Coping with voices in the schizophrenic brain

"I don't believe in anything. That's my cardinal rule. I do it for my mental health. If I believe in God, then I start talking to God and God starts talking to me. As soon as I start believing in something, then it talks to me. So, I don't believe in anything."

Sara, whose name we changed to protect her identity, was diagnosed with schizophrenia at age 19 during her senior year at New York University. She had not experienced any trauma as a child - no abuse, no bouts of depression, nothing that would raise any red flags. She led a more or less happy life. But in high school she experimented with drugs, and upon travelling abroad around the same time, she experienced intense culture shock.

This series of events may have been Sara's personalized recipe for mental illness, cooked up with all the flavors of her unique position in life, her temperament, and her family's history. Her mind became a prison; she felt as though people were constantly laughing at her. She could no longer distinguish fantasy from reality. She assumed she wouldn't go back to school.

"I thought that my life was over, that I would never be able to do anything," she says. "Because that's what the doctors told me."

Then she began to hear voices.

The Schizophrenic Brain

Schizophrenia is a disease that afflicts almost all walks of life. Because it can be so debilitating, scientists have been feverishly searching for its genetic basis. In July, researchers affiliated with the Psychiatric Genomics Consortium compared the genomes of nearly 37,000 people with schizophrenia to the genomes of more than 113,000 people without the disease. In the end, they identified 108 locations where the DNA sequence in schizophrenic people tends to differ. The finding was a major advance in the field of psychiatric genomics, one that could ultimately help scientists understand who is susceptible and why.

Still, the biological markers aren't always clear - often, a patient's genes for schizophrenia can lay dormant until certain circumstances trigger their expression, making a diagnosis based on DNA alone less than clear-cut. And with no blood test or brain scan available to detect schizophrenia's symptoms elsewhere in the body, diagnosis is based almost entirely on what the patient reports.

Treatment of mental illness is nested in confusion, too. Many therapists approach their practice from a different medical perspective than a cognitive psychologist or a geneticist. And while a geneticist might have access to the most current research, she isn't going to have direct daily contact with a patient's behavioral nuances like a psychiatrist. What's going on in the lab, in other words, is often divorced from what's being implemented "on the couch."

But it doesn't have to be that way.

Some scientists are arguing that our new understanding of a particular network in the brain is allowing neuroscientists, psychologists, and psychiatrists - even artists and writers - to understand each other in ways that wouldn't have made sense ten years ago. Called the default mode network, or DMN, it's a set of brain regions that are typically suppressed when a person is engaged in an external task (playing a sport, working on a budget), but activated during a so-called "resting state" (sitting quietly, day-dreaming).

"It's an extremely important platform for any kind of thought that is disengaged from the 'here-and-now,' " says Mary Helen Immordino-Yang, assistant professor of psychology at the University of Southern California's Brain and Creativity Institute. That includes processing other people's stories, reflecting on our own lives, planning for the future, or making important decisions. Immordino-Yang says the default mode network is "metabolically expensive." In other words, when your head is lost in the clouds, your brain is hard at work.

Though not the only "resting state" network that's active when we're staring off into space, the DMN is unusual in that it is reliable and identifiable, making it easy for scientists to study. Like a web of taut ropes overlaying and intersecting one another, the regions of the DMN - which include the medial prefrontal cortex and the posterior cingulate, both of which are involved in self-awareness, self-reflection, and so on - light up in concert, despite any distance separating them.

When neurologist Marcus Raichle and his colleagues discovered the DMN in 2001, it took the scientific community by surprise. How could rest and self-reflection excite the same brain regions in us all? Why are those regions so intimately correlated? Wouldn't a brain scan vary more from person to person depending on the content of an individual's thoughts? It turned out that the DMN has nothing to do with content and everything to do with context. This network is functioning all the time - focusing on a task merely tempers and subdues it.

"This is first time we've found a neural system that actually reveals your inner self," says Susan Whitfield-Gabrieli, a research scientist at MIT. In 2009, she and her colleagues found that in schizophrenic people, the DMN operates on overdrive. When clinically diagnosed patients enter an fMRI scanner and are asked to perform various tasks, the dial on their DMN doesn't turn down like it should. And when the patients are at rest, their DMN is hyper-connected, buzzing with surplus energy. What's more, they lack the ability to toggle out of the DMN, this highly self-referential state of being. "They're actually stuck in their default mode network," Whitfield-Gabrieli says.

So how does a schizophrenic person get unstuck? That's a question hundreds of experts from diverse backgrounds are trying to answer.

Coping with Voices

One lens through which experts are studying schizophrenia is anthropology. If the default mode network is related to identity and self-reflection - and if schizophrenia, in turn, is associated with the default mode network - then considering culture may help us understand how psychosis manifests itself globally. After all, how you experience your inner world depends partly on where you live and how you've grown up. The same is true of mental illness. "When immigrant groups move to a new cultural group, they take on the mental illness liabilities of the culture where they are," Immordino-Yang says. Because 60 to 80% of people diagnosed with schizophrenia hear voices, a good indicator of how a given culture views the disease might be how its people cope with its most well known but most misunderstood facets: auditory verbal hallucinations.

"Americans hate their voices. Their voices mean schizophrenia to them," says Tanya Luhrmann, an anthropologist at Stanford University. By contrast, people in India and Africa don't typically label their illnesses or their voices, she revealed in a study published in the British Journal of Psychiatry. "It's not that they don't recognize that they're struggling," she says. "But they talk about their experience as having much more of a natural role." For example, they may think of their auditory hallucinations as benevolent or spiritual - like a friend or even the voice of God.

People not diagnosed with a mental illness, too, hear voices. In some cases, what they experience may be something that would be classified as a hallucination if reported by a clinically psychotic person. "If you ask someone, 'have you ever heard a voice when you're alone?' the rate is somewhere between 15 to 80% depending on how you ask the question," Luhrmann says. If you couple it with an example of what might be considered an auditory verbal hallucination, the percentage of people who say "yes" goes up.

Testimonies from people who experience varying kinds of auditory hallucinations support the idea that voice-hearing is complex and culturally-dependent. Their range of experiences is vast. Some say they hear audible, crystalline voices that emanate from inside their heads. Others report cacophonous screeches and bangs coming from outside their bodies. Still others sense murmurs and whispers that crawl over from the next room. Finally, some people describe a phenomenon similar to what cognitive psychologists call "inner speech," the wordless soup of dialogue that you "hear" when deep in thought. For some, inner speech is acoustically more intense than it is for others. For example, they might say their mental landscape is made up of "loud thoughts" or "soundless voices."

For Sara, the voices she heard began as disembodied, made-up personalities. Then, after about a year of taking a handful of different medications to varying degrees of success, her voices became solely associated with real people and their private thoughts. Sara is now 33 - and though she's been well enough to go without medication for 11 years, she still hears this latter type of voice.

"If I hear somebody psychically communicating with me - which I don't believe in; I'm a complete atheist - then the sound will come from above their head or behind their hair...even from inside their stomach. It's somewhere besides their actual mouth," she says. "It's not as loud as their real voice. It's softer, but I don't think the tone and quality of the voice is compromised."

The reason why Sara can talk about her voices so intelligently is because she's cultivated a relationship with them, in a sense. Though she tries not to engage too much with them, she's learned to understand her voices and even use them to her advantage. If she's bored, they're sometimes entertaining. Occasionally she even asks them questions.

"Sometimes I'm worried about what people think of me," she says. "And so I ask them [what they think of me] in the air above their head, and I hear their voice say it."

Sara enjoys and even values some of her auditory hallucinations now, which is atypical of most American psychotic and post-psychotic patients. But that's not the case everywhere. A simple internet search in her early 20s led Sara to Intervoice, a network established in the U.K. and now widely recognized in 29 (mostly European) countries. The organization's central tenet is that hearing voices is a meaningful human experience and not necessarily a sign of mental illness. Members set up support groups where people can meet and talk about their experiences without fear of stigma.

Still, Intervoice has not caught on in the U.S. like it has in the U.K. and elsewhere. "There are real differences in the way Americans and Europeans think about voices," Luhrmann says. In Europe, people are generally more comfortable with the ambiguity between psychosis and religion, and there's more interest in applying humanities research to medicine.

For Sara, the idea that people could handle and live with their voices made the difference. "I decided I was going to be one of those people," she says. "Just a small glimmer of hope was all I needed."

Angela Woods, a medical humanities researcher at Durham University in the U.K., is leading a team of experts in a project called "Hearing the Voice," which works closely with the broader Intervoice network. It aims to dispel some of the myths about voice-hearing and to see how cognitive neuroscientists can work with writers, artists, clinicians, theologians, and even philosophers to grasp the full spectrum of schizophrenia itself.

"We wanted to call for a more nuanced, richer account of what it is like to hear voices," Woods says. An initial step in their research involved sending surveys to 158 people from around the world in an attempt to better understand what the experience is like. The team has hosted a number of different events to raise public awareness of schizophrenia and its many shades, including a "VoiceWalk" in a U.K. cemetery to bring people's voice-hearing stories to the fore and an event at the Durham Book Festival to promote a better understanding of how writers cope with disparate inner voices - their characters, their muse, their narrators, and so on.

Another way people can learn to cope with their voices is by bringing them into the lab. Whitfield-Gabrieli, in collaboration with Margaret Niznikiewicz of Harvard University, is training patients to regulate their auditory hallucinations by consciously controlling activation in their auditory cortex. Participants attempt to push their cortex activation levels up and down, without receiving any auditory stimuli other than the background noise of the fMRI scanner. Meanwhile, they receive visual feedback from the fMRI on their progress. Whitfield-Gabrieli says the hope is that patients can learn to mitigate their voices by focusing on what's going on in their own brain.

"Teaching people with psychosis to use their imagination to handle their voices is a promising tool," Luhrmann says. As a society, we can encourage positive relationships with auditory hallucinations by helping patients - schizophrenic or not - better understand them. That means allowing people to tag their voices as "me" or "not me," give the voices names, recognize what they're saying and why, and discover what personal significance, if any, a particular voice might have.

Whatever the auditory input may be, Luhrmann says people can have positive or negative experiences depending on the attitude they adopt. "People attend to different pieces of that good-bad spectrum depending on the way their culture invites them to attend," she says.

While there's no evidence yet that a learning-based method will work, Whitfield-Gabrieli has reason to believe it's possible. Research has linked increased DMN activity to the phenomenon of voice-hearing. While scientists still aren't entirely certain how or why people hear voices, they think that auditory hallucinations may be a misattributed form of inner speech. A hyperactive DMN agitates the auditory cortex, resulting in what could be a fundamental confusion between what the brain "hears" inside itself and what it actually hears as a result of real, external stimuli. Many factors, though - including social isolation - contribute to the health of a person's brain. Imagination can help with the healing process and reclaim a functioning relationship between the self, the auditory cortex, and inner speech.

Woods' and Luhrmann's work - as well as their colleagues' - dovetails with a study published about a month ago in the American Journal of Psychiatry, which concluded that the term "schizophrenia" actually encompasses eight genetically distinct disorders, not just one. The assertion, whether or not it holds up, suggests that mental well being comes in a variety of different "packages" depending on your genetic makeup. That goes for clinically diagnosed patients as well as healthy individuals.

"We should be wary of seeing a schizophrenic person as someone with a kind of deficiency," Woods says. Rather, it may be just another part of what it means to be human. A person might simply process language differently or ruminate on social interactions for too long. His or her inner speech might be more fragmented or circuitous. Individual differences in DMN activity account for the diverse ways the human mind freely wanders.

Searching for Answers

The default mode network may sound like a gold mine to psychiatrists and neuroscientists alike. The reality, though, is somewhat more complicated. Brain imaging, while promising, has yet to definitively solve major mental health issues like schizophrenia, depression, anxiety, and bipolar disorder.

Daniel Margulies of the Max Planck Institute for Human Cognitive and Brain Sciences argues that even if our scientific understanding of the DMN evolves, its weight in the science world has "opened up a way of talking about the relationship between the self and these disorders." The default mode network (and its relationship to voice-hearing), he says, can provide a gateway to understanding the full range of how people comprehend themselves - even if anomalies in the network aren't proven to be a direct cause of schizophrenia.

That may be what matters most, since schizophrenia is not necessarily about neurons or synapses. It's about the people it affects.

"Technology is giving us important information, but not the final answers," says David Farb, professor and chair of the Department of Pharmacology and Experimental Therapeutics at the Boston University School of Medicine. He advocates an approach that views diseases and disorders as "vast and complex chimeras of symptoms that can be mixed and matched." For example, depression may share symptoms with other disorders, like severe anxiety. It's also possible, he says, that a person may develop an anxiety disorder as they grow increasingly self-conscious of their schizophrenia, for example. In that case, Farb says that schizophrenia may be made even more complex by "an expression of learned helplessness."

By acquiring as much genetic and neurological information about a patient as possible, we may be able to intervene at an earlier stage and prevent schizophrenia before it develops. Whitfield-Gabrieli and Larry Seidman of Harvard University are studying at-risk people in Shanghai to find brain markers that predict whether or not someone will become schizophrenic. Interestingly, they've noticed a skew toward more female than male schizophrenic patients in China; in the U.S, schizophrenia is a predominantly male disorder, again pointing to the cultural element.

And that is what's so striking to the U.K. researchers associated with Hearing the Voice. We shouldn't assume that nature (rather than nurture) is the primary culprit when it comes to schizophrenia, they say. "If the default mode network is somehow connected with mind-wandering, self-referential cognition, you can't simply use objective measures," says Felicity Callard, another Durham University researcher involved in the project. "You have to get at what people think is going on in their own heads." In other words, to find a cure, we might have to put ourselves in other peoples' shoes.

"We should direct energy and funding and resources into exploring people's lives - not just their chemistry, their neuroanatomy, or their genes," Woods says. PSTD, for example, is a legitimate response to a traumatic event. Likewise, schizophrenia is a legitimate response to a lifetime of accumulated events, thoughts, interactions, and engrained beliefs. "We need to be able to ask, 'What happened to you?' That's not ruling genetics out, but it's taking things from another angle."

Farb suspects the answer might be simpler than that. Drugs that target genes regulating DMN connectivity or surgery that modifies key points of DMN activity, for example, could resolve schizophrenic symptoms. He acknowledges, though, that there may be other factors at play. Schizophrenia - like PTSD or chronic pain - may have a cumulative effect on the brain that's hard to anticipate. "While we may be able to correct the original deficit, we may still be left with others because they are a consequence of all of those years spent living with the disorder," he says. "It's really complicated to get a cure."

As a patient, Sara believes that the process needs to be individualized. Doctors should ask patients questions about their experiences and how they want to go about getting better. Woods agrees. "The more we treat schizophrenia as a mysterious entity that we're going to pin down in a piece of DNA," she says, "the more we'll miss the complicated, multifaceted aspects of existence that go into making someone have an experience of psychosis."

"And if people don't feel as though they're able to tell stories about their experiences, then it's hard to see that a cure would be particularly welcome, rich, or meaningful."

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