Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition.

Studies with experimental animals have revealed a mood-regulating neural pathway linking intrinsically photosensitive retinal ganglion cells (ipRGCs) and the prefrontal cortex (PFC), involved in the pathophysiology of mood disorders. Since humans also have light-intensity-encoding ipRGCs, we asked whether a similar pathway exists in humans. Here, functional MRI was used to identify PFC regions and other areas exhibiting light-intensity-dependent signals. We report 26 human brain regions having activation that either monotonically decreases or monotonically increases with light intensity. Luxotonic-related activation occurred across the cerebral cortex, in diverse subcortical structures, and in the cerebellum, encompassing regions with functions related to visual image formation, motor control, cognition, and emotion. Light suppressed PFC activation, which monotonically decreased with increasing light intensity. The sustained time course of light-evoked PFC responses and their susceptibility to prior light exposure resembled those of ipRGCs. These findings offer a functional link between light exposure and PFC-mediated cognitive and affective phenomena.

Functional role of area 8A in the posterior dorsolateral frontal region of the human brain: A single case study.

Area 8A has traditionally been considered to be the frontal eye field (FEF), i.e. the area for the motor production of eye movements. However, recent research has shown that the FEF lies posteriorly in premotor area 6. Research in macaque monkeys has demonstrated that, in contrast to premotor area 6, which is involved in the production of motor actions, area 8A is implicated in the cognitive allocation of attention to stimuli based on instruction cues. The aim of the present study was to elucidate the specific cognitive role of area 8A by examining a unique patient with a lesion restricted to area 8A, i.e. sparing the premotor cortex. This right-handed male patient underwent neuropsychological assessment and testing on two conditional associative-learning tasks: the motor hand conditional associative-learning task (MCALT) assessing the selection of motor actions based on instruction cues and the visual conditional associative-learning task (VCALT) assessing the selection of visual stimuli based on instruction cues. The patient's performance on the VCALT was significantly impaired compared to control subjects, but performance on the MCALT and on an Eye Movement Control Task was preserved. The present study provides evidence that area 8A is critical for the cognitive process regulating the allocation of attention to different stimuli in the environment, but not in the production of eye movements. These findings enhance understanding of the functional organization of the posterior dorsolateral frontal region in the human brain and suggest a specialized role of area 8A in high-level cognitive processes.

The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n1 = 30) and their age-paired controls (YC, n1 = 30), and compare it with octogenarian elder controls (EC, n1 = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD.

Nocturnal paroxysmal dystonia to sleep-related hypermotor epilepsy: A critical review.

Sleep-related paroxysmal motor episodes (SPMEs) have been described by various names, including nocturnal paroxysmal dystonia, nocturnal frontal lobe epilepsy (NFLE), and sleep-related hypermotor epilepsy. The underlying pathophysiology has been debated over the years, with these episodes assumed to be a form of paroxysmal dystonia or parasomnia versus a form of epilepsy. In most studies published on SPMEs and their variants (paroxysmal arousals, nocturnal paroxysmal dystonia, and episodic nocturnal wanderings) in the early 1990s, the authors speculated on the pathophysiology but did not commit to one idea. It was not until the mid-1990s that epilepsy became the leading prospect. We performed a narrative review of the major articles that have described this syndrome in a chronological fashion. We identified three eras, 1972-1993, 1994-1998, and 1999 to the present, each era marked by a landmark study. Our critical review of these early studies shows that the neurophysiological data supporting epilepsy as the sole basis for all SPME cases is very weak. In 1994-1995, a familial pattern of this syndrome was described and the term autosomal dominant NFLE was coined, with the authors claiming that all their patients had a form of frontal lobe epilepsy. With the exception of a few reference cases, the neurophysiological evidence that all patients had frontal lobe epilepsy was very weak. Compared to articles published on surgical series of frontal lobe epilepsy, the percentage of SPME cases with positive interictal/ictal electroencephalograms remained very low, seriously questioning the epileptic basis of the syndrome. Our critical review and analysis of the published literature shows that the evidence presented in favor of SPMEs being a homogenous focal epilepsy syndrome is very weak. Neurologists must recognize that SPMEs could be a form of movement disorder, parasomnia, or epilepsy. We recommend a pragmatic semiology-based classification of these episodes using the four-dimensional classification system.

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

A case of frontal lobe seizures with 'dancing-like' semiology.

BACKGROUND AND PURPOSE: 'Dancing-like' semiology is extremely rare and described in few case reports. It is characterized by rhythmic, oscillatory movements of the pelvis and/or limbs during which the subject appears to be dancing. It has been associated with both the frontal and temporal epileptic zone; however, the possible network involved in these fascinating seizures is unclear. METHODS: The case of a 45-year-old woman suffering from drug-resistant focal epilepsy with multi-day seizures of bizarre semiology is described. A structural and perfusion magnetic resonance imaging study (interictal and peri-ictal) and video-electroencephalograms were carried out, and several home videos were employed. A vagal stimulator was implanted. RESULTS: Home videos documented the 'dancing' semiology of seizures better than video- electroencephalogram recordings. The imaging study revealed a focal frontal polymicrogyria with a peri-ictal cerebral blood flow increase at the perisylvian lesion foci. The combination of add-on cenobamate and vagal nerve stimulation resulted in complete seizure freedom. CONCLUSION: The unusual and complex dancing-like semiology observed during our patient's seizures adds to the repertoire of fascinating complex motor manifestations of frontal lobe epilepsy.

Deficits of Facial Emotion Recognition in Elderly Individuals with Mild Cognitive Impairment.

INTRODUCTION: The study of facial emotion recognition is under-explored in subjects with mild cognitive impairment (MCI). We investigated whether deficits in facial emotion recognition are present in patients with MCI. We also analyzed the relationship between facial emotion recognition and different domains of cognitive function. METHODS: This study included 300 participants aged 60 years or older with cognitive decline. We evaluated 181 MCI and 119 non-MCI subjects using the Seoul Neuropsychological Screening Battery-Core (SNSB-C) and facial emotion recognition task using six facial expressions (anger, disgust, fear, happiness, sadness and surprise). A Generalized Linear Model (GLM) was used to assess the association between cognitive performance and accuracy of facial emotion recognition and to compare facial emotion recognition in the MCI group based on the impairment of five different domains of cognitive function. The model was adjusted for age, sex, years of education, and depressive symptoms. RESULTS: Patients with MCI had a lower score for accurately recognizing total facial emotion (0.48 vs. 0.53; ρ = 0.0003) and surprise (0.73 vs. 0.81; ρ = 0.0215) when compared to cognitively healthy subjects. We also discovered that frontal/executive function domain (Digit Symbol Coding [DSC, 0.38 vs. 0.49; p < 0.0001], Controlled Oral Word Association Test [COWAT, 0.42 vs. 0.49; p = 0.0001], Korean-Trail Making Test [K-TMT, 0.37 vs. 0.48; p = 0.0073], Korean-Color Word Stroop Test [K-CWST, 0.43 vs. 0.49; p = 0.0219]) and language domain (Korean-Boston Naming Test [S-K-BNT, 0.46 vs. 0.47; p = 0.003]) were statistically associated with the deficits of facial emotion recognition in patients with MCI. CONCLUSION: We observed a significant association between deficits in facial emotion recognition and cognitive impairment in elderly individuals.

Neural evidence of core foundations and conceptual change in preschool numeracy.

Symbolic numeracy first emerges as children learn the meanings of number words and how to use them to precisely count sets of objects. This development starts before children enter school and forms a foundation for lifelong mathematics achievement. Despite its importance, exactly how children acquire this basic knowledge is unclear. Here we test competing theories of early number learning by measuring event-related brain potentials during a novel number word-quantity comparison task in 3-4-year-old preschool children (N = 128). We find several qualitative differences in neural processing of number by conceptual stage of development. Specifically, we find differences in early attention-related parietal electrophysiology (N1), suggesting that less conceptually advanced children process arrays as individual objects and more advanced children distribute attention over the entire set. Subsequently, we find that only more conceptually advanced children show later-going frontal (N2) sensitivity to the numerical-distance relationship between the number word and visual quantity. The nature of this response suggested that exact rather than approximate numerical meanings were being associated with number words over frontal sites. No evidence of numerical distance effects was observed over posterior scalp sites. Together these results suggest that children may engage parallel individuation of objects to learn the meanings of the first few number words, but, ultimately, create new exact cardinal value representations for number words that cannot be defined in terms of core, nonverbal number systems. More broadly, these results document an interaction between attentional and general cognitive mechanisms in cognitive development. RESEARCH HIGHLIGHTS: Conceptual development in numeracy is associated with a shift in attention from objects to sets. Children acquire meanings of the first few number words through associations with parallel attentional individuation of objects. Understanding of cardinality is associated with attentional processing of sets rather than individuals. Brain signatures suggest children attribute exact rather than approximate numerical meanings to the first few number words. Number-quantity relationship processing for the first few number words is evident in frontal but not parietal scalp electrophysiology of young children.

Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Theory of mind in epilepsy.

Epilepsy is characterized by recurrent, chronic, and unprovoked seizures. Epilepsy has a significant negative impact on a patient's quality of life even if seizures are well controlled. In addition to the distress caused by seizures, patients with epilepsy (PwE) may suffer from cognitive impairment with serious social consequences such as poor interpersonal relationships, loss of employment, and reduced social networks. Pathological changes and functional connectivity abnormalities observed in PwE can disrupt the neural network responsible for the theory of mind. Theory of mind is the ability to attribute mental states to other people (intentions, beliefs, and emotions). It is a complex aspect of social cognition and includes cognitive and affective constructs. In recent years, numerous studies have assessed the relationship between social cognition, including the theory of mind, in PwE, and suggested impairment in this domain. Interventions targeting the theory of mind can be potentially helpful in improving the quality of life of PwE.

Neuropsychological outcome after frontal surgery for pediatric-onset epilepsy with focal cortical dysplasia in adolescent and young adult.

OBJECTIVE: We investigated neuropsychological outcome in patients with pharmacoresistant pediatric-onset epilepsy caused by focal cortical dysplasia (FCD), who underwent frontal lobe resection during adolescence and young adulthood. METHODS: Twenty-seven patients were studied, comprising 15 patients who underwent language-dominant side resection (LDR) and 12 patients who had languagenondominant side resection (n-LDR). We evaluated intelligence (language function, arithmetic ability, working memory, processing speed, visuo-spatial reasoning), executive function, and memory in these patients before and two years after resection surgery. We analyzed the relationship between neuropsychological outcome and resected regions (side of language dominance and location). RESULTS: Although 75% of the patients showed improvement or no change in individual neuropsychological tests after surgical intervention, 25% showed decline. The cognitive tests that showed improvement or decline varied between LDR and n-LDR. In patients who had LDR, decline was observed in Vocabulary and Phonemic Fluency (both 5/15 patients), especially after resection of ventrolateral frontal cortex, and improvement was observed in WCST-Category (7/14 patients), Block Design (6/15 patients), Digit Symbol (4/15 patients), and Delayed Recall (3/9 patients). In patients who underwent n-LDR, improvement was observed in Vocabulary (3/12 patients), but decline was observed in Block Design (2/9 patients), and WCST-Category (2/9 patients) after resection of dorsolateral frontal cortex; and Arithmetic (3/10 patients) declined after resection of dorsolateral frontal cortex or ventrolateral frontal cortex. General Memory (3/8 patients), Visual Memory (3/8 patients), Delayed Recall (3/8 patients), Verbal Memory (2/9 patients), and Digit Symbol (3/12 patients) also declined after n-LDR. CONCLUSION: Postoperative changes in cognitive function varied depending on the location and side of the resection. For precise presurgical prediction of neuropsychological outcome after surgery, further prospective studies are needed to accumulate data of cognitive changes in relation to the resection site.

Imbalance and gait impairment in Parkinson's disease: discussing postural instability and ataxia.

Gait and balance difficulties pose significant clinical challenges in Parkinson's disease (PD). The impairment of physiological mechanisms responsible for maintaining natural orthostatism plays a central role in the pathophysiology of postural instability observed in PD. In addition to the well-known rigidity and abnormalities in muscles and joints, various brain regions involved in the regulation of posture, balance, and gait, such as the basal ganglia, cerebellum, and brainstem regions like the pontine peduncle nucleus, are affected in individuals with PD. The recognition of the cerebellum's role in PD has been increasingly acknowledged. Cortical areas and their connections are associated with freezing of gait, a type of frontal lobe ataxia commonly observed in PD. Furthermore, impairments in the peripheral nervous system, including those caused by levodopatherapy, can contribute to gait impairment and imbalance in PD patients. Consequently, individuals with PD may exhibit frontal ataxia, sensory ataxia, and even cerebellar ataxia as underlying causes of gait disturbances and imbalance, starting from the early stages of the disease. The complex interplay between dysfunctional brain regions, impaired cortical connections, and peripheral nervous system abnormalities contributes to the multifaceted nature of gait and balance difficulties in PD. Understanding the intricate mechanisms is crucial for the development of effective therapeutic approaches targeting these specific deficits in PD.

Influence of an improvement in frontal lobe hemodynamics on neurocognitive function in adult patients with moyamoya disease.

BACKGROUND: In adults, moyamoya disease (MMD) often presents with slight neurocognitive impairment, which may result from frontal lobe hemodynamic insufficiency. METHODS: In this study, we performed revascularization surgery by superficial temporal artery-anterior cerebral artery (ACA) direct bypass in 20 adults with MMD with poor anterograde ACA flow (Group M). The pre- and postoperative neurocognitive test results of these patients were retrospectively analyzed. The comparative group (Group C) included 23 patients with unruptured aneurysms or brain tumors who underwent craniotomy, as well as the same neurocognitive tests as Group M. We calculated the compositive frontal lobe function index (CFFI) based on the results of seven neurocognitive tests for each patient, and the difference between the pre- and postoperative CFFI values (CFFI Post - Pre) was compared between the two groups. RESULTS: Frontal perfusion improved postoperatively in all patients in Group M. The CFFI Post - Pre was significantly higher in Group M than in Group C (0.23 ± 0.44 vs. - 0.20 ± 0.32; p < 0.001). After adjusting for postoperative age, sex, preoperative non-verbal intelligence quotient, and preoperative period of stress, Group M had a significantly higher CFFI Post - Pre than Group C in the multiple regression analysis (t value = 4.01; p < 0.001). CONCLUSION: Improving frontal lobe hemodynamics might be the key for improving neurocognitive dysfunction in adults with MMD. The surgical indication and method should be considered from the perspective of both stroke prevention and neurocognitive improvement or protection.

Frontal lobe disconnection: How I do it.

BACKGROUND: The objective of frontal lobe disconnection (FD) is to isolate the frontal lobe without removing brain parenchyma, to achieve epilepsy outcomes comparable to those for frontal lobectomy but with fewer complications, since a large post-operative cavity is not created. METHOD: Main surgical steps include "Identification of the central sulcus" to ensure the preservation of motor function, and "Frontal lobe disconnection" comprising: 1) fronto-parietal disconnection; 2) fronto-basal disconnection; 3) anterior corpus callosotomy; and 4) insula and basal ganglia disconnection. CONCLUSION: In performing FD, consideration of the disconnection boundary based on an anatomical understanding of white matter tracts is essential.

The impact of gestational diabetes on the development of fetal frontal lobe: A case-control study from a tertiary center.

PURPOSE: To determine the effects of gestational diabetes mellitus (GDM) on fetal frontal lobe development. METHODS: This study was conducted prospectively between May 2023 and August 2023 in Ankara City Hospital perinatology clinic. Maternal age, maternal body mass index (BMI), gestational week (GW), biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW), frontal antero-posterior diameter (FAPD), occipito-frontal diameter (OFD), FAPD/OFD ratio, and FAPD/HC ratio, were compared between GDM (n = 40) and low risk controls (n = 56). RESULTS: The mean maternal age was found higher in the GDM group compared to control group (p = 0.002). Maternal BMI was significantly higher in the GDM group than the control group (p = 0.01). Abdominal circumference (AC) was significantly higher in the GDM group compared to control group (p = 0.04). EFW was significantly higher in the GDM group compared to control group (p = 0.04). FAPD/OFD ratio was found to be higher in the GDM group than in the control group (p = 0.001). Among GDM patients, no statistically significant difference was found in the ultrasound measurements between the groups receiving insulin treatment and those without treatment. According to the correlation analysis results a moderate, positive, and statistically significant correlation was present between FAPD/OFD and GDM. In perinatal outcomes, the rate of neonatal intensive care unit admission was significantly higher in the GDM group. DISCUSSION: Fetal frontal lobe development seems to be affected by GDM.

The relationship between swallowing oral hesitation and cognition in frontal lobe stroke.

BACKGROUND & OBJECTIVE: Oral stage dysphagia mostly caused by frontal lobe lesions. We investigated the relationship between oral hesitation and cognitive impairment after frontal lobe stroke. METHODS: We consecutively collected 946 patients with stroke from January 2016 to December 2020. Among them, 38 patients had only frontal lobe lesions. Video fluoroscopic swallowing study (VFSS) was performed in 5 stages from water to solid food. Patients who progressed to solid food are very rare, so we focused on liquid and soft food. Diagnosis of stroke was limited to cases in which cerebral infarction or haemorrhage had been verified by magnetic resonance imaging (MRI). Cognitive impairment was evaluated by MMSE in patients with frontal lobe lesions. RESULT: Of the total 946 patients, 35 patients with frontal lobe lesions were enrolled in the study. Of them, 22 were judged to have cognitive impairment. The oral hesitation of the liquid component was analysed, and a conclusion was drawn that the group with cognitive impairment showed significant oral hesitation than the group without cognitive impairment. On the other hand, in the case of soft food, it was found that there was no correlation between cognition and oral hesitation. CONCLUSION: It was confirmed that oral hesitation during swallowing in patients with frontal lobe stroke had a meaningful relationship with cognition, and oral hesitation during swallowing was significantly higher in liquid swallowing rather than soft food.

["Witzelsucht". On the introduction and meaning of the term by Hermann Oppenheim in 1890 and its distinction from "moria"]. / Die "Witzelsucht". Über die Einführung und die Bedeutung des Begriffs von Hermann Oppenheim im Jahr 1890 und seine Abgrenzung zur "Moria".

Hermann Oppenheim (1858-1919) was a German neurologist without an academic career, who in his productive period around 1900 made a name for himself during his lifetime as a major player in the history of German neurology with his many contributions to multiple sclerosis, syphilis and the controversial study of traumatic neurosis; however, it is almost unknown that in 1890 he introduced the term "witzelsucht", which is still used internationally today. Moritz Jastrowitz dealt with behavioral abnormalities due to frontal brain injuries 1 year earlier and used the term "moria" for a form of mental disorder associated with a kind of childish behavior and inappropriate jocularity. Oppenheim was critical of this and differentiated his "witzelsucht" from this. With this term he wanted to describe humoristic feeble-mindedness in a much narrower sense, which stands in striking contrast to the usual symptoms in cases of cerebral tumors. Oppenheim recognized the frontal brain, particularly the right brain, to be an important functional unit for humorous behavior. Modern research has confirmed that the processing of humor requires a complex interaction of multiple brain regions. Damage to the right frontal lobe or to connecting structures can lead to the disorder "witzelsucht". Whether a simultaneous damage to the left hemisphere must be present or if this is dependent on the individual dominant hemisphere, needs further research.

Hemodynamic correlates of emotion regulation in frontal lobe epilepsy patients and healthy participants.

The ability to regulate emotions is indispensable for maintaining psychological health. It heavily relies on frontal lobe functions which are disrupted in frontal lobe epilepsy. Accordingly, emotional dysregulation and use of maladaptive emotion regulation strategies have been reported in frontal lobe epilepsy patients. Therefore, it is of clinical and scientific interest to investigate emotion regulation in frontal lobe epilepsy. We studied neural correlates of upregulating and downregulating emotions toward aversive pictures through reappraisal in 18 frontal lobe epilepsy patients and 17 healthy controls using functional magnetic resonance imaging. Patients tended to report more difficulties with impulse control than controls. On the neural level, patients had diminished activity during upregulation in distributed left-sided regions, including ventrolateral and dorsomedial prefrontal cortex, angular gyrus and anterior temporal gyrus. Patients also showed less activity than controls in the left precuneus for upregulation compared to downregulation. Unlike controls, they displayed no task-related activity changes in the left amygdala, whereas the right amygdala showed task-related modulations in both groups. Upregulation-related activity changes in the left inferior frontal gyrus, insula, orbitofrontal cortex, anterior and posterior cingulate cortex, and precuneus were correlated with questionnaire data on habitual emotion regulation. Our results show that structural or functional impairments in the frontal lobes disrupt neural mechanisms underlying emotion regulation through reappraisal throughout the brain, including posterior regions involved in semantic control. Findings on the amygdala as a major target of emotion regulation are in line with the view that specifically the left amygdala is connected with semantic processing networks.

Childhood trauma is associated with reduced frontal gray matter volume: a large transdiagnostic structural MRI study.

BACKGROUND: Childhood trauma increases risk for psychopathology and cognitive impairment. Prior research mainly focused on the hippocampus and amygdala in single diagnostic categories. However, other brain regions may be impacted by trauma as well, and effects may be independent of diagnosis. This cross-sectional study investigated cortical and subcortical gray matter volume in relation to childhood trauma severity. METHODS: We included 554 participants: 250 bipolar-I patients, 84 schizophrenia-spectrum patients and 220 healthy individuals without a psychiatric history. Participants filled in the Childhood Trauma Questionnaire. Anatomical T1 MRI scans were acquired at 3T, regional brain morphology was assessed using Freesurfer. RESULTS: In the total sample, trauma-related gray matter reductions were found in the frontal lobe (ß = -0.049, p = 0.008; q = 0.048), this effect was driven by the right medial orbitofrontal, paracentral, superior frontal regions and the left precentral region. No trauma-related volume reductions were observed in any other (sub)cortical lobes nor the hippocampus or amygdala, trauma-by-group (i.e. both patient groups and healthy subjects) interaction effects were absent. A categorical approach confirmed a pattern of more pronounced frontal gray matter reductions in individuals reporting multiple forms of trauma and across quartiles of cumulative trauma scores. Similar dose-response patterns were revealed within the bipolar and healthy subgroups, but did not reach significance in schizophrenia-spectrum patients. CONCLUSIONS: Findings show that childhood trauma is linked to frontal gray matter reductions, independent of psychiatric morbidity. Our results indicate that childhood trauma importantly contributes to the neurobiological changes commonly observed across psychiatric disorders. Frontal volume alterations may underpin affective and cognitive disturbances observed in trauma-exposed individuals.