Correlations among behavioral measures of orbitofrontal function

Orbitofrontal cortex plays an important role in guiding behavior based on emotional input and rewards. It receives multimodal higher order sensory information and mediates reinforcement for primary as well as secondary or conditioned forms of reinforcement (e.g., monetary rewards). Several behavioral measures have demonstrated putative sensitivity to orbitofrontal function: smell identification, delayed alternation, and response inhibition (go/no-go and antisaccades). A correlational study of performances on these tasks by healthy controls demonstrated some interrelationships: go/no-go correlated with antisaccades, left nostril smell correlated with go/no-go, and right nostril smell correlated with delayed alternation. Further analysis showed that certain smells correlated with tasks more strongly than others. Given the diversity of these tasks, it is suggested that these intercorrelations results from at least the partial overlap of the neural substrates for olfactory identification and tasks requiring response modification based on reinforcement contingencies.     

NEUROBEHAVIORAL CORRELATES OF IMPULSIVITY: EVIDENCE OF PREFRONTAL INVOLVEMENT

Impulsivity is associated with the functioning of prefrontal-subcortical circuits particularly, the orbitofrontal circuit, which is shown in neuro-imaging studies of neurological and psychological disorders. Objective behavioral measures, such as go/no-go, antisaccades, and delayed alternation, have demonstrated sensitivity to prefrontal function. This study examined the relationship between orbitofrontal-sensitive measures and impulsivity in healthy adults, as measured by the Barratt Impulsiveness Scale-11 (BIS). Go/no-go and antisaccades correlated positively and delayed alternations correlated negatively with BIS subscales, even after controlling for demographic influences. The results add to the validity of the BIS and support a role for prefrontal cortex in impulse control     

Neurobehavioral correlates of impulsivity: evidence of prefrontal involvement

Impulsivity is associated with the functioning of prefrontal-subcortical circuits particularly, the orbitofrontal circuit, which is shown in neuro-imaging studies of neurological and psychological disorders. Objective behavioral measures, such as go/no-go, antisaccades, and delayed alternation, have demonstrated sensitivity to prefrontal function. This study examined the relationship between orbitofrontal-sensitive measures and impulsivity in healthy adults, as measured by the Barratt Impulsiveness Scale-11 (BIS). Go/no-go and antisaccades correlated positively and delayed alternations correlated negatively with BIS subscales, even after controlling for demographic influences. The results add to the validity of the BIS and support a role for prefrontal cortex in impulse control.     

The nature of the medial wall deficit in the rat

Spatial and temporal (go/no-go) alternation tasks were run in a computerized Y-maze apparatus in an attempt to characterize the behavioral deficit which results from frontopolar and medial cortical lesions in rats. The medial cortex lesions caused a severe behavioral impairment on both tasks. The deficit is characterized as an inability to temporally organize recent events. This interpretation is consistent with theories of primate frontal lobe function based on similar data obtained in non-human primates and man.     

Activation of right inferior frontal gyrus during response inhibition across response modalities

The go/no-go task, which effectively taps the ability to inhibit prepotent response tendency, has consistently activated the lateral prefrontal cortex, particularly the right inferior frontal gyrus (rIFG). On the other hand, rIFG activation has rarely been reported in the antisaccade task, seemingly an oculomotor version of the manual go/no-go task. One possible explanation for the variable IFG activation is the modality difference of the two tasks: The go/no-go task is performed manually, whereas the antisaccade task is performed in the oculomotor modality. Another explanation is that these two tasks have different task structures that require different cognitive processes: The traditional antisaccade task requires (i) configuration of a preparatory set prior to antisaccade execution and (ii) response inhibition at the time of antisaccade execution, whereas the go/no-go task requires heightened response inhibition under a minimal preparatory set. To test these possibilities, the traditional antisaccade task was modified in the present functional magnetic resonance imaging study such that it required heightened response inhibition at the time of antisaccade execution under a minimal preparatory set. Prominent activation related to response inhibition was observed in multiple frontoparietal regions, including the rIFG. Moreover, meta-analyses revealed that the rIFG activation in the present study was observed in the go/no-go tasks but not in the traditional antisaccade task, indicating that the rIFG activation was sensitive to the task structure difference, but not to the response modality difference. These results suggest that the rIFG is part of a network active during response inhibition across different response modalities.     

Effects of lesions of prefrontal cortex and dorsomedial thalamus on delayed go/no-go alternation in rats

The effect of prefrontal cortex (PFC) and/or dorsomedial thalamus (DMT) lesions on a delayed go/no-go alternation task was studied in the rat. The lesion gave rise to the impairment of smooth alternation of one response to another, resulting in the generation of some successive repetitions of either response. However, either type of response was generated in virtually equal frequencies during pre- and post-surgery sessions. These results suggest that the DMT and PFC are involved in the memory and response control process for generating the alternation response, and they do not mediate either one type of response. Furthermore, DMT or DMT/PFC lesions induced a larger behavioral impairment than PFC lesions indicating that the DMT plays a major role in generating the alternation behavior based on the memory for the previous response.     

Uncoupling of contingent negative variation and alpha band event-related desynchronization in a go/no-go task.

OBJECTIVES: To examine how the differences in the sequences of brain activation during the go/no-go delayed response choice reaction time (RT) task are reflected into two concurrent methods of measuring brain electrical activity, the alpha band event-related desynchronization (alpha ERD) and the contingent negative variation (CNV). METHODS: alpha ERD and CNV were calculated using appropriate techniques from the same samples of electroencephalographic activity recorded during performance of a cued choice go/no-go delayed response RT task (i.e. S1 (go/no-go)--S2 paradigm) in 8 healthy subjects. RESULTS: All segments of the CNV traces were different in the go and the no-go conditions. The go CNV traces displayed a typical pattern of slow rising negativity reflecting the build-up of attentional resources necessary for adequate performance of the task. On the other hand, the no-go traces remained close to zero reflecting the 'withdrawal' of further preparation after evaluation of S1. During the same period, both go and no-go ERD traces showed a gradual decrease in alpha band power (desynchronization) that was evident until shortly before the presentation of S2. It was only in the 500 ms before S2 presentation that there was any indication that the go and no-go ERD traces were different, but this did not reach statistical significance. CONCLUSIONS: Our data show that the pattern of the go/no-go difference in alpha ERD traces does not correspond to the pattern that can be seen in the CNV traces. This suggests that there is no direct coupling of CNV and alpha ERD, most probably because they measure different aspects of cortical electrical activity. In addition, the extent of the no-go alpha ERD reveals that refraining from performance of a pre-programmed movement is by no means a passive/inactive process.     

A RELATIONSHIP BETWEEN SMELL IDENTIFICATION AND EMPATHY

Olfaction is a sense that has close relationships with the limbic system and emotion. Empathy is a vicarious feeling of others emotional states. The two functions are known to be subserved by common neuroanatomical structures, including orbitofrontal cortex, mediodorsal thalamus, and the amygdala. This study demonstrates a correlation between smell identification and empathy, using the Mehrabian and Epstein Empathy Questionnaire and Alberta Smell Test. Right nostril smell identification correlated with empathy, whereas the left nostril did not. Given the predominantly ipsilateral representation in the olfactory system, this is in accordance with right hemisphere dominance for emotional functions and empathy. Further, the emotional component of empathy (feeling another s emotions) correlated with smell, whereas a cognitive component (comprehending another s emotions) did not. This study is the first to demonstrate a relationship between empathy and smell in normal subjects, suggesting common neural substrates.     

Impaired action control in schizophrenia: the role of volitional saccade initiation

Schizophrenia patients show prefrontal cortex dysfunctions of neurodevelopmental origin, but the cognitive implications of these dysfunctions are not yet understood. This study used experimental variations of oculomotor tasks to evaluate the relative roles of volitional action initiation and the inhibition of reflexive behavior. Thirty schizophrenia patients and 30 control participants performed standard prosaccades (SP), standard antisaccades (SA), delayed prosaccades (DP), and delayed antisaccades (DA). The delayed tasks allowed separating the inhibition of erroneous prosaccades and the initiation of volitional saccades, which coincide in the SA task. Arrow-cued (AC) saccades were used to evaluate initiation without any inhibitory component. Erroneous prosaccades were less frequent in the delayed tasks than in the SA task. Error rates were generally larger in schizophrenia patients than in control participants, but the deficit was smaller in the delayed tasks than in the SA task. Correct saccade latencies of schizophrenia patients were normal in the SP task, but not on conditions of volitional saccade initiation (all other tasks). Volitional saccade latencies were positively correlated with error rates in the schizophrenia group. These results confirm that schizophrenia patients have a specific deficit in initiating volitional action, which may also contribute to the increased error rates.     

A relationship between smell identification and empathy

Olfaction is a sense that has close relationships with the limbic system and emotion. Empathy is a vicarious feeling of others' emotional states. The two functions are known to be subserved by common neuroanatomical structures, including orbitofrontal cortex, mediodorsal thalamus, and the amygdala. This study demonstrates a correlation between smell identification and empathy, using the Mehrabian and Epstein Empathy Questionnaire and Alberta Smell Test. Right nostril smell identification correlated with empathy, whereas the left nostril did not. Given the predominantly ipsilateral representation in the olfactory system, this is in accordance with right hemisphere dominance for emotional functions and empathy. Further, the emotional component of empathy (feeling another's emotions) correlated with smell, whereas a cognitive component (comprehending another's emotions) did not. This study is the first to demonstrate a relationship between empathy and smell in normal subjects, suggesting common neural substrates.     

Functional magnetic resonance imaging evidence for abnormalities in response selection in attention deficit hyperactivity disorder: differences in activation associated with response inhibition but not habitual motor response

Impaired response inhibition is thought to be a core deficit in attention deficit hyperactivity disorder (ADHD). Prior imaging studies investigating response inhibition in children with ADHD have used tasks involving different cognitive resources, thereby complicating the interpretation of their findings. In this study, a classical go/no-go task with a well-ingrained stimulus-response association (green = go; red = no-go) was used in order to minimize extraneous cognitive demands. Twenty-five children with ADHD and 25 typically developing (TD) children between the ages of 8 and 13 years and group-matched for IQ and performance on the go/no-go task were studied using event-related functional magnetic resonance imaging (fMRI). Analyses were used to examine differences in activation between the ADHD and TD groups for "go" (habitual motor response) and "no-go" (requiring inhibition of the motor response) events. Region-of-interest analyses revealed no between-group difference in activation in association with "go" events. For "no-go" events, the children with ADHD demonstrated significantly less activation than did TD controls within a network important for inhibiting a motor response to a visual stimulus, with frontal differences localized to the pre-supplementary motor area. Although blood oxygenation level-dependent fMRI data show no differences between children with ADHD and TD children in association with a habituated motor "go" response, during "no-go" events, which require selecting not to respond, children with ADHD show diminished recruitment of networks important for response inhibition. The findings suggest that abnormalities in circuits important for motor response selection contribute to deficits in response inhibition in children with ADHD and lend support to the growing awareness of ADHD-associated anomalies in medial frontal regions important for the control of voluntary actions.     

The role of the agranular insular cortex in working memory for food reward value and allocentric space in rats

The present experiment examined the effects of quinolinic acid (125 mM) lesions of the agranular insular area on working memory for food reward value and working memory for spatial locations. In both tasks a go/no-go procedure was used. Working memory for food reward value was assessed using a delayed conditional discrimination in which either a 20% or 45% sugar content cereal was associated with a reinforcement and the other cereal was not. In the spatial locations task, rats were allowed to enter 12 arms in a radial maze for a food reinforcement. Of the 12 arm presentations, three or four arms were presented for a second time in a session which did not contain a reinforcement. The number of trials between the 1st and 2nd presentation of an arm ranged from 0 to 6 (lags). Working memory was assessed by the latency to enter an arm during the 2nd presentation. In the food reward value task, agranular insular lesions produced memory deficits in a delay-dependent manner. In contrast, agranular insular lesions did not impair working memory for spatial locations. These results add to accumulating evidence suggesting that different types of working memory are distributed across separate prefrontal subregions.     

Cerebrospinal fluid IgG profiles and multiple sclerosis in Japan

Simple reaction, single choice reaction, and paired choice reaction tasks were examined in 11 patients with Parkinson's disease (PD) and 12 controls. Subjects were given an auditory go/no-go signal in the single choice reaction task, and paired visual and auditory go/no-go signals in the paired choice reaction task. The response following the auditory go/no-go signal was analyzed. The reaction and movement times were prolonged in patients with PD. Differences between simple and choice reaction times in PD patients did not differ from those in control subjects. The difference in movement time between simple and paired choice reaction tasks in PD patients was longer than that in control subjects, although the difference between simple and single choice reaction tasks was not significant between PD and control subjects. Sequential choices of visual and auditory stimulation may disturb the motor activity in PD patients.     

Alcohol consumption impairs stimulus- and error-related processing during a Go/No-Go Task

Alcohol consumption has been shown to increase the number of errors in tasks that require a high degree of cognitive control, such as a go/no-go task. The alcohol-related decline in performance may be related to difficulties in maintaining attention on the task at hand and/or deficits in inhibiting a prepotent response. To test these two accounts, we investigated the effects of alcohol on stimulus- and response-locked evoked potentials recorded during a go/no-go task that involved the withholding of key presses to rare targets. All participants performed the task prior to drinking and were then assigned randomly to either a control, low-dose, or moderate-dose treatment. Both doses of alcohol increased the number of errors relative to alcohol-free performance. Success in withholding a prepotent response was associated with an early-enhanced stimulus-locked negativity at inferior parietal sites, which was delayed when participants failed to inhibit the motor command. Moreover, low and moderate doses of alcohol reduced N170 and P3 amplitudes during go, no-go, and error trials. In comparison with the correct responses, errors generated large response-locked negative (Ne) and positive (Pe) waves at central sites. Both doses of alcohol reduced the Ne amplitude whereas the Pe amplitude decreased only after moderate doses of alcohol. These results are consistent with the interpretation that behavioral disinhibition following alcohol consumption involved alcohol-induced deficits in maintaining and allocating attention thereby affecting the processing of incoming stimuli and the recognition that an errant response has been made.     

The effect of periarcuate lesions in the monkey on the performance of symmetrically and asymmetrically reinforced visual and auditory go, no-go tasks

Monkeys with lesions restricted to the periarcuate region of the frontal cortex were impaired on go, no-go tasks in which, depending on the stimulus present on any given trial, they were rewarded either for pushing a manipulandum or for withholding this response for a given period of time. By contrast, these animals were able to learn at a normal rate go, no-go tasks in which they were rewarded if they responded in the presence of a "positive" stimulus, but not in the presence of a "negative" stimulus. In the latter situation, responding in the presence of the "negative" stimulus was extinguished through non-reward, whereas the tasks on which impairments were demonstrated required solution on the basis of a conditional rule: If stimulus A, respond, and if stimulus B, withhold responding, to receive reward. Because the 2 experimental situations were identical in every respect except for the one critical difference in the testing procedure, the present set of experiments provides a powerful demonstration of the involvement of the periarcuate cortex in conditional learning with exteroceptive stimuli.     

Evidence that response inhibition is a primary deficit in ADHD

The present study examined response inhibition in children with attention deficit hyperactivity disorder (ADHD; n = 58) and controls (n = 84) using three go/no-go tests -- one with high working memory demand (cognitive), one with low working memory demand (simple), and one with rewards and response costs (motivation linked) in which emphasis was on reward for responding to "go" stimuli. Results of a repeated measure analysis of variance showed a significant effect of diagnosis for errors of commission for the simple, cognitive, and motivation-linked go/no-go tests, such that children with ADHD made significantly more errors than controls. Furthermore, a significant effect of test was noted across groups, such that both children in the ADHD and control groups performed worse on the cognitive and motivation-linked tests than they did on the simple test. The diagnosis by test interaction was not significant, suggesting that ADHD participants showed a similar degree of impairment to that of controls, regardless of the degree of working memory load or feedback provided in the test. In children with ADHD, response inhibition appears to be a primary deficit that is observed even when executive function demands of tasks are minimal. Although increasing working memory demand appears to impede response inhibition, this effect is similar in ADHD and typically developing children.     

Discharge patterns of pallidal neurons with input from various cortical areas during movement in the monkey

Activities of pallidal neurons were studied in awake monkeys which were implanted with stimulating electrodes in the various cortical areas in the frontal lobe. Cortical inputs to each pallidal neuron were examined by inhibitory responses to stimulation through these electrodes. Discharge patterns of pallidal neurons were observed during performance of the reaction-time, delayed go/no-go discrimination and self-paced movement tasks. Most of the pallidal neurons with input from the arm of the motor cortex changed their firing rate in close relation to the arm movement (movement-related activity). Many of the neurons with input from the supplementary motor and cingulate areas showed sustained changes in discharge rate during the delay period in addition to movement-related activity. Most of the neurons with input from prefrontal cortex responded to light stimulus.     

Left prefrontal repetitive transcranial magnetic stimulation impairs performance in affective go/no-go task

Functional neuroimaging studies have associated affective go/no-go function with lateral prefrontal activation, but they have not established a causal role and have not determined whether one hemisphere is predominantly engaged. In the present study, 11 normal volunteers underwent slow repetitive transcranial magnetic stimulation of the left and right dorsolateral prefrontal cortex, and the occipital cortex prior to performance of a picture-based affective go/no-go task. We found an interfering effect of left prefrontal repetitive transcranial magnetic stimulation compared with both right prefrontal and occipital repetitive transcranial magnetic stimulation. This impairment concerned positive and negative task stimuli to a similar extent, and tended to be greater in shift compared with nonshift blocks. Our findings demonstrate a functionally relevant lateralization of the prefrontal contribution to affective go/no-go tasks.     

Olfactory dysfunction in Parkinson's disease.

OBJECTIVE: To evaluate olfactory function in Parkinson's disease. METHODS: A standardised odour identification test was used, together with an evoked potential assessment with hydrogen sulphide. In addition, histological analysis was performed on the olfactory bulbs of cadavers who died from Parkinson's disease. RESULTS: Over 70% of patients studied (71 of 96) were outside the 95% limit of normal on the identification test in an age matched sample and there was an unusual pattern of selective loss to certain odours, not hitherto described. The evoked potentials were significantly delayed but of comparable amplitude to a control matched population. Of the 73 patients studied only 37 had a technically satisfactory record containing a clear response to both gases and of these, 12 were delayed. For H2S there was more delay on stimulating the right nostril than the left. Some patients with normal smell identification test scores had delayed evoked potentials. In the pathological examination of olfactory bulbs from eight brains, changes characteristic of Parkinson's disease (Lewy bodies) were seen in every olfactory bulb, particularly in the anterior olfactory nucleus, and were sufficiently distinct to allow a presumptive diagnosis of Parkinson's disease. CONCLUSIONS: Olfactory damage in Parkinson's disease is consistent and severe and may provide an important clue to the aetiology of the disease.     

The key locus of common response inhibition network for no-go and stop signals

Response inhibition is one of the highest evolved executive functions of human beings. Previous studies revealed a wide variety of brain regions related to response inhibition, although some of them may not be directly related to inhibition but to task-specific effects or noninhibitory cognitive functions such as attention, response competition, or error detection. Here, we conducted event-related functional magnetic resonance imaging studies in which all subjects performed both stop-signal and go/no-go tasks in order to explore key neural correlates within the response inhibition network irrelevant to task designs and other cognitive processes. The successful inhibition in the stop-signal and go/no-go tasks, respectively, activated a set of predominantly right-lateralized hemispheric cortices. The common inhibitory regions across the two tasks included the right middle prefrontal cortex in addition to the right middle occipital cortex. Correlation analysis was carried out within these areas between intensity of activation and behavioral performance in the two tasks. Only the region located in the middle prefrontal cortex showed significant correlations in both tasks. We believe this region is the key locus for execution of response inhibition in the distributed inhibitory neural network.