Method of treating psychological disorders by brain stimulation within the thalamus

A method for treating psychological disorders such as obsessive compulsive disorder, Tourette's syndrome, depression, bipolar disorder, panic attacks, schizophrenia, and attention deficit disorder by stimulation of the thalamus, and in particular regions within the anterior and intralaminar nuclei of the thalamus. The method includes the steps of determining a common group of patients, each suffering from a common specific diagnosis for a psychological disorder; determining which common region of the patients' thalami are involved in carrying the pathological electrical signals which may otherwise be generated in dissimilar and disparate regions of the brains of the patients; surgically implanting an electrode and electrical signal generating device such that the electrode is positioned within the region of the thalamus identified as the common nexus; and selectively adjusting the level of electrical stimulation in accordance with the specific effect of the stimulation of the patient. In particular, the regions of the thalamus most frequently associated with psychological disorders are the anterior and intralaminar nuclei.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates generally to the treatment of psychological 
disorders by stimulating appropriate regions of the thalamus, and more 
particularly to a method of interrupting pathological electrical activity 
of the brain by electrical stimulation of the corresponding nucleus or 
nuclei of the thalamus, and most specifically to the stimulation of the 
central median nuclei, intralaminar nuclei, and/or the central lateral 
nuclei. 
2. Description of the Prior Art 
Within the field of neurosurgery, the use of electrical stimulation for 
treating pathologies, including such disorders as compulsive eating, 
chronic pain, and movement disorders, such as Parkinson's disease 
essential tremor, has been widely discussed in the literature. It has been 
recognized that electrical stimulation holds significant advantages over 
alternative methods of treatment, for example lesioning, inasmuch as 
lesioning can only destroy nerve activity. In many instances, the 
preferred effect is to stimulate or reversibly block nervous tissue. 
Electrical stimulation permits such stimulation of the target neural 
structures, and equally importantly, it does not require the destruction 
of the nervous tissue (it is a reversible process, which can literally be 
shut off or removed at will). 
Within this field, however, disorders manifesting gross physical 
dysfunction, not otherwise determinable as having emotional or psychiatric 
origins, comprise the vast majority of those pathologies treated by deep 
brain stimulation. A noteworthy example of treatment of a gross physical 
disorder by electrical stimulation is included in the work of Alim 
Benabid, and his research team, who have proposed a method of reducing, 
and in some cases eliminating, the temor associated with Parkinson's 
disease by the application of a high frequency electrical pulse directly 
to the subthalamic nucleus (see Neurosurgical Operative Atlas, Vol. 8, 
March 1999, pp. 195-207, Chronic Subthalamic Nucleus Stimulation For 
Parkinson's Disease; and New England Journal of Medicine, Vol. 339, 
October 1998, pp. 105-1111, Electrical Stimulation of the Subthalamic 
Nucleus in Advanced Parkinson's Disease). 
Conversely, direct neuro-augmentation treatments for disorders which have 
traditionally been treated by behavioral therapy or psychiatric drugs, has 
been largely limited to peripheral nerve stimulation. A noteworthy example 
is the effort to control compulsive eating disorders by stimulation of the 
vagus nerve which has been described by Wernicke, et al. in U.S. Pat. No. 
5,263,480. This treatment seeks to induce a satiety effect by stimulating 
the afferent vagal fibers of the stomach. For patients having weak 
emotional and/or psychological components to their eating disorders, this 
treament can be effective insofar as it eliminates the additional 
(quasi-normal) physio-chemical stimulus to continue eating. This is 
especially true for patients who exhibit subnormal independent functioning 
of these fibers of the vagus nerve. For compulsive eating patients who are 
not suffering from an insufficient level of afferent vagal nerve activity 
resulting from sufficient food intake, however, the over stimulation of 
the vagus nerve and potential resultant over abundance of satiety 
mediating chemicals (cholecystokinin and pancreatic glucagon) may have 
little effect. It has even been suggested that continued compulsive 
eating, despite overstimulation of the vagus nerve, may exacerbate the 
emotional component of the patient's disorder. This, therefore, begs the 
question, is vagus nerve stimulation useful in treating the psychological 
component of the disorder of compulsive eating, or is it simply a method 
of minimizing the additional, but natural, pressures to eat because of 
normal physical hunger. More generally, the question may be asked, is 
peripheral nerve stimulation of any kind the most appropriate method of 
treatment for disorders which are, at the core, the result of a pathology 
exhibited in the brain. 
If the answer to this question is that the stimulation of a peripheral 
nerve can result in the release of a chemical which specifically 
counteracts the psychological pathology, for example if the release of 
greater amounts of cholecystokinin and pancreatic glucagon had a direct 
effect on the pathology exhibited in the brain, then, for that patient, 
the treatment will have a greater probability of success. If, however, as 
is most probably the case, the increase in the level of activity of the 
peripheral nerve does not result in the release of such a chemical, and 
therefore, has no effect on the area of the brain responsible for the 
emotional/psychiatric component of the disorder, then the treatment will 
have a much lower probability of success. 
The impetus would, therefore, be to treat psychological disorders with 
direct modulation of activity in that portion of the brain which is 
causing the pathological behavior. Unfortunately, the ability to determine 
what region of the brain is responsible for a given patient's disorder is 
very difficult, and even more importantly, does not usually provide 
consistent patterns across a population of similarly afflicted patients. 
By this it is meant that the region of the brain which causes the 
behavioral pathology of one compulsive eating patient, for example, does 
not necessarily correspond in any way with the region of another 
compulsive eating patient. 
In some manner, however, the determination of what regions of the brain are 
exhibiting pathological function must be determined. Fortunately, a method 
for determining precisely this has been developed by a number of 
researchers. Normal brain function can be characterized by four discrete 
frequencies of electrical output. Other frequencies are almost exclusively 
associated with pathology. The use of magnetoencephalography (MEG scans) 
has permitted quantificaion of electrical activity in specific regions of 
the brain. It has been proposed that MEG scans may be used to identify 
regions exhibiting pathological electrical activity. The resolution of the 
MEG scans of the brain are highly accurate (sub-one millimeter accuracy), 
however, correlating the MEG scan with MRI images for the surgical 
purposes of identifying anatomical structures limits the overall 
resolution for surgical purposes to a volume of 10 to 30 cubic 
millimeters. As stated above, however, simply identifying the regions of 
the brain which are exhibiting pathological electrical activity for a 
specific patient is not sufficient to generalize across a large population 
of patients, even if they are exhibiting identical disorders. 
Fortunately, the architecture of the brain provides a substantial advantage 
in the search for a generic solution. This design advantage takes the form 
of a centralized signalling nexus through which many of the brain's 
disparate functions are channeled in an organized and predictable manner. 
More particularly, the thalamus is comprised of a large plurality (as many 
as one hundred, or more) of nerve bundles, or nuclei, which receives and 
channels nerve activity from all areas of the nervous system and 
interconnects various activities within the brain. The thalamus has been 
metaphorically described by some as the brain's equivalent of a highly 
organized train station. Many different train tracks come together, and 
many trains carrying many different cargos enter, however, if one has a 
schedule and a map, it is easy to find all the trains which carry coal 
(whether from Pennsylvania, West Virginia, Tennessee, or Arkansas), 
because all coal carriers are routed through the same tracks. It is this 
key which permits the treatment of common psychological disorders by brain 
stimulation of one specific area, rather than having to customize the 
(gross) placement of the stimulator for each patient. 
It is therefore the principal object of the present invention to provide a 
more generically applicable method for treating certain psychological 
disorders. 
It is further an object of the present invention to provide a fully 
reversible and adjustable method of treating certain psychological 
disorders. 
It is still further an object of the present invention to provide a method 
of treating certain psychological disorders the effectiveness of which may 
be evaluated rapidly. 
It is also an object of the present invention to provide a method of 
interventionally treating certain psychological disorders while minimizing 
the necessary pathological investigaion. 
SUMMARY OF THE INVENTION 
The preceding objects are provided in the present invention, which 
comprises new and novel methods of treating psychological disorders by 
implantation of stimulation electrodes at specific locations in the 
thalamus. In another aspect, the present invention also comprises new and 
novel methods for identifying the proper positioning of the electrodes 
within the thalamus for a given specific psychological disorder. More 
particularly, in the first aspect, the present invention comprises a 
method of therapeutically treating a psychological disorder by surgically 
implanting an electrode into a predetermined site within the brain of the 
patient, wherein the predetermined site is selected from the group of 
non-specific nuclei residing within the intralaminar nuclei or anterior 
thalamic nuclei. Referring more particularly to FIG. 1, the anterior 
thalamic nuclei 100 are located in the most anterior portion of the 
thalamus and are interconnected with the frontal lobes. The intralaminar 
nuclei 102 have more diffuse projections. Together these nuclei groups are 
the most likely associated with psychological disorders. The intralaminar 
nuclei 102 are located in the paramedian thalamus (dividing each of the 
lobes of the thalamus along a Y shaped vertical planar geometry which cuts 
through the posterior to anterior axis of each lobe). Referring now to 
FIG. 2, within the intralaminar group 102 are principally the anterior 
104, midline 106, and posterior 108 subgroups. The anterior subgroups 104 
include the central lateral (CL) and paracentralis regions. The posterior 
subgroups 108 include the centromedian-parafascicularis complex (Cm-Pf). 
The midline 106 and other related subgroups include the centre medial 
(CeM) nuclei and paraventricularis (Pv). 
The anterior thalamic nuclei are coupled most directly to the frontal lobes 
which are most associated with personality and behavior. The posterior 
subgroup of the intralaminar nuclei, including the 
centromedian-parafascicularis, is coupled most directly to the prefrontal, 
permotor, and parietal cortices. The anterior subgroup, including the 
central lateral and paracentralis nuclei, is most directly connected to 
the parietal, visual association, prefrontal, frontal, and superior 
temporal cortices as well as the frontal eye field. The midline and 
related intralaminar subgroups, including the paraventricularis, centre 
medial, midline nuclei, are connected to the orbital frontal cortex, the 
hippocampus, the limbic cortex, and the amygdala. 
In the first aspect of the invention, therefore, the proximal end of the 
electrode is coupled to an electrical signal source which, in turn, is 
operated to stimulate the predetermined treatment site in the thalamus of 
the brain, such that the clinical effects of the psychological disorder 
are reduced. 
In the second aspect, the present invention comprises a method of 
determining the proper therapeutic treatment, i.e., the proper position or 
placement of the electrodes, for a specific psychological disorder 
comprising the steps of identifying a large sampling of patients, each 
exhibiting a common specific psychological disorder and then identifying 
which common region or nuclei of their thalamuses exhibits pathological 
electrical activity during manifestations of the specific psychological 
disorder. The common regions demonstrating this pathological activity 
constitute the predetermined treatment site, whereafter a suitable means 
for affecting the activity of said predetermined treatment site may be 
employed to ameliorate the psychological disorder generically with a high 
probability of success. 
In particular, the regions identified above, including the anterior and 
intralaminar nuclei, are herein identified by their known anatomical 
connections and functional brain imaging as being actively involved in 
channeling or gating the pathological electrical activity associated with 
psychological disorders. It is important to note that these regions, their 
functions, and their connections are common structural features of human 
brains, and therefore are common targets across a large number of 
patients. As suggested above, this commonality of function and structure 
within the thalamus allows for common treatment targeting, even in 
instances wherein different patients have other disparate locations within 
their brains which also exhibit pathological electrical activity.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
While the present invention will be described more fully hereinafter with 
reference to the accompanying drawings, in which particular embodiments 
and methods of implantation are shown, it is to be understood at the 
outset that persons skilled in the art may modify the invention herein 
described while achieving the functions and results of this invention. 
Accordingly, the descriptions which follow are to be understood as 
illustrative and exemplary of specific structures, aspects and features 
within the broad scope of the present invention and not as limiting of 
such broad scope. 
The present invention comprises a method of identifying and treating 
patients who suffer from certain known psychological disorders. As 
suggested by this introductory statement, the specific steps involved with 
this method comprise two separate stages: first, the identification of 
patients and the preparation for surgical intervention; and second, the 
actual surgical procedure. 
With respect to the first of these stages, that is the pre-operative steps, 
the identification of suitable patients begins with the accumulation of 
physical, chemical, and historical behavioral data on each patient. A 
collection of patients who have been identified as exhibiting similar 
clinical symptoms are then grouped together and subject to a series of 
common non-invasive brain imaging studies. These brain imaging studies are 
intended to identify the regions of the brain, and more particularly, the 
regions of the thalmus, which exhibit clinically recognizable deviation 
from normal electrical activity. Several diagnostic tools are useful in 
this capacity, including fluoro-deoxyglucose-positron-emission tomography 
(FDG-PET), electro-encephalography (EEG), magnetic resonance imaging 
(MRI), and most importantly, magnetoencephelagraphy. 
A magnetoencephalograph (MEG) is a device which utilizes a plurality of 
spatially distributed, highly sensitive, superconducting circuits to 
register the electrical activity of the brain. The circuits can measure 
the frequency of the activity at different points in the brain by 
correlating the interferences registered in each superconducting circuit. 
As the normal frequencies of brain activity are known, and specific 
frequency ranges associated with neural dysfunction have been reported, it 
is possible to identify the specific regions of the brain exhibiting 
neural dysfunction. 
The correlation of specific areas of the brain which are not demonstrating 
nomal activity across a group of patients exhibiting similar clinical 
symptoms and who are similarly diagnosed is not assumed a priori. The 
nature of the brain's architecture provides a substantial advantage in 
this arena. The brain channels nearly all of its signalling activity 
through the thalamus. In an organized fashion, similar peripheral 
activity, i.e. activity in the peripheral areas of the brain which are 
associated with the same, or similar conditions, are channeled through the 
same areas of the thalamus. In this way, the thalamus acts as a train 
switching station, or as a post office, rerouting disparate signals along 
similar paths when the appropriate outcomes of the original signals are 
similar. This effect is nowhere more impresive than in the examples 
presently being illustrated. For example, two patients exhibiting similar 
clinical conditions, for example physical motion tics associated with 
florid Tourette's syndrome, may have very different peripheral brain 
dysfunction, but probably channel the abnormal electrical signals through 
the same nucleus within the thalamus. 
The precise mapping of this abnormal signalling, however, is not possible 
solely by using the MEG. While the use of the MEG is a substantial 
advantage in determining whether disparate abnormal peripheral activity is 
channeled through the thalamus in a similar way, the resolution of the 
device does not permit pinpoint accuracy in this determination. In fact, 
the resolution of the MEG is substantially less sharp than the implantable 
electrodes which are to be used in the surgical intervention. The 
correlation of actual data from test implantations as well as a deep 
understanding of the brain's architecture is necessary to identify the 
specific target nuclei. Additionally, however, the instruments utilized in 
guiding the surgeon in placing the actual electrodes into the thalamus 
have a similar degree of variability, or limit of resolution. Fortunately, 
the state of the art in surgical intervention and the resilience of the 
brain tissue permits a small degree of manipulation of the electrode once 
it is inserted. In fact, a number of advanced electrode designs have been 
presented which permit the micromanipulation of each of the electrical 
contacts' position without macromanipulation of the overall electrode. 
In the present invention, psychological disorders such as Tourette's 
syndrome, obsessive compulsive disorders (including individuals who 
exhibit extreme behavioral disfunction including excess washing, counting, 
checking, hoarding, or body dismorphic disorders in which individuals seek 
to surgically alter their appearance repeatedly because they are subject 
to the unwarranted belief that they are disfigured), depression, bipolar 
disorder, panic attacks, schizophrenia, and attention deficit disorder, 
are identified as having a probable commonality in thalamic activity 
associated with the anterior and intralaminar nuclei. Therefore, once a 
patient has been identified as exhibiting abnormal clinical behavior 
symptomatic of one of these disorders, subsequent pre-operative brain 
imaging scans are used to support the presumption that the abnormal 
signals associated with the disorder are being channelled through one of 
these related regions of the thalamus, and then surgical intervention with 
electrical stimulation is taken. 
Surgical intervention comprises the second stage of the treatment. It is 
the specific use of the stimulator, for treatment of psychological 
disorders which comprises the inventive step in the present method, and 
not the implantation technique itself. More particularly, the standard 
neurosurgical techniques for implantation of an electrical stimulation 
device into the brain may be utilized. In fact, referring to FIG. 3, in 
which a side cross-section of a human brain having a stimulation electrode 
110 implanted into the thalamus 112 (and more particularly, the 
intralaminar nuclei thereof) is provided, it shall be understood that the 
impantation of electrodes into various regions of the brain, including the 
thalamus is known. It is the application of this technique for the 
treatment of psychological disorders which has not previously been 
described. This technique, therefore, is as follows. 
Patients who are to have an electrode implanted into the brain, first have 
a steroetactic head frame, such as the Leksell, CRW, or Compass, is 
mounted to the patient's skull by fixed screws. Subsequent to the mounting 
of the frame, the patient undergoes a series of magnetic resonance imaging 
sessions, during which a series of two dimensional slice images of the 
patient's brain are built up into a quasi-three dimensional map in virtual 
space. This map is then correlated to the three dimensional stereotactic 
frame of reference in the real surgical field. In order to align these two 
coordinate frames, both the instruments and the patient must be situated 
in correspondence to the virtual map. The head frame is therefore rigidly 
mounted to the sugical table. Subsequently, a series of reference points 
are established relative aspects of the frame and patient's skull, so that 
the computer can adjust and calculate the correlation between the real 
world of the patient's head and the virtual space model of the patient MRI 
scans. The surgeon is able to target any region within the stereotactic 
space of the brain within 1 millimeter precision. Initial anatomical 
target localization is achieved either directly using the MRI images, or 
indirectly using interactive anatomical atlas programs which map the atlas 
image onto the steroetactic image of the brain. In the present invention, 
the target space is that occupied by the anterior and intralaminar nuclei. 
The surgery itself can be performed under either local or general 
anaesthetic. An initial incision is made in the scalp, preferably 2.5 
centimeters lateral to the midline of the skull, anterior to the coronal 
suture. A burr hole is then drilled in the skull itself; the size of the 
hole being suitable to permit surgical manipulation and implantation of 
the electrode. This size of the hole is generally about 14 millimeters. 
The dura is then opened, and a fibrin glue is applied to minimize cerebral 
spinal fluid leaks and the entry of air into the cranial cavity. A guide 
tube cannula with a blunt tip is then inserted into the brain parechyma to 
a point approximately one centimeter from the target tissue. At this time 
physiological localization starts with the ultimate aim of correlating the 
anatomical and physiological findings to establish the final stereotactic 
target structure. 
Physiological localization using single-cell microelectrode recording is 
preferable for definitive target determination. Sole reliance on 
anatomical localization can be problematic because of the possible 
discrepancies between the expected location (expected from the 
visualization provided by the virtual imaging of the MRI) and the actual 
position within the skull. Microelectrode recording povides exquisite 
physiological identification of neuronal firing patterns via direct 
measures of individual single unit neuronal acitivity. Single-cell 
microelectrode recordings obtained from intralaminar thalamic cells 
typically have a characteristic bursting activity. In addition to 
microelectrode recording, microstimulation and or macrostimulation may be 
performed to provide further physiological localization. 
Once the final target nuclei have been identified in the real spatial frame 
of reference, the permanent electrode is implanted. General principles 
guiding the final implantation of the electrode involve the placement of 
the electrode in a region, and in an orientation, allowing for maximal 
efficacy while minimizing the undesired side effects. The currently used 
brain stimulating electrodes are quadripolar electrodes. The electrode 
itself is approximately 1-1.5 millimeter diameter flexible elastomeric 
sheath which contains four wound wire leads. The leads terminate at the 
distal and proximal ends of the sheath in four electrically insulated 
cylindrical contact pad. The contact pads at the distal end are less than 
2 millimeters in length and are separated by an insulating distance, for 
example between 0.5 and 2 millimeters. At the proximal end, which is 
anywhere from 25 to 50 centimeters distance from the distal end, a 
corresponding series of contacts are provided so that the electrode may be 
coupled to a potential source, or to a coupling lead which permits remote 
disposition of the signal source. 
The initial application of the electrical signal through the electrode is 
then attempted. The range of signal types are between 0.1 to 20 volts, 
with a pulse width of 10 microseconds to 1000 microseconds, and a 
frequency of 2 to 2500 Hertz. The stimulation can be monopolar or bipolar 
depending upon the specific relative potentials applied to the electrical 
contacts relative to the patient's tissue. Various stimulation parameters 
are tested to assess side effects (such as motor contraction, 
paresthesias, visual disturbance, pain, and autonomic modulation) or 
clinical efficacy. Psychological disorders treated by electrostimulation, 
however, may take up to six months to demonstrate clinical efficacy. Long 
term adjustment of the signal being applied by the power source may be 
required to optimize the outcome. If the patient's symptoms do not 
subside, the surgeon will attempt to adjust all of the parameters until 
they do. 
As is readily obvious to anyone who has witnessed the unnecessary surgical 
procedure associated with the remote localization of the power source, it 
is desirable the burr cap structure itself comprise the signal source. 
However, as that option is not presently available the signal source 
generator must be disposed at a remote site in the patient's body. A 
specially designed plastic cap is generally provided to seat in the burr 
hole, and permit the proximal end of the electrode to pass out through the 
skull. The incision in the patient's skull is then sutured closed with the 
electrode temporarily stored under the skin. If the patient is not already 
under general anaesthesia, the patient is so disposed and a tunnel is 
formed under the dermal layers, connecting the incision in the scalp to 
the remote location for the signal generator (usually the infraclavicular 
region, beneath the collar bone - where cardiovascular pace makers are 
implanted). Subsequent joining of the electrode to a coupling (extending) 
lead from the signal source to the brain electrode is then necessary, 
however, generally the manner in which the electrode and the lead are 
coupled utilizes the same terminal contacts as would be used for direct 
coupling to the power source. 
Once the sugery is complete, a non-contrast CT scan is taken to ensure that 
there is no intracranial hematoma. Subsequently, various stimulation 
parameters are programmed and patients are assessed for any side effects 
as well as clinical efficacy. As behavioral and related cognitive 
improvement may not occur immediately, long-term benefits may not be 
achieved until multiple adjustmnts are accomplished. 
While there has been described and illustrated specific embodiments of new 
and novel methods of treatment for psychological disorders, it will be 
apparent to those skilled in the art that variations and modifications are 
possible without deviating from the broad spirit and principle of the 
present invention which shall be limited solely by the scope of the claims 
appended hereto.