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The neural system that bridges reward and cognition in humans: an fMRI study.

We test the hypothesis that motivational and cognitive processes are linked by a specific neural system to reach maximal efficiency. We studied six normal subjects performing a working memory paradigm (n-back tasks) associated with different levels of monetary reward during an fMRI session. The study showed specific brain activation in relation with changes in both the cognitive loading and the reward associated with task performance. First, the working memory tasks activated a network including the dorsolateral prefrontal cortex [Brodmann area (BA) 9/46] and, in addition, in the lateral frontopolar areas (BA 10), but only in the more demanding condition (3-back task). This result suggests that lateral prefrontal areas are organized in a caudo-rostral continuum in relation with the increase in executive requirement. Second, reward induces an increased activation in the areas already activated by working memory processing and in a supplementary region, the medial frontal pole (BA 10), regardless of the level of cognitive processing. It is postulated that the latter region plays a specific role in monitoring the reward value of ongoing cognitive processes. Third, we detected areas where the signal decreases (ventral-BA 11/47 and subgenual prefrontal cortices) in relation with both the increase of cognitive demand and the reward. The deactivation may represent an emotional gating aimed at inhibiting adverse emotional signals to maximize the level of performance. Taken together, these results suggest a balance between increasing activity in cortical cognitive areas and decreasing activity in the limbic and paralimbic structures during ongoing higher cognitive processing.

Adolescent↗

Subnucleus-specific loss of neurons in medial thalamus of schizophrenics.

The hypoactivity of dorsolateral prefrontal cortex in schizophrenics is well known. One cause of this hypoactivity may be defective corticocortical or thalamocortical connections. Recent imaging studies of the thalamus suggest reductions in volume of the whole thalamus and reduced activity in the medial group of thalamic nuclei, which may indicate loss of functional input to the cortex. Using stereological techniques in six pairs of individually matched brains from schizophrenics and controls, we measured the volumes and obtained estimates of the number of neurons in the three subnuclei (parvocellular, pc; densocellular, dc; magnocellular, mc) of the mediodorsal nucleus (MD) and from the ventral posterior medial nucleus. There was a significant reduction in total neuron number in MD as a whole but this neuron loss was largely restricted to MDpc and MDdc [-30.9 and -24.5%, respectively (P </= 0.01)]. MDmc and the control ventral posterior medial nucleus showed no significant changes in cell number. Because the subnuclei of MD have different connections and project to different areas of the frontal cortex, the specific loss of neurons in MDpc and MDdc has implications for the functional defects observed in schizophrenia.

Adult↗

Neural basis of protracted developmental changes in visuo-spatial working memory.

Developmental studies have shown that visuo-spatial working memory (VSWM) performance improves throughout childhood and adolescence into young adulthood. The neural basis of this protracted development is poorly understood. In this study, we used functional MRI (fMRI) to examine VSWM function in children, adolescents, and young adults, ages 7-22. Subjects performed a 2-back VSWM experiment that required dynamic storage and manipulation of spatial information. Accuracy and response latency on the VSWM task improved gradually, extending into young adulthood. Age-related increases in brain activation were observed in focal regions of the left and right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex (including Broca's area), left premotor cortex, and left and right posterior parietal cortex. Multiple regression analysis was used to examine the relative contributions of age, accuracy, and response latency on activation. Our analysis showed that age was the most significant predictor of activation in these brain regions. These findings provide strong evidence for a process of protracted functional maturation of bilateral fronto-parietal neural networks involved in VSWM development. At least two neural systems involved in VSWM mature together: (i) a right hemisphere visuo-spatial attentional system, and (ii) a left hemisphere phonological storage and rehearsal system. These observations suggest that visually and verbally mediated mnemonic processes, and their neural representations, develop concurrently during childhood and adolescence and into young adulthood.

Adolescent↗

Neuroanatomical correlates of retrieval in episodic memory: auditory sentence recognition.

This study used positron emission tomography (PET) to investigate the neuroanatomical correlates of remembering previously experienced events. Twelve young healthy adults listened to "old" meaningful sentences which they had studied 24 hr previously. As a control task the subjects listened to comparable "new" sentences that they had never heard before. Regional cerebral blood flow associated with each task was measured by PET scans using 15O-labeled water. Comparison (old-sentence task minus new-sentence task) of the PET images revealed an extended strip of increased blood flow in the right dorsolateral prefrontal cortex (Brodmann's areas 10, 46, and 9) and the anterior portion of area 6. Other principal regions of increased blood flow were situated around the left anterior cingulate sulcus and bilaterally in the parietal lobes (areas 7 and 40). Major decreases in blood flow were situated bilaterally in the temporal lobes (areas 21, 22, 41, and 42). A high proportion of activity changes seemed to be located in the depths of cortical sulci. Increases in blood flow are seen as reflecting the operations of a widely distributed neuronal network involving prefrontal and parietal cortical regions that subserves the conscious recollection of previously experienced events. Decreases in blood flow in the temporal auditory areas are interpreted as reflecting auditory priming. The prevalence of sulcal blood-flow changes may reflect extensive cortical gyrification; it may also indicate that memory-related processes rely on the densely packed neuropil of sulcal regions.

Adult↗

Activation of memory circuits during cue-elicited cocaine craving.

Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic regions implicated in several forms of memory when human volunteers who abuse cocaine are exposed to drug-related stimuli. Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial temporal lobe (amygdala), and cerebellum with self-reports of craving suggest that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving.

Adult↗

A neuronal model of a global workspace in effortful cognitive tasks.

A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.

Brain↗

Components of verbal working memory: evidence from neuroimaging.

We review research on the neural bases of verbal working memory, focusing on human neuroimaging studies. We first consider experiments that indicate that verbal working memory is composed of multiple components. One component involves the subvocal rehearsal of phonological information and is neurally implemented by left-hemisphere speech areas, including Broca's area, the premotor area, and the supplementary motor area. Other components of verbal working memory may be devoted to pure storage and to executive processing of the contents of memory. These studies rest on a subtraction logic, in which two tasks are imaged, differing only in that one task presumably has an extra process, and the difference image is taken to reflect that process. We then review studies that show that the previous results can be obtained with experimental methods other than subtraction. We focus on the method of parametric variation, in which a parameter that presumably reflects a single process is varied. In the last section, we consider the distinction between working memory tasks that require only storage of information vs. those that require that the stored items be processed in some way. These experiments provide some support for the hypothesis that, when a task requires processing the contents of working memory, the dorsolateral prefrontal cortex is disproportionately activated.

Brain↗

An empirical test of Woody and Bowers's dissociated-control theory of hypnosis.

Woody and Bowers's dissociated-control theory predicts impaired performance on tasks indexing frontally mediated supervisory attentional functions during hypnosis, especially for high susceptibles. This prediction is tested using Stroop task behavioral performance to measure aspects of anterior-mediated supervisory attentional function. All measures of anterior-mediated attentional functions significantly declined during hypnosis. Interactions be-tween susceptibility and hypnosis condition showed specific changes among hypnotized high susceptibles. Total Stroop errors (failures of attentional suppression) were significantly higher in hypnosis for high, but not low, susceptibles. Tellegen's experiential mental set was highest for hypnotized highs. Use of rehearsal strategy (instrumental set) decreased significantly in hypnosis but more so for highs than lows. Results suggest that "absorption" in hypnosis may be a consequence of dissociated anterior attentional control. It is proposed that dissociated control emerges from the functional disconnection of left dorsolateral prefrontal cortex and anterior cingulate cortex.

Adolescent↗

Magnetic resonance imaging studies in early-onset bipolar disorder: a critical review.

BACKGROUND: Neuroimaging studies of early-onset bipolar disorder (BD) are important in order to establish a fuller understanding of the underlying pathophysiology of the illness. The advantages of studying BD in children and adolescents include the relative absence of some confounds present in adult-onset research, such as lengthy duration of illness and exposure to treatments, greater number of mood episodes, and the presence of substance abuse or dependence. Finally, studying youths with the disorder may enhance our knowledge about the neural mechanisms of affective dysregulation and may specifically elucidate whether there are abnormalities that are unique to the early-onset form of the illness. METHODS: PubMed was used to identify peer-reviewed publications from the past 15 years (January 1990 to January 2005) that used brain-imaging techniques (anatomic, functional, and biochemical) to research early-onset BD. RESULTS: Eleven studies using anatomic magnetic resonance imaging (MRI), seven using magnetic resonance spectroscopy (MRS), and two using functional MRI (fMRI) were identified. Structural abnormalities were reported in total cerebral, white matter, superior temporal gyrus, putamen, thalamus, amygdala, and hippocampal volumes. Deficits in cortical gray matter were also reported. Using MRS, abnormalities were reported in the dorsolateral prefrontal cortex, anterior cingulate, and basal ganglia. One fMRI study found increased activation in the putamen and thalamus of BD youths compared to controls, and a second found abnormal prefrontal-subcortical activation in familial pediatric BD. CONCLUSION: Published MRI studies of early-onset BD are few. Nonetheless, extant data implicate abnormalities in brain regions thought to regulate mood and cognition. Synthesis of the findings into an overall model of anatomic and functional disruption is difficult due to the methodological variations among studies and the limitations of individual studies, such as the use of small sample sizes, the heterogeneity of sample characteristics, and the wide range of brain structures selected for analysis. Recommendations are offered to guide future research. It will be important for future studies to reproduce prior findings and determine which findings are unique to early-onset BD, relative to adult-onset illness. In addition, studies will need to establish the extent to which early-onset BD may overlap with comorbid disruptive, mood, anxiety, or psychotic disorders.

Age of Onset↗

Organic and psychogenic factors leading to executive dysfunctions in a patient suffering from surgery of a colloid cyst of the Foramen of Monro.

The authors report a 41-year-old female patient who had suffered from colloid cyst of the Foramen of Monro. After surgical intervention in which the cyst was completely removed, her hydrocephalus decreased to normal ventricle size measured by MRI. However, the patient became depressive and reported vast difficulties in everyday life decision-making. An examination twenty months after surgery indicated psychiatric symptoms and abnormalities in personality. Neuropsychological investigation revealed average to above average performance in anterograde memory, attention, information processing, and intelligence. In contrast, the patient was severely impaired in decision-making, complex executive functions, and social cognition. In 18F-2-fluoro-2-deoxy-D-glucose (18FDG-PET) hypometabolism in bilateral dorsolateral prefrontal cortex, cingulate cortex and left fusiform gyrus was observed. The authors conclude that in this case decision-making deficits and executive dysfunctions are influenced by both organic and psychogenic factors.

Adult↗

Disorganised memory after right dorsolateral prefrontal damage.

Neurophysiological and functional brain imaging studies suggest the importance of dorsolateral area 9/46 for modality-independent working memory. However, the behavioural manifestations following isolated damage to this area have not been clearly outlined. Here, we describe the dramatic derangement of pragmatic memory after circumscribed lesion of the right area 9/46. A 52 year-old woman had suffered a traumatic brain injury 13 years ago and sought help for what she thought was a severe memory disorder. She regularly missed appointments and had gradually lost all her friends. She had tried different strategies to compensate for her memory problem, such as writing notes on her wrist or using electronic organizers. Intelligence, attention, verbal long-term memory, and executive functions were normal. Furthermore, experimental exploration demonstrated intact time estimation, attribution of memories to ongoing reality, and anticipation of outcomes. However, she failed to rehearse and manipulate information in working memory (n-back task), confirming the findings of functional imaging studies that the mid-dorsolateral prefrontal cortex is involved in mental manipulation of information. This case exemplifies that an isolated lesion of the right area 9/46 may induce severe failure to schedule actions and memory retrieval, a disorder leading to severely disorganised behaviour and disability.

Brain Injuries↗

An examination of executive dysfunction associated with frontostriatal circuitry in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson's disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function.

Aged↗

Transcranial magnetic stimulation as a therapeutic tool in psychiatry.

Transcranial magnetic stimulation (TMS) is a patient-friendly stimulation technique of the brain with interesting perspectives. In clinical psychiatry, limited data are available on activity in psychosis and anxiety, but much research has been done in depression. Major concerns on published papers are the inconsistency of used parameter settings, the restraint numbers of patients in randomised trials, the lack of real sham controlled studies and the quasi inexistent reproducibility of results. The most stringent meta-analysis of TMS in affective disorders found a modest, statistically significant antidepressant effect after 2 weeks of daily treatment of high frequency repetitive left dorsolateral prefrontal cortex stimulation. Although most results are rather weak and not convincing enough to promote TMS as evidence-based antidepressive therapy, they show a measurable action that should not be ignored. Preclinical and clinical effects were observed analysing heterogeneous data, and results comparing TMS to electroconvulsive therapy (ECT) in affective disorders are encouraging. Efforts should continue with emphasis on increasing homogeneity and reproducibility in data. Further refinement of stimulation parameters should be established, so that new and large double-blind, long-term, sham-controlled trials can bring us to better understanding and standardising TMS procedure, finally leading to definitive conclusions about its efficacy in psychiatry.

Anxiety Disorders↗

Brain activation during craving for alcohol measured by positron emission tomography.

OBJECTIVE: Craving for alcohol is probably involved in acquisition and maintenance of alcohol dependence to a substantial degree. However, the brain substrates and mechanisms that underlie alcohol craving await more detailed elucidation. METHOD: Positron emission tomography was used to map regional cerebral blood flow (CBF) in 21 detoxified patients with alcohol dependence during exposure to alcoholic and non-alcoholic beverages. RESULTS: During the alcohol condition compared with the control condition, significantly increased CBF was found in the ventral putamen. Additionally, activated areas included insula, dorsolateral prefrontal cortex and cerebellum. Cerebral blood flow increase in these regions was related to self-reports of craving assessed in the alcoholic patients. CONCLUSIONS: In this investigation, cue-induced alcohol craving was associated with activation of brain regions particularly involved in brain reward mechanisms, memory and attentional processes. These results are consistent with studies on craving for other addictive substances and may offer strategies for more elaborate studies on the neurobiology of addiction.

Adult↗

Sex differences in the human brain's response to hunger and satiation.

BACKGROUND: Sex differences in eating behavior are well documented, but it is not known whether these differences have neuroanatomical correlates. Recent neuroimaging studies have provided functional maps of the human cerebral areas activated in response to hunger and satiation. OBJECTIVE: The objective of this study was to assess whether the brain's response to a meal is sex-specific. DESIGN: Using positron emission tomography, we measured regional cerebral blood flow, a marker of neuronal activity, to investigate the functional neuroanatomy of hunger (36-h fast) and satiation (in response to a liquid meal) in 22 women and 22 men. RESULTS: We observed extensive similarities, as well as some differences, between the sexes. In response to hunger, the men tended to have greater activation in the frontotemporal and paralimbic areas than did the women (P < 0.005). In response to satiation, the women tended to have greater activation in the occipital and parietal sensory association areas and in the dorsolateral prefrontal cortex than did the men (P < 0.005); in contrast, the men tended to have greater activation in the ventromedial prefrontal cortex than did the women (P < 0.005). CONCLUSIONS: Despite extensive similarities in the brain responses to hunger and satiation between the men and women, our study showed sex-specific brain responses to a meal that indicate possible differences between men and women in the cognitive and emotional processing of hunger and satiation. This study provides a foundation for investigating the brain regions and cognitive processes that distinguish normal and abnormal eating behavior in men and women.

Adult↗

Noun and verb retrieval by normal subjects. Studies with PET.

PET activation studies identify significant local changes in regional cerebral blood flow (rCBF) in contrasts of behavioural tasks with control states, and these local changes identify net changes in local synaptic activity. A number of studies on word retrieval have all demonstrated left frontal (dorsolateral and medial) involvement in the task. However, there have been differences in the responses observed in the left temporal lobe, with variously a deactivation (significant decrease in rCBF), no response and an activation (significant increase in rCBF). In the four studies described here, we have examined word (verbs and nouns) retrieval contrasted with a number of different control states. The studies confirmed extensive activation of the left dorsolateral prefrontal cortex and, medially, the anterior cingulate cortex and the supplementary motor area (SMA). Activations of the left posterior temporal lobe and the inferior parietal lobe were consistently demonstrated when word retrieval was contrasted with a rest state. Contrasts with other single word tasks controlled out the activation in the perisylvian part of the left posterior temporal lobe, suggesting a role for this region in lexical processing. The left inferolateral temporal cortex and the posterior part of the inferior parietal lobe were only activated by word retrieval, particularly verbs. It is proposed that these activated regions reflect access to semantic fields.

Adult↗

Non-spatial attention disorders in patients with frontal or posterior brain damage.

The few studies that have looked at attention in patients with brain damage suggest a prominent role for the frontal lobe in nonspatial attentional control. However, the studies usually focus on one variety of attention and do not address the nature of the alteration of attention. In addition, the behavioural consequences of nonspatial attentional deficit remain unknown. The aim of this study was to evaluate the role of focal brain damage on divided and focused attention and the relationship between attention disorders and behavioural changes. The study group consisted of patients with lesions of the prefrontal and posterior cortices and control subjects. The assessment of attention used reaction time tests that evaluated the ability to divide attention between two sources (detection tests) and to focus attention on one source (Go/No-Go Tests). The response retardation of the 'frontal' group became more pronounced as the number of sources to be monitored increased, suggesting the presence of a deficit of divided attention. Focused attention deficit was demonstrated in the 'frontal' group by the more frequent responses to irrelevant stimuli on Go/No-Go Tests. Both focused and divided attention deficits were prominent when the lesion included the left dorsolateral prefrontal cortex and the caudate nucleus. Selective deficit of divided or focused attention was shown in a few patients. Finally, the clinically assessed distractibility was related to disorders of divided and focused attention. This study provides additional evidence for the prominent role of the frontal lobe in nonspatial attention regulation and shows that it also operates in elementary perceptuomotor processes. The relationship between distractibility and attention indexes supports the idea that attention disorders may have a functional counterpart that is clinically assessable. The demonstration of selective deficit of divided or focused attention suggests that nonspatial attention depends upon different mechanisms and that it is not an undifferentiated general purpose mechanism. Further studies addressing the nature of the interactions between attentional mechanisms and other cognitive processes are required.

Adult↗

Brain activity during memory retrieval. The influence of imagery and semantic cueing.

The effects of imagery and semantic relatedness on cued retrieval of word pairs were examined in a functional imaging study of healthy volunteers. Subjects underwent 12 PET scans, preceded by the paced presentation of 12 paired associates. The associates were dichotomized into imageable and non-imageable groups. Within each group, the strength of semantic association between members of pairs was varied in an ordinal fashion. Subsequently, neural activity was measured while subjects were cued with the first item of each pair and required to recall the associated word. Recall of imageable words, when compared with non-imageable ones, was associated with activation of the precuneus, consistent with our hypothesis that this region is important in visual imagery at episodic retrieval. The reverse comparison, non-imageable versus imageable recall, was associated with activation of the left dorsolateral prefrontal cortex. Within both imageable and non-imageable groups, decreasing semantic association showed a corresponding increase in frontal activity bilaterally. One possible explanation is that of a practice-related effect, weaker-linked pairs having a greater number of pre-scan presentations. However, this explanation is incomplete as the most semantically distant, and most rehearsed, pairs (randomly linked) were associated with a reversal of this effect. This finding can be explained if frontal activity is associated with the difficulty of eliminating inappropriate responses at retrieval. For both randomly linked pairs and closely related pairs it is more likely that erroneous responses will be generated and, therefore, the work done to eliminate them will be greater. Our findings indicate that patterns of neural activity during cued recall depend upon the nature of the material and on the degree of association between the cue and the response.

Adult↗