Bilateral hypogeusia and food aversion due to lacunar infarct in the right dorsomedial pontine tegmentum.

A 70-year-old right-handed housewife suffered an acute loss of taste, an unpleasant change in the taste of foods and liquids, and a strong aversion to all kinds of food due to a small lacune in the right dorsomedial pontine tegmentum. Eating became so unpleasant that she lost 7 kg in three weeks. Olfaction and the sensibility of the tongue were spared. The right medial longitudinal fascicle, the central tegmental tract, or both, were injured by the tegmental lesion. A discrete right-sided lesion in the upper pontine tegmentum may cause a reversible syndrome consisting of bilateral hypogeusia which is more severe ipsilaterally.

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.

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.

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.

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.

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.

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.

Altruistic decisions following penetrating traumatic brain injury.

The cerebral correlates of altruistic decisions have increasingly attracted the interest of neuroscientists. To date, investigations on the neural underpinnings of altruistic decisions have primarily been conducted in healthy adults undergoing functional neuroimaging as they engaged in decisions to punish third parties. The chief purpose of the present study was to investigate altruistic decisions following focal brain damage with a novel altruistic decision task. In contrast to studies that have focused either on altruistic punishment or donation, the Altruistic Decision Task allows players to anonymously punish or donate to 30 charitable organizations involved with salient societal issues such as abortion, nuclear energy and civil rights. Ninety-four Vietnam War veterans with variable patterns of penetrating traumatic brain injury and 28 healthy veterans who also served in combat participated in the study as normal controls. Participants were asked to invest $1 to punish or reward real societal organizations, or keep the money for themselves. Associations between lesion distribution and performance on the task were analysed with multivariate support vector regression, which enables the assessment of the joint contribution of multiple regions in the determination of a given behaviour of interest. Our main findings were: (i) bilateral dorsomedial prefrontal lesions increased altruistic punishment, whereas lesions of the right perisylvian region and left temporo-insular cortex decreased punishment; (ii) altruistic donations were increased by bilateral lesions of the dorsomedial parietal cortex, whereas lesions of the right posterior superior temporal sulcus and middle temporal gyri decreased donations; (iii) altruistic punishment and donation were only weakly correlated, emphasizing their dissociable neuroanatomical associations; and (iv) altruistic decisions were not related to post-traumatic personality changes. These findings indicate that altruistic punishment and donation are determined by largely non-overlapping cerebral regions, which have previously been implicated in social cognition and moral experience such as evaluations of intentionality and intuitions of justice and morality.10.1093/brain/awy064_video1awy064media15758316955001.

Hemispheric Dominance for Stereognosis in a Patient With an Infarct of the Left Postcentral Sensory Hand Area.

The concept of left hemispheric dominance for praxis, speech, and language has been one of the pillars of neurology since the mid-19th century. In 1906, Hermann Oppenheim reported a patient with bilateral stereoagnosia (astereognosis) caused by a left parietal lobe tumor and proposed that the left hemisphere was also dominant for stereognosis. Surprisingly, few cases of bilateral stereoagnosia caused by a unilateral cerebral lesion have been documented in the literature since then. Here we report a 75-year-old right-handed man who developed bilateral stereoagnosia after suffering a small infarct in the crown of the left postcentral gyrus. He could not recognize objects with either hand, but retained the ability to localize stimuli applied to the palm of his left (ipsilesional) hand. He was severely disabled in ordinary activities requiring the use of his hands. The lesion corresponded to Brodmann area 1, where probabilistic anatomic, functional, and electrophysiologic studies have located one of the multiple somatosensory representations of the hand. The lesion was in a strategic position to interrupt both the processing of afferent tactile information issuing from the primary somatosensory cortex (areas 3a and 3b) and the forward higher-order processing in area 2, the secondary sensory cortex, and the contralateral area 1. The lesion also deprived the motor hand area of its afferent regulation from the sensory hand area (grasping), while leaving intact the visuomotor projections from the occipital cortex (reaching). Our patient supports Oppenheim's proposal that the left postcentral gyrus of some individuals is dominant for stereognosis.

Structural and functional brain rewiring clarifies preserved interhemispheric transfer in humans born without the corpus callosum.

Why do humans born without the corpus callosum, the major interhemispheric commissure, lack the disconnection syndrome classically described in callosotomized patients? This paradox was discovered by Nobel laureate Roger Sperry in 1968, and has remained unsolved since then. To tackle the hypothesis that alternative neural pathways could explain this puzzle, we investigated patients with callosal dysgenesis using structural and functional neuroimaging, as well as neuropsychological assessments. We identified two anomalous white-matter tracts by deterministic and probabilistic tractography, and provide supporting resting-state functional neuroimaging and neuropsychological evidence for their functional role in preserved interhemispheric transfer of complex tactile information, such as object recognition. These compensatory pathways connect the homotopic posterior parietal cortical areas (Brodmann areas 39 and surroundings) via the posterior and anterior commissures. We propose that anomalous brain circuitry of callosal dysgenesis is determined by long-distance plasticity, a set of hardware changes occurring in the developing brain after pathological interference. So far unknown, these pathological changes somehow divert growing axons away from the dorsal midline, creating alternative tracts through the ventral forebrain and the dorsal midbrain midline, with partial compensatory effects to the interhemispheric transfer of cortical function.

The hypothalamus at the crossroads of psychopathology and neurosurgery.

The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.

Remission of lifelong episodic dyscontrol after bilateral dorsolateral temporal lobe damage.

A 45-year-old married woman with fits of episodic dyscontrol since an early age suffered a bilateral injury of the dorsolateral temporal lobe after which such episodes vanished for good. The remission of her lifelong proneness to aggression was so remarkable that her relatives and friends unanimously welcomed her "new personality". The post-traumatic taming in this case was an unanticipated collateral effect of brain damage with a salutary change of personality. This change possibly resulted from the release, due to the bitemporal injury, of inclinations that had not hitherto been fully expressed in the patient's mind and behavior due to the overriding influence of episodic dyscontrol on her ordinary conduct.

Right hemisphere dominance for language in a woman with schizophrenia and a porencephalic cyst of the left hemisphere.

A large left hemisphere porencephalic cyst was incidentally found in a 48-year-old woman (MS) with a Diagnostic and Statistical Manual (DSM)-5 diagnosis of schizophrenia. The encephaloclastic characteristics of the cyst indicated that it was acquired between the 22nd and 24th gestational weeks, after the major waves of neuronal migration had tapered off. The cyst destroyed the left temporal and occipital lobes, and the inferior parietal lobule. Surprisingly, MS had no evidence of aphasia, alexia, agraphia, or ideational apraxia; in contrast, cognitive functions dependent on the integrity of the right hemisphere were severely impaired. To test the hypothesis that the development of language in MS took place at the expense of functions that are normally carried out by the right hemisphere, we investigated MS's correlates of oral comprehension with fMRI as a proxy for auditory comprehension and other cognitive functions strongly lateralized to the posterior left hemisphere, such as ideational praxis and reading. Comprehension of spoken language engaged the homologous of Wernicke's area in the right planum temporale. Porencephaly may represent a natural model of neuroplasticity supervening at predictable epochs of prenatal development.

Immediate story recall in elderly individuals with memory complaints: how much does it contribute to memory assessment?

BACKGROUND: Prose memory tests exhibit ecological validity, but the influence of non-memory functions on immediate recall in elderly subjects with memory complaints has not been fully investigated. This study examined (1) whether the ability to immediately recall a story can distinguish among clinical controls, amnesic mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) and (2) which cognitive functions contribute to immediate recall performance. METHODS: A total of 73 consecutive volunteers (50 women and 23 men) aged 47-88 (mean age = 71.85 ± 9.41) and with a mean schooling level of 12.51 (SD = 4.09) participated in the experiment. All individuals were seeking specialized evaluation because of memory complaints. Diagnoses were made by considering clinical, neuropsychological, and MRI assessments collected by a multidisciplinary team of neurologists, neuropsychologists, and speech-language therapists. A total of 26 individuals were classified as clinical controls; 27 as MCI patients; and 20 as having AD dementia. All individuals in the AD group had a Clinical Dementia Rating (CDR) ≤ 1. RESULTS: Immediate recall was only able to distinguish AD subjects from MCI patients and clinical controls (p > 0.05). Stepwise multiple linear regression analysis revealed that mental status (MMSE), semantic memory (WAIS-III vocabulary) and episodic memory (RAVLT primacy) explained approximately 62% of the variance in immediate recall. CONCLUSIONS: Understanding the value and limitations of immediate story recall in distinguishing between MCI and AD may help clinicians in better choosing cognitive tests to diagnose MCI.

Functional dissociation of ventral frontal and dorsomedial default mode network components during resting state and emotional autobiographical recall.

Humans spend a substantial share of their lives mind-wandering. This spontaneous thinking activity usually comprises autobiographical recall, emotional, and self-referential components. While neuroimaging studies have demonstrated that a specific brain "default mode network" (DMN) is consistently engaged by the "resting state" of the mind, the relative contribution of key cognitive components to DMN activity is still poorly understood. Here we used fMRI to investigate whether activity in neural components of the DMN can be differentially explained by active recall of relevant emotional autobiographical memories as compared with the resting state. Our study design combined emotional autobiographical memory, neutral memory and resting state conditions, separated by a serial subtraction control task. Shared patterns of activation in the DMN were observed in both emotional autobiographical and resting conditions, when compared with serial subtraction. Directly contrasting autobiographical and resting conditions demonstrated a striking dissociation within the DMN in that emotional autobiographical retrieval led to stronger activation of the dorsomedial core regions (medial prefrontal cortex, posterior cingulate cortex), whereas the resting state condition engaged a ventral frontal network (ventral striatum, subgenual and ventral anterior cingulate cortices) in addition to the IPL. Our results reveal an as yet unreported dissociation within the DMN. Whereas the dorsomedial component can be explained by emotional autobiographical memory, the ventral frontal one is predominantly associated with the resting state proper, possibly underlying fundamental motivational mechanisms engaged during spontaneous unconstrained ideation.

Pathological generosity: an atypical impulse control disorder after a left subcortical stroke.

Changes in socio-emotional behavior and conduct, which are characteristic symptoms of frontal lobe damage, have less often been described in patients with focal subcortical injuries. We report on a case of pathological generosity secondary to a left lenticulocapsular stroke with hypoperfusion of several anatomically intact cortical areas. A 49-year-old man developed excessive and persistent generosity as he recovered from a left lenticulocapsular hematoma. His symptoms resembled an impulse control disorder. (99m)Tc-HMPAO SPECT demonstrated hypoperfusion mostly in the ipsilateral striatum, dorsolateral, and orbitofrontal cortex. This case study adds pathological generosity to the range of behavioral changes that may result from discrete unilateral lesions of the lenticular nucleus and nearby pathways. In our particular case, post-stroke pathological generosity was not ascribable to disinhibition, apathy, mania, or depression. Because pathological generosity may lead to significant distress and financial burden upon patients and their families, it may warrant further consideration as a potential type of impulse control disorder.

Late recovery from acquired sociopathy in a boy with a left frontopolar injury.

The long-term outcome of acquired sociopathy with preservation of cognition is still unknown. Here, we present the long-term outcome of a severe antisocial change in personality that followed a traumatic left frontopolar injury in a previously gentle, loving, and introverted adolescent. Nine years after the accident, antisocial behaviors gradually became sporadic, while, at the same time, the patient's sense of responsibility and care for his family increased. He became more extroverted and assertive, yet flexible enough to deal with the hardships of his poor socioeconomic background. His "new personality" was, in fact, more adjusted than ever. We argue that his late recovery reflected a conjunction of factors, especially (i) his early age, (ii) the static nature of the injury, (iii) the preservation of the ventromedial frontal cortices and related basal forebrain regions, and (iv) an unusual asymmetric representation of social cognition in the cerebral hemispheres. Our case and the case of Franz Binz indicate that social recovery is possible after gross prefrontal injuries, even when they are no longer expected to occur. It also emphasizes the importance of reporting on the long-term follow-up of brain-injured patients.

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.

A neural signature of affiliative emotion in the human septohypothalamic area.

Comparative studies have established that a number of structures within the rostromedial basal forebrain are critical for affiliative behaviors and social attachment. Lesion and neuroimaging studies concur with the importance of these regions for attachment and the experience of affiliation in humans as well. Yet it remains obscure whether the neural bases of affiliative experiences can be differentiated from the emotional valence with which they are inextricably associated at the experiential level. Here we show, using functional MRI, that kinship-related social scenarios evocative of affiliative emotion induce septal-preoptic-anterior hypothalamic activity that cannot be explained by positive or negative emotional valence alone. Our findings suggest that a phylogenetically conserved ensemble of basal forebrain structures, especially the septohypothalamic area, may play a key role in enabling human affiliative emotion. Our finding of a neural signature of human affiliative experience bears direct implications for the neurobiological mechanisms underpinning impaired affiliative experiences and behaviors in neuropsychiatric conditions.