Impaired interval timing and Free Willy (not really)

Posted by kkiritah on June 10, 2013 in Cognition, Graduate Studies, Minor Proposition Posts, Neuroscience, UCSD | 1 Comment

This is really about: 

The role of interval timing dysfunction in the formation of first-rank symptoms in patients with schizophrenia?

Note 1: This is the first in a “series” of posts by the second- (or third-?) year students to tell you a little about our minor prop topics.  We all Some of us worked very hard on our proposals and learned a whole lot about these topics that, by definition, we will/may/should never actually study.  What a shame it would be if we never got to share our hard work with the world beyond our committees, right?  So here we are.  Please enjoy. 

Note 2:  I do not apologize for my love of links. (BTW, if you only click three more links in this post, make sure they are all Kurt Schneider.) 

---

The sense of agency—that is, the knowledge that you have consciously willed and executed your own actions—is believed to be inferred from the temporal relationship between our thoughts and actions.  For almost 20 years, Dr. Daniel Wegner, the epically-titled John Lindsley (?) Professor of Psychology in Memory of William James at Harvard University, has argued that our brains trick us into believing that our actions arise from our conscious commands to move, when in fact it is not our conscious command that drives the movement but an unconscious process that causes both the thought and the movement to occur separately^1,2. The temporal contiguity between the thought and the movement incorrectly implies a causal relationship between the two. (See Figure 1)

Benjamin Libet provided support for this hypothesis by showing that there is a delay between the initial neural activity associated with subjects’ movements and their detection of their intent to cause the movement.

Additionally, Wilder Penfield induced movements with electrical stimulation of the motor cortex in epileptic patients, and the patients did not report consciously willing the actions.  Therefore, actions can occur independent of our willing them¹.

Further evidence of our “mental trick” lies in the ability of healthy subjects to be tricked into believing that they have caused an event to occur when they have not.  For example, transcranial magnetic stimulation (TMS) was applied to the motor cortex to influence movement of the left or right index finger of healthy subjects.  The subjects reported consciously willing the movement despite the external influence of the TMS⁴.

Similarly, in a simple task, inspired by the Ouija board, in which a subject or an experimenter could move a shared mouse toward an object, subjects could be led to believe they had moved the mouse when only the experimenter was in control.  If the name of an object was paired with the experimenter’s movement of the mouse toward that object on the screen within 5 seconds, the subjects reported that they had moved the mouse intentionally².

Given these examples from healthy subjects, it is not difficult to imagine how rationalizations of abnormal events could lead to the experience that one’s actions are being controlled by an external source.

Indeed, an abnormal sense of agency is one of the more prominent symptoms of schizophrenia⁵. Patients lose the boundary between the self and others, causing them to believe that external forces control their thoughts and actions.  Although there are many types of delusions experienced by patients with other psychiatric illnesses, such as dementia, temporal lobe epilepsy, and Parkinson’s disease, auditory hallucinations, delusions of control, and other “loss-of-boundary” delusions are most commonly associated with schizophrenia.  Therefore, Kurt Schneider⁵ (not to be confused with Kurt Schneider or Kurt Schneider, aka Harry Earles) labeled these symptoms “first-rank symptoms” (FRS).  Despite years of research and several proposed mechanisms, the biological abnormalities leading to FRS remain unknown.

Possible Mechanisms for the Formation of FRS

As you may have deduced by now, one popular hypothesis proposes that a timing deficit exhibited in schizophrenic patients may be associated with formation of FRS.  Patients with schizophrenia have reported subjective evidence of time distortion⁶, and several studies have reported timing deficits in schizophrenic patients, typically underproduction of time intervals during reproduction tasks and overestimation of time in verbal reports⁷.  Christine Carroll and colleagues^8–10 have found that subjects with schizophrenia exhibit greater timing variability in the millisecond and several-second ranges in time perception and finger tapping tasks.

The connection between the timing deficit and delusions in schizophrenic patients is supported by physiological overlap between the regions implicated in time perception and those disrupted in schizophrenia.  The same fronto-striatal network disrupted in patients with schizophrenia¹¹ has been shown to be integral to the representation of time information^12,13 (see pacemaker-accumulator model above).  In particular, the transmission of dopamine in this network is crucial to both timing and the disruption observed in schizophrenia^14,15.  Despite the overlap in this circuitry, support for the relationship between disrupted timing and other symptoms of schizophrenia is weak.

A more recent area of interest to both schizophrenia and time perception research is the insula (The mind and body are integrated in the insula, says UCSD’s Dr. Martin Paulus) .  The insula is a key neural structure involved in the awareness of internal state, or interoception*, which contributes to the sense of self¹⁶.  It has been proposed that it is the awareness of self, mediated by the anterior insula in particular, that provides a basis by which people can estimate time intervals^17–19.  Evidence for this is provided by the fact that more salient internal events cause subjective dilation of time¹⁸.

MRI scans in patients with schizophrenia have revealed a significant inverse correlation between severity of delusions and the volume of the right insula²⁰, and a meta-analysis of insular volume has found a reduction of insular volume, particularly in the anterior insula, in patients with schizophrenia²¹.  In various affect and prosody studies, increased insular activity has been found in patients with schizophrenia¹⁶.     These latter studies do not report correlations of findings with degree of delusions.  Considering the potential relationship between time and sense of agency, however, the anterior insula is an ideal candidate region for the production of both symptoms, potentially linked by common mechanisms.

Just a Minor Proposition

At this point, I could list the various studies that have been done to test the link between these regions, interval timing, and FRS.  I could also tell you about my minor prop study.   I could, but I will not.  (Alas, I am running out of the energy and links necessary to continue… and I am sure your head is already spinning from all of this crazy information, and I don’t want you to feel overwhelmed).

If you are interested in learning more about this topic or would like to waste time clicking on more links unrelated to this post, send me an email (khiga@ucsd.edu), and I’ll see what I can do.

Thanks for reading.

Kerin K. Higa

---

*NeuroLex, holla!

References: They do exist, but the formatting is frustrating me.  Send me an email, and I will send them your way!

---

Kerin Higa is a second-year Ph.D. student in the Consortium for Translational Research in Neuropsychopharmacology, working with Drs. Mark Geyer, Xianjin Zhou, and Jared Young of UCSD’s Department of Psychiatry.  She is investigating potential mechanisms for the development of psychiatric disorders, including schizophrenia and major depression, using a combination of mouse behavior and molecular biology.  She mostly just likes pipetting and playing with mice and is glad she can get a degree for it. @kkiritah