Impact of schizophrenia‐risk gene dysbindin 1 on brain activation in bilateral middle frontal gyrus during a working memory task in healthy individuals

Working memory (WM) dysfunction is a hallmark feature of schizophrenia. Functional imaging studies using WM tasks have documented both prefrontal hypo‐ and hyperactivation in schizophrenia. Schizophrenia is highly heritable, and it is unclear which susceptibility genes modulate WM and its neural correlates. A strong linkage between genetic variants in the dysbindin 1 gene and schizophrenia has been demonstrated. The aim of this study was to investigate the influence of the DTNBP1 schizophrenia susceptibility gene on WM and its neural correlates in healthy individuals. Fifty‐seven right‐handed, healthy male volunteers genotyped for DTNBP1 SNP rs1018381 status were divided in heterozygous risk‐allele carriers (T/C) and homozygous noncarriers (C/C). WM was assessed by a 2‐back vs. 0‐back version of the Continuous Performance Test (CPT), while brain activation was measured with fMRI. DTNBP1 SNP rs1018381 carrier status was determined and correlated with WM performance and brain activation. Despite any differences in behavioral performance, risk‐allele carriers exhibited significantly increased activation of the bilateral middle frontal gyrus (BA 9), a part of the dorsolateral prefrontal cortex (DLPFC), compared to noncarriers. This difference did not correlate with WM performance. The fMRI data provide evidence for an influence of genetic variation in DTNBP1 gene region tagged by SNP rs1018381 on bilateral middle frontal gyrus activation during a WM task. The increased activation in these brain areas may be a consequence of “inefficient” or compensatory DLPFC cognitive control functions. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Altered neural function during episodic memory encoding and retrieval in major depression

Memory impairments are common in major depression. Neural processing during non‐emotional episodic memory in depressed patients has only sparsely been investigated, since the majority of studies have focused on emotional stimuli. The aim of this study was to explore neural correlates of episodic memory in depressive patients and to assess brain regions related to subsequent memory performance. Forty‐six participants (23 depressed patients) performed a non‐emotional episodic memory encoding and retrieval task while brain activation was measured with functional magnetic resonance imaging. Patients with depression showed decreased activation in the right prefrontal cortex and right cingulate cortex during memory encoding, but increased activation in the right inferior frontal gyrus (IFG) during recognition memory. While a strong association between hippocampal and parahippocampal activation during memory encoding with subsequent memory performance became evident in healthy controls, this relationship was absent in patients with depression. Taken together, these findings demonstrate that memory related brain regions are affected in their appropriate functioning during memory encoding in depressed patients. Therefore, patients with depression may rely to a greater degree on other brain regions such as the IFG during episodic memory retrieval. Hum Brain Mapp 35:4293–4302, 2014. © 2014 Wiley Periodicals, Inc .     

Neural mechanisms of voluntary and involuntary recall: a PET study

Neuropsychological and neuroimaging studies on episodic memory retrieval have primarily focused on volitional memory tasks. However, some conscious memories arise involuntarily, i.e. without a strategic retrieval attempt, yet little is known about the neural network underlying involuntary episodic memory. The aim of this study was to determine whether voluntary and involuntary recall are mediated by separate cortical networks. We used positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) in 12 healthy subjects during voluntary and involuntary cued recall of pictures and a control condition with no episodic memory requirements. Involuntary recall was elicited by using an incidental memory task. Compared to the control condition, voluntary and involuntary recall were both associated with significant regional cerebral blood flow (rCBF) increases in posterior cingulate gyrus (PCG; BA 23), left precuneus (BA 7), and right parahippocampal gyrus (BA 35/36). In addition, rCBF in right dorsolateral prefrontal cortex (PFC; BA 8/9) and left precuneus (BA 7) was significantly larger during voluntary compared to involuntary recall, while rCBF was enhanced in left dorsolateral PFC (BA 9) during involuntary recall. The findings corroborate an association of the right PFC with a strategic component of episodic memory retrieval. Moreover, they show for the first time that it is possible to activate the medial temporal lobe, the PCG, and the precuneus, regions normally associated with retrieval success, without this strategic element. The relatively higher activity in precuneus during voluntary compared to involuntary recall suggests that activity in this region co-varies not only with retrieval success but also with retrieval intentionality.     

Prefrontal activity associated with working memory and episodic long-term memory

Many recent neuroimaging studies have highlighted the role of prefrontal regions in the sustained maintenance and manipulation of information over short delays, or working memory (WM). In addition, neuroimaging findings have highlighted the role of prefrontal regions in the formation and retrieval of memories for events, or episodic long-term memory (LTM), but it remains unclear whether these regions are distinct from those that support WM. We used event-related functional magnetic resonance imaging (fMRI) to identify patterns of prefrontal activity associated with encoding and recognition during WM and LTM tasks performed by the same subjects. Results showed that the same bilateral ventrolateral prefrontal regions (at or near Brodmann's Areas [BA] 6, 44, 45, and 47) and dorsolateral prefrontal regions (BA 9/46) were engaged during encoding and recognition within the context of WM and LTM tasks. In addition, a region situated in the left anterior middle frontal gyrus (BA 10/46) was engaged during the recognition phases of the WM and LTM tasks. These results support the view that the same prefrontal regions implement reflective processes that support both WM and LTM.     

Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome

Background

Attention deficits belong to the main cognitive symptoms of schizophrenia and come along with altered neural activity in previously described cerebral networks. Given the high heritability of schizophrenia the question arises if impaired function of these networks is modulated by susceptibility genes and detectable in healthy risk allele carriers.

Methods

The present event-related fMRI study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 of the DTNBP1 (dystrobrevin-binding protein 1) gene on brain activity in 80 subjects while performing the attention network test (ANT). In this reaction time task three domains of attention are probed simultaneously: alerting, orienting and executive control of attention.

Results

Risk allele carriers showed impaired performance in the executive control condition associated with reduced neural activity in the left superior frontal gyrus [Brodmann area (BA) 9]. Risk allele carriers did not show alterations in the alerting and orienting networks.

Conclusions

BA 9 is a key region of schizophrenia pathology and belongs to a network that has been shown previously to be involved in impaired executive control mechanisms in schizophrenia. Our results identified the impact of DTNBP1 on the development of a specific attention deficit via modulation of a left prefrontal network.     

Functional asymmetry of human prefrontal cortex in verbal and non-verbal episodic memory as revealed by fMRI

Functional neuroimaging studies have demonstrated preferential involvement of bilateral prefrontal cortex during episodic memory encoding and retrieval. The aim of the present study is to address the question whether left prefrontal model for encoding holds when highly non-verbal material is used, and which region of the brain is critically related to successful retrieval. To do this, seven normal subjects were investigated using functional magnetic resonance imaging (fMRI) during encoding and retrieval of word and checkerboard pattern. Our results revealed that word encoding activated the left prefrontal cortices and right cerebellum, whereas pattern encoding activated the bilateral middle frontal gyrus, superior parietal lobule, premotor area, and occipital visual cortex. Word-specific activation was found in the ventral prefrontal cortices, and pattern-specific activation located in the right dorsal prefrontal cortex. Conjunction analysis during encoding of word and pattern showed that activity in the left dorsal prefrontal cortex and the right cerebellum might relate to common neural network for encoding regardless of the type of material. Finally, the present study demonstrates strong association between the left ventral prefrontal cortex and retrieval success for word. The evidence, that both encoding and retrieval of words activated the left ventral prefrontal cortex, indicates that this area is involved in active and strategic operation of the mnemonic representation. A lack of the right prefrontal activation during retrieval was interpreted as that activity in this region might relate to retrieval effort rather than success.     

Genetic variation of the α2b-adrenoceptor affects neural correlates of successful emotional memory formation

Objective: Enhanced memory for emotionally charged events helps us to remember potentially vital information. There are large interindividual differences in emotional‐memory enhancement, but little is known about their neurobiological basis. Recently, a functional deletion variant of the gene that codes for the α2b‐adrenoceptor (ADRA2B) has been shown to affect memory for emotional experiences. Initial neuroimaging evidence linked this behavioral effect to increased amygdala activity, but its influence on successful memory processing remains unknown. Therefore, the aim of this study was to investigate the effect of the common deletion in the ADRA2B gene on neural activity related to specific mnemonic processing, successful memory formation, and retrieval. Methods: Twenty‐three noncarriers (10 males) and 28 deletion carriers (13 males) with a mean age of 24 years were investigated while performing an emotional‐learning task with sad and happy scenes. Functional magnetic resonance imaging was acquired both during memory formation and retrieval. Results: Although there were no differences in memory performance between groups, the common deletion variant of ADRA2B was related to enhanced activity in the amygdala and inferior frontal gyrus during successful emotional memory formation, but not retrieval. Deletion carriers showed a larger differential response in these brain regions between later‐remembered and later‐forgotten stimuli than nondeletion carriers did. Conclusion: Our results demonstrate that the ADRA2B polymorphism influences emotional memory formation but not memory retrieval in the amygdala and left inferior frontal gyrus. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.     

Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition

OBJECTIVE: Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. METHOD: Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. RESULTS: Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal pole and had a less robust right prefrontal response. CONCLUSIONS: Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies.     

The influence of encoding strategy on episodic memory and cortical activity in schizophrenia.

BACKGROUND: Recent work suggests that episodic memory deficits in schizophrenia may be related to disturbances of encoding or retrieval. Schizophrenia patients appear to benefit from instruction in episodic memory strategies. We tested the hypothesis that providing effective encoding strategies to schizophrenia patients enhances encoding-related brain activity and recognition performance. METHODS: Seventeen schizophrenia patients and 26 healthy comparison subjects underwent functional magnetic resonance imaging scans while performing incidental encoding tasks of words and faces. Subjects were required to make either deep (abstract/concrete) or shallow (alphabetization) judgments for words and deep (gender) judgments for faces, followed by subsequent recognition tests. RESULTS: Schizophrenia and comparison subjects recognized significantly more words encoded deeply than shallowly, activated regions in inferior frontal cortex (Brodmann area 45/47) typically associated with deep and successful encoding of words, and showed greater left frontal activation for the processing of words compared with faces. However, during deep encoding and material-specific processing (words vs. faces), participants with schizophrenia activated regions not activated by control subjects, including several in prefrontal cortex. CONCLUSIONS: Our findings suggest that a deficit in use of effective strategies influences episodic memory performance in schizophrenia and that abnormalities in functional brain activation persist even when such strategies are applied.     

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.     

Associative memory encoding and recognition in schizophrenia: an event-related fMRI study.

BACKGROUND: We used an event-related functional Magnetic Resonance Imaging (fMRI) approach to examine the neural basis of the selective associative memory deficit in schizophrenia. METHODS: Fifteen people with schizophrenia and 18 controls were scanned during a pair and item memory encoding and recognition task. During encoding, subjects studied items and pairs of visual objects. In a subsequent retrieval task, participants performed an item recognition memory test (old/new decisions) and an associative recognition test (intact/rearranged decisions). The fMRI analysis of the recognition data was restricted to correct items only and a random effects model was used. RESULTS: At the behavioral level, both groups performed equally well on item recognition, whereas people with schizophrenia demonstrated lower performance on associative recognition relative to the control group. At the brain level, the comparison between associative and item encoding revealed greater activity in the control group in the left prefrontal cortex and cingulate gyrus relative to the schizophrenia group. During recognition, greater left dorsolateral prefrontal and right inferior prefrontal activations were observed in the control group relative to the schizophrenia group. CONCLUSION: This fMRI study implicates the prefrontal cortex among other brain regions as the basis for the selective associative memory encoding and recognition deficit seen in schizophrenia.     

Memory performance and fMRI signal in presymptomatic familial Alzheimer's disease

Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late‐onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation‐carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD‐relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes. Hum Brain Mapp 34:3308–3319, 2013. © 2012 Wiley Periodicals, Inc.     

Neural state and trait bases of mood-incongruent memory formation and retrieval in first-episode major depression

Mood-congruent cognitive biases constitute critical factors for the vulnerability to depression and its maintenance. One important aspect is impaired memory for positive information during depression and after recovery. To elucidate its state (during depression only) and trait (during depression and recovery) related neural bases, we investigated medication free depressed, recovered, and healthy individuals with functional MRI while they memorized and recognized happy and neutral face stimuli. The imaging results revealed group differences in mood-incongruent successful memory encoding and retrieval activity already in the absence of significant memory performance differences. State effects were observed in the amygdala and posterior cingulate cortex. Whereas the amygdala was generally involved in memory formation, its activity predicted subsequent forgetting of neutral faces in depressed patients. Furthermore, the amygdala and posterior cingulate cortex were involved in memory retrieval of happy faces in depressed patients only. Trait effects were observed in the fusiform gyrus and prefrontal cortex. The fusiform gyrus was involved in memory formation and retrieval of happy faces in both patient groups, whereas it was involved in memory formation and retrieval of neutral faces in healthy individuals. Similar trait effects were observed during memory retrieval in the orbitofrontal cortex and left inferior frontal gyrus. Thus, while memory processing of positive information in the amygdala and posterior cingulate cortex is biased during depression only, memory processing in the fusiform gyrus and prefrontal cortex is biased also after recovery. These distinct neural mechanisms may respectively constitute symptom maintenance and cognitive vulnerability factors for depression.     

Brain‐derived neurotrophic factor val66met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

Brain‐derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long‐term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype and functional activity in the hippocampus during episodic and working memory tasks in healthy young adults. Specifically, studies have found that met carriers exhibit both poorer performance and reduced neural activity within the medial temporal lobe (MTL) when performing episodic memory tasks. However, these studies have not been well replicated and have not considered the role of behavioral differences in the interpretation of neural differences. The current study sought to control for cognitive performance in investigating the role of the BDNF val66met genotype on neural activity associated with episodic memory. Across item and relational memory tests, met carriers exhibited increased MTL activation during both encoding and retrieval stages, compared to noncarriers. The results suggest that met carriers are able to recruit MTL activity to support successful memory processes, and reductions in cognitive performance observed in prior studies are not a ubiquitous effect associated with variants of the BDNF val66met genotype. © 2010 Wiley‐Liss, Inc.     

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.     

Common and unique neural activations in autobiographical, episodic, and semantic retrieval

This study sought to explore the neural correlates that underlie autobiographical, episodic, and semantic memory. Autobiographical memory was defined as the conscious recollection of personally relevant events, episodic memory as the recall of stimuli presented in the laboratory, and semantic memory as the retrieval of factual information and general knowledge about the world. Our objective was to delineate common neural activations, reflecting a functional overlap, and unique neural activations, reflecting functional dissociation of these memory processes. We conducted an event-related functional magnetic resonance imaging study in which we utilized the same pictorial stimuli but manipulated retrieval demands to extract autobiographical, episodic, or semantic memories. The results show a functional overlap of the three types of memory retrieval in the inferior frontal gyrus, the middle frontal gyrus, the caudate nucleus, the thalamus, and the lingual gyrus. All memory conditions yielded activation of the left medial-temporal lobe; however, we found a functional dissociation within this region. The anterior and superior areas were active in episodic and semantic retrieval, whereas more posterior and inferior areas were active in autobiographical retrieval. Unique activations for each memory type were also delineated, including medial frontal increases for autobiographical, right middle frontal increases for episodic, and right inferior temporal increases for semantic retrieval. These findings suggest a common neural network underlying all declarative memory retrieval, as well as unique neural contributions reflecting the specific properties of retrieved memories.     

Common and unique gray matter correlates of episodic memory dysfunction in frontotemporal dementia and alzheimer's disease

Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel‐based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age‐ and education‐matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole‐brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome. Hum Brain Mapp 35:1422–1435, 2014. © 201 Wiley Periodicals, Inc.     

Altered prefrontal brain activity in persons at risk for Alzheimer's disease: an fMRI study

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) is critical for adequate treatment and care. Recently it has been shown that functional magnetic resonance imaging (fMRI) can be important in preclinical detection of AD. The purpose of this study was to examine possible differences in memory-related brain activation between persons with high versus low risk for AD. This was achieved by combining a validated neurocognitive screening battery (the 7-minutes test) with memory assessment and fMRI. METHODS: One hundred two healthy community-living persons with subjective memory complaints were recruited through advertisement and tested with the 7-minutes test. Based on their test performance they were classified as having either high (n = 8) or low risk (n = 94) for AD. Six high-risk individuals and six age-, sex-, and education-matched low-risk individuals were investigated with fMRI while engaged in episodic memory tasks. RESULTS: The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences (p < .05 corrected). During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. CONCLUSION: Patterns of prefrontal brain activity related to episodic memory differ between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.     

Asymmetric frontal activation during episodic memory: the effects of stimulus type on encoding and retrieval

Recent functional neuroimaging studies have suggested that the left prefrontal cortex is preferentially involved in the encoding of episodic memory whilst the right prefrontal cortex is preferentially involved in the retrieval of episodic memory, irrespective of the type (e.g. modality) of information being remembered. In the present PET activation study, a 2 x 2 design was employed to investigate the relationship between encoding and retrieval of verbal and non-verbal material in episodic memory. Accordingly, seven healthy volunteers were scanned whilst encoding and then recalling stimuli which either emphasised visual or verbal processes. When encoding and retrieval tasks were compared directly, significantly greater prefrontal activation was observed in the encoding conditions, regardless of modality, although these changes were bilaterally distributed. In contrast when the verbal and visual memory tasks were compared directly, the former was associated with rCBF changes that were predominantly located in the left lateral frontal cortex whilst the latter was associated with rCBF changes that were predominantly located in the right lateral frontal cortex. These results suggest that encoding and retrieval may actually involve similar regions of the lateral prefrontal cortex when all factors relating to the type of stimulus material (i.e. modality), are appropriately controlled.     

Prefrontal activity and impaired memory encoding strategies in schizophrenia

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome.