Insular Cortex Disorders

What Causes Insular Cortex Disorders?

Problems with the function of the insular cortex may stem from damage to the brain, the effects of an underlying disorder, or genetic conditions that affect the development of the insula. Possible causes of dysfunction include:

• Damage from a stroke or a brain injury
• Damage caused by degenerative disease such as frontotemporal dementia
• Genetic factors that affect insular development. For example, this may be the case in schizophrenia.
• Some studies have suggested that systemic inflammation may affect the function of the insular cortex.

Are Insular Cortex Disorders Hereditary?

Scientists have not identified a direct link between genetics and insular cortex dysfunction. However, many disorders associated with insula problems do have an inherited component. For example, studies have shown that people with schizophrenia sometimes have a smaller than average insular cortex, and researchers believe genes play a role in schizophrenia risk. Therefore, it is possible that genes may affect the development or function of the insula.

Some degenerative diseases that can cause damage to the insular cortex also have a genetic component. For example, up to 40% of people with frontotemporal dementia have a family history of the disorder.

How Are Insular Cortex Disorders Detected?

The early warning signs of insular cortex dysfunction vary depending on the disorder that results from the dysfunction. Early symptoms could range from behavior or mood changes to cognitive or movement-related symptoms.

How Are Insular Cortex Disorders Diagnosed?

Diagnosis of disorders associated with the insular cortex begins by ruling out other medical problems that may be causing symptoms. After these exams, if the doctor suspects that a mental or degenerative disorder is the cause of the symptoms, they may recommend further medical testing and/or a psychiatric assessment.

Diagnostic steps may include:

• A physical exam. This exam aims to rule out other medical conditions that could be causing the symptoms.
• Psychological assessments. These assessments may take the form of questionnaires or talk sessions with a mental health professional to assess the patient’s mood, mental state, and mental health history. Family members or caregivers may also be asked to participate in these assessments.
• Brain imaging scans such as magnetic resonance imaging (MRI) and positron emission tracer (PET) scans may also be used to look for evidence of degenerative disorders or brain damage caused by a stroke or injury.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Are Insular Cortex Disorders Treated?

There is no cure for insular cortex dysfunction. However, medications may help the mental health symptoms of co-existing disorders, such as depression or anxiety disorders. Psychotherapy is also commonly used to treat these disorders.

Medications used to treat co-existing disorders may include:

• Antidepressants
• Mood-stabilizing drugs
• Antipsychotics

How Do Insular Cortex Disorders Progress?

In some cases, damage to the insular cortex may cause only minor symptoms. In other cases, symptoms may be severe. In the case of dysfunction caused by degenerative disorders, symptoms may worsen over time. Potential long-term consequences of dysfunction of the insular cortex include:

• Impaired sense of smell, taste, hearing, or touch
• Impaired sensitivity to pain
• Moodiness or irritability
• Problems maintaining relationships
• Problems with language
• Developmental delays
• Substance abuse
• Mental health-related issues

How Are Insular Cortex Disorders Prevented?

There is no known way to prevent insular cortex dysfunction. However, prompt treatment may relieve the effects of co-existing disorders and make it less likely that the sufferer will experience severe complications over time.

Insular Cortex Disorders Caregiver Tips

Taking care of a loved one with an insular cortex-related disorder can be taxing, both physically and emotionally. To help yourself and your loved one cope with the effects of the disease, keep these tips in mind:

• Learn all you can about the specific disorder your loved one suffers from. You’ll be better equipped to deal with the symptoms if you understand their cause. It’s crucial that you not take your loved one’s behavior personally and understand that it is part of the disease.
• Take care of yourself. Caregivers for people with brain-related disorders are at risk of physical and mental health issues themselves. Don’t hesitate to take time for yourself away from your loved one when you can, and seek help from a support group, either locally or online.
  • Additional background information can be found on Brain Injury Explanation’s website:  https://www.braininjury-explanation.com/consequences/impact-by-brain-area/insula

Insular Cortex Disorders Brain Science

The insular cortex is connected to many different parts of the brain and seems to influence a multitude of mental and physical functions. Dysfunction in the insular cortex can affect any of these areas. The brain areas connected to the insular cortex (and their functions) include:

• Primary and secondary somatosensory areas (processing and remembering sensory input)
• Anterior cingulate cortex (control and management of emotions)
• Amygdaloid body (response to fear or pleasure)
• Prefrontal cortex (planning, decision-making, social behavior)
• Superior temporal gyrus (sound and language processing, social cognition)
• Temporal pole (high-level cognitive functions)
• Orbitofrontal cortex (emotional and reward-related behavior)
• Frontal and parietal opercula (thought, understanding, planning, taste)
• Primary and association auditory cortices (processing and memory of sound)
• Visual association cortex (processing and memory of visual information)
• Olfactory bulb (processing of odors)
• Hippocampus (learning and memory)
• Entorhinal cortex (memory, navigation, time perception)
• Motor cortex (planning, control, and execution of voluntary movement)

Insular Cortex Disorders Research

Title: Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders (ModSoCCS)

Stage: Recruiting 

Principal Investigator: Dielle Miranda, MA     

Centre for Addiction and Mental Health

Toronto, Ontario

In this study, the investigators will be examining the effects of repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) on social cognitive impairments in individuals with schizophrenia spectrum disorders. Participants will be chosen by chance to receive either active rTMS stimulation, active iTBS stimulation, sham rTMS, or sham iTBS. The investigators predict that active 10Hz and iTBS stimulation will improve social cognitive impairments compared to sham stimulation. Researchers aim to identify which type of active stimulation is most effective at inducing changes in social cognition brain circuitry and, secondarily, which type of active stimulation is best tolerated and most effective at inducing changes in social cognitive performance.

This study is a randomized, double-blind, sham-controlled study that aims to use repetitive transcranial magnetic stimulation (rTMS), a form of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with Schizophrenia Spectrum Disorders. We will randomize 60 people with SSDs to three groups: 20 to a conventional form of rTMS (i.e. 10 Hz rTMS); 20 to intermittent theta burst stimulation (iTBS); and 20 to either sham 10Hz rTMS stimulation or sham iTBS. We will determine whether these treatments can change the functional connectivity of key SCog brain circuits by targeting a brain region known as the dorsomedial prefrontal cortex (DMPFC). Since each person’s anatomical and functional brain profile is slightly different, we will optimize the orientation and location of coil placement in each individual. Overall, our proposal follows a target engagement framework, including specifics regarding testing brain stimulation parameters (i.e., rTMS vs. iTBS) and individualizing coil placement for optimal targeting. We anticipate that active 10 Hz rTMS or iTBS will demonstrate target engagement compared to sham and potentially ameliorate SCog deficits in people with SSDs. Our primary goal is to identify which treatment best induces a change in SCog brain circuitry and, secondarily, which treatment is best tolerated and induces changes in social cognitive performance.

Title: Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia (Lithium)

Stage: Recruiting

Contact: Edward Huey, MD

Columbia University Medical Center

New York, NY 

Behavioral symptoms of Frontotemporal dementia (FTD), including agitation, aggression, and inappropriate repetitive behaviors are common, distressing to patients and caregivers, often lead to institutionalization, and can be very difficult and expensive to treat. There is a shortage of medication for treating these symptoms in FTD. Typically, antidepressants and antipsychotic medications are prescribed – which low efficacy and, with the latter class, carry serious adverse effects such as parkinsonism and increased cardiovascular-related mortality. The investigators propose a study of the efficacy of lithium carbonate compared to placebo in the treatment of agitation, aggression, and inappropriate repetitive behaviors in 60 patients with FTD in a randomized, double-blind, two-arm parallel 12-week trial. Lithium is a highly effective treatment for mania and symptoms of agitation or aggression in bipolar disorder. It also inhibits tau aggregation and phosphorylation, leading to considerable interest in its use as a disease-modifying treatment for tauopathies such as FTD and Alzheimer’s disease. Unfortunately, earlier trials using typical doses (i.e., doses prescribed for treatment of bipolar disorder) showed a high incidence of serious adverse effects (including confusion and delirium). For the proposed study, the investigators will: 1) use lower doses and lower target serum concentrations than have preceding trials (shown in preliminary data from a Columbia study and data from other labs to be well-tolerated) and 2) target behavioral symptoms rather than cognitive outcomes.

Title: Rehabilitating and Decelerating Language Loss in Primary Progressive Aphasia With tDCS Plus Language Therapy

Stage: Recruiting

Principal investigator: Argye E Hillis, MD, MS

Johns Hopkins School of Medicine

Baltimore, MD 

Primary Progressive Aphasia (PPA) is a debilitating disorder characterized by the gradual loss of language functioning, even though cognitive functioning is relatively well preserved until the advanced stages of the disease. There are three main PPA variants classified based on the pattern of language impairments and areas of atrophy, but anomia is present across all variants in the earliest stages. While there is a significant amount of research investigating multiple treatment approaches for individuals with aphasia resulting from stroke, individuals with PPA have far fewer treatment options to choose from. Recently, a growing body of literature on treatment in stroke-based aphasia has found promising results for pairing traditional language therapy with non-invasive neurostimulation via transcranial direct current stimulation (tDCS). The small number of studies of the effects of tDCS applied to the left inferior frontal gyrus (IFG) in PPA also yield promising results that show tDCS can enhance generalization to untreated structures. Research in stroke-based aphasia has also shown that language outcomes significantly improve when participants are treated with more complex language stimuli, because this treatment approach results in enhanced generalization. For example, therapy that has participants build sentences around verbs has been found to improve word-level verb and noun naming. The current proposal aims to investigate whether combining the benefits of tDCS, while providing verb retrieval therapy that uses sentence building to improve word-level retrieval deficits, will enhance word retrieval deficits in PPA and slow the loss of language functioning. Furthermore, the proposed study will investigate the atrophy patterns at baseline, to determine which atrophy patterns are predictive of improved word retrieval. Specifically, this proposal aims: 1) to determine whether tDCS to left IFG coupled with therapy promoting verb retrieval within sentences improve noun and verb retrieval in treated and untreated items in individuals with PPA, and 2) To investigate which patterns of atrophy are predictive of maintenance and generalization of word-retrieval in individuals with PPA following tDCS+therapy vs. sham+therapy. This proposed research will allow the investigators to evaluate the potential benefits and sustainability of tDCS in PPA, the generalization of trained items to untrained items, and the deceleration of language loss.