Impairments in an early stage of the decision-making process in patients with ventromedial prefrontal damage: preliminary results

Lesions of the ventromedial prefrontal cortex can result in a deficient decision-making behavior. So far, most experimental results in the neuropsychological decision-making research have been obtained with gambling tasks. Due to their high complexity, it is difficult to evaluate the underlying processes of the decision-making deficits. The aim of this study was to assess if patients with ventromedial prefrontal damage compared to patients with dorsolateral prefrontal damage and controls show a deficit in an early stage of the decision-making process. Nine patients with ventromedial prefrontal damage, three with dorsolateral prefrontal damage, and eleven healthy controls were tested with a newly developed decision task in which they had to search actively for the information they needed for their decisions. Our results show that patients with ventromedial prefrontal damage compared to the brain-lesioned dorsolateral prefrontal control group and healthy controls searched less for information with regard to risk defusing operators or consequences of their decisions indicating impairment already in the early stage of the decision-making process.     

Modifications of neuron activities of the dorsolateral prefrontal cortex during extrafoveal attention

In order to determine the involvement of the dorsolateral prefrontal cortex (PF) of monkeys in extrafoveal visual attention, PF neuron activities to the identical visual stimuli presented extrafoveally were compared during a simple visual fixation task and an extrafoveal attention task. Four out of 29 steady type neurons showed a clear change after the extrafoveal stimuli presented during the extrafoveal attention task. Ten out of 75 transient type neurons showed a subtle change during extrafoveal attention. It was concluded that a fraction of the prefrontal neurons of the steady type is involved in an attention mechanism to the extrafoveal vision.     

Reward related neuronal activity in monkey dorsolateral prefrontal cortex during feeding behavior

Extracellular single neuron activity was recorded in the dorsolateral prefrontal cortex (DL) during bar pressing for food reward. Most of the reward-related neurons were located around the rostral end of the principal sulcus. Neuronal activity was diminished, abolished, or reversed when quinine adulterated food (aversive food) was given as a reinforcement. Cue-related neurons tended to be located more caudally in the DL. The activity of these neurons was not modulated by the nature of the reward as much as that of the reward-related neurons. The results suggest that DL neurons are not functionally homogeneous.     

Architecture and morphology of the human ventromedial prefrontal cortex

A previous report identified the location of comparable architectonic areas in the ventral frontal cortex of the human and macaque brains [S. Mackey & M. Petrides (2010) Eur. J. Neurosci., 32 , 1940–1950]. The present article provides greater detail with regard to the definition of architectonic areas within the ventromedial part of the human ventral frontal cortex and describes their location: (i) in Montreal Neurological Institute proportional stereotactic space; and (ii) in relation to sulcal landmarks. Structural magnetic resonance scans of four brains were obtained before the preparation of the histological specimens, so that the architectonic parcellation could be reconstructed in its original three‐dimensional volume. The areal density of individual cortical layers was sampled quantitatively in the ventromedial prefrontal cortex of eight brains (16 hemispheres). The agranular cortex along the ventral edge of the corpus callosum and posterior margin of the ventromedial surface is replaced by a graded series of increasingly granular and more complexly laminated areas that succeed one another in a posterior‐to‐anterior direction. In parallel, the width of the supragranular layers (i.e. layers II and III) increases as compared with the infragranular layers (i.e. layers V and VI) from posterior to anterior. A measure of how rapidly cortical features change at areal boundaries also showed that the rate of change in the granule and pyramidal cell densities of layers IV and V, respectively, was greater at the borders between posterior areas than between anterior areas. This article will facilitate the anatomical identification and comparison of experimental data involving the human vmPFC.     

Cerebral blood flow in the ventromedial prefrontal cortex correlates with treatment response to low-frequency right prefrontal repetitive transcranial magnetic stimulation in the treatment of depression

Aims: Low‐frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, and its antidepressant effects have proven to correlate with decreases in cerebral blood flow (CBF) in the orbitofrontal cortex and subgenual cingulate cortex. However, a predictor of treatment response to low‐frequency right prefrontal rTMS in depression has not been identified yet. The aim of this study was to estimate regional CBF in the frontal regions and investigate the correlation with treatment response to low‐frequency right prefrontal rTMS in depression. Methods: We examined 26 depressed patients for the correlation between treatment response to rTMS and regional CBF in the frontal regions, by analyzing their brain scans with ^99mTc‐ethyl cysteinate dimer before rTMS treatment. CBF in 16 brain regions was estimated using fully automated region of interest analysis software. Two principal components were extracted from CBF in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. Results: Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions) and ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was not correlated with CBF in the dorsolateral prefrontal cortex, but it was correlated with CBF in the ventromedial prefrontal cortex. Conclusion: These findings suggest that CBF in the ventromedial prefrontal cortex may be a potential predictor of low‐frequency right prefrontal rTMS, and depressed patients with increased CBF in the ventromedial prefrontal cortex may show a better response.     

Ventrolateral prefrontal cortex is required for performance of a strategy implementation task but not reinforcer devaluation effects in rhesus monkeys

The ability to apply behavioral strategies to obtain rewards efficiently and make choices based on changes in the value of rewards is fundamental to the adaptive control of behavior. The extent to which different regions of the prefrontal cortex are required for specific kinds of decisions is not well understood. We tested rhesus monkeys with bilateral ablations of the ventrolateral prefrontal cortex on tasks that required the use of behavioral strategies to optimize the rate with which rewards were accumulated, or to modify choice behavior in response to changes in the value of particular rewards. Monkeys with ventrolateral prefrontal lesions were impaired in performing the strategy-based task, but not on value-based decision-making. In contrast, orbital prefrontal ablations produced the opposite impairments in the same tasks. These findings support the conclusion that independent neural systems within the prefrontal cortex are necessary for control of choice behavior based on strategies or on stimulus value.     

Properties and distribution of auditory neurons in the dorsolateral prefrontal cortex of the alert monkey

In alert monkeys, some prefrontal neurons located in the superior dorsolateral area were activated to acoustic stimuli delivered in a restricted range of directions with respect to the animal's head. The effective direction was usually contralateral to the animal. The function of the auditory neurons in connection to that of the visual ones, which are commonly found in the prefrontal cortex, is discussed.     

Time discrimination with positional responses after selective prefrontal lesions in monkeys

Monkeys with ablations of the cortex in the principal sulcus who were impaired on a spatial delayed reaction test were unimpaired on a time discrimination test in which length of time since the last trial signalled the spatial position of the correct foodwell. The finding undermines the view that the classical delayed reaction deficit after lateral prefrontal lesions reflects the loss of temporal structuring of the stream of sensory input. The result is consistent instead with the alternative view that the classical deficit reflects a spatial memory disorder. Monkeys with inferior prefrontal ablations were impaired on both spatial tasks, and on object discrimination reversal as well; analysis of their deficits indicated that they were instances of perseverative interference. Finally, monkeys with ablations of the cortex in the arcuate sulcus were not consistently impaired on any of the tasks. There is no evidence from these results that prefrontal cortex plays any role in time perception.     

Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task

An important function of the prefrontal cortex (PFC) is the control of goal-directed behaviour. This requires information as to whether actions were successful in obtaining desired outcomes such as rewards. While lesion studies implicate a particular PFC region, the orbitofrontal cortex (OFC), in reward processing, neurons encoding reward have been reported in both the OFC and the dorsolateral prefrontal cortex (DLPFC). To compare and contrast their roles, we recorded simultaneously from both areas while two rhesus monkeys (Macaca mulatta) performed a reward preference task. The monkeys had to choose between pictures associated with different amounts of a juice reward. Neuronal activity in both areas reflected the reward amount. However, neurons in the DLPFC encoded both the reward amount and the monkeys' forthcoming response, while neurons in the OFC more often encoded the reward amount alone. Further, reward selectivity arose more rapidly in the OFC than the DLPFC. These results are consistent with reward information entering the PFC via the OFC, where it is passed to the DLPFC and used to control behaviour.     

Rhinal and dorsolateral prefrontal cortex lesions produce selective impairments in object and spatial learning and memory in canines

To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed nonmatching to sample, or DNMS) and a spatial (delayed nonmatching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-second delay, suggesting disrupted retention of the general task rules; however, this impairment was transient, and long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a nonmatching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals.     

Activity in ventromedial prefrontal cortex co-varies with revealed social preferences: evidence for person-invariant value

Although altruistic and selfish behaviors seem fundamentally incommensurable humans regularly choose between them. One model of such choices suggests that individuals ascribe a common form of subjective value to their own outcomes and those of others. To test this ‘person invariance’ hypothesis, we asked individuals to choose between allocating varying amounts of money to themselves or to a partner. Participants’ choice patterns provided an estimate of the relative value they placed on their own and others’ gains. These estimates were used to isolate neural activity correlating with the subjective value of gains irrespective of the recipient (self or other) during a separate set of trials in which rewards were offered only to the self or partner. Activity in ventromedial prefrontal cortex scaled with this person-invariant value parameter, consistent with earlier demonstrations that this region supports common value computation. These data suggest that individuals reduce the value associated with their own and others’ experiences to a common subjective scale, which is used to guide social decision-making.     

The cerebellum and cognition: cerebellar lesions do not impair spatial working memory or visual associative learning in monkeys

Anatomical studies in non-human primates have shown that the cerebellum has prominent connections with the dorsal, but not the ventral, visual pathways of the cerebral cortex. Recently, it has been shown that the dorsolateral prefrontal cortex (DPFC) and cerebellum are interconnected in monkeys. This has been cited in support of the view that the cerebellum may be involved in cognitive functions, e.g. working memory. Six monkeys (Macaca fascicularis) were therefore trained on a classic test of working memory, the spatial delayed alternation (SDA) task, and also on a visual concurrent discrimination (VCD) task. Excitotoxic lesions were made in the lateral cerebellar nuclei, bilaterally, in three of the animals. When retested after surgery the lesioned animals were as quick to relearn both tasks as the remaining unoperated animals. However, when the response times (RT) for each task were directly compared, on the SDA task the monkeys with cerebellar lesions were relatively slow to decide where to respond. We argue that on the SDA task animals can prepare their responses between trials whereas this is not possible on the VCD task, and that the cerebellar lesions may disrupt this response preparation. We subsequently made bilateral lesions in the DPFC of the control animals and retested them on the SDA task. These monkeys failed to relearn the task. The results show that, unlike the dorsal prefrontal cortex, the cerebellum is not essential for working memory or the executive processes that are necessary for correct performance, though it may contribute to the preparation of responses.     

Selective deficit in personal moral judgment following damage to ventromedial prefrontal cortex

Recent fMRI evidence has detected increased medial prefrontalactivation during contemplation of personal moral dilemmas comparedto impersonal ones, which suggests that this cortical regionplays a role in personal moral judgment. However, functionalimaging results cannot definitively establish that a brain areais necessary for a particular cognitive process. This requiresevidence from lesion techniques, such as studies of human patientswith focal brain damage. Here, we tested 7 patients with lesionsin the ventromedial prefrontal cortex and 12 healthy individualsin personal moral dilemmas, impersonal moral dilemmas and non-moraldilemmas. Compared to normal controls, patients were more willingto judge personal moral violations as acceptable behaviors inpersonal moral dilemmas, and they did so more quickly. In contrast,their performance in impersonal and non-moral dilemmas was comparableto that of controls. These results indicate that the ventromedialprefrontal cortex is necessary to oppose personal moral violations,possibly by mediating anticipatory, self-focused, emotionalreactions that may exert strong influence on moral choice andbehavior.     

抑郁症对海马及背外侧前额叶皮质神经元变与1HMRS表现及明尼苏达多项个性测量的相关性

Background and Purpose The present study was undertaken to elucidate neuro-structural and neuro-chemical characteristics of hippocampi and dorsolateral prefrontal cortex in patients with depressive disorder by using 1H-MRS and to study the association between 1H-MRS and Minnesota Mutiphasic Personality Inventory-2 in relation to the severity of the depression.. Methods Magnetic resonance imaging and 1H-MRS were performed on 33 patients with depressive disorder and age-18 and gender-matched healthy controls. Minnesota Mutiphasic Personality Inventory-2 test was performed on all depressive subjects and control subjects. Results Magnetic resonance imaging and 1H-MRS examinations showed widened sulcus and cisterns as well as the absence of abnormal signal in depressive patients. In addition, the N-acetyl aspartate/total creatine ratios in the bilateral hippocampi and dorsolateral prefrontal cortex were significantly lower in depressive patients than in the control subjects (P<0.01). In contrast, the choline-containing compounds/total creatine ratios in dorsolateral prefrontal cortex were remarkably higher in depressive patients than in the control subjects (Left: P<0.01, Right: P<0.01), the ratios of which were also significantly positively correlated with the depression scores of the patients assessed by Minnesota Mutiphasic Personality Inventory-2 scale (Right: r = 0.8787, Left: r = 0.9347). Conclusions 1H-MRS can be used to reveal reduced neuronal viability or function in the hippocampus and dorsolateral prefrontal cortex and altered membrane phospholipid metabolism in the dorsolateral prefrontal cortex in patients with depressive disorder. The 1H-MRS findings partially reflect the severity of the depressive disorder.     

Depletion of MAP2 expression and laminar cytoarchitectonic changes in dorsolateral prefrontal cortex in adult autistic individuals

The neuropathological substrates underlying the characteristic clinical phenotype of autism are unknown. Neuroimaging studies have identified a decrease in task-related activation in the dorsolateral prefrontal cortex in autism. In the current study, we have analysed the dorsolateral prefrontal cortex in two adult individuals with a clinical diagnosis of autism, using Nissl staining and MAP2 immunohistochemistry. There was unchanged density of both neuronal and glial cell pools, although the autistic individuals had ill-defined neocortical cellular layers, substantially depleted MAP2 neuronal expression, and reduced dendrite numbers. Further studies on a larger number of individuals with autism are needed to establish the clinical relevance of the described changes, especially to determine whether the loss of dendritic markers is age associated or disease specific.     

Activation in dorsolateral prefrontal cortex in response to maternal criticism and praise in recovered depressed and healthy control participants.

BACKGROUND: High family levels of expressed emotion reliably predict relapse in patients with schizophrenia and mood disorders; however, the neural mechanisms linking expressed emotion and relapse are unexplored. Dysfunctional activity in the dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of depression. Functional magnetic resonance imaging (fMRI) was used to assess focal activation changes in DLPFC in response to a novel psychosocial challenge stimulus developed from the expressed emotion construct. METHODS: Healthy control subjects and fully remitted unipolar depressed participants completed blood oxygen level-dependent fMRI while they heard their own mothers making critical and praising comments about them. RESULTS: Relative to control subjects, participants with a history of depression failed to activate DLPFC when they heard critical remarks. There were no differences between the two groups in their DLPFC responses to maternal praise. CONCLUSIONS: Even if fully well at the time of testing, participants with a known vulnerability to depression respond differently to the psychosocial challenge of being criticized. These findings might have implications for our understanding of vulnerability to depression and to depressive relapse.     

Increased hippocampus to ventromedial prefrontal connectivity during the construction of episodic future events

Both the hippocampus and ventromedial prefrontal cortex (vmPFC) appear to be critical for episodic future simulation. Damage to either structure affects one's ability to remember the past and imagine the future, and both structures are commonly activated as part of a wider core network during future simulation. However, the precise role played by each of these structures and, indeed, the direction of information flow between them during episodic simulation, is still not well understood. In this study, we scanned participants using functional magnetic resonance imaging while they imagined future events in response to object cues. We then used dynamic causal modeling to examine effective connectivity between the left anterior hippocampus and vmPFC during the initial mental construction of the events. Our results show that while there is strong bidirectional intrinsic connectivity between these regions (i.e., irrespective of task conditions), only the hippocampus to vmPFC connection increases during the construction of episodic future events, suggesting that the hippocampus initiates event simulation in response to retrieval cues, driving activation in the vmPFC where episodic details may be further integrated.