brain regions that produce P300-like responses.It remains unknown to what extent the medial-temporalP300 contributes to the P300 recorded at the scalp.Rugg et al 10 studied the P300 response of a single individualwith amnesia due to an infiltrating glioma in the leftMTL. In both auditory and visual oddball experiments,Rugg et al found normal P300 effects in this amnesicpatient. Another report of an individual with amnesia due toa lesion of the left MTL found that the P300 was similarlyintact. 11 Two case studies of bilateral medial temporalpathology also found auditory and visual P300s that werecomparable to those in normal controls. 12,13 A group studyof five patients with damage restricted to bilateral MTL dueto various etiologies 14 found no significant differences inauditory or visual P300 amplitude or latency between theamnesic patients and controls.Honda et al 15studied a heterogeneous group ofamnesic patients and found that the integrity of the auditoryP300 response depended on the extent of MTL damageas detected by structural imaging (MRI, CT). Robust P300responses were found in patients in whom no lesions were9