Frontal lobe closed-lip schizencephaly as an atypical cause of adult-onset seizures.

Schizencephaly arises from irregular neuronal migration leading to clefts development in the cerebral cortex. The condition is often detected in childhood and it is extremely rare to go unnoticed. This case highlights a 45-year-old male with no previous medical history who presented with a seizure for the first time in the emergency department after which an MRI was done and detected schizcenphaly which at this point was the first time for the patient to be diagnosed with this condition. The available data on schizcencphaly in the literature is very little and the data on the condition when diagnosed in adulthood is even less, hence our case report aims to shed light on this unthought etiology of adult-onset seizures which could have major potential risks if not detected. Adults who receive a diagnoses later in life may face prognosis issues hence imaging should be encouraged to be a part of seizure workup to avoid underdiagnoses of brain abnormalities that may go unnoticed in childhood.

The network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy.

Introduction: Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or "irritative" network. Methods: Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups. Results: There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment. Discussion: The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.

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.

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.

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.

Language and the Cerebellum: Structural Connectivity to the Eloquent Brain.

Neurobiological models of receptive language have focused on the left-hemisphere perisylvian cortex with the assumption that the cerebellum supports peri-linguistic cognitive processes such as verbal working memory. The goal of this study was to identify language-sensitive regions of the cerebellum then map the structural connectivity profile of these regions. Functional imaging data and diffusion-weighted imaging data from the Human Connectome Project (HCP) were analyzed. We found that (a) working memory, motor activity, and language comprehension activated partially overlapping but mostly unique subregions of the cerebellum; (b) the linguistic portion of the cerebello-thalamo-cortical circuit was more extensive than the linguistic portion of the cortico-ponto-cerebellar tract; (c) there was a frontal-lobe bias in the connectivity from the cerebellum to the cerebrum; (d) there was some degree of specificity; and (e) for some cerebellar tracts, individual differences in picture identification ability covaried with fractional anisotropy metrics. These findings yield insights into the structural connectivity of the cerebellum as relates to the uniquely human process of language comprehension.

Assessment of frontal lobe functions in a sample of male cannabis users currently in abstinence: correlations with duration of use and their functional outcomes.

BACKGROUND: Previous research literature reported different results regarding the long-term effects that cannabis use can exert on the frontal lobe neurocognitive functions of its users. Another body of research suggested that cannabis use negatively affects the person's general level of occupational and psychosocial functioning consequently to these alterations. Some other research results did not support these findings. To date, it is still debatable whether chronic cannabis use triggers negative neurocognitive effects in chronic users even after a period of abstinence. Research data exploring consequent adverse outcomes on the general individual occupational and psychosocial functioning is not yet conclusive. RESULTS: We conducted this study to examine the residual neurocognitive effects of cannabis use, whether it is affected by duration of cannabis use before abstinence, and its relation to individual's global assessment of functioning exhibited in the person's occupational and social life whether it's family or friends. Our sample comprised 80 male participants (18-45 years old) who were grouped into 4 groups (3 groups with different durations of use and a control group), with no significant difference between the four studied groups regarding age, education, and socioeconomic level. The Kruskal Wallis test was used to test the significance of differences in the distribution of total frontal lobe battery results and the general assessment of function scores using GAF scores between study groups. Post hoc testing was performed to adjust for multiple comparisons using Bonferroni method. CONCLUSION: Data analysis showed that cannabis users experienced general functional disturbances that encompass impairments in social and occupational life aspects. These impairments in function are correlated with the presence of neurocognitive deficits even after a period of abstinence. Both having significant positive correlation with longer duration of cannabis use.

Association of severe hyposmia and frontal lobe dysfunction in patients with Parkinson's disease.

BACKGROUNDS AND OBJECTIVES: Severe hyposmia (SH) is a prodromal symptom of dementia associated with Parkinson's disease (PD) caused by Lewy bodies deposited in the limbic regions that connect the frontal and temporal lobes. We aimed to clarify the association between hyposmia and frontal lobe dysfunction (FLD) among patients with PD. METHODS: Patients with PD and Hoehn & Yahr stage 1-3 at on-periods without apparent dementia were screened. FLD was defined as a score of ≤14 on the Frontal Assessment Battery (FAB). SH was defined as an average recognition threshold >4 in the T&T Olfactometer. For each subscore, a recognition score of ≥4 was defined as SH. We examined whether SH and its subscores were associated with FLD and evaluated which FAB subscore might be lower in PD patients with SH using Poisson regression analysis with a robust variance estimator. RESULTS: We included 189 patients (median age, 68 years; 107 [57 %] male). FLD was observed in 53 (28 %) patients. Multivariable analysis showed that SH (PR 1.789, 95 % confidence intervals (CI) 1.115-2.872, p = 0.016) was associated with FLD. Regarding odor domains, only SH for fruity smells was associated with FLD (PR 1.970, 95 % CI 1.306-2.972, p = 0.001). Patients with SH had a higher subscore only for FAB-1 (similarity [conceptualization], p = 0.030), indicating linguistically mediated executive dysfunction. CONCLUSION: In patients with PD, SH is associated with FLD, especially with linguistically mediated executive dysfunction. Particularly, SH for fruity smells may be a sensitive indicator of FLD.

Frontal brain volume correlates of impaired executive function in schizophrenia.

Cognitive impairments affect functional capacity in individuals with schizophrenia (SZH), but their neural basis remains unclear. The Wisconsin Card Sorting Test (WCST), and the Stroop Task (SCWT), are paradigmatic tests which have been used extensively for examining executive function in SZH. However, few studies have explored how deficits on these tasks link to brain volume differences commonly seen in SZH. Here, for the first time, we tested associations between FreeSurfer-derived frontal brain volumes and performance on both WCST and SCWT, in a well-matched sample of 57 SZH and 32 control subjects. We also explored whether these associations were dissociable from links to symptom severity in SZH. Results revealed correlations between volumes and task performance which were unique to SZH. In SZH only, volumes of right middle frontal regions correlated with both WCST and Stroop performance: correlation coefficients were significantly different to those present in the control group, highlighting their specificity to the patient group. In the Stroop task, superior frontal regions also showed associations with Stroop interference scores which were unique to SZH. These findings provide important detail around how deficits on these two paradigmatic executive function tasks link to brain structural differences in SZH. Results align with converging evidence suggesting that neuropathology within right middle frontal regions (BA9 and BA46) might be of particular import in SZH. No volumetric associations with symptom severity were found, supporting the notion that the structural abnormalities underpinning cognitive deficits in SZH differ from those associated with symptomatology.

Secretory Meningioma of the Right Frontal Lobe: Clinical Presentation and Pathological Insights.

This article presents a case study of a rare convexity meningioma located in the frontal lobe of the right cerebellar hemisphere. Meningiomas comprise a substantial part of central nervous system neoplasms and are classified into benign, atypical, or anaplastic categories, each encompassing a variety of histological subtypes, among which the secretory meningioma is notably rare. A 77-year-old male presented with a clinical history of headache, impaired memory functions, an initial form of apathetic-abulic syndrome, and a single seizure, which were considered to be indicative of epileptic symptoms that had been present for several weeks. The imaging studies conducted showed a convexity tumor characterized by a rounded morphology and homogeneous contrast enhancement, positioned adjacent to the frontal lobe's cortical surface. This clinical report details the pathology of a secretory type of meningioma, which is distinguished by the atypical epithelial differentiation of meningothelial cells, resulting in hyaline fiber production. The neoplasm's anatomical accessibility permitted successful surgical resection. The tumor's position was appropriate for surgical removal, and the histological variant, along with the patient's favorable clinical course, is of particular scientific interest.

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.

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.

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.

Case Report: Focal, generalized, or both: does generalized network involvement preclude successful epilepsy surgery?

We present two cases with focal seizures where scalp electroencephalography (EEG) had prominent features of a developmental and epileptic encephalopathy (DEE): Case 1: a 17-year-old male with complex motor seizures whose EEG demonstrated a slow spike-and-wave pattern and generalized paroxysmal fast activity (GPFA). Case 2: a 12-year-old male with startle-induced asymmetric tonic seizures whose EEG also had a slow spike-and-wave pattern. Both patients had intracranial EEG assessment, and focal cortical resections resulted in long-term seizure freedom and resolution of generalized findings. These cases exemplify patients with focal epilepsy with networks that share similarities to generalized epilepsies, and importantly, these features did not preclude curative epilepsy surgery.

Motor Intentions Decoded from fMRI Signals.

Motor intention is a high-level brain function related to planning for movement. Although studies have shown that motor intentions can be decoded from brain signals before movement execution, it is unclear whether intentions relating to mental imagery of movement can be decoded. Here, we investigated whether differences in spatial and temporal patterns of brain activation were elicited by intentions to perform different types of motor imagery and whether the patterns could be used by a multivariate pattern classifier to detect such differential intentions. The results showed that it is possible to decode intentions before the onset of different types of motor imagery from functional MR signals obtained from fronto-parietal brain regions, such as the premotor cortex and posterior parietal cortex, while controlling for eye movements and for muscular activity of the hands. These results highlight the critical role played by the aforementioned brain regions in covert motor intentions. Moreover, they have substantial implications for rehabilitating patients with motor disabilities.

Unraveling the Pathogenesis of Post-Stroke Depression in a Hemorrhagic Mouse Model through Frontal Lobe Circuitry and JAK-STAT Signaling.

Post-stroke depression is a common complication that imposes significant burdens and challenges on patients. The occurrence of depression is often associated with frontal lobe hemorrhage, however, current understanding of the underlying mechanisms remains limited. Here, the pathogenic mechanisms associated with the circuitry connectivity, electrophysiological alterations, and molecular characteristics are investigated related to the frontal lobe in adult male mice following unilateral injection of blood in the medial prefrontal cortex (mPFC). It is demonstrated that depression is a specific neurological complication in the unilateral hematoma model of the mPFC, and the ventral tegmental area (VTA) shows a higher percentage of connectivity disruption compared to the lateral habenula (LHb) and striatum (STR). Additionally, long-range projections originating from the frontal lobe demonstrate higher damage percentages within the connections between each region and the mPFC. mPFC neurons reveal reduced neuronal excitability and altered synaptic communication. Furthermore, transcriptomic analysis identifies the involvement of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway, and targeting the JAK-STAT pathway significantly alleviates the severity of depressive symptoms. These findings improve the understanding of post-hemorrhagic depression and may guide the development of efficient treatments.

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.

Clinical application of transcranial neuroendoscopy combined with supraorbital keyhole approach in minimally invasive surgery of the anterior skull base.

To explore the techniques, safety, and feasibility of minimally invasive neurosurgery through the supraorbital eyebrow arch keyhole approach by neuroendoscopy. Retrospective analysis of clinical data of patients with various cranial diseases treated by transcranial neuroendoscopic supraorbital eyebrow keyhole approach in our hospital from March 2021 to October 2023. A total of 39 complete cases were collected, including 21 cases of intracranial aneurysms, 9 cases of intracranial space occupying lesions, 5 cases of brain trauma, 3 cases of cerebrospinal fluid rhinorrhea, and 1 case of cerebral hemorrhage. All patients' surgeries were successful. The good prognosis rate of intracranial aneurysms was 17/21 (81%), and the symptom improvement rate of intracranial space occupying lesions was 8/9 (88.9%). Among them, the initial symptoms of one patient with no improvement were not related to space occupying, while the total effective rate of the other three types of patients was 9/9 (100%). The average length of the craniotomy bone window of the supraorbital eyebrow arch keyhole is 3.77 ± 0.31 cm, and the average width is 2.53 ± 0.23 cm. The average postoperative hospital stay was 14.77 ± 6.59 days. The average clearance rate of hematoma by neuroendoscopy is 95.00% ± 1.51%. Our results indicate that endoscopic surgery through the supraorbital eyebrow arch keyhole approach is safe and effective for the treatment of anterior skull base lesions and cerebral hemorrhage. However, this retrospective study is a single center, small sample study, and the good surgical results do not exclude the subjective screening of suitable patients by clinical surgeons, which may have some bias. Although the clinical characteristics such as indications and contraindications of this surgical method still require further prospective and multicenter clinical research validation, our study still provides a new approach and choice for minimally invasive surgical treatment of anterior skull base lesions.

Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs.

Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.