INTEGRATING EXPOSURE AND RESPONSE PREVENTION AND HABIT REVERSAL TECHNIQUES TO TREAT A TOURETTIC SUBTYPE OF OBSESSIVE-COMPULSIVE DISORDER (TOURETTIC OCD).

Conditions: Obsessive – Compulsive Disorder; Tic Disorder, Chronic Motor or Vocal; Tic Disorders; Tic Disorder, Combined Vocal and Multiple Motor; Tourette Disease; Tourette Disorder; Tourettes Syndrome; Gilles de la Tourette Syndrome

Interventions: Behavioral: Exposure and Response Prevention (ERP); Behavioral: Habit Reversal Training (HbRT; Behavioral: Psychoeducation and Supportive Intervention

Sponsors: University College London Hospitals

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BFRBs vs. OCD: Similarities and Differences

This blog was originally posted by the TLC Foundation for BFRBs

Body-focused repetitive behaviors (BFRBs) and obsessive-compulsive disorder (OCD) are two distinct mental health conditions that share some similarities but also have significant differences. BFRBs involve repetitive, self-grooming behaviors that can cause physical damage, such as hair pulling or skin picking. On the other hand, OCD is a condition characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions) performed to alleviate anxiety. 

While both conditions involve repetitive behaviors and can impact daily life, their underlying mechanisms, triggers, and treatment approaches differ. This article explores the key similarities and differences between BFRBs and OCD to better understand these complex conditions.

Similarities Between BFRBs and OCD

Most professionals view BFRBs and OCD as similar conditions due to the similarity in symptoms, such as compulsivity and repetitive behaviors. These two conditions share several similar systems and are usually a reaction to triggering factors such as stress and anxiety. Below are some of their similarities.

Repetitive Behaviors

Individuals dealing with BFRBs often engage in various repetitive behaviors such as hair pulling, lip biting, or skin picking. These actions are usually challenging to control and are frequently triggered by stress or anxiety. One may indulge in the habit subconsciously to find instant relief from the trigger. 

Individuals with OCD often experience intrusive thoughts that result in repetitive behaviors known as compulsions. Some common compulsions include washing hands and repetitively checking or counting to alleviate the stress caused by obsessive thoughts. In both conditions, the repetitive behaviors are often exacerbated by stress and anxiety, and individuals may adapt these behaviors as a coping mechanism.

Impulse Control

Closely related to repetitive behaviors is the concept of impulse control. Both BFRBs and OCD involve challenges in this area, albeit in different ways. Individuals with BFRBs and OCD may find it hard to control the urge to perform repetitive behaviors. This is because these repetitive behaviors often relieve tension. Despite knowing the consequences of these behaviors, the desire to indulge in them is usually irresistible. 

For example, individuals with BFRBs understand that hair pulling may affect their appearance, but they cannot refrain from doing it. OCD occurs as a result of intrusive thoughts whereby one believes that if they do not perform a specific action, the stressor won’t go away. These intrusive thoughts often cause anxiety, which can be eased by engaging in the said repetitive behavior.

Onset and Course

Having examined the behavioral aspects, let’s now consider how these conditions develop over time. The onset of these two conditions shares several similarities regarding age, triggers, and psychological mechanisms. 

The onset of both conditions is usually during childhood or adolescence and often coincides with various developmental changes and stressors. For individuals with BFRBs, the repetitive behaviors alleviate stress and anxiety instantly. At the same time, for those with OCD, performing the compulsions temporarily relieves them from the stress caused by their intrusive thoughts. The cognitive patterns involve repetitive actions, intrusive thoughts, and a lack of impulse control. In BFRBs, the urge to engage in these repetitive behaviors can be intrusive and persistent, while in OCD, one’s obsessions create a sense of urgency, which leads to the adoption of compulsive actions.

Neurobiological Factors

To fully understand the similarities between BFRBs and OCD, we must delve deeper into their biological underpinnings. Both conditions have a genetic origin and are associated with neurobiological factors. Neurobiological studies indicate that the impulse control and emotional regulation difficulties for people with BFRBs and OCD are often caused by abnormalities in brain regions that are responsible for impulse control and habit formation. Therefore, the underlying brain mechanism may result in the onset and development of both conditions. It is not uncommon for individuals to have both BFRBs and OCD or for both conditions to coincide with other mental health conditions, usually depression and anxiety. The overlap is generally because they typically share common underlying factors that play a part in their severity and development.

Differences Between OCD and BFRBs

While BFRBs and OCD share several commonalities, it’s equally important to understand their distinct characteristics, from the symptoms to the underlying mechanisms. Let’s explore the key differences that distinguish these two conditions.

Nature of the Behavior

First and foremost, let’s examine how the behaviors associated with each condition differ in their fundamental nature. Individuals dealing with these two conditions adopt diverse behaviors as coping mechanisms for their triggers. In BFRBs, the behaviors adopted, such as trichotillomania (hair-pulling) or cheek-biting, usually result in physical harm. However, regardless of the consequences, one always feels relieved when picking their skin or pulling their hair. 

OCD, on the other hand, involves a wide range of compulsions, from washing to organizing, checking, and counting. Compulsive behaviors are performed due to intrusive thoughts that make one think that if they fail to indulge in a specific behavior, they might get hurt, or there might be other negative consequences.

Presence of Obsessions

Another crucial distinction lies in the cognitive processes behind these behaviors. Generally, BFRBs do not involve obsessive thoughts. The primary focus on BFRBs is usually more on the physical behavior and not the fear of specific consequences. 

However, the major characteristic of OCD is intrusive thoughts, which increase the urge to indulge in particular behaviors for relief. The thoughts are usually persistent with unwanted images that result in distress. 

People with BFRBs DO NOT report that if they do not pick on their skin, something terrible will happen. Instead, they report that picking or pulling their hair helps relieve them from intense and negative emotions. These behaviors, therefore, serve a self-regulatory function, unlike in OCD, where the repetitive behavior calms them from their intrusive thoughts.

Triggers

The nature of triggers for each condition is closely related to the presence or absence of obsessions. The primary trigger in BFRBs is stress and anxiety, but for OCD, the main trigger is intrusive thoughts, which then result in anxiety. OCD and BFRBs triggers differ in several ways, often resulting in different outcomes. OCD triggers often result in one taking measures to prevent harm, while for BFRBs, one uses the adopted behaviors to regulate and manage intense emotions. The nature of thoughts is an essential distinguishing factor, seeing as OCD involves intrusive and obsessive thoughts that trigger specific behaviors adopted to prevent harm. The purpose of compulsions in OCD is to reduce the anxiety caused by the obsessive thoughts, while in BFRBs, the behaviors are for emotional relief.

Awareness

Beyond triggers, the level of conscious awareness also differentiates these two conditions. Those dealing with BFRBs usually find themselves biting their nails or even pulling their hair subconsciously. Individuals with OCD are generally aware of their intrusive thoughts and are compelled to adopt specific behaviors as a response to these thoughts. Individuals with OCD are often aware of their compulsions and understand when they are being irrational, but they are unable to control themselves. Compared to people with OCD, those with BFRBs often find their behaviors more rewarding than distressing.

Treatment

Finally, while both conditions may benefit from cognitive behavioral therapy, the specific approach to treatment varies significantly. For individuals with BFRBs, the focus is on behavior modification and awareness, achieved through habit reversal training. For OCD, the emphasis is often placed on exposure to anxiety-provoking thoughts to help an individual tolerate anxiety, which prevents compulsive behavior.

Bottom Line 

While BFRBs and OCD can coexist, they are distinct disorders with unique manifestations despite sharing some similarities. The key distinctions between these conditions are evident in their underlying mechanisms and treatment approaches.

Both involve compulsive behaviors, but their purposes differ. BFRBs primarily serve as subconscious tools for emotional regulation. OCD compulsions are conscious attempts to alleviate anxiety and prevent perceived harmful consequences. BFRB behaviors often occur with limited conscious awareness, while OCD sufferers are typically more aware of their compulsive actions.

Both conditions can significantly affect daily functioning and social interactions.BFRBs may lead to physical injuries and lowered self-esteem due to visible effects. OCD can cause severe anxiety and time-consuming rituals that interfere with daily activities.BFRB treatment emphasizes behavior modification and awareness techniques, while OCD treatment often involves exposure therapy to reduce anxiety responses.

Understanding these distinctions is crucial for accurate diagnosis and effective treatment. While both conditions present challenges, with proper support and intervention, individuals with BFRBs or OCD can learn to manage their symptoms and improve their overall quality of life.

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Nucleus accumbens DRD2 receptor agonism attenuates escape behavior

Animals learn to approach and escape stimuli in their environment, in part through the representation of rewarding or aversive outcomes in the nucleus accumbens (NAc). The regulation of reward motivation in the NAc by dopamine signaling at DRD1 and DRD2 receptors has been the subject of extensive study. However, the process by which aversive stimuli are signaled within this system to promote motivated escape behavior is less well characterized. Conventional wisdom posits that rewarding and aversive stimuli ultimately affect DRD1 or DRD2-receptor expressing medium spiny neurons (MSNs) in an opposing manner to differentially modulate motivated behavior. However, recent studies have challenged this view and demonstrate the need to better characterize the processes that mediate aversion learning. To determine if DRD2 dopamine receptor activation disrupts escape behavior, 21 male and female Sprague Dawley rats were treated with an intra-NAc core DRD2 receptor agonist, quinpirole, while escape behavior was negatively reinforced by the termination of aversive white noise. This treatment attenuated escape, a result that is consistent with the view that aversion-induced reductions in dopamine promote escape behavior through decreased DRD2 receptor signaling in the NAc, and potential disinhibition of an aversion-sensitive striatal output circuit.

Institutional Member Updates: Summer 2026

Institutional Members are clinics and programs in the US and around the globe that offer residential and/or intensive treatment for OCD and related disorders, are specialty outpatient clinics with a large staff dedicated to treating OCD, or provide low-cost treatment options through research studies.

Below are quarterly updates from our Institutional Members organized alphabetically. Click the (+) to open each menu and read updates and find contact information for clinics near you:

Do you work at a residential program, intensive outpatient program (ITP), or specialty outpatient clinic and looking to advertise your services? Learn more about becoming an Institutional Member and having your program updates included below!

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Awakening from the Trance

This blog was originally posted by the TLC Foundation for BFRBs

Trichotillomania touches on all levels of human experience, from the neurological to the spiritual. It represents the interactions of brain chemistry, but also habituated physiological responses, sensory processing, behavior patterns, characteristic emotional states, perceptual styles and beliefs, and the sense of interconnectedness with others and the experience of faith. It is more than just a behavior, although it is most apparent when it manifests itself in that way.

Trichotillomania can be treated at all of these levels through different treatment approaches: medication, relaxation and response prevention, behavior modification, hypnotherapy, psychotherapy, cognitive therapy and visualization, group therapy and spiritual practices. The most effective approach will depend on the specific needs and circumstances of each individual at specific times, as well as on the compatibility of the personalities of the treatment provider and patient/participant.

In this article I will present my own view of treatment with a particular focus on how to understand and address the aspect of trance.

“Trance” is not a clinical term, but it is one which most pullers seem to recognize immediately as a significant part of the hair pulling experience: particularly when reading or watching TV. However, I believe that any time one is pulling, one has entered a trance state and that trance states occur with great frequency even at other times. To look at how to make use of this concept I will first describe what I think treatment needs to address.

Trichotillomania as a symptom: My approach is to look at what the behavior of pulling means to a particular person, and what it means about them. I view pulling as a symptom which indicates something about what is going on in that person’s life and can be best understood if we look at the context in which it occurs – both over time (how did it evolve), and ecologically (how does it fit into the network of the person’s relationships, commitments, self-perceptions, experiences of their own body and emotional states, etc.).

Symptoms are an indication of the existence of some other process. Just as a fever may reflect a viral infection, a repetitive behavior reflects an underlying mental activity. The symptom develops in response to the activity and one of its functions is to achieve some control over the consequences of that mental activity. I believe that trichotillomania indicates an attempted solution to a psychological challenge (or opportunity) one is facing in one’s life. However, it is an ineffective solution for two reasons. Firstly, it doesn’t alter the situation which has become challenging, and so the underlying causes remain unchanged. Secondly, by drawing attention onto itself it obscures those underlying causes. It distracts attention from them.

But the behavior, none the less, does have some purpose and utility. It relieves the anxiety of becoming too aware that there are challenges and opportunities which one feels unprepared to confront.

The role of emotions:

The mechanism which could be drawing one’s attention to these challenges and opportunities is the experience of emotional reaction. Emotions serve to amplify our perceptions of situations by making the good seem better and the bad seem worse. In that way, they lead us to focus on what is important to us so that we will take action. Being able to notice and interpret our emotions is something we learn as we grow up. Emotions represent a kind of language for helping us make meaningful choices as we engage with life.

But if these emotions were felt to be too overwhelming – if what they indicated felt too bad to be tolerated because we did not learn how to resolve the situations they drew attention to – then we eliminated them from our emotional vocabulary and we restricted our awareness of them. Now, when those situations reoccur, rather than notice our feelings of hopelessness and helplessness, we may turn to other mechanisms, more basic ones rooted in physical sensations, to occupy ourselves and restore some sense of order to the world.

So, in this model, the behavior of hair pulling is not an indicator of psychological inadequacy, but rather a lack of awareness. It reflects a split between awareness/thoughts and sensations/feelings. It is the result of an unknown mental process, something one has not been able to assimilate into one’s conscious thought, for which no words or language have been developed.

If this could be understood then I believe there would be less justification for feelings of shame connected with Trichotillomania, because Trichotillomania represents an underlying process outside of personal awareness, and thus is not something voluntarily chosen. (It would also answer the following disturbing statement frequently made to hair pullers: “You could stop if you really wanted to.”)

I have so far described how emotional activity and unconscious thoughts affect us in ways which we do not recognize. Despite this lack of recognition, we still need to adjust to them and regulate or organize ourselves. A good example of this is the way in which a fussy baby, if not picked up or fed when it wants to be, learns to get its thumb into its mouth and suck on it. It is finding a way to organize its reactions to its world by retreating into an attitude of self-sufficiency. In this way it solves the problems of the conflict it experiences between the emotions it feels and the lack of a way to take effective action about them in the outside world. It restores order by returning to a sensation-based activity which it has control over. It has learned to retreat into a trance.

The similarities between this example and the experience of hair pulling are striking. So how is Trichotillomania like a trance, exactly?

Trance:

The (Oxford) dictionary defines “trance” in these ways: a suspension of consciousness; a state of mental abstraction from external things; absorption, exaltation, rapture, ecstasy. Going into a trance is turning away from the world, suspending engagement with it, and entering a twilight zone of self-enchantment. The experience is one of being in between states: neither in one’s own mind, nor aware of one’s body. One has turned away, both from the rest of the world and from the rest of oneself.

It is a state in which one doesn’t think about what one feels, and doesn’t act on what one feels. One has turned away from the parts of the self which are concerned with action and purposefulness. In the trance state, a part of the personality takes over which doesn’t care about anything (except the act of pulling) and ignores the existence of time or consequences to one’s actions. It is the opposite of the perfectionist attitude so common to many hair pullers. Becoming entranced in the act of reading, for example, one detaches from the here and now, and allows this part of the personality to “come out”: while the cat’s away, the mouse plays. It is a secure, dependable, magical place in which one can avoid dealing with the stimulation of one’s spontaneous emotional responses to life.

If we look again at the role of emotions as amplifiers of perceptions, we see that what is happening in this state is that one is neither thinking about, nor acting on, what the emotions could be indicating. And as they indicate what is important so that action can be taken, the trance state eliminates the possibility of taking the action required.

How does this detaching process become chronic?

I believe it is the result of repeated experiences of failing to take effective action on what one’s emotions tell one is important. This failure can have many causes, but the result is that these important situations become perceived as challenging and threatening because they are felt as over stimulating. To protect oneself from discomfort, one disassociates from the situation. The part of oneself which perceives or feels what is going on is split off from consciousness. What remains conscious is the part which doesn’t feel and which preserves a sense of order and calm. Gradually, a gap develops between this external presentation of the self – as coherent, caring, positive – and an inner state of feeling confused, frustrated, and overwhelmed.

A false self develops, a self which appears to be more in control than is actually felt, and which one tries to believe in. The fear of having this façade penetrated adds greatly to the level of stress felt by hair pullers. Because this false self cannot be dropped when one’s gut reactions tell one to, one becomes trapped in a vicious circle that leaves one over stimulated (including the times when one merely seems to be bored), detaching from one’s body, and trying to regain control. A strong need is felt to reconnect to the body and feel grounded.‍

Trichotillomania as a return to the body:

The route to feeling in one’s body again is through becoming hyperaware and hypersensitive to sensation. This is a more basic and elementary experience of oneself: one cannot think or feel what is happening, so one uses a physical behavior to establish a link between unconscious inner experience and being in the real, physical world. This provides a solution to the twilight state of feeling detached. The sensation-focused behavior provides a substitute sense of being connected, and its ritualistic aspect creates a sense of soothing order rather than chaos.

So, looked at in this way, the act of pulling a hair actually represents the second stage of entering into a trance. The trance is triggered by the habitual reaction of disassociating rather than facing a situation which one perceives as overwhelming. But while an attitude of order and calm is being adopted (a state of “mental abstraction”), the experience of being detached from the feelings in the body becomes disorienting and the urgent need is felt to focus on the sensation of touching, playing with, and pulling hair. This provides the experience of concreteness and connectedness which allows the trance to continue.

Awakening:

What is needed is a process for regaining consciousness and turning back to engaging with life. How does one wake up? How can one build a sort of observational platform from which to watch the process of entering into a trance; one which can be separate from the process itself? I would suggest that rather than start with the ultimate goal of avoiding trance states altogether (which may be unreachable), a more pragmatic approach would be to learn how to wake up once one starts.

When we drive long distances on freeways and our attention wanders, we sometimes find ourselves drifting over into the next lane. If there were raised lane markers on the road, they would then alert us by causing a noise and a vibration as the car drove over them. That is the kind of alarm system we are looking for. It doesn’t prevent our minds from wandering, but it brings us back to the here-and-now experience before we get into trouble.

Such a system does exist: it is the sensation of a hair being pulled out. Once one hair is pulled, the opportunity exists to break the trance. That hair can be a signal to come back to the here and now rather than getting into the trouble of starting a pulling binge. (The goal of stopping at one hair pulled would also very likely include the benefit of making it much easier to commit to a realistic process of bringing the behavior within tolerable limits.)

How can one learn to stop at just one? Setting such a goal becomes much more possible if one understands one’s reasons for avoiding the goal until now. I have discussed in this article how Trichotillomania is a process which provides an attempted solution to an underlying tension. There is an inevitable anxiety about relinquishing a familiar, dependable behavior. A part of oneself therefore resists changing it and depends on the benefits it brings. This part has no intention of allowing any changes to occur unless one is prepared for the emotional experiences that follow, and it protects one from them.

A way to understand this resistance to change would be to think of the patterns of our behavior as a balanced mobile hanging from the ceiling. All its parts are interconnected and form a stable pattern. If we remove one of the parts, all of the others start to swing wildly until they settle into a new, substantially different formation. The intermediate stage of unbalanced, indeterminate movement could be likened to the feeling of overstimulation from one’s emotions when the ritualistic trance is denied.

To prepare for this change, an expanded awareness of emotional experience and what it teaches is indispensable. The remainder of this article offers some suggestions for work that can be done alone to expand this ability. This task is made much easier and more effective, however, when it is done in the context of a healing dialogue: either in individual or group therapy, or in a support group. This option deserves serious consideration because the act of communicating to another person helps bring one’s inner experiences into focus. Additionally, when there is the trust that the other person is willing not only to listen but to actively attempt to grasp what the speaker means from the speaker’s own point of view, the feeling of validation and recognition received makes awareness of the emotional states more bearable.

Reading the signals:

Part of the personal preparation which can be done is to establish intent to learn from what is found when one tries to read the signals. This would require a willingness to recognize that there are good reasons for what one feels rather than prejudging emotions as wrong, inappropriate, or proof of all the “bad” things one has come to believe about oneself. It also requires a willingness to feel discomfort, hurt, and vulnerability so that there can be a return to wholeness and the sense of being fully alive.

1. The most direct step is simply to ask yourself questions such as: What am I feeling? What is on my mind? Is something bothering me? What do I want right now? Is there something I should be doing? Special attention should be paid to the first answer that comes to mind, even if it very quickly disappears or seems insignificant. You should have an open mind and be prepared to be surprised. Before asking yourself these questions, stop the activity you are doing, if possible. If answers do not emerge the following techniques can be tried.

2. Let your body speak. Allow yourself to become aware of where you feel tension or discomfort. Imagine that that part of you has a voice and can answer the questions in Step One. Try asking follow-up questions to learn more.

3. Try exaggerating the physical state that you are in. That is, whatever movement your body is making or would like to make, take it to an extreme as if you were a very melodramatic actor or dancer who had no inhibitions. Again, think about how your body is expressing answers to the questions in Step One.

4. Visualize yourself as a child of about five and ask the questions of her or him. The answers should seem to be in the language of a 5-year-old. It might help to hold an object such as a cushion or stuffed animal to you as you try to make contact with yourself in this way. It also might help to combine this with some exaggeration of body expression. Additional questions you might ask could be: What do you need from me? Is somebody upsetting you? (See Reference 1.)

5. Write a question to the child, then switch your pen to your other hand and write the answer with that hand. You should write very quickly and with no attempt to make the writing more legible. Then switch your pen back to your original hand for a further question. Continue the dialogue, and the switching of hands, until no further clarification is necessary. The purpose of this technique is to facilitate the spontaneous flow of ideas. (See Reference 2.)

6. Write out the questions as complete sentences to be completed and complete the same question five times as quickly as possible. The questions would be rewritten as follows: Right now, I want….; or: I am upset because…. Allow any response to come forward. Often, a few unrevealing responses will be followed by one unexpected and more valuable one. (See Reference 3.)

7. Hold the hair which has just been pulled out and ask yourself: What did this hair give itself up for? A significant reason for the failure to stop hair pulling is the frequent presence of trance states, which enable one to deny the consequences of the behavior. Additionally, the experience of trance encourages one to focus on physical sensations such as the feeling of a hair being pulled, so as to achieve a greater sense of being connected to reality.

I have described how one enters a trance when certain situations trigger a habituated expectation of becoming overwhelmed. In self-defense one suspends consciousness of the challenge and retreats into a state of emotional detachment. The alternative to the trance, then, is to identify and assimilate the emotional cues about the situation so that appropriate action can be taken. The sensation of the first hair being pulled can serve as an alarm to awaken one from the trance and begin this process of self-evaluation and a return to an alert engagement with life.

Reference 1: Margaret Paul. Inner Bonding. San Francisco: Harper Collins, 1990.Reference 2: Lucia Cappachione. The Power of Your Other Hand. North Hollywood, CA: Newcastle Publishing, 1988.Reference 3: Nathaniel Branden. How to Raise Your Self-Esteem. New York: Bantam, 1987.

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Eye-Tracking Technologies for Cognitive Assessment After Acquired Brain Injury: Systematic Review

Background: Acquired brain injury (ABI) is a heterogeneous umbrella term encompassing traumatic and nontraumatic etiologies and is frequently associated with persistent cognitive dysfunction. Conventional neuropsychological assessment remains central to clinical evaluation, but feasibility and measurement precision may be limited in individuals with motor impairment, aphasia, reduced stamina, or fluctuating arousal. Eye tracking offers an objective, low-burden approach that can quantify gaze behavior during task engagement and may provide complementary process-level markers of cognition. Objective: This study aimed to systematically synthesize the evidence on eye-tracking paradigms used as a primary approach for cognitive assessment in ABI and to summarize findings by cognitive domain, paradigm, and clinical interpretability. Methods: We conducted a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020–compliant systematic review and registered the protocol in PROSPERO (CRD420251038768). PubMed, Web of Science, the Cochrane Library, Embase, EBSCOhost, PsycINFO, and Scopus were searched from inception to April 10, 2025. We included peer-reviewed English-language studies enrolling children or adults with ABI in which eye tracking was the primary assessment modality used to quantify at least one cognitive domain or clinically relevant cognitive-communication process. Two reviewers independently screened studies, extracted data, and assessed methodological quality using design-appropriate tools (Risk of Bias 2, Risk of Bias in Non-Randomized Studies of Interventions, Quality Assessment of Diagnostic Accuracy Studies 2, and the Newcastle-Ottawa Scale). A structured narrative synthesis was performed because of heterogeneity in paradigms and outcome definitions. Results: Twenty-seven studies met the inclusion criteria (N=872 participants; females: n=354 and males: n=518), with most evidence derived from mild traumatic brain injury cohorts, and fewer studies involving stroke, mixed etiologies, and disorders of consciousness. Across domains, antisaccade and related paradigms were commonly associated with differences in inhibitory control and executive function, while predictive tracking, smooth pursuit, and target-blanking paradigms frequently captured alterations in attentional prediction and timing. Virtual reality (VR) free-viewing paradigms identified visuospatial exploration asymmetries in stroke-related neglect, and gaze-based human-computer interface approaches demonstrated above-chance task performance in a subset of patients with disorders of consciousness. Evidence for incremental validity beyond conventional assessment was mixed and often indirect, and safety reporting was uncommon. Overall certainty of evidence was generally low and limited by small sample sizes, cross-sectional designs, and heterogeneity in acquisition procedures, metrics, and analytic pipelines. Conclusions: Eye tracking shows potential as an adjunctive, process-level approach for quantifying specific cognition-relevant behaviors after ABI, particularly within paradigms targeting inhibitory control and predictive attention. Current evidence is insufficient to support broad diagnostic claims or the routine replacement of conventional neuropsychological assessment. Future research should prioritize harmonized paradigms and reporting standards, external validation of classification models, longitudinal designs, and explicit feasibility and safety reporting to clarify when eye tracking provides incremental clinical value for precision neurorehabilitation.
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TNBC Ecotypes Reveal Molecular Signatures Tied to Chemotherapy Response

Researchers at The University of Texas MD Anderson Cancer Center have identified immune cell and tumor-specific features in triple-negative breast cancer (TNBC) that may help predict which patients are most likely to respond to chemotherapy before treatment begins, according to a study published in Nature. Using single-cell and spatial transcriptomic analyses of pretreatment tumor samples, the team identified specific macrophage subtypes and cancer-cell gene expression programs associated with response to neoadjuvant chemotherapy (NAC). The team also developed a 13-gene panel and a machine learning model that could help classify tumors according to their likelihood of responding to chemotherapy.

“This study provides novel insights into the gene-expression programs and the different cell states of the tumor microenvironment in patients with triple-negative breast cancer,” said Nicholas Navin, PhD, chair of systems biology at MD Anderson. “Importantly, we’ve identified certain programs and macrophage subtypes that are associated with good responses to neoadjuvant chemotherapy, which has tremendous potential to improve patient outcomes.”

TNBC accounts for between 10% and 20% of breast cancer cases. Because it lacks estrogen, progesterone, and HER2 receptors, treatment options are limited, resulting in a higher rate of recurrence compared with other form of breast cancer. Chemotherapy is the main treatment approach, particularly in early-stage disease, where neoadjuvant chemotherapy can achieve pathological complete response in 40% to 50% of patients. However, treatment outcomes vary widely from patient to patient, and researchers have been looking for ways that can better predict response before therapy begins.

For this study, the researchers analyzed pretreatment core biopsy samples from treatment-naive patients with early-stage TNBC. They performed single-cell RNA sequencing on 427,857 cells collected from 101 patients and spatial transcriptomic profiling on tumors from 44 patients. The findings also were compared with normal breast tissue data from the Human Breast Cell Atlas.

Based on their testing the researchers classified TNBC tumors into four patient-level “archetypes” based on cancer-cell gene expression patterns. They also identified 13 metaprograms that reflected heterogeneity within tumors at the single-cell level.

The tumor microenvironment consisted of 49 immune and stromal cell states organized into eight cellular communities, or ecotypes, defined by the co-occurrence of cancer cells and surrounding immune cell populations. Researchers found these cellular neighborhoods were associated both with tumor archetypes and chemotherapy response.

The study homed in on macrophages, a type of immune cell that has received less attention in TNBC research than T cells. The investigators said that seven of eight macrophage cell states were significantly associated with treatment response, while none of the 14 T-cell and natural killer-cell states showed significant associations with NAC response.

Macrophage subtypes linked to interferon signaling and complement activity, identified as Mac-IFN and Mac-lip-C1Q, were more abundant in patients who achieved pathological complete response. By comparison, two macrophages associated with angiogenesis and extracellular matrix remodeling, called Mac-angio and Mac-ECM, were enriched in patients with residual disease after chemotherapy.

The team also found that tumors linked to good response to NAC showed increased interferon signaling and elevated expression of human leukocyte antigen class II genes. Researchers said these findings indicate that cancer cells themselves may actively participate in modulating immune signaling related to chemotherapy response.

As part of their work, the researchers developed a 13-gene transcriptional signature panel developed from the single-cell analyses that can be used as a predictive model for chemotherapy response. Researchers said the model’s predictions correlated with chemotherapy response and overall survival across multiple public TNBC cohorts.

These new findings have the potential to influence how patients with TNBC are treated in the future by helping clinicians identify which patients are more likely to benefit from standard chemotherapy and which patients may need alternative therapeutic strategies earlier.

In addition, “these findings suggest that targeting specific macrophage subtypes could potentially provide new therapeutic opportunities in TNBC,” the researchers wrote.

The MD Anderson team noted that the study is one of the first large-scale single-cell genomic studies of TNBC integrating cancer cells, immune cells and treatment-response data. Earlier research exploring tumor heterogeneity has often lacked therapy response information, focused only on cancer cells or immune cells separately, or included relatively small patient cohorts.

Whether single-cell RNA seq could eventually become a basis for predictive diagnostics remains an open question. Today, the method is still expensive and technically challenging, two hindrances to it wider adoption. The researchers noted, however, that advances in sample multiplexing and other methods compatible with formalin-fixed paraffin-embedded tissue could make it feasible in the future.

Clinton Yam, MD, an associate professor of breast medical oncology at MD Anderson, said the findings could support more individualized approaches to TNBC care.

“These insights provide an important foundation for improving our understanding of why different TNBC tumors respond differently to chemotherapy, and the findings have strong potential to inform future strategies aimed at better predicting treatment response and guiding more individualized care for patients with triple-negative breast cancer.”

Future research will focus on validating the predictive models in prospective patient cohorts and evaluating TNBC treated with chemo-immunotherapy, which has become the standard of care when TNBC is detected early. The researchers also plan to study longitudinal tumor samples collected before, during, and after treatment to better understand how cancer cells and the tumor microenvironment evolve over time and how those changes relate to chemotherapy response and survival.

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The efficacy and safety of transcranial direct current stimulation in patients with ADHD: a systematic review and meta-analysis

ObjectiveThis meta-analysis evaluated the efficacy and safety of transcranial direct current stimulation (tDCS) for treating Attention-Deficit/Hyperactivity Disorder (ADHD).MethodsFollowing PRISMA guidelines, we analyzed 28 randomized controlled trials (RCTs) involving 1,864 participants. Outcomes encompassed core ADHD symptoms, hot and cold executive functions (EFs)—including inhibitory control, working memory, and cognitive flexibility—as well as safety profiles based on adverse events. A multilevel meta-analysis was performed using a random-effects model. Subgroup analyses and meta-regressions were conducted to explore potential moderating factors.ResultsCompared to sham stimulation, tDCS did not significantly improve core ADHD symptoms (standardized mean difference (SMD) = –0.29, 95% CI [–0.59, 0.01], p= 0.05). Similarly, no significant overall effects were observed for cold EFs: inhibitory control (Hedges’ g(g)= –0.11, 95% CI [–0.26, 0.05], p=0.19), working memory (g= 0.13, 95% CI [–0.06, 0.32], p= 0.26), or cognitive flexibility (SMD = –0.42, 95% CI [–1.13, 0.29], p= 0.24). The effect on hot EFs was also non-significant (g = 0.27, 95% CI [–0.14, 0.70], p = 0.19). Exploratory analyses indicated that anode placement at Fp2 was associated with improvement in both inhibitory control (g= –0.52, 95% CI [–0.93, –0.11], p=0.01) and working memory (g = 0.72, 95% CI [0.22, 1.22], p = 0.004), although the overall test for interaction was not significant for inhibitory control (p= 0.19). The most common adverse reactions were mild and transient local skin symptoms, such as itching and redness (RR = 1.42, p=0.04).ConclusiontDCS was well-tolerated but did not demonstrate significant overall efficacy for core ADHD symptoms or executive functions. Anodal stimulation at Fp2 showed potential selective benefits warranting further investigation. tDCS is not currently recommended as a standalone treatment for ADHD. Future research should optimize stimulation protocols and explore combined interventions with behavioral or cognitive therapies.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024612055.