Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.     

Functional activation of the human frontal cortex during the performance of verbal working memory tasks

Regional cerebral blood flow was measured with positron emission tomography during the performance of verbal working memory tasks. The same type of verbal response (i.e., reciting numbers) was required in the control and the two experimental tasks. In the control task, the subjects were required to count aloud. In the two experimental tasks, the subjects were required to maintain within working memory the numbers they generated (self-ordered task) or the numbers generated by the experimenter (externally ordered task). Examination of the difference in activation between these conditions revealed strong bilateral activation within the mid-dorsolateral frontal cortex during both experimental tasks. There was, however, no evidence of additional activation within the mid-dorsolateral frontal cortex when monitoring self-generated responses as compared with the monitoring of externally generated responses. These results provide evidence regarding the role of the mid-dorsolateral frontal cortex in mnemonic processing that are in agreement with recent findings from work with non-human primates.     

Separate neural bases of two fundamental memory processes in the human medial temporal lobe

The participation of medial temporal-lobe structures in memory performance was examined by functional magnetic resonance imaging of local blood oxygenation level-dependent signals. Signals were measured during encoding into memory complex scenes or line drawings and during retrieval from memory of previously studied line drawings or words. Encoding tasks yielded increased signals for unfamiliar information in a posterior medial-temporal region that were focused in the parahippocampal cortex. Retrieval tasks yielded increased signals for successfully remembered information in an anterior medial-temporal region that were focused in the subiculum. These results indicate that separate components of the human medial temporal-lobe memory system are active during distinct memory processes.     

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.     

Executive Functioning, Memory, and Learning in Phenylketonuria.

The executive deficit hypothesis of treated phenylketonuria (PKU) suggests that dopaminergic depletion in the lateral prefrontal cortex leads to selective executive impairment. This was examined by comparing adults with PKU on a lifelong diet with a matched healthy control group. Those with PKU were impaired on selective and sustained attention, working memory (Self-Ordered Pointing), and letter fluency. However, they failed to show differential sensitivity to increased cognitive load on the attentional and working memory tasks, and they did not differ significantly on the remaining executive tasks (rule finding, inhibition, and multitasking). Nor did they differ significantly on recall or recognition memory. Overall, the findings provided little support for the executive deficit hypothesis. A possible explanation in terms of slowed information processing speed is explored. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regional brain activity during tasks devoted to the central executive of working memory

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.     

Identification of distinct elements of the stromal microenvironment that control human hematopoietic stem/progenitor cell growth and differentiation

The role of left prefrontal cortex in lexical-semantic processing remains a matter of some debate. Functional neuroimaging experiments have reported blood flow changes in left inferior prefrontal cortex (LIPC) during tasks that involve word retrieval and semantic processing. Some of these studies have also implicated LIPC in repetition priming. To determine the necessity of prefrontal cortex for these types of memory and to elucidate their time-course, behavioral and event-related potential (ERP) correlates of lexical processing and repetition priming were examined in 11 stroke patients with lesions centered in dorsolateral prefrontal cortex (areas 9 and 46). Damage extended inferiorly and posteriorly to areas 6, 8, 44, and 45 in some subjects, so patients were subdivided into anterior and posterior frontal subgroups. Visually presented words and pronounceable non-words were repeated after one of three delays. Subjects categorized stimuli as either words or non-words in a lexical decision task. Controls showed significant word priming at all three delays. Old words elicited more positive-going potentials than new words, beginning at 300 ms and lasting until 500-700 ms. This ERP repetition effect was reduced, but not eliminated, by both anterior and posterior frontal lesions. However, behavioral priming was intact in the patients, suggesting that prefrontal cortex may modulate the neural generators in posterior cortical regions that are critical for priming. Left posterior frontal lesions resulted in impaired performance in the lexical decision task and a reduction in the amplitude of the late positive component (LPC). These latter findings suggest that left posterior prefrontal cortex is important for the categorization and selection processes required by lexical-semantic tasks.     

Temporal dynamics of brain activation during a working memory task

Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving. Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available 'online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance. However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may also be involved in active maintenance. We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.     

Cognitive planning in humans: neuropsychological, neuroanatomical and neuropharmacological perspectives

In recent years, considerable progress has been made in understanding the cognitive and neuroanatomical basis of high-level planning behaviour through a combination of neuropsychological, neuropharmacological and functional neuroimaging approaches. In this article, early evidence suggesting a relationship between planning impairments and damage to the frontal lobe is reviewed and several contemporary studies of planning behaviour in patients with circumscribed frontal lobe excisions are described in detail. These neuropsychological investigations, together with recent functional neuroimaging studies of normal control subjects, have identified a specific area within the mid-dorsolateral frontal cortex of humans which appears to be critically involved in the cognitive processes that mediate efficient planning. The functions of this region, both in cognitive planning and in related functions such as working memory, are then discussed in the context of a general theoretical framework for understanding the functional organization of "executive" processes within the human lateral frontal cortex. In the final sections, the relationship between the planning deficits observed after intrinsic frontal lobe damage and those exhibited by patients with neuropathology of primarily sub-cortical origin, such as Parkinson's disease, is discussed. A central model for much of this work has been the concept of cortico-striatal circuitry which emphasizes the relationship between the neocortex and the striatum. The combined evidence from comparative studies in patients and from functional neuroimaging studies on Parkinson's disease suggests that altered cortico-striatal interactions may disrupt normal planning function at a number of levels, possibly consequent upon intrinsic striatal pathology on the one hand and the partial loss of (frontal) cortical input to the basal ganglia on the other.     

The role of prefrontal cortex in working memory: examining the contents of consciousness

Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory.     

The functional neuroanatomy of episodic memory: the role of the frontal lobes, the hippocampal formation, and other areas

Because it allows direct mapping of synaptic activity during behavior in the normal subject, functional neuroimaging with the activation paradigm, especially positron emission tomography, has recently provided insight into our understanding of the functional neuroanatomy of episodic memory over and above established knowledge from lesional neuropsychology. The most striking application relates to the ability to distinguish the structures implicated in the encoding and the retrieval of episodic information, as these processes are extremely difficult to differentiate with behavioral tasks, either in healthy subjects or in brain-damaged patients. Regarding encoding and retrieval, the results from most studies converge on the involvement of the prefrontal cortex in these processes, with a hemispheric encoding/retrieval asymmetry (HERA) such that the left side is preferentially involved in encoding, and the right in retrieval. However, there are still some questions, for instance, about bilateral activation during retrieval and a possible specialization within the prefrontal cortex. More expected from human and monkey lesional data, the hippocampal formation appears to play a role in both the encoding and the retrieval of episodic information, but the exact conditions which determine hippocampal activation and its fine-grained functional neuroanatomy have yet to be fully elucidated. Other structures are activated during episodic memory tasks, with asymmetric activation that fits the HERA model, such as preferentially left-sided activation of the association temporal and posterior cingulate areas in encoding tasks and preferentially right-sided activation of the association parietal cortex, cerebellum, and posterior cingulate in retrieval tasks. However, this hemispheric asymmetry appears to depend to some extent on the material used. These new data enhance our capacity to comprehend episodic memory deficits in neuropsychology, as well as the neural mechanisms underlying the age-related changes in episodic memory performances.     

Organization of the visual reticular thalamic nucleus of the rat

The visual sector of the reticular thalamic nucleus has come under some intense scrutiny over recent years, principally because of the key role that the nucleus plays in the processing of visual information. Despite this scrutiny, we know very little of how the connections between the reticular nucleus and the different areas of visual cortex and the different visual dorsal thalamic nuclei are organized. This study examines the patterns of reticular connections with the visual cortex and the dorsal thalamus in the rat, a species where the visual pathways have been well documented. Biotinylated dextran, an anterograde and retrograde tracer, was injected into different visual cortical areas [17; rostral 18a: presumed area AL: (anterolateral); caudal 18a: presumed area LM (lateromedial); rostral 18b: presumed area AM (anteromedial); caudal 18b: presumed area PM (posteromedial)] and into different visual dorsal thalamic nuclei (posterior thalamic, lateral geniculate nuclei), and the patterns of anterograde and retrograde labelling in the reticular nucleus were examined. From the cortical injections, we find that the visual sector of the reticular nucleus is divided into subsectors that each receive an input from a distinct visual cortical area, with little or no overlap. Further, the resulting pattern of cortical terminations in the reticular nucleus reflects largely the patterns of termination in the dorsal thalamus. That is, each cortical area projects to a largely distinct subsector of the reticular nucleus, as it does to a largely distinct dorsal thalamic nucleus. As with each of the visual cortical areas, each of the visual dorsal thalamic (lateral geniculate, lateral posterior, posterior thalamic) nuclei relate to a separate territory of the reticular nucleus, with little or no overlap. Each of these dorsal thalamic territories within the reticular nucleus receives inputs from one or more of the visual cortical areas. For instance, the region to the reticular nucleus that is labelled after an injection into the lateral geniculate nucleus encompasses the reticular regions which receive afferents from cortical areas 17, rostral 18b and caudal 18b. These results suggest that individual cortical areas may influence the activity of different dorsal thalamic nuclei through their reticular connections.     

Functional mapping of human memory using PET: Comparisons of conceptual and perceptual tasks.

Tested whether different neurological regions subserved the conceptual and perceptual memory components by using positron emission tomography (PET). Regional cerebral blood flow (RCBF) of 14 Ss (mean age 25 yrs) during 2 conceptual tasks of semantic cued recall and semantic association was compared to a control condition in which Ss made semantic associations to nonstudied words. RCBF during 2 perceptual tasks of word fragment cued recall and word fragment completion was also compared to a word fragment nonstudied control condition. There were clear dissociations in RCBF that reflected differences in brain regions subserving the 2 types of memory processes. Conceptual processing produced more activation in the left frontal and temporal cortex and the lateral aspect of the bilateral inferior parietal lobule. Perceptual memory processing activated the right frontal and temporal cortex and the bilateral posterior areas. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-Term Memory Deficits in Schizophrenia: Primary or Secondary Dysfunction?

Long-term memory impairment is often found in schizophrenia. The question remains whether this is caused by other cognitive deficits. One hundred eighteen first-episode patients were compared with 45 control participants on several memory tasks. The role of processing speed and central executive functions on memory performance was examined with regression analysis for all participants and for patients separately. Deficits were found in general verbal learning performance and retrieval in episodic memory and semantic memory. Processing speed reduced disease-related variance in all memory variables. Coordination, organization of information, and speed of processing were the best predictors for long-term memory deficits in patients. The amount of explained variance, however, is small, especially in general verbal learning performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance.

Excitotoxic lesions of the medial frontal cortex and anterior cingulate cortex in rats have been shown to produce dissociable impairments on a reaction time visual attention (5-choice) task. Because these cortical areas project to the medial striatal region, the authors predicted similar deficits after lesions of this striatal area compared with the lateral area. Compared with sham-operated controls, rats with quinolinic acid-induced medial striatal lesions showed all the behavioral changes associated with medial frontal cortex and anterior cingulate cortex lesions. In contrast, lateral striatal lesions produced profound disturbances in the performance of the task. Control tests showed little evidence of gross deficits in either group of rats in terms of motivation, locomotor function, or Pavlovian appetitive conditioning. These data suggest that the medial and lateral striatum have contrasting roles in the control of instrumental responding related to the primary sources of their cortical innervation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functionally dissociating aspects of event memory: the effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat

Reciprocal interactions between the hippocampus and the perirhinal and parahippocampal cortices form core components of a proposed temporal lobe memory system. For this reason, the involvement of the hippocampus in event memory is thought to depend on its connections with these cortical areas. Contrary to these predictions, we found that NMDA-induced lesions of the putative rat homologs of these cortical areas (perirhinal plus postrhinal cortices) did not impair performance on two allocentric spatial tasks highly sensitive to hippocampal dysfunction. Remarkably, for one of the tasks there was evidence of a facilitation of performance. The same cortical lesions did, however, disrupt spontaneous object recognition and object discrimination reversal learning but spared initial acquisition of the discrimination. This pattern of results reveals important dissociations between different aspects of memory within the temporal lobe. Furthermore, it shows that the perirhinal-postrhinal cortex is not a necessary route for spatial information reaching the hippocampus and that object familiarity-novelty detection depends on different neural substrates than do other aspects of event memory.     

Prefrontal cortex and rule abstraction: Where and whether? Theoretical comment on Moore et al. (2009).

The primate dorsolateral prefrontal cortex is implicated in diverse aspects of behavioral regulation, cognitive control, and memory. However, direct neuropsychological evidence supporting a requirement of this area in functions other than spatial working memory has been scarce. T. L. Moore, S. P. Schettler, R. J. Killiany, D. L. Rosene, and M. B. Moss (see record 2009-04037-001) have shown, for the first time, that lesions of dorsolateral prefrontal cortex in the rhesus monkey (including areas 9 and 46) substantially impair performance in a test of executive function modeled on the Wisconsin Card Sorting Task. The pattern of impairment is consistent with a role for dorsolateral prefrontal areas in rule abstraction but may relate to a role for this area in rule maintenance as well. Interestingly, monkeys with dorsolateral prefrontal lesions do not appear to perseverate in their use of particular rules in the task, different from the common impairment associated with frontal lobe damage in humans. These findings indicate that dorsolateral prefrontal cortex is necessary for some aspects of rule-guided behavior in the primate brain and help illuminate the involvement of different prefrontal areas in different aspects of executive function and rule-guided behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional anatomy of musical processing in listeners with absolute pitch and relative pitch

We used both structural and functional brain imaging techniques to investigate the neural basis of absolute pitch (AP), a specialized skill present in some musicians. By using positron emission tomography, we measured cerebral blood flow during the presentation of musical tones to AP possessors and to control musicians without AP. Listening to musical tones resulted in similar patterns of increased cerebral blood flow in auditory cortical areas in both groups, as expected. The AP group also demonstrated activation of the left posterior dorsolateral frontal cortex, an area thought to be related to learning conditional associations. However, a similar pattern of left dorsolateral frontal activity was also observed in non-AP subjects when they made relative pitch judgments of intervals, such as minor or major. Conversely, activity within the right inferior frontal cortex was observed in control but not in AP subjects during the interval-judgment task, suggesting that AP possessors need not access working memory mechanisms in this task. MRI measures of cortical volume indicated a larger left planum temporale in the AP group, which correlated with performance on an pitch-naming task. Our findings suggest that AP may not be associated with a unique pattern of cerebral activity but rather may depend on the recruitment of a specialized network involved in the retrieval and manipulation of verbal-tonal associations.     

Neural correlates of semantic and episodic memory retrieval

To investigate the functional neuroanatomy associated with retrieving semantic and episodic memories, we measured changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) while subjects generated single word responses to achromatic line drawings of objects. During separate scans, subjects either named each object, retrieved a commonly associated color of each object (semantic condition), or recalled a previously studied uncommon color of each object (episodic condition). Subjects were also scanned while staring at visual noise patterns to provide a low level perceptual baseline. Relative to the low level baseline, all three conditions revealed bilateral activations of posterior regions of the temporal lobes, cerebellum, and left lateralized activations in frontal regions. Retrieving semantic information, as compared to object naming, activated left inferior temporal, left superior parietal, and left frontal cortices. In addition, small regions of right frontal cortex were activated. Retrieving episodic information, as compared to object naming, activated bilateral medial parietal cortex, bilateral retrosplenial cortex, right frontal cortex, thalamus, and cerebellum. Direct comparison of the semantic and episodic conditions revealed bilateral activation in temporal and frontal lobes in the semantic task (left greater than right), and activation in medial parietal cortex, retrosplenial cortex, thalamus, and cerebellum (but not right frontal regions) in the episodic task. These results support the assertion that distinct neural structures mediate semantic and episodic memory retrieval. However, they also raise questions regarding the specific roles of left temporal and right frontal cortices during episodic memory retrieval, in particular.     

Neuropsychological correlates of short-term memory distractor tasks among patients with surgical repair of anterior communicating artery aneurysms.

The relative utility of the visual consonant trigram (VCT) and release from proactive inhibition (PI) versions of the short-term memory (STM) distractor task in investigating the separate but related cognitive realms of memory and executive frontal lobe functioning were explored in patients with anterior communicating artery (ACoA) aneurysms n?=?24. Compared with normal controls n?=?19, ACoA patients were impaired on clinical measures of memory and on measures of executive functioning, including concept formation and fluent word generation. Furthermore, ACoA patients were impaired on the VCT task but not on the release-from PI task, indicating a differential sensitivity of these tasks to the impairment manifested by ACoA patients. Regression modeling indicated that the VCT and release-from-PI tasks were closely associated with clinical memory tests, although the release-from-PI-task was also associated with fluency, an executive functioning domain. In general, our results fail to support the broad generalization that impaired performance on STM distractor tasks is necessarily symptomatic of frontal lobe dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)