Purpose: Some enigmatic remarks and behaviors of Socrates have been a subject of debate among scholars. We investigated the possibility of underlying epilepsy in Socrates by analyzing pathographic evidence in ancient literature from the viewpoint of the current understanding of seizure semiology. Methods: We performed a case study from a literature survey. Results: In 399 BCE, Socrates was tried and executed in Athens on the charge of “impiety.” His charges included the “introduction of new deities” and “not believing in (...) the gods of the state,” because he publicly claimed that he was periodically and personally receiving a “divine sign,” or daimonion, that directed him in various actions. We found textual evidence that his daimonion was probably a simple partial seizure (SPS) of temporal lobe origin. It was a brief voice that usually prohibited Socrates from initiating certain actions. It started when he was a child, and it visited Socrates unpredictably. Moreover, we found at least two descriptions of Socrates’ unique behavior that are consistent with complex partial seizures (CPSs). The fact that Socrates had been experiencing both SPSs and CPSs periodically since childhood makes the diagnosis of temporal lobe epilepsy (TLE) likely. Conclusions: We hypothesize that Socrates had a mild case of TLE without secondary generalization. This is the first report in 2,400 years to present a pathographic diagnosis of TLE in Socrates based on specific diagnostic features in the ancient textual evidence. Our study demonstrates that the knowledge of modern epileptology could help understand certain behaviors of historic figures. (shrink)

Religiosity is a prominent feature of the Geschwind syndrome, a behavioural pattern found in some cases of temporal lobe epilepsy. Since the 1950s, when Wilder Penfield induced spiritual feelings by experimental manipulation of the temporal lobes, development of brain imaging technology has revealed neural correlates of intense emotional states, spurring the growth of neurotheology. In their secular empiricism, psychiatry, neurology and psychology are inclined to pathologise deviant religious expression, thereby reinforcing the dualism of objective and phenomenal (...) worlds. Considering theological perspectives and the idea of cosmic consciousness, the authors urge a holistic approach to the spiritual events of epileptic aura, potentially leading to a deeper understanding of the mind and its transcendent potential. (shrink)

In this systematic review, we aim to describe the association between temporal lobe epilepsy and sleep, with bidirectional links in mechanisms and therapeutic aspects. Sleep stages may variably impact seizure occurrence, secondary generalization and the development, frequency and distribution of interictal epileptiform discharges. Conversely, epilepsy affects sleep micro- and macroarchitecture. TLE, the most frequent form of drug resistant epilepsy, shares an enduring relationship with sleep, with some intriguing potential mechanisms specific to anatomic localization, linking the (...) two. Sleep characteristics of TLE may also inform localizing properties in persons with DRE, since seizures arising from the temporal lobe seem to be more common during wakefulness, compared to seizures of extratemporal origin. Polysomnographic studies indicate that persons with TLE may experience excessive daytime somnolence, disrupted sleep architecture, increased wake after sleep onset, frequent shifts in sleep stages, lower sleep efficiency, decreased rapid eye movement sleep, and possibly, increased incidence of sleep apnea. Limited literature suggests that effective epilepsy surgery may remedy many of these objective and subjective sleep-related concerns, via multipronged effects, apart from reduced seizure frequency. Additionally, sleep abnormalities also seem to influence memory, language and cognitive-executive function in both medically controlled and refractory TLE. Another aspect of the relationship pertains to anti-seizure medications, which may contribute significantly to sleep characteristics and abnormalities in persons with TLE. Literature focused on specific aspects of TLE and sleep is limited, and heterogeneous. Future investigations are essential to understand the pathogenetic mechanisms linking sleep abnormalities on epilepsy outcomes in the important sub-population of TLE. (shrink)

To define the determinants of impaired facial emotion recognition (FER) in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS), we examined 76 patients with unilateral MTLE-HS, 36 prior to antero-mesial temporal lobectomy (AMTL) and 40 after AMTL, and 28 healthy control subjects with a FER test consisting of 60 items (20 each for anger, fear, and happiness). Mean percentages of the accurate responses were calculated for different subgroups: right vs. left MTLE-HS, early (age (...) at onset <6 years) vs. late-onset, and before vs. after AMTL. After controlling for years of education, duration of epilepsy and number of antiepileptic drugs (AEDs) taken, on multivariate analysis, fear recognition was profoundly impaired in early-onset right MTLE-HS patients compared to other MTLE patients and control subjects. Happiness recognition was significantly better in post-AMTL MTLE-HS patients compared to pre-AMTL patients while anger and fear recognition did not differ. We conclude that patients with right MTLE-HS with age at seizure onset <6 years are maximally predisposed to impaired fear recognition. In them, right AMTL does not further worsen FER abilities. Longitudinal studies comparing FER in the same patients before and after AMTL will be required to refine and confirm our cross-sectional observations. (shrink)

Preoperative mapping of language and declarative memory functions in temporal lobe epilepsy patients is essential since they frequently encounter deterioration of these functions and show variable degrees of cerebral reorganization. Due to growing evidence on language and declarative memory interdependence at a neural and neuropsychological level, we propose the GE2REC protocol for interactive language-and-memory network mapping. GE2REC consists of three inter-related tasks, sentence generation with implicit encoding and two recollection memory tasks: recognition and recall. This protocol has (...) previously been validated in healthy participants, and in this study, we showed that it also maps the LMN in the left TLE. Compared to healthy controls, left TLE showed widespread inter- and intra-hemispheric reorganization of the LMN through reduced activity of regions engaged in the integration and the coordination of this meta-network. We also illustrated how this protocol could be implemented in clinical practice individually by presenting two case studies of LTLE patients who underwent efficient surgery and became seizure-free but showed different cognitive outcomes. This protocol can be advantageous for clinical practice because it is short and easy to perform; allows brain mapping of essential cognitive functions, even at an individual level; engages language-and-memory interaction allowing to evaluate the integrative processes within the LMN; provides a more comprehensive assessment by including both verbal and visual modalities, as well as various language and memory processes. Based on the available postsurgical data, we presented preliminary results obtained with this protocol in LTLE patients that could potentially inform the clinical practice. This implies the necessity to further validate the potential of GE2REC for neurosurgical planning, along with two directions, guiding resection and describing LMN neuroplasticity at an individual level. (shrink)

BackgroundTemporal lobe epilepsy is the most prevalent refractory focal epilepsy and is more likely accompanied by cognitive impairment. The fully understanding of the neuronal activity underlying TLE is of great significance.ObjectiveThis study aimed to comprehensively explore the potential brain activity abnormalities affected by TLE and detect whether the changes were associated with cognition.MethodsSix static intrinsic brain activity indicators [amplitude of low-frequency fluctuation, fractional ALFF, regional homogeneity, degree centrality, global signal correlation, and voxel-mirrored homotopic connectivity ] and their (...) corresponding dynamic indicators, such as dynamic ALFF, dynamic fALFF, dynamic ReHo, dynamic DC, dynamic VMHC, and dynamic GSCorr, in 57 patients with unilateral TLE and 42 healthy volunteers were compared. Correlation analyses were also performed between these indicators in areas displaying group differences and cognitive function, epilepsy duration, and severity.ResultsMarked overlap was present among the abnormal brain regions detected using various static and dynamic indicators, primarily including increased ALFF/dALFF/fALFF in the bilateral medial temporal lobe and thalamus, decreased ALFF/dALFF/fALFF in the frontal lobe contralateral to the epileptogenic side, decreased fALFF, ReHo, dReHo, DC, dDC, GSCorr, dGSCorr, and VMHC in the temporal neocortex ipsilateral to the epileptogenic foci, decreased dReHo, dDC, dGSCorr, and dVMHC in the occipital lobe, and increased ALFF, fALFF, dfALFF, ReHo, and DC in the supplementary motor area ipsilateral to the epileptogenic foci. Furthermore, most IBA indicators in the abnormal brain region significantly correlated with the duration of epilepsy and several cognitive scale scores.ConclusionThe combined application of static and dynamic IBA indicators could comprehensively reveal more real abnormal neuronal activity and the impairment and compensatory mechanisms of cognitive function in TLE. Moreover, it might help in the lateralization of epileptogenic foci and exploration of the transmission and inhibition pathways of epileptic activity. (shrink)

Objective: The aim of the current study was to investigate the alterations in the neural networks of patients with temporal lobe epilepsy during working memory encoding.Methods: Patients with TLE and healthy volunteers completed a WM task, during which 34-channel electroencephalogram signals were recorded. The neural networks during WM encoding were calculated in TLE patients with and without WM deficits.Results: Functional connectivity strength decreased, and the theta network was altered in the TLE-WM group, although no significant differences in (...) clinical features were observed between the TLE-N and TLE-WM groups.Conclusions: Not all patients with TLE present with cognitive impairments and alterations in the theta network were identified in TLE patients with functional cognitive deficits.Significance: The theta network may represent a sensitive measure of cognitive impairment and could predict cognitive outcomes among patients with TLE. (shrink)

Objective The establishment of patient-centered measures capable of empirically determining meaningful cognitive change after surgery can significantly improve the medical care of epilepsy patients. Thus, this study aimed to develop reliable change indices (RCIs) and standardized regression-based (SRB) change norms for a comprehensive neuropsychological test battery in the German language. Methods Forty-seven consecutive patients with temporal lobe epilepsy underwent neuropsychological assessments, both before and 12 months after surgery. Practice-effect-adjusted RCIs and SRB change norms for each test (...) score were computed. To assess their usefulness, the presented methods were applied to a clinical sample, and binary logistic regression analyses were conducted to model the odds of achieving improvement in quality of life (QOL) after surgery. Results The determined RCIs at 90% confidence intervals and the SRB equations for each test score included in the test battery are provided. Cohen’s kappa analyses revealed a moderate mean agreement between the two measures, varying from slight to almost perfect agreement across test scores. Using these measures, a negative association between improvement in QOL and decline in verbal memory functions after surgery was detected (adjusted odds ratio = 0.09, p = 0.006). Significance To the best of our knowledge, this study is the first to develop RCIs and SRB change norms necessary for the objective determination of neuropsychological change in a comprehensive test battery in the German language, facilitating the individual monitoring of improvement and decline in each patients’ cognitive functioning and psychosocial situations after epilepsy surgery. The application of the described measures revealed a strong negative association between improvement in QOL and decline in verbal memory functions after surgery. (shrink)

Drug resistant epilepsy is one of the most complex, multifactorial and polygenic neurological syndrome. Besides its dynamicity and variability, it still provides us with a model to study brain-behavior relationship, giving cues on the anatomy and functional representation of brain function. Given that onset zone of focal epileptic seizures often affects different anatomical areas, cortical but limited to one hemisphere, this condition also let us study the functional differences of the left and right cerebral hemispheres. One lateralized function in (...) the human brain is emotional prosody, and it can be a useful ictal sign offering hints on the location of the epileptogenic zone. Besides its importance for effective communication, prosody is not considered an eloquent domain, making resective surgery on its neural correlates feasible. We performed an Electronic databases search (Medline and PsychINFO) from inception to July 2017 for studies about prosody in epilepsy. The search terms included “epilepsy,” “seizure,” “emotional prosody,” and “vocal affect.” This review focus on emotional prosody processing in epilepsy as it can give hints regarding plastic functional changes following seizures (preoperatively), resection (post operatively), and also as an ictal sign enabling the assessment of dynamic brain networks. Moreover, it is argued that such reorganization can help to preserve the expression and reception of emotional prosody as a central skill to develop appropriate social interactions. (shrink)

This essay provides a medical theory that could clarify enigmas surrounding the historical Socrates. It offers textual evidence that Socrates had temporal lobe epilepsy and that its two types of seizure manifested as recurrent voices and peculiar behaviour, both of which were notorious hallmarks of Socrates. Common and immediate criticisms against the methodology of retrospective diagnosis are addressed first. Next, the diagnostic reasoning is presented in detail. The possibility of temporal lobe personality in Socrates is (...) also considered. The important implication of this theory is that one of the charges against Socrates, introducing new divinities, was a now well-known neurologic symptom. (shrink)

The cognitive and behavioral functions of the frontal lobes have been of great interest to neuroscientists, neurologists, psychologists and psychiatrists. Recent technical advances have made it possible to trace their neuroanatomical connections more precisely and to conduct evoked potential and neuroimaging studies in patients. This book presents a broad and authoritative synthesis of research progress in this field. It encompasses neuroanatomical studies; experiments involving temporal organization and working memory tasks in non-human primates; clinical studies of patients following frontal (...) class='Hi'>lobe excisions for intractable epilepsy; metabolic imaging in schizophrenia and affective disorder; neurobehavioral studies of patients with dementia, frontal lobe tumors, and head injuries; magnetic resonance imaging methods for studying human frontal lobe anatomy; theoretical approaches to describing frontal lobe functions; and rehabilitation of patients with frontal lobe damage including their core problem of diminished awareness. Written by a distinguished group of neuroscientists, psychologists and clinicians, Frontal Lobe Function and Dysfunction provides the best current source of information on this region of the brain and its role in cognition, behavior and clinical disorders. (shrink)

(1) The induced colours led to perceptual grouping and pop-out, (2) a grapheme rendered invisible through ‘crowding’ or lateral masking induced synaesthetic colours — a form of blindsight — and (3) peripherally presented graphemes did not induce colours even when they were clearly visible. Taken collectively, these and other experiments prove conclusively that synaesthesia is a genuine percep- tual phenomenon, not an effect based on memory associations from childhood or on vague metaphorical speech. We identify different subtypes of number–colour synaesthesia (...) and propose that they are caused by hyperconnectivity between col- our and number areas at different stages in processing; lower synaesthetes may have cross-wiring (or cross-activation) within the fusiform gyrus, whereas higher synaesthetes may have cross-activation in the angular gyrus. This hyperconnec- tivity might be caused by a genetic mutation that causes defective pruning of con- nections between brain maps. The mutation may further be expressed selectively (due to transcription factors) in the fusiform or angular gyri, and this may explain the existence of different forms of synaesthesia. If expressed very diffusely, there may be extensive cross-wiring between brain regions that represent abstract concepts, which would explain the link between creativity, metaphor and synaesthesia (and the higher incidence of synaesthesia among artists and poets). Also, hyperconnectivity between the sensory cortex and amygdala would explain the heightened aversion synaesthetes experience when seeing numbers printed in the ‘wrong’ colour. Lastly, kindling (induced hyperconnectivity in the temporal lobes of temporal lobe epilepsy [TLE] patients) may explain the purported higher incidence of synaesthesia in these patients. We conclude with a synaesthesia-based theory. (shrink)

The neuropsychology of religious activity in normal and selected clinical populations is reviewed. Religious activity includes beliefs, experiences, and practice. Neuropsychological and functional imaging findings, many of which have derived from studies of experienced meditators, point to a ventral cortical axis for religious behavior, involving primarily the ventromedial temporal and frontal regions. Neuropharmacological studies generally point to dopaminergic activation as the leading neurochemical feature associated with religious activity. The ventral dopaminergic pathways involved in religious behavior most closely align with (...) the action-extrapersonal system in the model of 3-D perceptual–motor interactions proposed by Previc . These pathways are biased toward distant space and also mediate related extrapersonally dominated brain functions such as dreaming and hallucinations. Hyperreligiosity is a major feature of mania, obsessive-compulsive disorder, schizophrenia, temporal-lobe epilepsy and related disorders, in which the ventromedial dopaminergic systems are highly activated and exaggerated attentional or goal-directed behavior toward extrapersonal space occurs. The evolution of religion is linked to an expansion of dopaminergic systems in humans, brought about by changes in diet and other physiological influences. (shrink)

High-frequency oscillations (HFO) are a promising biomarker for the identification of epileptogenic tissue. While HFO rates have been shown to predict seizure outcome, it is not yet clear whether their morphological features might improve this prediction. We validated HFO rates against seizure outcome and delineated the distribution of HFO morphological features. We collected stereo-EEG recordings from 20 patients (231 electrodes; 1,943 contacts). We computed HFO rates (the co-occurrence of ripples and fast ripples) through a validated automated detector during non-rapid eye (...) movement sleep. Applying machine learning, we delineated HFO morphological features within and outside epileptogenic tissue across mesial temporal lobe (MTL) and Neocortex. HFO rates predicted seizure outcome with 85% accuracy, 79% specificity, 100% sensitivity, 100% negative predictive value, and 67% positive predictive value. The analysis of HFO features showed larger amplitude in the epileptogenic tissue, similar morphology for epileptogenic HFO in MTL and Neocortex, and larger amplitude for physiological HFO in MTL. We confirmed HFO rates as a reliable biomarker for epilepsy surgery and characterized the potential clinical relevance of HFO morphological features. Our results support the prospective use of HFO in epilepsy surgery and contribute to the anatomical mapping of HFO morphology. (shrink)

Neurological syndromes in which consciousness seems to malfunction, such as temporal lobe epilepsy, visual scotomas, Charles Bonnet syndrome, and synesthesia offer valuable clues about the normal functions of consciousness and ‘qualia’. An investigation into these syndromes reveals, we argue, that qualia are different from other brain states in that they possess three functional characteristics, which we state in the form of ‘three laws of qualia’. First, they are irrevocable: I cannot simply decide to start seeing the sunset (...) as green, or feel pain as if it were an itch; second, qualia do not always produce the same behaviour: given a set of qualia, we can choose from a potentially infinite set of possible behaviours to execute; and third, qualia endure in short-term memory, as opposed to non-conscious brain states involved in the on-line guidance of behaviour in real time. We suggest that qualia have evolved these and other attributes because of their role in facilitating non-automatic, decision-based action. We also suggest that the apparent epistemic barrier to knowing what qualia another person is experiencing can be overcome by using a ‘bridge’ of neurons; and we offer a hypothesis about the relation between qualia and one's sense of self. (shrink)

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a large number of (...) subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. 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Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

Neurological syndromes in which consciousness seems to malfunction, such as temporal lobe epilepsy, visual scotomas, Charles Bonnet syndrome, and synesthesia offer valuable clues about the normal functions of consciousness and ‘qualia’. An investigation into these syndromes reveals, we argue, that qualia are different from other brain states in that they possess three functional characteristics, which we state in the form of ‘three laws of qualia ’ based on a loose analogy with Newton’s three laws of classical mechanics. (...) First, they are irrevocable: I cannot simply decide to start seeing the sunset as green, or feel pain as if it were an itch; second, qualia do not always produce the same behaviour: given a set of qualia, we can choose from a potentially infinite set of possible behaviours to execute; and third, qualia endure in short-term memory, as opposed to non-conscious brain states involved in the on-line guidance of behaviour in real time. We suggest that qualia have evolved these and other attributes (e.g. they are ‘filled in’) because of their role in facilitating non-automatic, decision-based action. We also suggest that the apparent epistemic barrier to knowing what qualia another person is experiencing can be overcome simply by using a ‘bridge ’ of neurons; and we offer a hypothesis about the relation between qualia and one’s sense of self. (shrink)

Individuals with Parkinson’s disease and temporal lobe epilepsy have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures.Dreams were characterised in early-stage PD and TLE patients with dream diaries classified by the Hall van de Castle system and were compared with matched controls.In PD, there were significant differences between patients’ dreams and those of (...) controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features.TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction.The dreams of PD and TLE patients share important features. (shrink)

Frédéric Chopin is the epitome of the romantic artist; he had a chronic pulmonary disease that ultimately caused his death at the age of 39. An overlooked neurological condition is discussed in this paper. We consider the possibility of a temporal lobe epilepsy, as throughout his life Chopin had hallucinatory episodes, which can accompany seizure disorders.

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task.Methods: Twenty-five patients with pharmaco-resistant epilepsy, (...) including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects.Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and pari... (shrink)

Long-Term Potentiation (LTP) is a kind of synaptic plasticity that many contemporary neuroscientists believe is a component in mechanisms of memory. This essay describes the discovery of LTP and the development of the LTP research program. The story begins in the 1950's with the discovery of synaptic plasticity in the hippocampus (a medial temporal lobe structure now associated with memory), and it ends in 1973 with the publication of three papers sketching the future course of the LTP research (...) program. The making of LTP was a protracted affair. Hippocampal synaptic plasticity was initially encountered as an experimental tool, then reported as a curiosity, and finally included in the ontic store of the neurosciences. Early researchers were not investigating the hippocampus in search of a memory mechanism; rather, they saw the hippocampus as a useful experimental model or as a structure implicated in the etiology of epilepsy. The link between hippocampal synaptic plasticity and learning or memory was a separate conceptual achievement. That link was formulated in at least three different ways at different times: reductively (claiming that plasticity is identical to learning), analogically (claiming that plasticity is an example or model of learning), and mechanistically (claiming that plasticity is a component in learning or memory mechanisms). The hypothesized link with learning or memory, coupled with developments in experimental techniques and preparations, shaped how researchers understood LTP itself. By 1973, the mechanistic formulation of the link between LTP and memory provided an abstract framework around which findings from multiple perspectives could be integrated into a multifield research program. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:My Ability to FlourishPaulette KoehlerIn twenty years of convulsions, I’ve never heard a neurologist mention the word “epilepsy.” Over this time, the intensity of my original simple partial seizures, “simple” signifying retained consciousness and “partial” indicating disturbances restricted to a specific area of my brain, grew to the complex level on my left temporal lobe. I believe this development was influenced by my use of prescribed (...) medications. Several neurologists from Los Angeles to San Francisco directed various electroencephalograms (EEGs), including a week–long, prescription–free EEG in the hospital; magnetic resonance imaging tests (MRIs); computed tomography (CT) scans anywhere from forty–five minutes to four hours each; and blood profiles to help determine my situation. For legal reasons, one neurologist even had me sign a release stating that he was not able to diagnose my situation.Test results present limited information about my brain and without ever saying, “I don’t know,” these neurologists communicated my test results by utilizing technical terms and thus not always answering my questions. After explaining that my head turns to the left while my right hand shakes, symptoms that have been recognized and reported by several friends and family members, my doctor replied that a seizure on the left side of my brain should cause my head to turn to the right and then changed the subject. I felt like asking, “Am I doing it wrong?”The brain is different from other parts of our anatomy in that it can’t be replaced like a kidney, heart or other organ. It cannot be removed like tonsils, an appendix or even a limb. It can be physically studied or repaired while functioning but the resulting percentage of survival or proper operation of the body after surgery is minimal and the number of people requiring such attention is so low that the amount is scanty. A dead brain limits the analysis of its functions.My “disabilities” involve spontaneous uncontrolled loss of consciousness, exhaustion, mood swings, and the suspension of driving privileges. Activity interference, extra naps, losing friends and not being able to get around are definite disadvantages. However, everyone needs to manage personal problems. No one is perfect.Public transit schedules and directions don’t always offer me the transportation I need. Fortunately, the combination of a bus ride with walking or running can serve my needs while also helping me to keep physically healthy.Limited benefits include discounted transit and the option to ride instead of walking or running. A trip to Nana’s on the train is always a treat.I’d rather not be branded “disabled” even though those who understand my situation address me with compassionate, sympathetic attention, [End Page E4] always asking how I physically feel. I feel fine. A seizure is only a quick, conscious loss of time and an occasional scrape on the knee. I’m more annoyed when I notice strangers looking suspiciously at my public transport discount card as if I don’t really deserve it.Like the “disability” brand, the medications I’ve taken, Dilantin, Neurontin, Depakote, Keppra and Lamictal, among others, all of which produced serious side effects without reducing the frequency of my seizures have only been a cover–up, preventing a search for the true cause and effective treatment of my seizures. Being identified as disabled has only limited my daily schedule. I am not disabled, as society has unfortunately characterized me.My seizures began in 1993, the year our FDA started approving rBGH, recombinant bovine growth hormone, man–made for the use on dairy cows to enhance their milk production. As a result, milk on the market increased while keeping the price from rising, as demonstrated in Economics I. Can the use of rBGH act on my brain in any way?One neurologist, in order to avoid the responsibility of inappropriate recommendations, presented his thoughts in the form of questions, encouraging me to consider options.“You’ve tried all of these medications?”“Has your diet alteration made any difference in your seizures?”“Have you tried organic foods?”His inquiries persuaded me to contemplate whether drugs are an answer to my problem, pay attention to differences in my life and... (shrink)

Objective: Electrical stimulation potentially delineates epileptogenic cortex through induction of typical seizures. Although frequently employed, its value for epilepsy surgery remains controversial. Similarly, ES is used to identify symptomatogenic zones, but with greater success and a long-standing evidence base. Recent work points to new seizure symptoms such as ictal central apnea that may enhance presurgical hypotheses. The aims of this review are 2-fold: to determine the value of ES-induced seizures in epilepsy surgery and to analyze current evidence on (...) ICA as a new surrogate of symptomatogenic cortex.Methods: Three databases were searched for ESIS. Investigators independently selected studies according to pre-specified criteria. Studies reporting postoperative outcome in patients with ESIS were included in a meta-analysis. For ES-induced apnea, a thorough search was performed and reference list searching was employed.Results: Of 6,314 articles identified for ESIS, 25 were considered eligible to be reviewed in full text. Fourteen studies were included in the qualitative synthesis ; six studies were included in the meta-analysis. The meta-analysis showed that favorable outcome is associated with ESIS prior to surgery. In addition, the overall estimation of the occurrence of favorable outcome among cases with ESIS is 68.13%. On the other hand, recent studies have shown that stimulation of exclusively mesial temporal lobe structures elicits central apnea and represents symptomatogenic anatomic substrates of ICA. This is in variance with traditional teaching that mesial temporal ES is non-symptomatogenic.Conclusions: ES is a tool highly likely to aid in the delineation of the epileptogenic zone, since ESIS is associated with favorable postoperative outcomes. There is an urgent need for prospective evaluation of this technique, including effective stimulation parameters and surgical outcomes, that will provide knowledge base for practice. In addition, ES-induced apnea studies suggest that ICA, especially when it is the first or only clinical sign, is an important semiological feature in localizing the symptomatogenic zone to mesial temporal lobe structures, which must be considered in SEEG explorations where this is planned, and in surgical resection strategies. (shrink)

Current models of cortical speech and language processing include multiple regions within the temporal lobe of both hemispheres. Human communication, by necessity, involves complex interactions between regions subserving speech and language processing with those involved in more general cognitive functions. To assess these interactions, we utilized an ecologically salient conversation-based approach. This approach mandates that we first clarify activity patterns at the earliest stages of cortical speech processing. Therefore, we examined high gamma (70-150 Hz) responses within the electrocorticogram (...) (ECoG) recorded simultaneously from Heschl’s gyrus (HG) and lateral surface of the superior temporal gyrus (STG). Subjects were neurosurgical patients undergoing evaluation for treatment of medically intractable epilepsy. They performed an expanded version of the Mini-mental state examination (MMSE), which included additional spelling, naming, and memory-based tasks. ECoG was recorded from HG and the STG using multicontact depth and subdural electrode arrays, respectively. Differences in high gamma activity during listening to the interviewer and the subject's self-generated verbal responses were quantified for each recording site and across sites within HG and STG. The expanded MMSE produced widespread activation in auditory cortex of both hemispheres. No significant difference was found between activity during listening to the interviewer's questions and the subject's answers in posteromedial HG (auditory core cortex). A different pattern was observed throughout anterolateral HG and posterior and middle portions of lateral STG (non-core auditory cortical areas), where activity was significantly greater during listening compared to speaking. No systematic task-specific differences in the degree of suppression during speaking relative to listening were found in posterior and middle STG. Individual sites could, however, exhibit task-related variability in the degree of suppression during speaking compared to listening. The current study demonstrates that ECoG recordings can be acquired in time-efficient dialog-based paradigms, permitting examination of language and cognition in an ecologically salient manner. The results obtained from auditory cortex serve as a foundation for future studies addressing patterns of activity beyond auditory cortex that subserve human communication. (shrink)

Rationale: High-frequency oscillations in intracranial EEG are used to delineate the epileptogenic zone during presurgical diagnostic assessment in patients with epilepsy. HFOs are historically divided into ripples, fast ripples, and their co-occurrence. In a previous study, we had validated the rate of FRandRs during deep sleep to predict seizure outcome. Here, we ask whether epileptic FRandRs might be confounded by physiological FRandRs that are unrelated to epilepsy.Methods: We recorded iEEG in the medial temporal lobe MTL in (...) 17 patients while they performed cognitive tasks. The three cognitive tasks addressed verbal working memory, visual working memory, and emotional processing. In our previous studies, these tasks activated the MTL. We re-analyzed the data of these studies with the automated detector that focuses on the co-occurrence of ripples and FRs.Results: For each task, we identified those channels in which the HFO rate was modulated during the task condition compared to the control condition. However, the number of these channels did not exceed the chance level. Interestingly, even during wakefulness, the HFO rate was higher for channels within the seizure onset zone than for channels outside the SOZ.Conclusion: Our prospective definition of an epileptic HFO, the FRandR, is not confounded by physiological HFOs that might be elicited by our cognitive tasks. This is reassuring for the clinical use of FRandR as a biomarker of the EZ. (shrink)

ObjectiveThe Spatial Learning Task of Lhermitte and Signoret is an object-location arbitrary associative learning task. The task was originally developed to evaluate adults with severe amnesia. It is currently used in populations where the memory system either is not yet fully developed or where it has been compromised (e.g. epilepsy, traumatic brain injury, electroconvulsive therapy, cerebrovascular disease and dementia). Normative data have been published for paediatric cohorts and for older adults, however no data exist for the intervening adult years.MethodHere, (...) we address this gap, collecting normative data from 101 adults aged 18–45.ResultsOur data indicate that performance on the Spatial Learning Task is not influenced by age, gender, level of education or overall IQ. Less than 10% of the variance in learning scores is associated with variability in verbal memory. Ninety percent of participants achieved perfect scores on two successive trials (T2Cr) within five or fewer trials on the Spatial Learning Task. A T2Cr score of 6 is suggestive of impairment and a T2Cr score of 7 or more is statistically abnormal.ConclusionThese data expand the clinical utility of the Spatial Learning Task in the adult population. Future work should examine performance in lower IQ cohorts, including intellectual disability, and explore sensitivity to disease factors such as laterality of mesial temporal lobe damage. (shrink)

In the verbal domain, there is only very weak evidence favoring the view that working memory is an active state of long-term memory. We strengthen existing evidence by reviewing two recent fMRI studies of verbal working memory, which clearly demonstrate activation in the superior temporal lobe, a region known to be involved in processing speech during comprehension tasks.

Recent studies have revealed that the temporal lobe, a cortical region thought to be in charge of episodic and semantic memory, is involved in creative insight. This work examines the contributions of discrete temporal regions to insight. Activity in the medial temporal regions is indicative of novelty recognition and detection, which is necessary for the formation of novel associations and the “Aha!” experience. The fusiform gyrus mainly affects the formation of gestalt-like representation and perspective taking. The (...) anterior and posterior middle temporal gyri are individually associated with extensive semantic processing and inhibiting salient or routine word associations, which are necessary to form non-salient, novel and remote associations. The anterior and posterior superior temporal gyri are individually responsible for integrating/binding and accessing various types of available conceptual representations. Based on the current knowledge, an integrated model of the temporal lobe's role in insight and some future directions are proposed. (shrink)

Episodic memories are shaped by the representational format of their contents. These formats are not only determined by medial temporal lobe areas, but essentially also by the neocortical regions which these areas control. The representational formats of medial temporal lobe and neocortex are sufficient to determine both, memory contents and subjective memory qualities, without the further need for an attribution system.

Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the (...) tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery. (shrink)

The recent ability to inactivate specific genes in mice has significantly accelerated our understanding of molecular, cellular, and even behavioral aspects of normal and disease processes. However, this ability has also demonstrated the extreme complexity of genetic determination in mammals, in particular, that genes in the same family or pathway can be functionally redundant and that a given gene often has multiple roles. Thus, inactivation of a gene often does not indicate its complete spectrum of functions. To circumvent this problem, (...) many new tools and novel applications of classic techniques have been developed to place spatial and temporal restrictions on the genomic alterations. These approaches include chimera and mosaic studies, organ transplantation, complementation assays, dominant negative mutants, conditional gene knockouts, and lineage-specific gene rescue. Not only has this opened up more sophisticated ways to make genomic alterations, but it has provided the opportunity to create animal models for sporadic human genetic diseases. BioEssays 20:200–208, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

We highlight recent progress in neuroimaging and neuropsychological research on memory mechanisms in the medial temporal lobe that speaks to the involuntary nature of memory retrieval processes. We suggest that evidence form these studies supports Barzykowski and Moulin's proposal that memory signals involved in experiences of familiarity and déjà vu can be generated in the absence of retrieval intentionality.