Selective spatial processing deficits in an at-risk subgroup of the fragile X premutation

Until a decade ago, it was assumed that males with the fragile X premutation were unaffected by any cognitive phenotype. Here we examined the extent to which CGG repeat toxicity extends to visuospatial functioning in male fragile X premutation carriers who are asymptomatic for a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Thirty-three premutation males aged 20-68 years [divided into two groups: 16 low-repeat carriers (CGG ≥ 55 ≤ 100) and 17 high-repeat carriers (CGG>100)] with a family history of fragile X syndrome and 62 non-affected adult males with normal FMR1 alleles were recruited. Subjects underwent neuropsychological tests of visuospatial and visual working memory functioning and visuoperceptual processing. On measures of visuospatial processing, the high-repeat carriers performed significantly worse than the normal allele group when age and IQ were covaried out. With increasing age and only in carriers of a larger (>100 repeats) premutation allele was there a greater decrement in visuospatial working memory functioning. Performance on spatial and perceptual judgement tasks failed to show similar specificity in males within the upper premutation range. We conclude that identification of selective visuospatial impairments in carriers of a larger premutation allele indicates greater CGG repeat toxicity in specific neural regions. Longitudinal follow-up studies will be needed to determine whether subtle decline in visuospatial functioning is associated with the later onset of motor symptoms of FXTAS.     

Framing deductive reasoning with emotional content: An fMRI study

In the literature concerning the study of emotional effect on cognition, several researches highlight the mechanisms of reasoning ability and the influence of emotions on this ability. However, up to now, no neuroimaging study was specifically devised to directly compare the influence on reasoning performance of visual task-unrelated with semantic task-related emotional information.In the present functional fMRI study, we devised a novel paradigm in which emotionally negative vs. neutral visual stimuli (context) were used as primes, followed by syllogisms composed of propositions with emotionally negative vs. neutral contents respectively. Participants, in the MR scanner, were asked to assess the logical validity of the syllogisms. We have therefore manipulated the emotional state and arousal induced by the visual prime as well as the emotional interference exerted by the syllogism content.fMRI data indicated a medial prefrontal cortex deactivation and lateral/dorsolateral prefrontal cortex activation in conditions with negative context. Furthermore, a lateral/dorsolateral prefrontal cortex modulation caused by syllogism content was observed. Finally, behavioral data confirmed the influence of emotional task-related stimuli on reasoning ability, since the performance was worse in conditions with syllogisms involving negative emotions. Therefore, on the basis of these data, we conclude that emotional states can impair the performance in reasoning tasks by means of the delayed general reactivity, whereas the emotional content of the target may require a larger amount of top-down resources to be processed.     

Anterior cingulate cortex and cognitive control: Neuropsychological and electrophysiological findings in two patients with lesions to dorsomedial prefrontal cortex

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial prefrontal lesions, a hypothesis has been advanced claiming that the ACC is not involved in cognitive operations. In the current study, two comparably rare patients with unilateral lesions to dorsal medial prefrontal cortex (MPFC) encompassing the ACC were assessed with neuropsychological tests as well as Event-Related Potentials in two experimental paradigms known to engage prefrontal cortex (PFC). These included an auditory Novelty Oddball task and a visual Stop-signal task. Both patients performed normally on the Stroop test but showed reduced performance on tests of learning and memory. Moreover, altered attentional control was reflected in a diminished Novelty P3, whereas the posterior P3b to target stimuli was present in both patients. The error-related negativity, which has been hypothesized to be generated in the ACC, was present in both patients, but alterations of inhibitory behavior were observed. Although interpretative caution is generally called for in single case studies, and the fact that the lesions extended outside the ACC, the findings nevertheless suggest a role for MPFC in cognitive control that is not restricted to error monitoring.     

No intrinsic number bias: Evaluating the role of perceptual discriminability in magnitude categorization

Accumulating evidence suggests that there is a spontaneous preference for numerical, compared to non-numerical (e.g., cumulative surface area), information. However, given a paucity of research on the perception of non-numerical magnitudes, it is unclear whether this preference reflects a specific bias towards number, or a general bias towards the more perceptually discriminable dimension (i.e., number). Here, we found that when the number and area of visual dot displays were matched in mathematical ratio, number was more perceptually discriminable than area in both adults and children. Moreover, both adults and children preferentially categorized these ratio-matched stimuli based on number, consistent with previous work. However, when number and area were matched in perceptual discriminability, a different pattern of results emerged. In particular, children preferentially categorized stimuli based on area, suggesting that children's previously observed number bias may be due to a mismatch in the perceptual discriminability of number and area, not an intrinsic salience of number. Interestingly, adults continued to categorize the displays on the basis of number. Altogether, these findings suggest a dominant role for area during childhood, refuting the claim that number is inherently and uniquely salient. Yet they also reveal an increased salience of number that emerges over development. Potential explanations for this developmental shift are discussed.

Research Highlights

• Previous work found that children and adults spontaneously categorized dot array stimuli by number, over other magnitudes (e.g., area), suggesting number is uniquely salient.
• However, here we found that when number and area were matched by ratio, as in prior work, number was significantly more perceptually discriminable than area.
• When number and area were made equally discriminable (‘perceptually-matched’), children, contra adults, spontaneously categorized stimuli by area over number (and other non-numerical magnitudes).
• These findings suggest that area may be uniquely salient early in childhood, with the previously-observed number bias not emerging until later in development.

     

Would a neuroscience of violence aid in understanding legal culpability?

Defense attorneys in criminal cases are beginning to argue that their clients were biologically predisposed to committing their crimes and therefore were less responsible for their behavior. Indeed, if our brains cause our behavior, and our brains are the way they are because of genetic composition, insults, disease, and life experiences, it becomes difficult to argue that any punishment as justified retribution for behavior is cogent. In this essay, I address the question of whether understanding the neuroscience behind human behavior should alter our legal notion of responsibility. We will examine this query in greater detail, using violence as a case study, asking whether understanding the neuroscience underlying violent behavior impacts our notion of personal or legal culpability. I shall argue that it does not. I proceed by first briefly sketching what we know about human violence and the biology behind it. Then I turn to a quick discussion of psychopaths, their connections to violence, and what we think we know about the biology of their brains. Finally, I come to the question of whether we should consider violent people with specific brain abnormalities as mad or bad, which will feed into the question of whether such people are responsible for their criminal behavior. I conclude with some very general and very brief speculations on what this discussion has to tell us about nature of being human.     

Developmental imaging genetics: Linking dopamine function to adolescent behavior

Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach.