The Neuroanatomy of Speech Processing: A Large-scale Lesion Study.

The neural basis of language has been studied for centuries, yet the networks critically involved in simply identifying or understanding a spoken word remain elusive. Several functional-anatomical models of critical neural substrates of receptive speech have been proposed, including (1) auditory-related regions in the left mid-posterior superior temporal lobe, (2) motor-related regions in the left frontal lobe (in normal and/or noisy conditions), (3) the left anterior superior temporal lobe, or (4) bilateral mid-posterior superior temporal areas. One difficulty in comparing these models is that they often focus on different aspects of the sound-to-meaning pathway and are supported by different types of stimuli and tasks. Two auditory tasks that are typically used in separate studies-syllable discrimination and word comprehension-often yield different conclusions. We assessed syllable discrimination (words and nonwords) and word comprehension (clear speech and with a noise masker) in 158 individuals with focal brain damage: left (n = 113) or right (n = 19) hemisphere stroke, left (n = 18) or right (n = 8) anterior temporal lobectomy, and 26 neurologically intact controls. Discrimination and comprehension tasks are doubly dissociable both behaviorally and neurologically. In support of a bilateral model, clear speech comprehension was near ceiling in 95% of left stroke cases and right temporal damage impaired syllable discrimination. Lesion-symptom mapping analyses for the syllable discrimination and noisy word comprehension tasks each implicated most of the left superior temporal gyrus. Comprehension but not discrimination tasks also implicated the left posterior middle temporal gyrus, whereas discrimination but not comprehension tasks also implicated more dorsal sensorimotor regions in posterior perisylvian cortex.

Does brain damage caused by stroke versus trauma have different neuropsychological outcomes? A lesion-matched multiple case study.

Traumatic brain injury (TBI) and stroke both have the potential to cause significant damage to the brain, with resultant neuropsychological impairments. How these different mechanisms of injury influence cognitive and behavioral changes associated with brain damage, however, is not well understood. Moreover, previous research directly comparing TBI and stroke has not accounted carefully for lesion location and size. Here, using a detailed lesion-matching approach that was used previously to compare neuropsychological outcomes in stroke versus tumor, we compared the neuropsychological profiles of 14 patients with focal lesions caused by TBI to those of 27 lesion-matched patients with stroke. Each patient with TBI was matched to two patients with stroke, based on lesion location and size (except 1 TBI case where only 1 stroke match was available). Demographic attributes (age, gender, handedness, education) were also matched in the TBI: stroke triplets, as much as possible. The patients with TBI versus stroke had similar performances across all cognitive and behavioral measures, with no significant or clinically meaningful differences. A supplemental analysis on developmental- versus adult-onset TBI cases (with their respective stroke matches) also yielded non-significant results, with TBI and stroke groups being statistically indistinguishable. Our results suggest that focal lesions caused by TBI versus stroke have similar neuropsychological outcomes in the chronic recovery phase, when location and size of lesion are comparable across TBI versus stroke mechanisms of injury.

Lesions in different prefrontal sectors are associated with different types of acquired personality disturbances.

"Frontal lobe syndrome" is a term often used to describe a diverse array of personality disturbances following frontal lobe damage. This study's guiding premise was that greater neuroanatomical specificity could be achieved by evaluating specific types of personality disturbances following acquired frontal lobe lesions. We hypothesized that three acquired personality disturbances would be associated with lesion involvement of distinct sectors of the prefrontal cortex (PFC): 1) emotional-social disturbance and ventromedial PFC, 2) hypoemotional disturbance and dorsomedial PFC, and 3) dysexecutive and dorsolateral PFC. In addition, we hypothesized that distressed personality disturbance would not be associated with focal PFC lesions in any sector. Each hypothesis was pre-registered and tested in 182 participants with adult-onset, chronic, focal brain lesions studied with an observational, cross-sectional design. Pre- and postmorbid personality was assessed by informant-rating with the Iowa Scales of Personality Change, completed by a spouse or family member. Two complementary analytic approaches were employed: 1) a hypothesis-driven region-of-interest (ROI) regression analysis examining the associations of lesions in specific PFC sectors with acquired personality disturbances; 2) a data-driven multivariate lesion-behavior mapping analysis, which was not limited to pre-specified regions. Each hypothesis received some support: (i) Emotional/social personality disturbance was most strongly associated with ventromedial PFC lesions in both statistical approaches. (ii) Hypoemotional disturbance was associated with dorsomedial PFC lesions in the ROI analyses, without any significant lesion-symptom mapping associations. (iii) Dysexecutive personality disturbance was associated with bilateral dorsolateral PFC lesions and ventromedial PFC lesions; lesion-symptom mapping showed maximal association of executive dysfunction with damage of the right middle frontal gyrus within the dorsolateral PFC. (iv) Distressed personality disturbance was not associated with lesions in any PFC sector. Altogether, the findings can be interpreted to indicate that damage to different prefrontal sectors may disrupt different anatomical-functional systems and result in distinct personality disturbances.

Approach to Cognitive Impairment in Parkinson's Disease.

Cognitive dysfunction is common in Parkinson's disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvement of memory and other domains. Subtle symptoms in the premotor and early phases of PD progress to mild cognitive impairment (MCI) which may be present at the time of diagnosis. Eventually, a large majority of PD patients develop dementia with advancing age and longer disease duration, which is usually accompanied by immobility, hallucinations/psychosis, and dysautonomia. Dopaminergic medications and deep brain stimulation help motor dysfunction, but may have potential cognitive side effects. Central acetylcholinesterase inhibitors, and possibly memantine, provide modest and temporary symptomatic relief for dementia, although there is no evidence-based treatment for MCI. There is no proven disease-modifying treatment for cognitive impairment in PD. The symptomatic and disease-modifying role of physical exercise, cognitive training, and neuromodulation on cognitive impairment in PD is under investigation. Multidisciplinary approaches to cognitive impairment with effective treatment of comorbidities, proper rehabilitation, and maintenance of good support systems in addition to pharmaceutical treatment may improve the quality of life of the patients and caregivers.

"Frontal lobe syndrome"? Subtypes of acquired personality disturbances in patients with focal brain damage.

Conceptualizations of the nature of acquired personality disturbances after brain damage, especially to prefrontal cortex, have progressed from clinical observations of a large, disparate set of disturbances to theories concerning neuroanatomically-based subgroups with prefrontal damage. However, hypothesized subtypes have not yet been studied systematically. Based on our previous investigations of acquired personality disturbances, we hypothesized five subtypes of acquired personality disturbances: Executive Disturbances, Disturbed Social Behavior, Emotional Dysregulation, Hypo-emotionality/De-Energization, and Distress, as well as an undisturbed group. Subtypes were investigated in 194 adults with chronic, stable, focal lesions located in various aspects of prefrontal lobes and elsewhere in the brain, using two different cluster analysis techniques applied to ratings on the Iowa Scales of Personality Change. One technique was a hypothesis-driven approach; the other was a set of strictly empirical analyses to assess the robustness of clusters found in the first analysis. The hypothesis-driven analysis largely supported the hypothesized set of subtypes. However, in contrast to the hypothesis, it suggested that disturbed social behavior and emotional dysregulation are not two distinct subtypes, but two aspects of one multifaceted type of disturbance. Additionally, the so-labeled "executive disturbances" group also showed disturbances in other domains. Results from the second (empirical) set of cluster analyses were consistent with findings from the hypothesis-driven cluster analysis. Overall, findings across the two cluster analyses indicated four subtypes of acquired personality disturbances: (1) executive disturbances in association with generalized disturbance, (2) dysregulation of emotions and behavior, (3) hypo-emotionality and de-energization, and (4) distress/anxiety. These findings show strong correspondence with subtypes suggested by prominent models of prefrontal systems based on neuroanatomically-defined circuits. Clarification of distinctive subtypes of acquired personality disturbances is a step toward enhancing our ability to tailor rehabilitative interventions for patients with prefrontal brain injuries.

Neural networks supporting audiovisual integration for speech: A large-scale lesion study.

Auditory and visual speech information are often strongly integrated resulting in perceptual enhancements for audiovisual (AV) speech over audio alone and sometimes yielding compelling illusory fusion percepts when AV cues are mismatched, the McGurk-MacDonald effect. Previous research has identified three candidate regions thought to be critical for AV speech integration: the posterior superior temporal sulcus (STS), early auditory cortex, and the posterior inferior frontal gyrus. We assess the causal involvement of these regions (and others) in the first large-scale (N = 100) lesion-based study of AV speech integration. Two primary findings emerged. First, behavioral performance and lesion maps for AV enhancement and illusory fusion measures indicate that classic metrics of AV speech integration are not necessarily measuring the same process. Second, lesions involving superior temporal auditory, lateral occipital visual, and multisensory zones in the STS are the most disruptive to AV speech integration. Further, when AV speech integration fails, the nature of the failure-auditory vs visual capture-can be predicted from the location of the lesions. These findings show that AV speech processing is supported by unimodal auditory and visual cortices as well as multimodal regions such as the STS at their boundary. Motor related frontal regions do not appear to play a role in AV speech integration.

The Neurobiology of Agrammatic Sentence Comprehension: A Lesion Study.

Broca's area has long been implicated in sentence comprehension. Damage to this region is thought to be the central source of "agrammatic comprehension" in which performance is substantially worse (and near chance) on sentences with noncanonical word orders compared with canonical word order sentences (in English). This claim is supported by functional neuroimaging studies demonstrating greater activation in Broca's area for noncanonical versus canonical sentences. However, functional neuroimaging studies also have frequently implicated the anterior temporal lobe (ATL) in sentence processing more broadly, and recent lesion-symptom mapping studies have implicated the ATL and mid temporal regions in agrammatic comprehension. This study investigates these seemingly conflicting findings in 66 left-hemisphere patients with chronic focal cerebral damage. Patients completed two sentence comprehension measures, sentence-picture matching and plausibility judgments. Patients with damage including Broca's area (but excluding the temporal lobe; n = 11) on average did not exhibit the expected agrammatic comprehension pattern-for example, their performance was >80% on noncanonical sentences in the sentence-picture matching task. Patients with ATL damage ( n = 18) also did not exhibit an agrammatic comprehension pattern. Across our entire patient sample, the lesions of patients with agrammatic comprehension patterns in either task had maximal overlap in posterior superior temporal and inferior parietal regions. Using voxel-based lesion-symptom mapping, we find that lower performances on canonical and noncanonical sentences in each task are both associated with damage to a large left superior temporal-inferior parietal network including portions of the ATL, but not Broca's area. Notably, however, response bias in plausibility judgments was significantly associated with damage to inferior frontal cortex, including gray and white matter in Broca's area, suggesting that the contribution of Broca's area to sentence comprehension may be related to task-related cognitive demands.

Longitudinal decline of driving safety in Parkinson disease.

OBJECTIVE: To longitudinally assess and predict on-road driving safety in Parkinson disease (PD). METHODS: Drivers with PD (n = 67) and healthy controls (n = 110) drove a standardized route in an instrumented vehicle and were invited to return 2 years later. A professional driving expert reviewed drive data and videos to score safety errors. RESULTS: At baseline, drivers with PD performed worse on visual, cognitive, and motor tests, and committed more road safety errors compared to controls (median PD 38.0 vs controls 30.5; p < 0.001). A smaller proportion of drivers with PD returned for repeat testing (42.8% vs 62.7%; p < 0.01). At baseline, returnees with PD made fewer errors than nonreturnees with PD (median 34.5 vs 40.0; p < 0.05) and performed similar to control returnees (median 33). Baseline global cognitive performance of returnees with PD was better than that of nonreturnees with PD, but worse than for control returnees (p < 0.05). After 2 years, returnees with PD showed greater cognitive decline and larger increase in error counts than control returnees (median increase PD 13.5 vs controls 3.0; p < 0.001). Driving error count increase in the returnees with PD was predicted by greater error count and worse visual acuity at baseline, and by greater interval worsening of global cognition, Unified Parkinson's Disease Rating Scale activities of daily living score, executive functions, visual processing speed, and attention. CONCLUSIONS: Despite drop out of the more impaired drivers within the PD cohort, returning drivers with PD, who drove like controls without PD at baseline, showed many more driving safety errors than controls after 2 years. Driving decline in PD was predicted by baseline driving performance and deterioration of cognitive, visual, and functional abnormalities on follow-up.

Sleep remains disturbed in patients with obstructive sleep apnea treated with positive airway pressure: a three-month cohort study using continuous actigraphy.

OBJECTIVE: Some patients with obstructive sleep apnea (OSA) remain sleepy despite positive airway pressure (PAP) therapy. The mechanisms by which this occurs are unclear but could include persistently disturbed sleep. The goal of this study was to explore the relationships between subjective sleepiness and actigraphic measures of sleep during the first three months of PAP treatment. METHODS: We enrolled 80 patients with OSA and 50 comparison subjects prior to treatment and observed them through three months of PAP therapy. PAP adherence and presence of residual respiratory events were determined from PAP machine downloads. Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and actigraphic data were collected before and at monthly intervals after starting PAP. RESULTS: Patients with OSA were sleepier and showed a greater degree of sleep disruption by actigraphy at the baseline. After three months of PAP, only ESS and number of awakenings (AWAKE#) normalized, while wake after sleep onset and sleep efficiency remained worse in patients with OSA. FOSQ was improved in patients with OSA but never reached the same level as that of comparison subjects. ESS and FOSQ improved slowly over the study period. CONCLUSIONS: As a group, patients with OSA show actigraphic evidence of persistently disturbed sleep and sleepiness-related impairments in day-to-day function after three months of PAP therapy. Improvements in sleepiness evolve over months with more severely affected patients responding quicker. Persistent sleep disruption may partially explain residual sleepiness in some PAP-adherent OSA patients.

Startle Habituation and Midfrontal Theta Activity in Parkinson Disease.

The ability to adapt to aversive stimuli is critical for mental health. Here, we investigate the relationship between habituation to startling stimuli and startle-related activity in medial frontal cortex as measured by EEG in both healthy control participants and patients with Parkinson disease (PD). We report three findings. First, patients with PD exhibited normal initial startle responses but reduced startle habituation relative to demographically matched controls. Second, control participants had midfrontal EEG theta activity in response to startling stimuli, and this activity was attenuated in patients with PD. Finally, startle-related midfrontal theta activity was correlated with the rate of startle habituation. These data indicate that impaired startle habituation in PD is a result of attenuated midfrontal cognitive control signals. Our findings could provide insight into the frontal regulation of startle habituation.

FEEDBACK FROM NATURALISTIC DRIVING IMPROVES TREATMENT COMPLIANCE IN DRIVERS WITH OBSTRUCTIVE SLEEP APNEA.

As part of a study in drivers with obstructive sleep apnea (OSA), we conducted a randomized clinical trial to assess whether individualized feedback can increase compliance with continuous positive airway pressure (CPAP) therapy. After completing 3.5 months of naturalistic driving monitoring, OSA drivers were randomized either to receive an intervention, which was feedback regarding their own naturalistic driving record and CPAP compliance, or to receive no such intervention. In the week immediately after the intervention date, drivers receiving feedback (n=30) improved their CPAP usage by an average of 35.8 minutes per night (p=0.008; 95% CI=9.6, 62.0) to a mean level of 296 minutes. By contrast, CPAP usage in the non-feedback group (n=36) decreased an average of 27.5 minutes per night (p=0.022; 95% CI=4.0, 51.0) to a mean level of 236 minutes. The mean group-specific changes were higher (better) in the feedback group than in the non-feedback group during the first, second, and third weeks of follow-up (p<0.001, p=0.001, and p=0.027, respectively). By weeks 4 through 10, the effect of the feedback had lost its significance (p>0.25 in all cases). Our study suggests that CPAP compliance can be increased using individualized feedback, but that follow-up feedback sessions or reminders may be necessary for sustained improvement.

Parietal damage impairs learning of a visuomotor tracking skill.

This study evaluated the consequences of damage to the parietal lobe for learning a visuomotor tracking skill. Thirty subjects with a single unilateral brain lesion (13 with and 17 without parietal damage) and 23 demographically comparable healthy subjects performed the Rotary Pursuit task. For each group, time on target increased significantly across the four learning blocks. Subjects with parietal lesions had smaller improvements on the Rotary Pursuit from the 1st to the 4th block than subjects with lesions in other brain areas and healthy comparison subjects. The improvements on task performance from the 1st to the 2nd and from the 1st to the 3rd learning blocks were similar between groups. The parietal lobe appears to play an important role in the acquisition of a new visuomotor tracking skill, in particular during a relatively late phase of learning.

Susceptibility to social pressure following ventromedial prefrontal cortex damage.

Social pressure influences human behavior including risk taking, but the psychological and neural underpinnings of this process are not well understood. We used the human lesion method to probe the role of ventromedial prefrontal cortex (vmPFC) in resisting adverse social pressure in the presence of risk. Thirty-seven participants (11 with vmPFC damage, 12 with brain damage outside the vmPFC and 14 without brain damage) were tested in driving simulator scenarios requiring left-turn decisions across oncoming traffic with varying time gaps between the oncoming vehicles. Social pressure was applied by a virtual driver who honked aggressively from behind. Participants with vmPFC damage were more likely to select smaller and potentially unsafe gaps under social pressure, while gap selection by the comparison groups did not change under social pressure. Participants with vmPFC damage also showed prolonged elevated skin conductance responses (SCR) under social pressure. Comparison groups showed similar initial elevated SCR, which then declined prior to making left-turn decisions. The findings suggest that the vmPFC plays an important role in resisting explicit and immediately present social pressure with potentially negative consequences. The vmPFC appears to contribute to the regulation of emotional responses and the modulation of decision making to optimize long-term outcomes.

Speech repetition as a window on the neurobiology of auditory-motor integration for speech: A voxel-based lesion symptom mapping study.

For more than a century, speech repetition has been used as an assay for gauging the integrity of the auditory-motor pathway in aphasia, thought classically to involve a linkage between Wernicke's area and Broca's area via the arcuate fasciculus. During the last decade, evidence primarily from functional imaging in healthy individuals has refined this picture both computationally and anatomically, suggesting the existence of a cortical hub located at the parietal-temporal boundary (area Spt) that functions to integrate auditory and motor speech networks for both repetition and spontaneous speech production. While functional imaging research can pinpoint the regions activated in repetition/auditory-motor integration, lesion-based studies are needed to infer causal involvement. Previous lesion studies of repetition have yielded mixed results with respect to Spt's critical involvement in speech repetition. The present study used voxel-based lesion symptom mapping (VLSM) to investigate the neuroanatomy of repetition of both real words and non-words in a sample of 47 patients with focal left hemisphere brain damage. VLSMs identified a large voxel cluster spanning gray and white matter in the left temporal-parietal junction, including area Spt, where damage was significantly related to poor non-word repetition. Repetition of real words implicated a very similar dorsal network including area Spt. Cortical regions including Spt were implicated in repetition performance even when white matter damage was factored out. In addition, removing variance associated with speech perception abilities did not alter the overall lesion pattern for either task. Together with past functional imaging work, our results suggest that area Spt is integral in both word and non-word repetition, that its contribution is above and beyond that made by white matter pathways, and is not driven by perceptual processes alone. These findings are highly consistent with the claim that Spt is an area of sensory-motor translation in speech processing.

Paths from mother-child and father-child relationships to externalizing behavior problems in children differing in electrodermal reactivity: a longitudinal study from infancy to age 10.

Electrodermal hyporeactivity (or low skin conductance level, SCL) has been long established as a correlate of and diathesis for antisocial behavior, aggression, disregard for rules of conduct and feelings of others, and generally, externalizing behavior problems in children and adults. Much less is known, however, about how individual differences in children's SCL and qualities of their early experiences in relationships with parents interact to produce antisocial outcomes. In a community sample of 102 families (51 girls), we examined children's SCL, assessed in standard laboratory tasks at age 8 (N = 81), as a moderator of the links between parent-child socialization history and children's externalizing behavior problems at ages 8 and 10, reported by mothers and fathers in well-established instruments and by children in clinical interviews. Mother- and father-child socialization history was assessed in frequent, intensive observations. Parent-child mutually responsive orientation (MRO) was observed from infancy to age 10, parental power assertion was observed from 15 months to age 6 ½, and children reported their attachment security in interviews at age 8 and 10. For children with lower SCL, variations in mothers' power assertion and father-child MRO were associated with parent-rated externalizing problems. The former interaction was consistent with diathesis-stress, and the latter with differential susceptibility. For children with higher SCL, there were no links between socialization history and externalizing problems.

EFFECTIVENESS OF A HEADS-UP ADAPTIVE LANE DEVIATION WARNING SYSTEM FOR MIDDLE-AGED & OLDER ADULTS.

46 participants (24 younger and 22 older) completed at least one out of four simulated drives designed to test the effectiveness of an Adaptive Lane Deviation Warning (LDW) system, and they drove through both a warnings-on and warnings-off version of each drive. Findings showed that LDW was effective in reducing reaction time for lane deviation corrections for both older (by 1.2 seconds) and younger drivers (by 1.6 seconds). The older and younger drivers did not differ in correction RTs when the warnings were turned off. But older drivers showed slower correction RTs than younger drivers in the warning-on drives. The data indicate that these benefits were specific to LDW rather than general improvement in driving performance. Cognitive processing speed emerged as a particularly robust predictor of benefits from the LDW compared to other domains of cognitive function.

Habituation of parasympathetic-mediated heart rate responses to recurring acoustic startle.

Startle habituation is a type of implicit and automatic emotion regulation. Diminished startle habituation is linked to several psychiatric or neurological disorders. Most previous studies quantified startle habituation by assessing skin conductance response (SCR; reflecting sympathetic-mediated sweating), eye-blink reflex, or motor response. The habituation of parasympathetic-mediated heart rate responses to recurrent startle stimuli is not well understood. A variety of methods and metrics have been used to quantify parasympathetic activity and its effects on the heart. We hypothesized that these different measures reflect unique psychological and physiological processes that may habituate differently during repeated startle stimuli. We measured cardiac inter-beat intervals (IBIs) to recurring acoustic startle probes in 75 eight year old children. Eight acoustic stimuli of 500 ms duration were introduced at intervals of 15-25 s. Indices of parasympathetic effect included: (1) the initial rapid decrease in IBI post-startle mediated by parasympathetic inhibition (PI); (2) the subsequent IBI recovery mediated by parasympathetic reactivation (PR); (3) rapid, beat-to-beat heart rate variability (HRV) measured from the first seven IBIs following each startle probe. SCR and motor responses to startle were also measured. Results showed that habituation of PR (IBI recovery and overshoot) and SCRs were rapid and robust. In addition, changes in PR and SCR were significantly correlated. In contrast, habituation of PI (the initial decrease in IBI) was slower and relatively modest. Measurement of rapid HRV provided an index reflecting the combination of PI and PR. We conclude that different measures of parasympathetic-mediated heart rate responses to repeated startle probes habituate in a differential manner.

Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

OBJECTIVES: To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. METHODS: Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. RESULTS: Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p < 0.05 to p < 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p < 0.05). CONCLUSIONS: Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition.

Arrested development: early prefrontal lesions impair the maturation of moral judgement.

Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.