Jordan Grafman

The role of the anterior prefrontal cortex in human cognition

Complex problem-solving and planning involve the most anterior part of the frontal lobes including the fronto-polar prefrontal cortex (FPPC), which is especially well developed in humans compared with other primates,. The specific role of this region in human cognition, however, is poorly understood. Here we show, using functional magnetic resonance imaging, that bilateral regions in the FPPC alone are selectively activated when subjects have to keep in mind a main goal while performing concurrent (sub)goals. Neither keeping in mind a goal over time (working memory) nor successively allocating attentional resources between alternative goals (dual-task performance) could by themselves activate these regions. Our results indicate that the FPPC selectively mediates the human ability to hold in mind goals while exploring and processing secondary goals, a process generally required in planning and reasoning.

Clock Drawing in Alzheimer's Disease: A Novel Measure of Dementia Severity

We have tested a simple and reliable measure of visuospatial ability in Alzheimer patients — the Clock Drawing Test. To determine the usefulness of this measure, we asked 67 Alzheimer patients and 83 normal controls to draw the face of a clock reading the time of 2:45. Six independent observers blindly evaluated the results with ratings from 10 (best) to 1 (worst). The mean performance score of Alzheimer subjects was 4.9 ± 2.7 compared to 8.7 ± 1.1 for normal controls (P < .001). Inter‐rater reliability for the clocks drawn by Alzheimer patients was highly significant (r = 0.86; P < .001), and there was relatively little overlap between ratings for Alzheimer patients and normal controls. Furthermore, correlations were highly significant (P < .001) between the mean score of clock drawings and three independent global measures of dementia severity. Although the Clock Drawing Test is certainly not a definitive indicator of Alzheimers disease, the test is easy to administer and provides a useful measure of dementia severity for both research and office settings where sophisticated neuropsychological testing is not available.

Frontal lobe injuries, violence, and aggression A report of the Vietnam Head Injury Study

Knowledge stored in the human prefrontal cortex may exert control over more primitive behavioral reactions to environmental provocation. Therefore, following frontal lobe lesions, patients are more likely to use physical intimidation or verbal threats in potential or actual confrontational situations. To test this hypothesis, we examined the relationship between frontal lobe lesions and the presence of aggressive and violent behavior. Fifty-seven normal controls and 279 veterans, matched for age, education, and time in Vietnam, who had suffered penetrating head injuries during their service in Vietnam, were studied. Family observations and self-reports were collected using scales and questionnaires that assessed a range of aggressive and violent attitudes and behavior. Two Aggression/Violence Scale scores, based on observer ratings, were constructed. The results indicated that patients with frontal ventromedial lesions consistently demonstrated Aggression/Violence Scale scores significantly higher than controls and patients with lesions in other brain areas. Higher Aggression/Violence Scale scores were generally associated with verbal confrontations rather than physical assaults, which were less frequently reported. The presence of aggressive and violent behaviors was not associated with the total size of the lesion nor whether the patient had seizures, but was associated with a disruption of family activities. These findings support the hypothesis that ventromedial frontal lobe lesions increase the risk of aggressive and violent behavior.

Human fronto–mesolimbic networks guide decisions about charitable donation

Humans often sacrifice material benefits to endorse or to oppose societal causes based on moral beliefs. Charitable donation behavior, which has been the target of recent experimental economics studies, is an outstanding contemporary manifestation of this ability. Yet the neural bases of this unique aspect of human altruism, which extends beyond interpersonal interactions, remain obscure. In this article, we use functional magnetic resonance imaging while participants anonymously donated to or opposed real charitable organizations related to major societal causes. We show that the mesolimbic reward system is engaged by donations in the same way as when monetary rewards are obtained. Furthermore, medial orbitofrontal–subgenual and lateral orbitofrontal areas, which also play key roles in more primitive mechanisms of social attachment and aversion, specifically mediate decisions to donate or to oppose societal causes. Remarkably, more anterior sectors of the prefrontal cortex are distinctively recruited when altruistic choices prevail over selfish material interests.

Safety and cognitive effect of frontal DC brain polarization in healthy individuals

Background: Data from the human motor cortex suggest that, depending on polarity, direct current (DC) brain polarization can depress or activate cortical neurons. Activating effects on the frontal lobe might be beneficial for patients with frontal lobe disorders. This phase 1 study tested the safety of frontal DC, including its effects on frontal and other brain functions. Methods: The authors applied 20 minutes of anodal, cathodal, or sham DC to the left prefrontal cortex in three groups of right-handed subjects and looked for effects on global measures of processing and psychomotor speed, emotion, and verbal fluency, a measure of local cortical function. In one experiment (n = 30), the authors tested before and after 1 mA DC and monitored EEG in 9 subjects. In two other experiments using 1 mA (n = 43) and 2 mA (n = 30), the authors tested before and then starting 5 minutes after the onset of DC. Results: All subjects tolerated DC well. There were no significant effects on performance with 1 mA DC. At 2 mA, verbal fluency improved significantly with anodal and decreased mildly with cathodal DC. There were no clinically significant effects on the other measures. Conclusions: Limited exposure to direct current polarization of the prefrontal cortex is safe and can enhance verbal fluency selectively in healthy subjects. As such, it deserves consideration as a procedure to improve frontal lobe function in patients.

Modeling other minds

Nine normal volunteers performed a ‘theory of mind’ task while their regional brain blood flow pattern was recorded using the PET [15O]H2O technique. Control conditions induced subjects to attend to the visual and semantic attributes of known objects. In a third condition, subjects had to infer the function of an unfamiliar object from its form. In the ‘theory of mind’ condition, subjects had to infer function based on the form of both familiar and unfamiliar objects and in addition, model the knowledge and rationality of another mind about the function of these objects. Performance during the ‘theory of mind’ condition evoked the activation of a distributed set of neural networks with prominent activation of the left medial frontal lobe (Brodmann area 9) and left temporal lobe (Brodmann areas 21, 39/19, 38). This result suggests that when inferential reasoning depends on constructing a mental model about the beliefs and intentions of others, the participation of the prefrontal cortex is required. When access to such knowledge is affected by central nervous system dysfunction, such as that found in autism, modeling other minds may prove difficult.

The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex

A primary aim in the neuroscientific study of depression is to identify the brain areas involved in the pathogenesis of symptoms. In this review, we describe evidence from studies employing various experimental approaches in humans (functional imaging, lesion method, and brain stimulation) that converge to implicate the ventromedial and dorsolateral sectors of prefrontal cortex as critical neural substrates for depression, albeit with distinct functional contributions. The putative roles of ventromedial and dorsolateral prefrontal cortex in depression are discussed in light of the results.

The neural basis of human moral cognition

Moral cognitive neuroscience is an emerging field of research that focuses on the neural basis of uniquely human forms of social cognition and behaviour. Recent functional imaging and clinical evidence indicates that a remarkably consistent network of brain regions is involved in moral cognition. These findings are fostering new interpretations of social behavioural impairments in patients with brain dysfunction, and require new approaches to enable us to understand the complex links between individuals and society. Here, we propose a cognitive neuroscience view of how cultural and context-dependent knowledge, semantic social knowledge and motivational states can be integrated to explain complex aspects of human moral cognition.

Summation priming and coarse semantic coding in the right hemisphere

There are now numerous observations of subtle right hemisphere (RH) contributions to language comprehension. It has been suggested that these contributions reflect coarse semantic coding in the RH. That is, the RH weakly activates large semantic fieldsincluding concepts distantly related to the input wordwhereas the left hemisphere (LH) strongly activates small semantic fieldslimited to concepts closely related to the input (Beeman, 1993a,b). This makes the RH less effective at interpreting single words, but more sensitive to semantic overlap of multiple words. To test this theory, subjects read target words preceded by either Summation primes (three words each weakly related to the target) or Unrelated primes (three unrelated words), and target exposure duration was manipulated so that subjects correctly named about half the target words in each hemifield. In Experiment 1, subjects benefited more from Summation primes when naming target words presented to the left visual field-RH (Ivf-RH) than when naming target words presented to the right visual field-LH (rvf-LH), suggesting a RH advantage in coarse semantic coding. In Experiment 2, with a low proportion of related prime-target trials, subjects benefited more from Direct primes (one strong associate flanked by two unrelated words) than from Summation primes for rvf-LH target words, indicating that the LH activates closely related information much more strongly than distantly related information. Subjects benefited equally from both prime types for Ivf-RH target words, indicating that the RH activates closely related information only slightly more strongly, at best, than distantly related information. This suggests that the RH processes words with relatively coarser coding than the LH, a conclusion consistent with a recent suggestion that the RH coarsely codes visual input (Kosslyn, Chabris, Mar-solek, & Koenig, 1992).

Functional networks in emotional moral and nonmoral social judgments.

Reading daily newspaper articles often evokes opinions and social judgments about the characters and stories. Social and moral judgments rely on the proper functioning of neural circuits concerned with complex cognitive and emotional processes. To examine whether dissociable neural systems mediate emotionally charged moral and nonmoral social judgments, we used a visual sentence verification task in conjunction with functional magnetic resonance imaging (fMRI). We found that a network comprising the medial orbitofrontal cortex, the temporal pole and the superior temporal sulcus of the left hemisphere was specifically activated by moral judgments. In contrast, judgment of emotionally evocative, but non-moral statements activated the left amygdala, lingual gyri, and the lateral orbital gyrus. These findings provide new evidence that the orbitofrontal cortex has dedicated subregions specialized in processing specific forms of social behavior.