Anterior hippocampus orchestrates successful encoding and retrieval of non-relational memory: an event-related fMRI study

Episodic memory encoding and retrieval processes have been linked to different neural networks. However, the common brain regions associated with non-relational memory processing during successful encoding (subsequent memory effect) and successful retrieval (recognition effect) have not yet been investigated. Further, the majority of functional imaging studies have been conducted in young subjects, whereas patients from lesion studies, where most neuropsychological models are still based upon, are usually older. Inferences from younger subjects cannot necessarily be applied to the elderly, an issue becoming particularly relevant with our ageing society. Using an event-related fMRI approach we studied 29 healthy elderly subjects (mean age 67.8, SD 5.4 years) with a non-associative task of intentional word list encoding and retrieval. For each subject, behavioural responses were individually classified into four event types (hits test, misses test, false alarms, correct rejections). Brain areas activated during successful memory encoding comprised the anterior left hippocampus extending into the surrounding parahippocampal gyrus. Regions associated with successful memory retrieval involved a wide-spread network of anterior left parahippocampal gyrus, bilateral temporal cortices and bilateral ventral and dorsal prefrontal areas. Regions contributing to both successful encoding and retrieval, evidenced by a conjunction analysis, revealed prominent left lateralized activations of the anterior hippocampus and the inferior parietal lobe. Our results indicate that the anterior left hippocampus plays an important role during successful memory encoding and during successful memory retrieval in a task of simple, non-associative wordlist learning in healthy elderly subjects.     

Encoding and immediate retrieval tasks in patients with epilepsy: A functional MRI study of verbal and visual memory

Purpose

Medial lobe temporal structures and more specifically the hippocampus play a decisive role in episodic memory. Most of the memory functional magnetic resonance imaging (fMRI) studies evaluate the encoding phase; the retrieval phase being performed outside the MRI. We aimed to determine the ability to reveal greater hippocampal fMRI activations during retrieval phase.

Effortful retrieval reduces hippocampal activity and impairs incidental encoding

Functional imaging studies frequently report that the hippocampus is engaged by successful episodic memory retrieval. However, considering that concurrent encoding of the background environment occurs during retrieval and influences medial temporal lobe activity, it is plausible that hippocampal encoding functions are reduced with increased attentional engagement during effortful retrieval. Expanding upon evidence that retrieval efforts suppress activity in hippocampal regions implicated in encoding, this study examines the influence of retrieval effort on encoding performance and the interactive effects of encoding and retrieval on hippocampal and neocortical activity. Functional magnetic resonance imaging was conducted while subjects performed a word recognition task with incidental picture encoding. Both lower memory strength and increased search duration were associated with encoding failure and reduced hippocampal and default network activity. Activity in the anterior hippocampus tracked encoding, which was more strongly deactivated when incidental encoding was unsuccessful. These findings highlight potential contributions from background encoding processes to hippocampal activations during neuroimaging studies of episodic memory retrieval. © 2013 Wiley Periodicals, Inc.     

Successful verbal retrieval in elderly subjects is related to concurrent hippocampal and posterior cingulate activation

OBJECTIVE: Memory decline and hippocampal atrophy are two major aspects of Alzheimer's disease. Using a response-related fMRI design, we investigated the relationship between successful verbal retrieval and concurrent cerebral activation in elderly subjects in different stages of cognitive decline. We chose a correlational over the more traditional categorical approach to increase the power of detecting relevant activations. METHODS: Eleven subjects with Alzheimer's disease, 21 elderly subjects with mild cognitive impairment, and 29 age-matched cognitively unimpaired subjects learned 180 nouns. While measuring brain activation with fMRI, the subjects had to classify these 180 learned plus 180 new distractor words as known or new. Response-related fMRI analysis was used to identify cerebral activation by correctly remembered words (hits) that correlated with retrieval success in the whole group. RESULTS: Successful verbal retrieval was significantly correlated with concurrent activation of the left hippocampus and posterior cingulate gyrus. CONCLUSION: The study confirms the importance of adequate hippocampal function for successful verbal retrieval in the elderly. In addition, our study supports connectivity studies indicating a functional relationship between the hippocampus and the posterior cingulate gyrus during successful verbal retrieval in the elderly in different stages of cognitive decline.     

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.     

A genome-wide supported variant in CACNA1C influences hippocampal activation during episodic memory encoding and retrieval

The alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene is one of the best replicated susceptibility loci for bipolar disorder, schizophrenia and major depression. It is involved in learning, memory and brain plasticity. Genetic studies using functional magnetic resonance imaging (fMRI) reported evidence of association with the CACNA1C single nucleotide polymorphism rs1006737 with functional correlates of episodic memory encoding and retrieval, especially activations in the hippocampus. These results, however, are inconsistent with regard to the magnitude and directionality of effect. In the present study, brain activation was measured with fMRI during an episodic memory encoding and retrieval task using neutral faces in two independent samples of 94 and 111 healthy subjects, respectively. Within whole brain analyses, a main effect of genotype emerged mainly in the right hippocampus during encoding as well as retrieval within the first sample: Carriers of the minor allele (A) exhibited lower activations compared to G/G allele carriers. This effect could be replicated within the second sample, however, only for the retrieval condition. The results strengthen findings that rs1006737 is associated with neural systems related to memory processes in hippocampal regions which are detectable in healthy subjects.     

Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia

Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia.     

Differences of cerebral activation between superior and inferior learners during motor sequence encoding and retrieval

Cerebral activation during memory encoding and retrieval might depend on subjects' learning capacity, either by corresponding to better performance in superior learners or by reflecting increased effort in inferior learners. To investigate these alternative hypotheses, the study compared cerebral activation during encoding and retrieval of a motor sequence in groups of subjects with superior and inferior learning performances. Ten healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a motor sequence encoding paradigm (i.e. finger tapping sequence) and a retrieval paradigm (i.e. reproduction of the learned sequence). Subjects were divided into superior and inferior learners according to the correctness of sequence reproduction during retrieval. During encoding, there was strong bilateral activation in the middle frontal gyrus, the supplementary motor area (SMA), the lateral parietal lobe and the cerebellum. During retrieval, again strong activation was found in identical areas of the prefrontal cortex, the parietal lobe and the cerebellum. During encoding, inferior learners showed more left-sided activations in the left middle frontal and inferior parietal gyri. Superior learners showed increased activation in the corresponding right-sided brain areas during encoding as well as during retrieval. Differences of cerebral activations in the prefrontal and parietal cortex during encoding and retrieval were found to be related to retrieval performance, i.e. success and effort. Further intervention studies are needed to assess whether these interindividual differences are the cause or the consequence of differences in memory performance.     

Understanding failure of visual paired associate learning in amnestic mild cognitive impairment

Impairment in visual paired associate learning occurs often in with amnestic mild cognitive impairment (aMCI), a condition considered to be an early stage of Alzheimer's disease (AD). To date, studies of aMCI have characterized impaired visual paired associate learning only in terms of summary scores such as total errors or total trials to criterion. The aim of this study was to determine the nature and magnitude of errors made on a continuous paired associate learning (CPAL) task designed to allow analysis of the component processes involved in paired associate learning. Twenty-one individuals with aMCI and 54 healthy age-matched older adults (HC) performed the CPAL task in which they had to learn six pattern-location pairings over six trials. Results suggested that aMCI patients performed significantly worse on the CPAL, both in learning rate and in error accumulation. Qualitative analyses of CPAL performance revealed that in aMCI there were significantly more errors on all indices except perseverative errors. When expressed as a percentage of total errors, abnormalities occurred only for within-search and exploratory errors. These findings suggest that poor performance on visual paired associate learning tasks in aMCI reflects impairments in both learning and executive function.     

Prefrontal and parietal cortex in human episodic memory: an interference study by repetitive transcranial magnetic stimulation

Neuroimaging findings, including repetitive transcranial magnetic stimulation (rTMS) interference, point to an engagement of prefrontal cortex (PFC) in learning and memory. Whether parietal cortex (PC) activity is causally linked to successful episodic encoding and retrieval is still uncertain. We compared the effects of event-related active or sham rTMS (a rapid-rate train coincident to the very first phases of memoranda presentation) to the left or right intraparietal sulcus, during a standardized episodic memory task of visual scenes, with those obtained in a fully matched sample of subjects who received rTMS on left or right dorsolateral PFC during the same task. In these subjects, specific hemispheric effects of rTMS included interference with encoding after left stimulation and disruption of retrieval after right stimulation. The interference of PC-rTMS on encoding/retrieval performance was negligible, lacking specificity even when higher intensities of stimulation were applied. However, right PC-rTMS of the same intensity lengthened reaction times in the context of a purely attentive visuospatial task. These results suggest that the activity of intraparietal sulci shown in several functional magnetic resonance studies on memory, unlike that of the dorsolateral PFC, is not causally engaged to a useful degree in memory encoding and retrieval of visual scenes. The parietal activations accompanying the memorization processes could reflect the engagement of a widespread brain attentional network, in which interference on a single 'node' is insufficient for an overt disruption of memory performance.     

Functional networks in motor sequence learning: abnormal topographies in Parkinson's disease

We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinson's disease (PD) using 15O-water (H2 15O) positron emission tomography (PET) and network analysis. All subjects were scanned while learning motor sequences in a task emphasizing explicit learning, and during a kinematically controlled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysis of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary motor area (preSMA), anterior cingulate cortex, and in the left caudate/putamen. A second independent covariance pattern was associated with retrieval performance. This topography was characterized by bilateral activations in the premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning-related topographies failed to predict acquisition performance in PD patients and predicted retrieval performance less accurately in the controls. A separate network analysis was performed to identify discrete learning-related topographies in the PD cohort. In PD patients, acquisition performance was associated with a covariance pattern characterized by activations in the left PFdl, ventral prefrontal, and rostral premotor regions, but not in the striatum. Retrieval performance in PD patients was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning networks are associated with additional cortical activation compensating for abnormalities in basal ganglia function.     

Verbal fluency activates the left medial temporal lobe: a functional magnetic resonance imaging study

Verbal fluency tests (VFTs) are suggested to assess frontal lobe function. This view is supported by functional imaging studies that report left frontal activation during VFTs. VFTs require retrieval of semantically associated words from long-term memory storage. The neural networks that participate in this process, however, are largely unknown. These neural networks are of interest, given that patients with early Alzheimer's disease, typically without frontal pathology, are often impaired in VFTs. In the present study, functional magnetic resonance imaging was performed to determine brain activation areas during VFTs in young subjects. In the activation task, category fluency was contrasted with orderly listing of numbers. As judged from using this comparison, there was activation in the left medial temporal lobe, in the inferior frontal and retrosplenial cortices bilaterally, and in the left superior parietal lobule. Left medial temporal lobe activation was present in 13 of the 14 study subjects either in the hippocampal formation (11 of 14) or in the posterior parahippocampal gyrus (12 of 14). These results suggest that the medial temporal lobe is required for the process of retrieval by category. Functional magnetic resonance imaging combined with a category fluency task may provide a new method to study patients with early Alzheimer's disease.     

Encoding of novel picture pairs activates the perirhinal cortex: an fMRI study

It is well established in nonhuman primates that the medial temporal lobe (MTL) structures, the hippocampus and the entorhinal and perirhinal cortices, are necessary for declarative memory encoding. In humans, the neuropathological and neuropsychological changes in early Alzheimer's disease (AD) further support a role for the rhinal cortex in the consolidation of new events into long-term memory. Little is known, however, regarding the function of the rhinal cortex in humans in vivo. To examine the participation of the interconnected MTL structures as well as the whole-brain network of activated brain areas in visual associative long-term memory, functional magnetic resonance imaging (fMRI) was used to determine the brain regions that are activated during encoding and retrieval of paired pictures in 12 young control subjects. The most striking finding in the MTL activation pattern was the consistent activation of the perirhinal cortex in the encoding-baseline and encoding-retrieval comparisons with a strict statistical threshold (P < 0.00001). In contrast, no perirhinal cortex activation was detected in the retrieval-baseline or retrieval-encoding comparisons even with a low statistical threshold (P < 0.05). The location of the perirhinal activation area was in the transentorhinal part of the perirhinal cortex, in the medial bank of the collateral sulcus. The hippocampus and the more posterior parahippocampal gyrus were activated in both encoding and retrieval conditions. During the encoding processing, MTL activations were more consistent and the hippocampal activation area located more anteriorly than during retrieval. The frontal, parietal, temporal, and occipital association cortices were also activated in the encoding-baseline and retrieval-baseline comparisons. The data suggest that encoding, but not retrieval, of novel picture pairs activates the perirhinal cortex. To our knowledge, this is the first fMRI study reporting encoding activation in this transentorhinal part of the perirhinal cortex, the site of the very earliest neuropathological changes in AD.     

Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease.

OBJECTIVE: To examine patterns of brain activation during verbal episodic retrieval in normal elderly subjects and patients in an early phase of AD. BACKGROUND: It is established that 1) a profound episodic memory impairment is a cardinal symptom of AD; and 2) some of the earliest brain changes in this disease occur in regions critical to episodic memory, such as the hippocampus and neighboring regions. Yet, it remains largely unknown whether the episodic memory deficit seen in AD is paralleled by concomitant alterations in brain activity during actual task performance in these or other brain areas. METHODS: Using PET, blood flow was assessed in normal elderly subjects and patients with early AD during two retrieval conditions involving completion of word stems: baseline and cued recall. RESULTS: The patients with AD showed a marked performance deficit in cued recall, although the two groups were indistinguishable in the baseline task condition. Both groups showed bilateral activity in orbital and dorsolateral prefrontal cortex, left precuneus, and right cerebellum, as well as decreased activity in distinct left temporal regions during cued recall. The normal elderly alone activated the left parietal cortex and the left hippocampal formation during episodic retrieval. By contrast, AD-related increases in activity during cued recall were observed in the left orbital prefrontal cortex and left cerebellum. CONCLUSIONS: The similar patterns of activations in the two groups suggest that a large distributed network involved in episodic memory retrieval functions relatively normally in early AD. Those retrieval activations seen in the normal elderly, as opposed to the patients, may reflect AD-related failures in semantic processing and successful recollection of the target information, respectively. Finally, the AD-related increases in activity were interpreted in terms of compensatory reactions to the difficulties in performing the episodic memory task.     

Fronto‐temporal dysregulation in asymptomatic bipolar I patients: A paired associate functional MRI study

Bipolar disorder is associated with persistent declarative memory disturbances, but the neural basis of these deficits is not well understood. We used fMRI to investigate brain activity during performance on a face‐name paired associate task, which allows for the dissociation of encoding and recall‐related memory processes. Fifteen clinically remitted bipolar I disorder patients and 24 demographically matched healthy comparison subjects were scanned during task performance. At the voxel level, bipolar patients showed reduced cortical activation, relative to controls, in multiple task‐related brain regions during encoding. During recognition, bipolar patients under‐activated left hippocampal and parahippocampal regions, despite adequate task performance. Region of interest analyses indicated that, during encoding, bipolar patients had greater bilateral dorsolateral prefrontal (DLPFC) activity than healthy subjects. In contrast, during recognition patients showed hypo‐activation relative to controls in the right, but not the left, DLPFC. Although hippocampal activity did not differ between groups during encoding, bipolar patients failed to activate hippocampal regions to the same extent as healthy subjects during recognition. Finally, while better task performance was associated with recognition‐related hippocampal activity in healthy subjects, bipolar patients showed an inverse relationship between task performance and hippocampal activity. Remitted bipolar patients over‐engaged dorsolateral prefrontal regions when learning face‐name pairs, but relative hypoactivation in both prefrontal and medial temporal regions during recognition. These findings suggest a neural basis for the long‐term memory deficits consistently observed in patients with bipolar disorder; further, as these patterns appear in symptomatically remitted patients, they are unlikely to be an artifact of mood symptoms. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Medial temporal lobe activation during episodic encoding and retrieval: a PET study

Recent neuroimaging studies have obtained evidence of activation in the medial temporal lobe (MTL) during episodic encoding and retrieval. On the basis of a meta-analysis of MTL activations in studies that used positron emission tomography (PET), Lepage et al. (Hippocampus 1998;8:313-322) suggested that episodic encoding tends to involve the anterior MTL, whereas episodic retrieval tends to involve the posterior MTL. In a meta-analysis of studies that used PET and functional magnetic resonance imaging, Schacter and Wagner (Hippocampus 1999;9:7-24) reported weaker evidence for such a rostrocaudal distribution of encoding and retrieval activations. However, these meta-analyses were based largely on studies that examined encoding or retrieval separately. Here, we report a direct, within-subjects comparison of MTL activation during episodic encoding and retrieval by using PET. Results indicated that both encoding and retrieval were associated with blood flow increases in similar MTL regions with little indication that encoding and retrieval are preferentially associated with activity in the anterior versus the posterior MTL. Direct comparisons revealed greater blood flow increases in posterior MTL during encoding than retrieval.     

Learning complex arithmetic--an fMRI study

Aim of the present functional magnet resonance imaging (fMRI) study was to detect modifications of cerebral activation patterns related to learning arithmetic. Thirteen right-handed subjects were extensively trained on a set of 18 complex multiplication problems. In the following fMRI session, trained and untrained problems (closely matched for difficulty) were presented in blocked order alternating with a number matching task and a fact retrieval task. Importantly, left hemispheric activations were dominant in the two contrasts between untrained and trained condition, suggesting that learning processes in arithmetic are predominantly supported by the left hemisphere. Contrasting untrained versus trained condition, the left intraparietal sulcus showed significant activations, as well as the inferior parietal lobule. A further significant activation was found in the left inferior frontal gyrus. This activation may be accounted for by higher working memory demands in the untrained as compared to the trained condition. Contrasting trained versus untrained condition a significant focus of activation was found in the left angular gyrus. Following the triple-code model [Science 284 (1999) 970], the shift of activation within the parietal lobe from the intraparietal sulcus to the left angular gyrus suggests a modification from quantity-based processing to more automatic retrieval. The present study shows that the left angular gyrus is not only involved in arithmetic tasks requiring simple fact retrieval, but may show significant activations as a result of relatively short training of complex calculation.     

Intact implicit learning in schizophrenia

OBJECTIVE: Schizophrenia impairs performance on explicit, but not implicit, memory tasks, indicating that conscious awareness at retrieval is a critical determinant of impaired memory. The authors investigated implicit learning, i.e., knowledge acquisition in the absence of conscious awareness, in patients with schizophrenia. METHOD: An artificial grammar learning task was used to assess implicit learning in 48 patients with schizophrenia and 24 healthy comparison subjects. The subjects were first presented with letter strings that were generated according to the rules of a finite-state grammar paradigm. They were then required to indicate whether new letter strings were "grammatical," depending on whether or not the strings corresponded to the rules. IQ, working memory, explicit memory, verbal fluency, and speed of processing were also assessed. RESULTS: Patients performed significantly worse than the comparison subjects on cognitive tasks that assessed episodic memory, verbal fluency, working memory, and speed of processing. In contrast, patients classified as being correct more grammatical than nongrammatical letter strings, and the magnitude of the difference was similar to that observed in healthy comparison subjects. CONCLUSIONS: Implicit learning, as assessed with an artificial grammar learning task, is intact in patients with schizophrenia. Conscious awareness might be a critical determinant of memory impairment both at encoding and at retrieval.     

Hippocampal dysfunction in patients with mild cognitive impairment: a functional neuroimaging study of a visuospatial paired associates learning task

Mild cognitive impairment (MCI) patients report memory problems greater than those normally expected with ageing, but do not fulfil criteria for clinically probable Alzheimer's disease. Accumulating evidence demonstrates that impaired performance on the Paired Associates Learning (PAL) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) may be sensitive and specific for early and differential diagnosis of Alzheimer's disease. We adapted the basic CANTAB PAL task for functional magnetic resonance imaging (fMRI) in order to examine the functional brain deficits, at encoding and retrieval separately, in patients with MCI compared to healthy matched volunteers. As well as investigating the main effects of encoding and retrieval, we characterized neural responses in the two groups to increasing memory load. We focused on changes in BOLD response in the hippocampus and related structures, as an a priori region of interest based on what is known about the neuropathology of the early stages of Alzheimer's disease and previous information on the neural substrates of the PAL task. We also used structural MRI in the same patients to assess accompanying structural brain abnormalities associated with MCI.In terms of the BOLD response, the bilateral hippocampal activation in the MCI and control groups depended upon load, the MCI patients activating significantly more than controls at low loads and significantly less at higher loads. There were no other differences between MCI patients and controls in terms of the neural networks activated during either encoding or retrieval of the PAL task, including the prefrontal, cingulate and temporal cortex. The functional deficit in hippocampal activation in the MCI patients was accompanied by structural differences in the same location, suggesting that the decrease in hippocampal activation may be caused by a decrease in the amount of grey matter. This is one of the first studies to have used both encoding and retrieval phases of a memory paradigm for fMRI in MCI patients, and to have shown that the BOLD response in MCI patients can show both hyperactivation and hypoactivation in the same individuals as a function of memory load and encoding/retrieval. The findings suggest that performance on PAL might be a useful cognitive biomarker for early detection of Alzheimer's disease, especially when used in conjunction with neuroimaging.     

Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study

OBJECTIVE: Memory impairment has been well documented in schizophrenia. In a previous study, the authors investigated patterns of brain activity during episodic encoding and recognition of words in remitted, stable schizophrenia outpatients being treated with novel antipsychotics. The same procedure was used in this study to investigate unmedicated patients during an acute episode of schizophrenia. METHOD: Functional magnetic resonance imaging was used to study regional brain activation in 10 unmedicated patients experiencing an acute episode of schizophrenia and 10 healthy comparison subjects during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite intact recognition performance, patients with schizophrenia showed reduced activation of anterior prefrontal, posterior cingulate, and retrosplenial areas relative to comparison subjects during word encoding. During word recognition, reduced activation was found in the patients' dorsolateral prefrontal and limbic/paralimbic regions. On the other hand, higher metabolism in bilateral anterior prefrontal cortices was observed. CONCLUSIONS: The results suggest that different neural pathways are engaged during episodic encoding and recognition of words in patients experiencing an acute episode of schizophrenia relative to healthy comparison subjects. Furthermore, acute psychosis may prevent practice effects, reflected in a failure to engage brain regions associated with successful episodic memory retrieval in healthy subjects.