Diane Swick

Prefrontal cortex regulates inhibition and excitation in distributed neural networks

Prefrontal cortex provides both inhibitory and excitatory input to distributed neural circuits required to support performance in diverse tasks. Neurological patients with prefrontal damage are impaired in their ability to inhibit task-irrelevant information during behavioral tasks requiring performance over a delay. The observed enhancements of primary auditory and somatosensory cortical responses to task-irrelevant distractors suggest that prefrontal damage disrupts inhibitory modulation of inputs to primary sensory cortex, perhaps through abnormalities in a prefrontal-thalamic sensory gating system. Failure to suppress irrelevant sensory information results in increased neural noise, contributing to the deficits in decision making routinely observed in these patients. In addition to a critical role in inhibitory control of sensory flow to primary cortical regions, and tertiary prefrontal cortex also exerts excitatory input to activity in multiple sub-regions of secondary association cortex. Unilateral prefrontal damage results in multi-modal decreases in neural activity in posterior association cortex in the hemisphere ipsilateral to damage. This excitatory modulation is necessary to sustain neural activity during working memory. Thus, prefrontal cortex is able to sculpt behavior through parallel inhibitory and excitatory regulation of neural activity in distributed neural networks.

Left inferior frontal gyrus is critical for response inhibition

BackgroundLesion studies in human and non-human primates have linked several different regions of prefrontal cortex (PFC) with the ability to inhibit inappropriate motor responses. However, recent functional neuroimaging studies have specifically implicated right inferior PFC in response inhibition. Right frontal dominance for inhibitory motor control has become a commonly accepted view, although support for this position has not been consistent. Particularly conspicuous is the lack of data on the importance of the homologous region in the left hemisphere. To investigate whether the left inferior frontal gyrus (IFG) is critical for response inhibition, we used neuropsychological methodology with carefully characterized brain lesions in neurological patients.ResultsTwelve individuals with damage in the left IFG and the insula were tested in a Go/NoGo response inhibition task. In alternating blocks, the difficulty of response inhibition was easy (50% NoGo trials) or hard (10% NoGo trials). Controls showed the predicted pattern of faster reaction times and more false alarm errors in the hard condition. Left IFG patients had higher error rates than controls in both conditions, but were more impaired in the hard condition, when a greater degree of inhibitory control was required. In contrast, a patient control group with orbitofrontal cortex lesions showed intact performance.ConclusionRecent neuroimaging studies have focused on a highly specific association between right IFG and inhibitory control. The present results indicate that the integrity of left IFG is also critical for successful implementation of inhibitory control over motor responses. Our findings demonstrate the importance of obtaining converging evidence from multiple methodologies in cognitive neuroscience.

Are the neural correlates of stopping and not going identical? Quantitative meta-analysis of two response inhibition tasks

Neuroimaging studies have utilized two primary tasks to assess motor response inhibition, a major form of inhibitory control: the Go/NoGo (GNG) task and the Stop-Signal Task (SST). It is unclear, however, whether these two tasks engage identical neural systems. This question is critical because assumptions that both tasks are measuring the same cognitive construct have theoretical and practical implications. Many papers have focused on a right hemisphere dominance for response inhibition, with the inferior frontal gyrus (IFG) and the middle frontal gyrus (MFG) receiving the bulk of attention. Others have emphasized the role of the pre-supplementary motor area (pre-SMA). The current study performed separate quantitative meta-analyses using the Activation Likelihood Estimate (ALE) method to uncover the common and distinctive clusters of activity in GNG and SST. Major common clusters of activation were located in the right anterior insula and the pre-SMA. Insular activation was right hemisphere dominant in GNG but more bilaterally distributed in SST. Differences between the tasks were observed in two major cognitive control networks: (1) the fronto-parietal network that mediates adaptive online control, and (2) the cingulo-opercular network implicated in maintaining task set (Dosenbach et al., 2007) and responding to salient stimuli (Seeley et al., 2007). GNG engaged the fronto-parietal control network to a greater extent than SST, with prominent foci located in the right MFG and right inferior parietal lobule. Conversely, SST engaged the cingulo-opercular control network to a greater extent, with more pronounced activations in the left anterior insula and bilateral thalamus. The present results reveal the anterior insulas importance in response inhibition tasks and confirm the role of the pre-SMA. Furthermore, GNG and SST tasks are not completely identical measures of response inhibition, as they engage overlapping but distinct neural circuits.

Dissociation between conflict detection and error monitoring in the human anterior cingulate cortex

The relative importance of the anterior cingulate cortex (ACC) for the detection and resolution of response conflicts versus its role in error monitoring remains under debate. One disputed issue is whether conflict detection and error monitoring can be viewed as unitary functions performed by the same region of the ACC, or whether these processes can be dissociated functionally and anatomically. We used a combination of electrophysiological and neuropsychological methods to assess these competing hypotheses. A neurological patient with a rare focal lesion of rostral-to-middorsal ACC was tested in an event-related potential study designed to track the time course of neural activity during conflicts and erroneous responses. Compared with controls, the error-related negativity component after incorrect responses was attenuated in the patient, accompanied by lower error-correction rates. Conversely, the stimulus-locked component on correct conflict trials, the N450, was enhanced, and behavioral performance was impaired. We hypothesize that intact regions of lateral prefrontal cortex were able to detect response conflict, but damage to the dorsal ACC impaired response inhibition, which may be due to disconnection from cingulate and supplementary motor areas. The results implicate rostral-dorsal ACC in error monitoring and suggest this function can be dissociated from conflict-detection processes.

Effects of frontal lobe damage on interference effects in working memory

Working memory is hypothesized to comprise a collection of distinct components or processes, each of which may have a unique neural substrate. Recent neuroimaging studies have isolated a region of the left inferior frontal gyrus that appears to be related specifically to one such component: resolving interference from previous items in working memory. In the present study, we examined working memory in patients with unilateral frontal lobe lesions by using a modified version of an item recognition task in which interference from previous trials was manipulated. In particular, we focused on patient R.C., whose lesion uniquely impinged on the region identified in the neuroimaging studies of interference effects. We measured baseline working memory performance and interference effects in R.C. and other frontal patients and in age-matched control subjects and young control subjects. Comparisons of each of these groups supported the following conclusions. Normal aging is associated with changes to both working memory and interference effects. Patients with frontal damage exhibited further declines in working memory but normal interference effects, with the exception of R.C., who exhibited a pronounced interference effect on both response time and accuracy. We propose that the left inferior frontal gyrus subserves a general, nonmnemonic function of selecting relevant information in the face of competing alternatives and that this function may be required by some working memory tasks.

Time course and specificity of event-related potentials to emotional expressions

To clarify the time course of neural responses to faces with different emotional expressions, we used event-related potential (ERP) and reaction time measures. Faces expressing four different emotions (happy, neutral, fearful, disgusted) and houses were shown in both upright and inverted orientations while subjects performed an immediate-repeats task. Results indicated that upright fearful expressions enhanced the frontocentral P200. However, emotional effects on the N170 and late positive component interacted with face orientation and were not selective for any specific expression. A unique negative component for upright disgust faces was observed at ∼300 ms at occipital regions. These results provide evidence for emotion-specific ERPs associated with fear and disgust, distinct from other non-specific configurational and attentional effects.

Response selection in the human anterior cingulate cortex

The anterior cingulate cortex (ACC) has been proposed as part of the brains attentional control network, but the exact nature of its involvement in cognitive and motor operations is under debate. Assessing effects of human ACC damage directly addresses the problem of ACC function. We report that executive control processes of a patient with a focal right hemisphere anterior cingulate lesion were not compromised. However, her performance level depended on the response modality used. Under the same task requirements, she was impaired when giving manual responses, but not vocal responses. Thus, we provide neuropsychological evidence for functional specialization within the human ACC.

Neural fate of seen and unseen faces in visuospatial neglect: A combined event-related functional MRI and event-related potential study

To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception.

Anterior cingulate cortex and the Stroop task: neuropsychological evidence for topographic specificity

Neuroimaging studies have implicated the anterior cingulate cortex (ACC) in many aspects of attention and cognition. Major theories of ACC function have proposed a role in conflict monitoring, executive control, response selection, and general arousal. Although the ACC is often treated as a unitary structure, extensive evidence suggests it exhibits anatomical and functional specificity. ACC activity during the Stroop color word interference task has been of particular interest. The purpose of the present study was to determine whether two different ACC subregions are necessary for intact color naming performance in the Stroop task. One experiment utilized blocked trial and mixed trial designs to emulate neuroimaging studies and to compare interference and facilitation effects, respectively. A third variant manipulated the probabilities of congruent and incongruent trials to alter levels of interference and cognitive control, or engagement of strategic processes, on a block by block basis. Two patients with focal lesions in either right mid-caudal (patient D.L.) or left rostral to mid-dorsal ACC (patient R.N.) exhibited distinctive performance profiles in these three versions of the Stroop task, providing further support for topographic specificity of function within the human ACC. Contrary to predictions from some neuroimaging experiments, damage to right mid-caudal ACC was associated with normal levels of interference and accurate performance on incongruent trials. Instead, D.L. showed reduced levels of facilitation relative to controls. Further, interference was not modulated by the probability manipulation in D.L., suggesting equivalently high levels of cognitive control in both conditions. Conversely, damage to left mid-dorsal ACC resulted in consistently lower accuracy on incongruent trials, indicating deficits in maintaining task set and inhibiting the automatic response. These results can help to constrain interpretations of ACC activations in functional imaging experiments of the Stroop task.

Contributions of Prefrontal Cortex to Recognition Memory: Electrophysiological and Behavioral Evidence

To clarify the involvement of prefrontal cortex in episodic memory, behavioral and event-related potential (ERP) measures of recognition were examined in patients with dorsolateral prefrontal lesions. In controls, recognition accuracy and the ERP old-new effect declined with increasing retention intervals. Although frontal patients showed a higher false-alarm rate to new words, their hit rate to old words and ERP old-new effect were intact, suggesting that recognition processes were not fundamentally altered by prefrontal damage. The opposite behavioral pattern was observed in patients with hippocampal lesions: a normal false-alarm rate and a precipitous decline in hit rate at long lags. The intact ERP effect and the change in response bias during recognition suggest that frontal patients exhibited a deficit in strategic processing or postretrieval monitoring, in contrast to the more purely mnemonic deficit shown by hippocampal patients.