- Email: [email protected]
Its all starting to add up
connections in the normal human brain. One also needs to pay close attention to TMS parameters such as stimulation intensity and frequency, and coil orientation As mentioned above, these parameters are known to influence changes in muscle activity when stimulating the primary motor cortex, and will most likely affect local and distal CBF response in other regions as well. We cannot assume that these effects will be similar throughout the cerebral cortex. A series of careful studies is necessary to evaluate the sensitivity of the TMVPET method to the stimulation parameters, as well as possible interregional variations. Finally, Wassermann and Grafman rightly stress the importance of considering the mental state of the subject during a TMS/PET experiment. They suggest that ‘procedures such as sham stimulation and having subjects perform functionally related tasks requiring continuous attention will often be necessary’. It is important to note that in our first study, the subjects received stimulation in all six scans. Only the number of stimuli differed across scans, with the order of scans being randomized. Only two of the six subjects noticed differences in the number of stimuli in different scans. Such a parametric design minimized the possible effects, on CBF, of two qualitatively different mental sets that would have been associated with the ‘stimulation on’ vs ‘stimulation off’ design, respectively. Nevertheless, we will be develop-
ing modifications that should eliminate altogether the possibility of the subject distinguishing the true from the sham stimulation. Indeed we prefer this approach rather than having the subject perform another task. The latter would seriously confound the study. In conclusion, we agree with the commentators that the largest potential of the combined TMS/PET studies lies in the assessment of changes in neural connectivity in relation to normal and abnormal behavior. We must begin to explore possible modifications of connectivity in relation to motor and perceptual learning, reorganization of the human brain following injury, possible abnormalities of connectivity in patients with schizophrenia, and normal development of connections in childhood and adolescence. Some of these goals can be achieved with PET, whereas others may require a combination of TMS with other measurement techniques such as electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). While combined TMSlEEG studies have already been carried outg, it remains to be seen whether TMS can be readily accomplished in the MR scanner. The principle will be the same though: stimulate the brain at a precise location and measure the response elsewhere.
Summaries of recently scientists. Readers who identifying appropriate contact the Editor.
papers of interest to cognitive to contribute to this section, by writing short summaries, should
published would like papers and
calculation following
deficits damage
different
brain areas, including
have to
been many
parts of
the frontal and the right posterior cortex, acalculia arising from damage to these areas may be a secondary consequence of a more general disruption to planning or visuo-spatial abilities that are widely believed to be mediated by these areas. In contrast, the classical acalculia that arises after damage to left inferior parietal cortex, or the less frequent acalculia that has been reported after isolated left subcortical damage, may result from a more fundamental deficit in number processing. Indeed, it has been suggested that both disorders result from impaired memory for stored arithmetic facts. Certainly both deficits involve an inability to per-
(1986)
R.W., Krause, Cottico-cortical
coherence: 3 Friston,
.. . . . .. . .. . . . .. . . . .. . . . .. . .. . . . . .. .. . . K.
Lokalisationslehre
(1909)
et
6, 156-l
form 6x7,
simple calculations (for example, or 11-3) even though the ability
to read numbers
and write
them
down
to dictation is frequently preserved. Dehaene and Cohen now report the results of an extensive neuropsychological evaluation of the number processing abilities of two single case studies with acalculia. One patient had extensive damage to the right inferior parietal lobule, while the other had damage to left subcortical structures including the lenticular nucleus, head of the caudate, internal capsule and insula. The patient with damage to left inferior parietal cortex demonstrated a category specific impairment in quantitative numerical knowledge which was observed in subtraction and number bisection tasks (name the number that falls between 7
Copyright Trends
in
0 1997, Elsevier
Cognitive
Sciences
EEG
43
(1996)
Functional brain
and Cereb.
64 during
tomography:
a new
Transcranial
magnetic
positron
emission
method
of the
J. Neurosc;.
scaling
in the
stimulation connectivity
human
for
studying
cerebral
cortex
17. 317&3184
5 Ziemann.
et
U.
antlepileptic
al.
(1996)
drugs
excitability
in
magnetic
stimulation
on
Effects
humans:
a
study
of
cortex
motor
transcranial
Ann.
Neural.
40,
367-378 6 Priori,
A.
et
inhibition
al.
and
(1994)
the
changes
after transcranial
brain
and
patients
cortical system.
in the silent stimulation
with
drug-induced
Motor
dopaminergic
Pharmacological subjects.
period
in normal
Parkinson’s
disease
parkinsonism
Brain
117,
3 17-323
etal.
7 Paus, T .
of cerebral cortex:
(1995)
blood
Extra-retinal flow
implications
J. Neurophysiol. 8 Talairach.
for saccadic
and
tool
At/as Imaging,
R.J. et al. stimulation,
Neurolmage
P.
(1988)
of the Human
Proportional
to Cerebral
magnetic
visual
suppression
Tournoux,
Stereotactic
Approach
modulation
in the human
74, 2179-2183 J.
Co-planar
Barth
to add up
model
al.
4 Paus, T . et al. (1997)
Vergleichende
der Groshirnrinde,
EEG
connectivity
3 Ilmoniemi,
1 Brodmann.
M.
and
multidimensional
functional
.. .
References
Hrybyk,
64, 123-l
K.J.
topography: Cortex
P.J. and associations
a two-compartmental
C/in. Neurophysiol.
Brain: 3.Dimensional
. . .. . .
Its all starting Although observed
2 Thatcher,
System: An Verlag
(1997) a new
Multichannel brain
mapping
5. 5518
and 9) but had preserved knowledge of arithmetic facts that would normally be expected to be learned by rote (reciting numbers in sequence 1,2,3,4). In contrast, the patient with subcortical damage displayed a selective deficit in rote verbal knowledge, including but not limited to arithmetic tables (reciting numbers or letters in sequence), with intact knowledge of numerical quantities. The authors conclude that this double dissociation between role verbal and quantitative knowledge of arithmetic
suggests
that
numerical
knowledge
is
processed in different formats within distinct anatomical networks in the brain. Although it is likely that most calculations involve the simultaneous activation of several anatomical areas,
these
data
do support
recent
number
processing models which fractionate numerical knowledge into modules that specialize in quantitative number processing and rote verbal arithmetic memory, respectively. Reference Dehaene,
S. and Cohen,
ways for calculation: rote verbal metic
Science -
and quantitative
Cortex
Cerebral
path-
dissociation
between
knowledge
of arith-
33, 219-250
Ltd. All rights Vol.
L. (1997)
double
1,
No.
reserved. 6,
1364.6613/97/$17.00 September
1997
ing modifications that should eliminate altogether the possibility of the subject distinguishing the true from the sham stimulation. Indeed we prefer this approach rather than having the subject perform another task. The latter would seriously confound the study. In conclusion, we agree with the commentators that the largest potential of the combined TMS/PET studies lies in the assessment of changes in neural connectivity in relation to normal and abnormal behavior. We must begin to explore possible modifications of connectivity in relation to motor and perceptual learning, reorganization of the human brain following injury, possible abnormalities of connectivity in patients with schizophrenia, and normal development of connections in childhood and adolescence. Some of these goals can be achieved with PET, whereas others may require a combination of TMS with other measurement techniques such as electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). While combined TMSlEEG studies have already been carried outg, it remains to be seen whether TMS can be readily accomplished in the MR scanner. The principle will be the same though: stimulate the brain at a precise location and measure the response elsewhere.
Summaries of recently scientists. Readers who identifying appropriate contact the Editor.
papers of interest to cognitive to contribute to this section, by writing short summaries, should
published would like papers and
calculation following
deficits damage
different
brain areas, including
have to
been many
parts of
the frontal and the right posterior cortex, acalculia arising from damage to these areas may be a secondary consequence of a more general disruption to planning or visuo-spatial abilities that are widely believed to be mediated by these areas. In contrast, the classical acalculia that arises after damage to left inferior parietal cortex, or the less frequent acalculia that has been reported after isolated left subcortical damage, may result from a more fundamental deficit in number processing. Indeed, it has been suggested that both disorders result from impaired memory for stored arithmetic facts. Certainly both deficits involve an inability to per-
(1986)
R.W., Krause, Cottico-cortical
coherence: 3 Friston,
.. . . . .. . .. . . . .. . . . .. . . . .. . .. . . . . .. .. . . K.
Lokalisationslehre
(1909)
et
6, 156-l
form 6x7,
simple calculations (for example, or 11-3) even though the ability
to read numbers
and write
them
down
to dictation is frequently preserved. Dehaene and Cohen now report the results of an extensive neuropsychological evaluation of the number processing abilities of two single case studies with acalculia. One patient had extensive damage to the right inferior parietal lobule, while the other had damage to left subcortical structures including the lenticular nucleus, head of the caudate, internal capsule and insula. The patient with damage to left inferior parietal cortex demonstrated a category specific impairment in quantitative numerical knowledge which was observed in subtraction and number bisection tasks (name the number that falls between 7
Copyright Trends
in
0 1997, Elsevier
Cognitive
Sciences
EEG
43
(1996)
Functional brain
and Cereb.
64 during
tomography:
a new
Transcranial
magnetic
positron
emission
method
of the
J. Neurosc;.
scaling
in the
stimulation connectivity
human
for
studying
cerebral
cortex
17. 317&3184
5 Ziemann.
et
U.
antlepileptic
al.
(1996)
drugs
excitability
in
magnetic
stimulation
on
Effects
humans:
a
study
of
cortex
motor
transcranial
Ann.
Neural.
40,
367-378 6 Priori,
A.
et
inhibition
al.
and
(1994)
the
changes
after transcranial
brain
and
patients
cortical system.
in the silent stimulation
with
drug-induced
Motor
dopaminergic
Pharmacological subjects.
period
in normal
Parkinson’s
disease
parkinsonism
Brain
117,
3 17-323
etal.
7 Paus, T .
of cerebral cortex:
(1995)
blood
Extra-retinal flow
implications
J. Neurophysiol. 8 Talairach.
for saccadic
and
tool
At/as Imaging,
R.J. et al. stimulation,
Neurolmage
P.
(1988)
of the Human
Proportional
to Cerebral
magnetic
visual
suppression
Tournoux,
Stereotactic
Approach
modulation
in the human
74, 2179-2183 J.
Co-planar
Barth
to add up
model
al.
4 Paus, T . et al. (1997)
Vergleichende
der Groshirnrinde,
EEG
connectivity
3 Ilmoniemi,
1 Brodmann.
M.
and
multidimensional
functional
.. .
References
Hrybyk,
64, 123-l
K.J.
topography: Cortex
P.J. and associations
a two-compartmental
C/in. Neurophysiol.
Brain: 3.Dimensional
. . .. . .
Its all starting Although observed
2 Thatcher,
System: An Verlag
(1997) a new
Multichannel brain
mapping
5. 5518
and 9) but had preserved knowledge of arithmetic facts that would normally be expected to be learned by rote (reciting numbers in sequence 1,2,3,4). In contrast, the patient with subcortical damage displayed a selective deficit in rote verbal knowledge, including but not limited to arithmetic tables (reciting numbers or letters in sequence), with intact knowledge of numerical quantities. The authors conclude that this double dissociation between role verbal and quantitative knowledge of arithmetic
suggests
that
numerical
knowledge
is
processed in different formats within distinct anatomical networks in the brain. Although it is likely that most calculations involve the simultaneous activation of several anatomical areas,
these
data
do support
recent
number
processing models which fractionate numerical knowledge into modules that specialize in quantitative number processing and rote verbal arithmetic memory, respectively. Reference Dehaene,
S. and Cohen,
ways for calculation: rote verbal metic
Science -
and quantitative
Cortex
Cerebral
path-
dissociation
between
knowledge
of arith-
33, 219-250
Ltd. All rights Vol.
L. (1997)
double
1,
No.
reserved. 6,
1364.6613/97/$17.00 September
1997