Delayed recovery from ataxic dementia following liposuction.

A 19-year-old student developed hypoventilation and cyanosis at the end of a cosmetic liposuction procedure. She was awake, but severely abulic, disoriented, and unable to stand and walk due to severe locomotor ataxia. Neuropsychological evaluation showed psychomotor slowness, and deficits in memory encoding and retrieval, and on executive, and visuospatial and visuoperceptual tests; oral comprehension and constructional praxis were spared. ¹H-MRS showed a reduction of NAA. A year later, her cognitive and neurological exam, and NAA returned to normal, and she resumed her normal life. The severity of the acute manifestations of hypoxic encephalopathy not always entail a poor prognosis.

The extended neural architecture of human attachment: An fMRI coordinate-based meta-analysis of affiliative studies.

Functional imaging studies and clinical evidence indicate that cortical areas relevant to social cognition are closely integrated with evolutionarily conserved basal forebrain structures and neighboring regions, enabling human attachment and affiliative emotions. The neural circuitry of human affiliation is continually being unraveled as functional magnetic resonance imaging (fMRI) becomes increasingly prevalent, with studies examining human brain responses to various attachment figures. However, previous fMRI meta-analyses on affiliative stimuli have encountered challenges, such as low statistical power and the absence of robustness measures. To address these issues, we conducted an exhaustive coordinate-based meta-analysis of 79 fMRI studies, focusing on personalized affiliative stimuli, including one's infants, family, romantic partners, and friends. We employed complementary coordinate-based analyses (Activation Likelihood Estimation and Signed Differential Mapping) and conducted a robustness analysis of the results. Findings revealed cluster convergence in cortical and subcortical structures related to reward and motivation, salience detection, social bonding, and cognition. Our study thoroughly explores the neural correlates underpinning affiliative responses, effectively overcoming the limitations noted in previous meta-analyses. It provides an extensive view of the neural substrates associated with affiliative stimuli, illuminating the intricate interaction between cortical and subcortical regions. Our findings significantly contribute to understanding the neurobiology of human affiliation, expanding the known human attachment circuitry beyond the traditional basal forebrain regions observed in other mammals to include uniquely human isocortical structures.

Kraepelin's schizophasia: Chaotic speech with preservation of comprehension and activities of daily living.

BACKGROUND: In his classic account of dementia praecox Kraepelin reserved a few pages for a small number of psychotic patients with disorganized speech but who retained the ability to cope with their daily lives. CASE REPORT: A 49-year-old homemaker has been suffering from a continuous hallucinatory-delusional state since she was 24 years old. Her verbal and written language was chaotic and full of neologisms, but fluent and grammatically correct. Speech disorganization was roughly proportional to the need to express ideas and thoughts through creative speech. She followed verbal, written, and visuo-gestural commands and flawlessly repeated words and sentences of variable length. She read aloud and discussed the news properly. She ran the house, cooked for her relatives, and went to the supermarket and the bank alone. She knew the prices of common goods and handled money with ease. The unique coexistence of (i) chaotic speech, (ii) preservation of aural, written, and gestural comprehension, and (iii) organized non-verbal behavior, in patients (iv) in a chronic delusional-hallucinatory state is the hallmark of the syndrome of "schizophasia" originally described by Kraepelin. The main features of Kraepelin's schizophasia are vividly illustrated by videos and photos of the patient during her daily life. DISCUSSION: The differential diagnosis of schizophasia is reviewed, especially with the sensory aphasias (Wernicke's and transcortical), from which the confusional speech of our patient was differentiated by her preserved ability to repeat and understand spoken and written language. Because her primary language abilities were spared, the cardinal deficit seems to lie at the interface where thoughts and ideas are encoded into expressive language. CONCLUSION: The expression "Kraepelin's schizophasia" should be restricted to the speech-behavioral dissociation first observed by Kraepelin in chronic psychotic patients. The term "schizophasia", in turn, should be kept as a generic designation for any language alteration in schizophrenia.

Aberrant impulse control circuitry in obesity.

The ventromedial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) circuit has been implicated in impulsive reward-seeking. This disinhibition has been implicated in obesity and often manifests as binge eating, which is associated with worse treatment outcomes and comorbidities. It remains unclear whether the vmPFC-NAc circuit is perturbed in impulsive eaters with obesity. Initially, we analyzed publicly available, high-resolution, normative imaging data to localize where vmPFC structural connections converged within the NAc. These structural connections were found to converge ventromedially in the presumed NAc shell subregion. We then analyzed multimodal clinical and imaging data to test the a priori hypothesis that the vmPFC-NAc shell circuit is linked to obesity in a sample of female participants that regularly engaged in impulsive eating (i.e., binge eating). Functionally, vmPFC-NAc shell resting-state connectivity was inversely related to body mass index (BMI) and decreased in the obese state. Structurally, vmPFC-NAc shell structural connectivity and vmPFC thickness were inversely correlated with BMI; obese binge-prone participants exhibited decreased vmPFC-NAc structural connectivity and vmPFC thickness. Finally, to examine a causal link to binge eating, we directly probed this circuit in one binge-prone obese female using NAc deep brain stimulation in a first-in-human trial. Direct stimulation of the NAc shell subregion guided by local behaviorally relevant electrophysiology was associated with a decrease in number of weekly episodes of uncontrolled eating and decreased BMI. This study unraveled vmPFC-NAc shell circuit aberrations in obesity that can be modulated to restore control over eating behavior in obesity.

Modern neurosurgical techniques for psychiatric disorders.

Psychosurgery refers to an ensemble of more or less invasive techniques designed to reduce the burden caused by psychiatric diseases in patients who have failed to respond to conventional therapy. While most surgeries are designed to correct apparent anatomical abnormalities, no discrete cerebral anatomical lesion is evident in most psychiatric diseases amenable to invasive interventions. Finding the optimal surgical targets in mental illness is troublesome. In general, contemporary psychosurgical procedures can be classified into one of two primary modalities: lesioning and stimulation procedures. The first group is divided into (a) thermocoagulation and (b) stereotactic radiosurgery or recently introduced transcranial magnetic resonance-guided focused ultrasound, whereas stimulation techniques mainly include deep brain stimulation (DBS), cortical stimulation, and the vagus nerve stimulation. The most studied psychiatric diseases amenable to psychosurgical interventions are severe treatment-resistant major depressive disorder, obsessive-compulsive disorder, Tourette syndrome, anorexia nervosa, schizophrenia, and substance use disorder. Furthermore, modern neuroimaging techniques spurred the interest of clinicians to identify cerebral regions amenable to be manipulated to control psychiatric symptoms. On this way, the concept of a multi-nodal network need to be embraced, enticing the collaboration of psychiatrists, psychologists, neurologists and neurosurgeons participating in multidisciplinary groups, conducting well-designed clinical trials.

Safety and Feasibility of Nucleus Accumbens Surgery for Drug Addiction: A Systematic Review.

BACKGROUND: Substance addiction encompasses the incapacity to discontinue urgent drug use; many severely disabled patients might be considered appropriate candidates for surgery due to the high rates of relapse despite conservative treatment. A crucial finding in the brain of these patients is increased extracellular concentrations of dopamine in the nucleus accumbens (NAcc). OBJECTIVES: To determine the efficacy and safety of NAcc surgery for the treatment of substance dependence. MATERIALS AND METHODS: Adhering to PRISMA guidelines, we performed a systematic review to identify all original studies in which NAcc surgery was performed to treat relapsing drug addiction with a minimum follow-up of six months. From database inception to April 10, 2020, we searched PubMed, Scopus, and LILACS. Two reviewers independently selected studies and extracted data. The main outcome was the relapse rate. The GRADE methods were applied to evaluate the quality of evidence. This study was registered with PROSPERO CRD42020177054. RESULTS: Fifteen studies involving 359 participants met inclusion criteria; eight (56%) included NAcc deep brain stimulation (DBS) in 13 patients with addiction for alcohol (N = 6, 46.1%), opioid (N = 4, 30.7%), and nicotine (N = 3, 15.3%); seven studies (N = 346, 44%) performed NAcc radiofrequency (RF) ablation for opioid (N = 334) and alcohol (N = 12) dependence. Relapse rates were 38.4% for DBS and 39% for RF ablation. CONCLUSIONS: Despite available studies reporting a benefit in the treatment of drug addictions with NAcc surgery, this systematic review stresses the need for carefully planned prospective studies in order to further address the efficacy and indications.

A presumptive association between obsessive compulsions and asymmetric temporal lobe atrophy: a case report.

BACKGROUND: The relatively isolated atrophy of the temporal lobes leads to a clinical radiological pattern, referred to as the temporal variant of frontotemporal dementia. While semantic dementia and behavioral variant frontotemporal dementia are classically related to this syndrome, the logopenic variant of primary progressive aphasia has been less commonly reported. This case report aims to give a pictorial description of a case in which a patient with asymmetric temporal lobe atrophy presented with the logopenic variant of primary progressive aphasia and complex rituals of cleanliness. CASE PRESENTATION: We report on the case of a 68-year-old, right-handed White woman with complex rituals and progressive speech impairment. The obsessive-compulsive rituals represented an exacerbation of lifelong preoccupations with cleanliness and orderliness that were praised by her relatives. Neuropsychological assessment revealed a striking impairment of language and memory, with relative sparing of tool-use praxis and visuospatial skills. Magnetic resonance imaging and 18fluorodeoxyglucose-positron emission tomography scans showed bilateral asymmetrical temporal lobe atrophy and hypometabolism. A year later, she was still able to entertain conversation for a short while, but her vocabulary and fluency had further declined. Praxis and visuospatial skills remained intact. She did not experience pathological elation, delusions, or hallucinations. The disease followed a relentless progression into a partial Klüver-Bucy syndrome, abulia, and terminal dementia. She died from acute myocardial infarction 8 years after the onset of aphasia. The symptoms and their temporal course supported a diagnosis of logopenic variant of primary progressive aphasia due to asymmetric temporal variant frontotemporal lobar degeneration. CONCLUSIONS: This report gives a pictorial description of a temporal variant of frontotemporal dementia in a patient who presented with worsening of a lifelong obsessive-compulsive disorder and logopenic variant of primary progressive aphasia.

Striatal and septo-hypothalamic responses to anticipation and outcome of affiliative rewards.

Humans are intrinsically motivated to bond with others. The ability to experience affiliative emotions (such as affection/tenderness, sexual attraction, and admiration/awe) may incentivize and promote these affiliative bonds. Here, we interrogate the role of the critical reward circuitry, especially the Nucleus Accumbens (NAcc) and the septo-hypothalamic region, in the anticipation of and response to affiliative rewards using a novel incentive delay task. During Functional Magnetic Resonance Imaging (FMRI), participants (n = 23 healthy humans; 14 female) anticipated and watched videos involving affiliative (tenderness, erotic desire, and awe) and nonaffiliative (i.e., food) rewards, as well as neutral scenes. On the one hand, anticipation of both affiliative and nonaffiliative rewards increased activity in the NAcc, anterior insula, and supplementary motor cortex, but activity in the amygdala and the ventromedial prefrontal cortex (vmPFC) increased in response to reward outcomes. On the other hand, affiliative rewards more specifically increased activity in the septo-hypothalamic area. Moreover, NAcc activity during anticipation correlated with positive arousal for all rewards, whereas septo-hypothalamic activity during the outcome correlated with positive arousal and motivation for subsequent re-exposure only for affiliative rewards. Together, these findings implicate a general appetitive response in the NAcc to different types of rewards but suggests a more specific response in the septo-hypothalamic region in response to affiliative rewards outcomes. This work also presents a new task for distinguishing between neural responses to affiliative and non-affiliative rewards.

The neuroscience of social feelings: mechanisms of adaptive social functioning.

Social feelings have conceptual and empirical connections with affect and emotion. In this review, we discuss how they relate to cognition, emotion, behavior and well-being. We examine the functional neuroanatomy and neurobiology of social feelings and their role in adaptive social functioning. Existing neuroscience literature is reviewed to identify concepts, methods and challenges that might be addressed by social feelings research. Specific topic areas highlight the influence and modulation of social feelings on interpersonal affiliation, parent-child attachments, moral sentiments, interpersonal stressors, and emotional communication. Brain regions involved in social feelings were confirmed by meta-analysis using the Neurosynth platform for large-scale, automated synthesis of functional magnetic resonance imaging data. Words that relate specifically to social feelings were identfied as potential research variables. Topical inquiries into social media behaviors, loneliness, trauma, and social sensitivity, especially with recent physical distancing for guarding public and personal health, underscored the increasing importance of social feelings for affective and second person neuroscience research with implications for brain development, physical and mental health, and lifelong adaptive functioning.

A case of developmental pedophilia unmasked by frontotemporal dementia.

A 65-year-old right-handed man gradually became socially indifferent and less active. Four years later, he was indicted for molesting children on multiple occasions. Psychomotor slowness and executive impairment contrasted with sparing of language, semantic memory, visuospatial perception, construction praxis, and right-left orientation. Neuroimaging showed asymmetric atrophy of dorsomedial frontal and anterior temporal lobes, and hypoperfusion of medial prefrontal cortex consistent with a diagnosis of behavioral variant of frontotemporal dementia. Further information revealed that the patient exhibited pedophilic behavior several years prior to symptom onset. We conclude that preexisting developmental pedophilia was "unmasked" by the underlying progressive frontotemporal degeneration.

Case Report: Catatonic Stupor in Behavioral Variant Frontotemporal Dementia.

Catatonia is a psychomotor syndrome common to several medical and neuropsychiatric disorders. Here, we report on the case of a 95-year-old woman who underwent a radical change in personality characterized by sexual disinhibition, and physical and verbal aggressiveness. Over several months, she developed verbal stereotypies, gait deterioration, and double incontinence. She eventually developed mutism and an active opposition to all attempts to be fed or cared for. Benzodiazepines, olanzapine and electroconvulsive therapy were of no benefit. Magnetic resonance imaging revealed asymmetric (more severe on the right) frontotemporal, parietal, and upper brainstem atrophy. She died from sepsis without recovering from stupor seven years after the onset of symptoms. We believe that the initial behavioral disinhibition was related to the frontotemporal injury, whereas catatonic stupor reflected the progression of the degenerative process to the parietal cortices. Our case adds to the small number of cases of catatonia as a symptom of degenerative dementia. It also supports the idea that damage to the parietal cortex gives rise to pathological avoidance of which catatonic stupor represents an extreme form.

Upholding Scientific Duty Amidst Poisonous Disinformation.

Because of a recent politically-biased Lancet editorial, the world's opinion has been directed against the Brazilian government over the rising numbers of COVID-19 cases in the country. This is an example of reporting data without accounting for important covariates. Epidemiological figures should always be corrected for population size. In fact, Brazil is not even on the list of the 10 countries with the highest number of deaths per 100,000 people. Belgium, the United Kingdom, and Spain are the most affected countries in this regard. The disinformation presented by a renowned medical journal has ignited severe criticisms against a Chief-of-State for not promoting a generalized lockdown in a country of continental size. As scientists, we have a duty to stress the caveats of science instead of fueling political attacks, and we should refrain from jumping to uninformed conclusions without considering well-analyzed data. Moreover, while there is no evidence to endorse the efficacy of a generalized lockdown in socioeconomically vulnerable populations, it is undoubtedly associated with severe nationwide adverse effects.

Exploring response inhibition and error monitoring in obsessive-compulsive disorder.

Behavioral evidence of impaired response inhibition (RI) and hyperactive error monitoring (EM) in obsessive-compulsive disorder (OCD) is inconsistent. Recent neuroimaging work suggests that EM plays a role in RI impairments in OCD, but this has rarely been investigated using behavioral measures. The aims of this study were to (1) compare RI and EM performance between adults with OCD and non-psychiatric controls (NPC) while investigating possible moderators, and (2) assess whether excessive EM influences RI in OCD. We compared RI and EM performance on the Stop-Signal Task (SST) between 92 adults with OCD and 65 NPC from two Brazilian sites. We used linear regression to investigate which variables (group, age, medication use, clinical symptomatology) influenced performance, as well as to examine possible associations between RI and EM. OCD and NPC did not differ in RI and EM. However, age moderated RI performance in OCD with a medium effect size, reflecting differential effects of age on RI between groups: age was positively associated with RI in OCD but not NPC. Further, OCD severity predicted EM with a medium to large effect size, suggesting that more symptomatic patients showed greater monitoring of their mistakes. Finally, group moderated the relationship between RI and EM with a small effect size. Our findings suggest that demographic factors may influence RI, whereas clinical factors may influence EM. Further, we found preliminary behavioral evidence to indicate that impaired RI and excessive EM are related in OCD.

The Neurology of Acquired Pedophilia.

The clinicoanatomic cases of acquired pedophilia that have been published in the medical and forensic literature up to 2019 are reviewed. Twenty-two cases fit our inclusion criteria. All but one were men, and in only one case the injury was localized to the left hemisphere. Hypersexuality was present in 18 cases. The damaged areas fell within the frontotemporoinsular cortices and related subcortical nuclei; however, the anterior hypothalamus was spared. Damage to parts of the right frontotemporoinsular lobes with sparing of the anterior hypothalamus seems to be critical for the emergence of acquired pedophilia.

Self-reported and neurocognitive impulsivity in obsessive-compulsive disorder.

BACKGROUND: Although a behavioural addiction model of obsessive-compulsive disorder (OCD) has been proposed, it is still unclear if and how self-report and neurocognitive measures of impulsivity (such as risk-taking-, reflection- and motor-impulsivities) are impaired and/or inter-related in this particular clinical population. METHODS: Seventeen OCD patients and 17 age-, gender-, education- and IQ-matched controls completed the Barratt Impulsivity Scale, the Obsessive-Compulsive Inventory-Revised, and the Beck Depression Inventory and were evaluated with the Yale-Brown Obsessive-Compulsive Scale and three computerized paradigms including reward (the Cambridge Gambling Task), reflection (the Information Sampling Task) and motor impulsivity (Stop Signal Task). RESULTS: Despite not differing from healthy controls in any neurocognitive impulsivity domain, OCD patients demonstrated increased impulsivity in a self-report measure (particularly attentional impulsivity). Further, attentional impulsivity was predicted by severity of obsessive-compulsive symptoms. CONCLUSIONS: Our findings suggest that OCD is characterized by a subjective (rather than objective) impulsivity; in addition, self-reported impulsivity was largely determined by severity of OCD symptoms.

Moral Motivation and the Basal Forebrain.

Moral motivations drive humans to sacrifice selfish needs to serve the needs of others and internalized sociocultural norms. Over the past two decades, several brain regions have been associated with different aspects of moral cognition and behaviour. Only more recently, however, investigations have highlighted the importance of the basal forebrain for moral motivation. This includes the septo-hypothalamic region, implicated in kinship bonding across mammal species, and the closely connected subgenual frontal cortex. Understanding the neuroanatomy of moral motivation and its impairments will be fundamental for future research aiming to promote prosocial behaviour and mental health.

Narrative impairment, white matter damage and CSF biomarkers in the Alzheimer's disease spectrum.

BACKGROUND: Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied. OBJECTIVES: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum. RESULTS: Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aß1-42 ratio in CSF. CONCLUSIONS: AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF. METHODS: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.

Moral conduct and social behavior.

Over the past 150 years, the frontal lobes (FLs) have been implicated in the neural mediation of both normal and abnormal moral conduct and social behavior (MCSB). Despite the remarkable advances that have permeated this period up to the present, a comprehensive account of the neural underpinnings of MCSB has stubbornly defied the best minds of psychology, psychiatry, and neurology. The goal of this chapter is to review a few practical and conceptual achievements that have proved heuristically valuable as an impetus for further advance of knowledge. In virtually all cases in which MCSB was compromised by brain damage, the injuries were located (i) in the prefrontal cortices, (ii) in their connections with the temporal poles and anterior insula, or (iii) in related subcortical structures and pathways, such as the thalamic dorsomedial nucleus or the anterior thalamic radiation. The clinicoanatomic associations among these structures originated the "frontal network systems" concept, which satisfactorily explains the occurrence of classical FL syndromes in patients with lesions outside the prefrontal cortices. Overall, clinicoanatomic observational studies and experimental evidence from patients with acquired sociopathy/psychopathy indicate that abnormalities of MCSB are the final common pathway of single or mixed impairments of subordinate psychologic and neural domains that support MCSB. Independent studies on normal volunteers concur with this view, indicating that MCSB is shaped by the dynamic interplay of subordinate psychologic domains, such as moral sensitivity and judgment, and their neural correlates.

Blame-rebalance fMRI neurofeedback in major depressive disorder: A randomised proof-of-concept trial.

Previously, using fMRI, we demonstrated lower connectivity between right anterior superior temporal (ATL) and anterior subgenual cingulate (SCC) regions while patients with major depressive disorder (MDD) experience guilt. This neural signature was detected despite symptomatic remission which suggested a putative role in vulnerability. This randomised controlled double-blind parallel group clinical trial investigated whether patients with MDD are able to voluntarily modulate this neural signature. To this end, we developed a fMRI neurofeedback software (FRIEND), which measures ATL-SCC coupling and displays its levels in real time. Twenty-eight patients with remitted MDD were randomised to two groups, each receiving one session of fMRI neurofeedback whilst retrieving guilt and indignation/anger-related autobiographical memories. They were instructed to feel the emotion whilst trying to increase the level of a thermometer-like display on a screen. Active intervention group: The thermometer levels increased with increasing levels of ATL-SCC correlations in the guilt condition. Control intervention group: The thermometer levels decreased when correlation levels deviated from the previous baseline level in the guilt condition, thus reinforcing stable correlations. Both groups also received feedback during the indignation condition reinforcing stable correlations. We confirmed our predictions that patients in the active intervention group were indeed able to increase levels of ATL-SCC correlations for guilt vs. indignation and their self-esteem after training compared to before training and that this differed significantly from the control intervention group. These data provide proof-of-concept for a novel treatment target for MDD patients and are in keeping with the hypothesis that ATL-SCC connectivity plays a key role in self-worth. https://clinicaltrials.gov/ct2/show/results/NCT01920490.

Cortical lateralization of cheirosensory processing in callosal dysgenesis.

The paradoxical absence of a split-brain syndrome in most cases of callosal dysgenesis has originated three main hypotheses, namely, (i) bilateral cortical representation of language, (ii) bilateral thalamocortical projections of somatosensory pathways conveyed by the spinothalamic-medial lemniscus system, and (iii) a variable combination of (i) and (ii). We used functional neuroimaging to investigate the cortical representation and lateralization of somatosensory information from the palm of each hand in six cases of callosal dysgenesis (hypothesis [ii]). Cortical regions of interest were contralateral and ipsilateral S1 (areas 3a and 3b, 1 and 2 in the central sulcus and postcentral gyrus) and S2 (parts of areas 40 and 43 in the parietal operculum). The degree of cortical asymmetry was expressed by a laterality index (LI), which may assume values from -1 (fully left-lateralized) to +1 (fully right-lateralized). In callosal dysgenesis, LI values for the right and the left hands were, respectively, -1 and + 1 for both S1 and S2, indicating absence of engagement of ipsilateral S1 and S2. In controls, LI values were - 0.70 (S1) and - 0.51 (S2) for right hand stimulation, and 0.82 (S1) and 0.36 (S2) for left hand stimulation, reflecting bilateral asymmetric activations, which were significantly higher in the hemisphere contralateral to the stimulated hand. Therefore, none of the main hypotheses so far entertained to account for the callosal dysgenesis-split-brain paradox have succeeded. We conclude that the preserved interhemispheric transfer of somatosensory tactile information in callosal dysgenesis must be mediated by a fourth alternative, such as aberrant interhemispheric bundles, reorganization of subcortical commissures, or both.