Brenda Milner: Pioneer of the Study of the Human Frontal Lobes

Although the behavioral effects of damage to the frontal lobes date back to at least the late 19th century even midway through the 20th century very little was known about human frontal lobe function and there was a general consensus that the frontal lobe did not play a key role in cognition. This all changed when Brenda Milner published a chapter in a 1964 volume entitled: The Frontal Granular Cortex and Behavior. Milner’s chapter, “Some effects of frontal lobectomy in man,” was the first systematic study of the effect of frontal lobe excisions on cognition in human patients. Milner had access to a unique population of frontal excision patients at the Montreal Neurological Institute that were being treated by Wilder Penfield and his associates for a wide range of neurological disorders, including intractable epilepsy. Milner and her colleagues engaged in a more than 50-year study that has had a formidable impact on our understanding of frontal lobe function. Paralleling studies of frontal lobe function in non-humans they influence on understanding the evolution and function of the prefrontal cortex of mammals. Thus, although Brenda Milner is best known for her studies of human memory, she has had an equally important contribution to our understanding of the frontal lobes.

Differences in Frontal Lobe Dysfunction in Patients with Episodic and Chronic Migraine

Neuroimaging and neuropsychological investigations have indicated that migraineurs exhibit frontal lobe-related cognitive impairment. We investigated whether orbitofrontal and dorsolateral functioning differed between individuals with episodic migraine (EM) and chronic migraine (CM), focusing on orbitofrontal dysfunction because it is implicated in migraine chronification and medication overuse headache (MOH) in migraineurs. This cross-sectional study recruited women with CM with/without MOH (CM + MOH, CM − MOH), EM, and control participants who were matched in terms of age and education. We conducted neuropsychological assessments of frontal lobe function via the Trail Making Test (TMT) A and B, the Wisconsin Card Sorting Test (WCST), and the Iowa Gambling Task (IGT). We enrolled 36 CM (19 CM + MOH, 17 CM–MOH), 30 EM, and 30 control participants. The CM patients performed significantly (p < 0.01) worse on the TMT A and B than the EM patients and the control participants. The WCST also revealed significant differences, with poorer performance in the CM patients versus the EM patients and the control participants. However, the net scores on the IGT did not significantly differ among the three groups. Our findings suggest that the CM patients exhibited frontal lobe dysfunction, and, particularly, dorsolateral dysfunction. However, we found no differences in frontal lobe function according to the presence or absence of MOH.

Associations of Genetic Polymorphisms and Neuroimmune Markers With Some Parameters of Frontal Lobe Dysfunction in Schizophrenia

We investigated the associations of DRD3 rs6280, HTR1A rs6295, BDNF rs6265, SCL6A4 rs16965628, and 5HT2A rs7322347 with schizophrenia in a case–control study, and associations of these genetic variants with several clinical features. We also investigated markers of inflammatory response (C-reactive protein, IL-2, IL-6, IL-10), the activity of leukocytic elastase (LE) and α1-proteinase inhibitor (a1-PI), antibodies to S100B and myelin basic protein (MBP) in schizophrenia. Clinical symptoms were assessed on three scales: Positive and Negative Syndrome Scale, The Bush – Francis Catatonia Rating Scale and Frontal Assessment Battery. All SNPs were typed using predesigned TaqMan SNP genotyping assays. The biomarkers related to the immune system were routinely tested using ELISA kits. The association with schizophrenia was found for DRD3 rs6280 (p = 0.05) and HTR2A rs7322347 (p = 0.0013). We found differences between groups by parameters of LE and a1-PI and LE/a1-PI (p &lt; 0.001). And IL-6 was evaluated in the schizophrenia group (p &lt; 0.001). We showed that patients with the TT allele (BDNF rs6265) had more severe impairments in frontal lobe function. a1-PI can serve as a marker for assessing the severity of frontal lobe damage in patients with frontal dementia. We found some biological parameters reflecting the severity of frontal dysfunction in schizophrenia.

Association of White Matter Hyperintensity Progression with Cognitive Decline in Patients with Amnestic Mild Cognitive Impairment

Background: White matter hyperintensities (WMH) on MRI have been reported to increase the risk of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). However, effects of the progression of WMH on the cognition of patients with MCI remains unclear to date. Objective: To investigate the association between WMH progression and cognitive decline in amnestic MCI patients. Methods: Thirty-eight subjects with amnestic MCI were analyzed prospectively every year for 2 years. Fourteen MCI subjects dropped out on the final visit, and therefore 24 subjects with MCI were analyzed for the entire duration. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 FLAIR using the 3D-slicer. The associations between PVH/DWMH progression and cognitive decline were investigated. Results: An increase in DWMH volume significantly correlated with changes in Mini-Mental State Examination and category verbal fluency scores, whereas an increase in PVH volume did not correlate with changes in any item. Conclusion: DWMH progression was closely associated with a decline in frontal lobe function and semantic memory, suggesting that WMH progression might affect some AD pathophysiologies in amnestic MCI patients.

A Frontal Account of False Alarms

Prior research has demonstrated that the frontal lobes play a critical role in the top–down control of behavior, and damage to the frontal cortex impairs performance on tasks that require executive control (e.g., Burgess & Stuss, 2017; Stuss & Levine, 2002). Across executive functioning tasks, performance deficits are often quantified as the number of false alarms per the total number of nontarget trials. However, most studies of frontal lobe function focus on individual task performance and do not discuss commonalities of errors committed across different tasks. Here, we describe a neurocognitive account that explores the link between deficient frontal lobe function and increased false alarms across an array of experimental tasks from a variety of task domains. We review evidence for heightened false alarms following frontal deficits in episodic long-term memory tests, working memory tasks (e.g., n-back), attentional tasks (e.g., continuous performance tasks), interference control tasks (e.g., recent probes), and inhibitory control tasks (e.g., go/no-go). We examine this relationship via neuroimaging studies, lesion studies, and across age groups and pathologies that impact the pFC, and we propose 11 issues in cognitive processing that can result in false alarms. In our review, some overlapping neural regions were implicated in the regulation of false alarms. Ultimately, however, we find evidence for the fractionation and localization of certain frontal processes related to the commission of specific types of false alarms. We outline avenues for additional research that will enable further delineation of the fractionation of the frontal lobes' regulation of false alarms.

Dementia with aphasia and mirror phenomenon: examination of the mechanism using neuroimaging and neuropsychological findings: a case report

Background Aphasia often appears in persons living with dementia; however, aphasia and the mirror phenomenon are rarely present at the same time. Case presentation Here, we report a case of fluent conversation with a person in a mirror or a magazine, and examine the underlying mechanism using brain imaging and neuropsychological findings. We found that the appearance of the mirror phenomenon may be associated with a visuospatial dysfunction caused by a decreased function of the posterior region of the right temporal and parietal lobe. Moreover, active talking to a person in a mirror or a person in a magazine could be associated with disinhibition caused by a decline in bilateral frontal lobe function. Conclusions This case represents a very valuable and interesting presentation because it is the first report of a long-term follow-up of the course of dementia using neurological imaging, and of the neuropsychological analysis of the mechanism of conversation with a mirror image combined with aphasia.

Value of the Frontal Assessment Battery Tool for Assessing the Frontal Lobe Function in Stroke Patients

Objective To examine the correlation between the Frontal Assessment Battery (FAB) test, which is used to assess the frontal lobe function, and anatomical lesions as well as the ability of the test to detect frontal lobe dysfunction.Methods Records of stroke patients undergoing a FAB test and Mini-Mental State Examination (MMSE) were retrospectively reviewed. The patients were divided into three groups according to the lesions determined by an imaging study: frontal lobe cortex lesions, frontal subcortical circuit lesions, and other lesions. The FAB scores of the three groups were compared using the Kruskal-Wallis test. The validity of the FAB test to detect frontal lobe dysfunction was assessed by a comparison with the Computerized Neuropsychological Function Test (CNT) using the Spearman correlation coefficient. The correlation coefficients between the FAB test and MMSE were analyzed further based on the MMSE cutoff score.Results Patients with frontal cortex lesions had significantly lower total and subtest scores according to the FAB test than the other patients. The FAB test correlated better with the CNT than the MMSE, particularly in the executive function and memory domains. A high MMSE score (r=0.435) indicated a lower correlation with the FAB test score than a low MMSE score (r=0.714).Conclusion The FAB test could differentiate frontal lobe lesions from others in stroke patients and showed a good correlation with the CNT. Moreover, the FAB test can be used in patients with high MMSE scores to detect frontal lobe dysfunction and determine the treatment strategies for stroke patients.

The effect of driving simulator program on elderly drivers

Background: The purpose of the present study was to present evidence for driving interventions for the elderly by conducting programs that can improve visual perception and cognitive function in a driving simulator for elderly drivers and analyse their effects.Methods: Three elderly subjects who were 65 years or older, did not have physical and cognitive impairments, and were able to drive themselves participated in the present study. A total of 12 intervention sessions, of which subjects participated in 10 sessions of nine different visual perception and cognitive function programs available in a driving simulator, were conducted and pre- and post-program assessments were conducted (two assessments in total). The assessments included the evaluation of visual perception, frontal lobe function, concentration, safe driving behaviour, and self-efficacy.Results: The results showed positive effects of the driving simulator program on the visual perception, frontal lobe function, concentration, safe driving behaviour, and self-efficacy of all subjects. Changes in the simulator results showed remarkable improvement in the response evaluation, judgment evaluation, and predictive power evaluation, but showed difficulties in interference tasks and depth perception in common.Conclusions: The results showed positive effects of driving simulator training on the driving ability of the elderly, and consistent provision of such training is expected to improve the quality of life of the elderly by securing the safety of driving and actively supporting social participation.

Reduced Enhancement of Memory for Faces Encoded by Semantic and Socioemotional Processes in Patients with Parkinson’s Disease

Objectives:Patients with Parkinson’s disease (PD) exhibit impaired semantic and socioemotional processes, which are thought to be related to dysfunctions in the fronto-striatal circuit. However, little is known about how the memory enhancement by these processes was reduced in PD. The present study investigated this issue.Methods:The retrieval performance of face memories encoded by semantic and socioemotional processes was compared between 24 PD patients and 24 age-matched healthy controls (HC). During encoding, participants were presented with unfamiliar faces and made judgment about them in three encoding conditions of semantic judgment (Semantics), attractiveness judgment (Attractiveness), and form judgment (Form). In Semantics, participants rated to what degree each face looked like an office worker, whereas in Attractiveness, participants rated how attractive each face was. The Form condition as a control required participants to judge the shape of each face. During retrieval after encoding, participants made old or new judgment for target and distracter faces.Results:In HC, the retrieval of faces encoded by Semantics and Attractiveness was significantly more accurate than that encoded by Form, whereas this memory enhancement was not identified in PD. In addition, individual scores in frontal lobe function and long-term memory correlated with the retrieval performance of memories encoded in Semantics and Attractiveness but not Form.Conclusions:These findings suggest that the processing of semantic and socioemotional signals conveyed from faces could be impaired in PD and that the impairment of these processes could decrease the enhancement of face memories by semantic and socioemotional elaborations.